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ObjectiveCerebral amyloidosis and severe tauopathy in the brain are key pathological features of Alzheimer’s disease (AD). Despite a strong influence of the intestinal microbiota on AD, the causal relationship between the gut microbiota and AD pathophysiology is still elusive.DesignUsing a recently developed AD-like pathology with amyloid and neurofibrillary tangles (ADLPAPT) transgenic mouse model of AD, which shows amyloid plaques, neurofibrillary tangles and reactive gliosis in their brains along with memory deficits, we examined the impact of the gut microbiota on AD pathogenesis.ResultsComposition of the gut microbiota in ADLPAPT mice differed from that of healthy wild-type (WT) mice. Besides, ADLPAPT mice showed a loss of epithelial barrier integrity and chronic intestinal and systemic inflammation. Both frequent transfer and transplantation of the faecal microbiota from WT mice into ADLPAPT mice ameliorated the formation of amyloid β plaques and neurofibrillary tangles, glial reactivity and cognitive impairment. Additionally, the faecal microbiota transfer reversed abnormalities in the colonic expression of genes related to intestinal macrophage activity and the circulating blood inflammatory monocytes in the ADLPAPT recipient mice.ConclusionThese results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD in ADLPAPT mice, providing new insights into the relationship between the gut (colonic gene expression, gut permeability), blood (blood immune cell population) and brain (pathology) axis and AD (memory deficits). Thus, restoring gut microbial homeostasis may have beneficial effects on AD treatment.

Calf diarrhea is associated with enteric infections, and also provokes the overuse of antibiotics. Therefore, proper treatment of diarrhea represents a therapeutic challenge in livestock production and public health concerns. Here, we describe the ability of a fecal microbiota transplantation (FMT), to ameliorate diarrhea and restore gut microbial composition in 57 growing calves. We conduct multi-omics analysis of 450 longitudinally collected fecal samples and find that FMT-induced alterations in the gut microbiota (an increase in the family Porphyromonadaceae ) and metabolomic profile (a reduction in fecal amino acid concentration) strongly correlate with the remission of diarrhea. During the continuous follow-up study over 24 months, we find that FMT improves the growth performance of the cattle. This first FMT trial in ruminants suggest that FMT is capable of ameliorating diarrhea in pre-weaning calves with alterations in their gut microbiota, and that FMT may have a potential role in the improvement of growth performance. Here, the authors report the results of a longitudinal multi-omics trial of the use of fecal microbiota transplantation (FMT) to ameliorate diarrhea and restore gut microbial composition in 57 growing calves, and find that oral FMT induces alterations in the gut microbiota correlate with the remission of diarrhea and improves the growth performance of the cattle.

Correlations of partitioned particles carry essential information about their quantumness 1 . Partitioning full beams of charged particles leads to current fluctuations, with their autocorrelation (namely, shot noise) revealing the particles’ charge 2 , 3 . This is not the case when a highly diluted beam is partitioned. Bosons or fermions will exhibit particle antibunching (owing to their sparsity and discreteness) 4 – 6 . However, when diluted anyons, such as quasiparticles in fractional quantum Hall states, are partitioned in a narrow constriction, their autocorrelation reveals an essential aspect of their quantum exchange statistics: their braiding phase 7 . Here we describe detailed measurements of weakly partitioned, highly diluted, one-dimension-like edge modes of the one-third filling fractional quantum Hall state. The measured autocorrelation agrees with our theory of braiding anyons in the time domain (instead of braiding in space); with a braiding phase of 2 θ  = 2π/3, without any fitting parameters. Our work offers a relatively straightforward and simple method to observe the braiding statistics of exotic anyonic states, such as non-abelian states 8 , without resorting to complex interference experiments 9 . A simple experimental method identifies the statistical phase of highly diluted abelian anyons weakly partitioned in fractional quantum Hall states and reveals their braiding statistics.

A collider where particles are injected onto a beam splitter from opposite sides has been used for identifying quantum statistics of identical particles. The collision leads to bunching of the particles for bosons and antibunching for fermions. In recent experiments, a collider was applied to a fractional quantum Hall regime hosting Abelian anyons. The observed negative cross-correlation of electrical currents cannot be understood with fermionic antibunching. Here we predict, based on a conformal field theory and a non-perturbative treatment of non-equilibrium anyon injection, that the collider provides a tool for observation of the braiding statistics of various Abelian and non-Abelian anyons. Its dominant process is not direct collision between injected anyons, contrary to common expectation, but braiding between injected anyons and an anyon excited at the collider. The dependence of the resulting negative cross-correlation on the injection currents distinguishes non-Abelian SU(2) k anyons, Ising anyons, and Abelian Laughlin anyons. Colliders are used to probe particles’ quantum statistical properties. Now, a theoretical proposal for a collider for anyons (a type of topological quasiparticles occurring in 2D systems) is reported, which can be used to explore the braiding statistics of various Abelian and non-Abelian anyons.

Over the past 20 years, many efforts have been made to understand and control decoherence in 2D electron systems. In particular, several types of electronic interferometers have been considered in GaAs heterostructures, in order to protect the interfering electrons from decoherence. Nevertheless, it is now understood that several intrinsic decoherence sources fundamentally limit more advanced quantum manipulations. Here, we show that graphene offers a unique possibility to reach a regime where the decoherence is frozen and to study unexplored regimes of electron interferometry. We probe the decoherence of electron channels in a graphene quantum Hall PN junction, forming a Mach-Zehnder interferometer 1 , 2 , and unveil a scaling behavior of decay of the interference visibility with the temperature scaled by the interferometer length. It exhibits a remarkable crossover from an exponential decay at higher temperature to an algebraic decay at lower temperature where almost no decoherence occurs, a regime previously unobserved in GaAs interferometers. Quantum Hall edge channels provide a platform to study electron interference, however understanding decoherence in these systems remains an open problem. Jo et al. realize a regime of suppressed decoherence in an electronic Mach-Zehnder interferometer formed in a graphene quantum Hall pn junction.

Optical throughput and optical path length are key parameters to obtain high signal to noise ratio and sensor sensitivity for the detection of skin tissue components based on short wavelength infrared (SWIR) spectroscopy. These parameters should be taken into account at the stage of optical system design. We aim to develop a method to estimate the optical efficiency and the effective water path length of a newly designed SWIR spectroscopy skin measurement system using Monte-Carlo photon migration simulation. To estimate the optical efficiency and the effective water path length, we investigated the characteristics of Monte-Carlo photon migration simulation utilizing one layered simple skin model. Simulation of photon transport in skin was conducted for transmission, transflection, and reflection optical configurations in both first overtone (1540 ~ 1820 nm) and combination (2040 ~ 2380 nm) wavelength ranges. Experimental measurement of skin spectrum was done using Fourier transform infrared spectroscopy based system to validate the estimation performance. Overall, the simulated results for optical efficiency and effective water path length are in good agreements with the experimental measurements, which shows the suggested method can be used as a means for the performance estimation and the design optimization of various in-vivo SWIR spectroscopic system.

IntroductionThe global burden of chronic immune-mediated inflammatory diseases (IMIDs) is increasing, and rising prevalence rates significantly affect socioeconomic factors and quality of life. Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), along with ankylosing spondylitis (AS), are prominent chronic IMIDs that share overlapping pathophysiological mechanisms. Recent research has highlighted the importance of the gut microbiota in the pathogenesis of these diseases, suggesting that shared microbial dysbiosis may contribute to their development. Comprehensive research focusing on the gut and oral microbial characteristics and environmental factors is essential to elucidate the fundamental pathophysiology and develop personalised management strategies for IBD and AS. In-depth analyses and insights based on multiomics approaches are required to achieve these objectives.Methods and analysisThis protocol describes a nationwide prospective observational study of CD, UC and AS in a Korean population. Over 5 years, we aim to recruit at least 900 patients with IBD and 200 first-degree relatives (FDRs), 500 patients with AS and 200 of their FDRs, and 2244 healthy controls. We will systematically collect clinical data and biological samples, including saliva, stool, blood and tissue biopsies, for integrative multiomics analyses focusing primarily on the microbiome. Highly advanced full-length 16S ribosomal RNA gene sequencing and shotgun metagenomics will be used to characterise the microbial composition of saliva and stool samples. Quantitative microbiome profiling will be used to address the pathological, physiological and ecological differences between microbial groups that may be masked by their relative abundance. Metabolomic analyses will be conducted on saliva, stool and plasma samples to assess functional metabolic profiles. Culturomics will be used to isolate, identify and characterise the diversity of microbial species, including rare or previously unrecognised species, to provide a comprehensive understanding of the microbiota associated with these diseases.Ethics and disseminationEthical approval was obtained from the Ethics Committee of Kyung Hee University Hospital, Hanyang University Hospital, Kangbuk Samsung Hospital, Yeungnam University Hospital, Kyungpook National University Hospital, Chonnam National University Hospital, Wonkwang University Hospital, Catholic University Daejeon St. Mary’s Hospital, Soon Chun Hyang University Hospital Cheonan, Chung-Ang University Hospital, Inje University Haeundae Paik Hospital, Dankook University Hospital, Hanyang University Guri Hospital, Kyung Hee University Hospital at Gangdong, Chung-Ang University Gwangmyeong Hospital and Keimyung University Dongsan Hospital. Our research team will provide detailed information about the study, including an information sheet explaining its aims and procedures, prior to enrolment. Prospective participants will be informed that they have the right to withdraw from the study at any time, without penalty. Participants will be assured of the anonymity and confidentiality of any data they provide throughout the study, using participant numbers and the storage of sensitive data in locked cabinets. Participants will be enrolled in the study only after providing written informed consent to the research staff. The results of this study will be disseminated to healthcare and academic professionals through publications in peer-reviewed journals and presentations at international conferences.Trial registration numberThis prospective observational study is registered at ClinicalTrials.gov ((ID: NCT06124833, data first posted: 9 November 2023); (ID: NCT06076083, data first posted: 21 November 2023) and (ID: NCT06183697, data first posted: 27 December 2023)).

Mitochondrial function and innate immunity are intimately linked; however, the mechanisms how mitochondrion-shaping proteins regulate innate host defense remains largely unknown. Herein we show that mitofusin-2 (MFN2), a mitochondrial fusion protein, promotes innate host defense through the maintenance of aerobic glycolysis and xenophagy via hypoxia-inducible factor (HIF)-1α during intracellular bacterial infection. Myeloid-specific MFN2 deficiency in mice impaired the antimicrobial and inflammatory responses against mycobacterial and listerial infection. Mechanistically, MFN2 was required for the enhancement of inflammatory signaling through optimal induction of aerobic glycolysis via HIF-1α, which is activated by mitochondrial respiratory chain complex I and reactive oxygen species, in macrophages. MFN2 did not impact mitophagy during infection; however, it promoted xenophagy activation through HIF-1α. In addition, MFN2 interacted with the late endosomal protein Rab7, to facilitate xenophagy during mycobacterial infection. Our findings reveal the mechanistic regulations by which MFN2 tailors the innate host defense through coordinated control of immunometabolism and xenophagy via HIF-1α during bacterial infection.Silwal, Kim et al. show that mitofusin-2 (MFN2), a mitochondrial fusion protein, promotes innate host defense through coordinated orchestration of immunometabolism and xenophagy via HIF-1α in macrophages during bacterial infection. This study provides insights into how mitochondria-shaping protein is involved in host defense against intracellular bacterial infection.

Experimental Objective: During red blood cell (RBC) transfusion, inflammation promotes the production of anti-RBC alloantibodies that can cause significant hemolytic events. Avoiding RBC antigen exposure is the only strategy to prevent RBC alloimmunization in transfusion recipients. Identifying mechanisms that inhibit alloimmunization may lead to novel prophylactic interventions. One potential regulatory mechanism is the activation of the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2), a master regulator of antioxidant pathways. Pharmacologic Nrf2 activators induce antioxidant production and improve the sequelae of inflammatory diseases. Thus, we tested the hypothesis that a Nrf2 activator, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]-imidazole (CDDO-Im), regulates inflammation-induced RBC alloimmunization. Methods: WT and Nrf2-deficient mice were treated with inflammatory stimuli and CDDO-Im prior to transfusion with RBCs expressing the KEL antigen (KEL+ RBCs). Anti-KEL IgM and IgG were measured in the serum of transfused mice. Nrf2-activated gene expression and interferon activity were measured in mice and human macrophages pre-treated with CDDO-Im and interferon stimuli. Results: Here, we report that CDDO-Im induces Nrf2-activated gene expression and inhibits type 1 interferon activity, which promotes RBC alloimmunization in transfusion models. In mice transfused with KEL+ RBCs, pre-treatment with CDDO-Im inhibited inflammation-induced anti-KEL antibody production and increased the post-transfusion recovery of KEL+ RBCs in a Nrf2-dependent manner. CDDO-Im also inhibited RBC alloimmunization in mice with pre-existing inflammation. Conclusions: These results indicate that the activation of the Nrf2 antioxidant pathway regulates RBC alloimmunization to the KEL antigen in a pre-clinical model. If these findings translate to other models and human studies, Nrf2 activators may represent a potential prophylactic intervention to inhibit alloimmunization.

Purpose Chemotherapy-induced nausea and vomiting (CINV) is a common adverse events in cancer patients and can negatively affect their quality of life (QoL). This study aimed to evaluate the clinical efficacy of an electric massage chair (EMC) for the treatment of CINV. Methods A randomized phase II cross-over trial was conducted on solid cancer patients who received moderate (MEC) to high emetogenic chemotherapy (HEC). The participants were randomly assigned to receive their first chemotherapy either on a standard bed (Group A) or in an EMC (Group B) during the infusion. The patients were then crossed over to the next cycle. CINV and QoL questionnaires were collected from the participants. Results A total of 59 patients completed the trial protocol and were included in the analysis, with 29 and 30 patients in Groups A and B, respectively. The mean INVR (Index of Nausea, Vomiting, and Retching) score in the 2nd day of the first cycle was higher in Group B (3.63 ± 5.35) than Group A (2.76 ± 4.78), but the difference was not statistically significant ( p  = 0.5367). The complete response rate showed little difference between the groups. Among the high-emetic risk subgroups, patients who received HEC ( p  = 0.04595), younger patients ( p  = 0.0108), and non-colorectal cancer patients ( p  = 0.0495) presented significantly lower CINV scores when EMC was applied. Conclusion Overall, there was no significant difference in INVR scores between standard care and EMC. Applying EMC at the first chemotherapy infusion may help preserve QoL and reduce CINV in high-risk patients. Trial registration KCT0008200, 17/02/2023, Retrospectively registered.