Impairment of Dendrodendritic Inhibition in the Olfactory Bulb of APP/PS1 Mice

Olfactory dysfunction is an early event in Alzheimer’s disease (AD). However, the mechanism underlying the AD-related changes in the olfactory bulb (OB) remains unknown. Granule cells (GCs) in the OB regulate the activity of mitral cells (MCs) through reciprocal dendrodendritic synapses, which is crucial for olfactory signal processing and odor discrimination. Nevertheless, the relationships between the morphological and functional changes of dendrodendritic synapses, particularly the local field potentials (LFPs) as a consequence of olfactory disorders in patients with AD have not been investigated. Here, we studied the morphological and functional changes induced by dendrodendritic inhibition in GCs onto MCs in the OB of amyloid precursor protein (APP)/PS1 mice and age-matched control mice during aging, particular, we focused on the effects of olfactory disorder in the dendrodendritic synaptic structures and the LFPs. We found that olfactory disorder was associated with increased amyloid-β (Aβ) deposits in the OB of APP/PS1 mice, and those mice also exhibited abnormal changes in the morphology of GCs and MCs, a decreased density of GC dendritic spines and impairments in the synaptic interface of dendrodendritic synapses between GCs and MCs. In addition, the aberrant enhancements in the γ oscillations and firing rates of MCs in the OB of APP/PS1 mice were recorded by multi-electrode arrays (MEAs). The local application of a GABAAR agonist nearly abolished the aberrant increase in γ oscillations in the external plexiform layer (EPL) at advanced stages of AD, whereas a GABAAR antagonist aggravated the γ oscillations. Based on our findings, we concluded that the altered morphologies of the synaptic structures of GCs, the dysfunction of reciprocal dendrodendritic synapses between MCs and GCs, and the abnormal γ oscillations in the EPL might contribute to olfactory dysfunction in AD

Anaerobic Fungi Isolated From Bactrian Camel Rumen Contents Have Strong Lignocellulosic Bioconversion Potential

This study aims to obtain anaerobic fungi from the rumen and fecal samples and investigates their potential for lignocellulosic bioconversion. Multiple anaerobic strains were isolated from rumen contents (CR1–CR21) and fecal samples (CF1–CF10) of Bactrian camel using the Hungate roll tube technique. After screening for fiber degradability, strains from rumen contents (Oontomyces sp. CR2) and feces (Piromyces sp. CF9) were compared with Pecoramyces sp. F1 (earlier isolated from goat rumen, having high CAZymes of GHs) for various fermentation and digestion parameters. The cultures were fermented with different substrates (reed, alfalfa stalk, Broussonetia papyrifera leaves, and Melilotus officinalis) at 39°C for 96 h. The Oontomyces sp. CR2 had the highest total gas and hydrogen production from most substrates in the in vitro rumen fermentation system and also had the highest digestion of dry matter, neutral detergent fiber, acid detergent fiber, and cellulose present in most substrates used. The isolated strains provided higher amounts of metabolites such as lactate, formate, acetate, and ethanol in the in vitro rumen fermentation system for use in various industrial applications. The results illustrated that anaerobic fungi isolated from Bactrian camel rumen contents (Oontomyces sp. CR2) have the highest lignocellulosic bioconversion potential, suggesting that the Bactrian camel rumen could be a good source for the isolation of anaerobic fungi for industrial applications

Monensin and Nisin Affect Rumen Fermentation and Microbiota Differently In Vitro

Nisin, a bacteriocin, is a potential alternative to antibiotics to modulate rumen fermentation. However, little is known about its impacts on rumen microbes. This study evaluated the effects of nisin (1 and 5 μM) on in vitro rumen fermentation characteristics, microbiota, and select groups of rumen microbes in comparison with monensin (5 μM), one of the most commonly used ionophores in ruminants. Nisin had greater effects than monensin in inhibiting methane production and decreasing acetate/propionate ratio. Unlike monensin, nisin had no adverse effect on dry matter digestibility. Real-time PCR analysis showed that both monensin and nisin reduced the populations of total bacteria, fungi, and methanogens, while the population of protozoa was reduced only by monensin. Principal component analysis of bacterial 16S rRNA gene amplicons showed a clear separation between the microbiota shaped by monensin and by nisin. Comparative analysis also revealed a significant difference in relative abundance of some bacteria in different taxa between monensin and nisin. The different effects of monensin and nisin on microbial populations and bacterial communities are probably responsible for the discrepancy in their effects on rumen fermentation. Nisin may have advantages over monensin in modulating ruminal microbial ecology and reducing ruminant methane production without adversely affecting feed digestion, and thus it may be used as a potential alternative to monensin fed to ruminants

Infiltrating circulating monocytes provide an important source of BMP4 at the early stage of spinal cord injury

Bone morphogenetic protein (BMP)4 plays a critical role in regulating neuronal and glial activity in the course of spinal cord injury (SCI). The underlying cause and cellular source of BMP4 accumulation at the injured spinal cord remain unclear. Here, we observed that plasma BMP4 levels are statistically higher in SCI patients than in healthy donors. When comparing rats in the sham group (T9 laminectomy without SCI) with rats in the SCI group, we found a persistent decline in BBB scores, together with necrosis and mononuclear cell accumulation at the contusion site. Moreover, during 2 weeks after SCI both plasma and cerebrospinal fluid levels of BMP4 displayed notable elevation, and a positive correlation. Importantly, percentages of circulating BMP4-positive (BMP4(+)) monocytes and infiltrating MDMs were higher in the SCI group than in the sham group. Finally, in the SCI+clodronate liposome group, depletion of monocytes effectively attenuated the accumulation of both BMP4(+) MDMs and BMP4 in the injured spinal cord. Our results indicated that, following SCI, infiltrating MDMs provide an important source of BMP4 in the injured spinal cord and, therefore, might serve as a potential therapeutic target

Effects of ferric derisomaltose on postoperative anaemia in adult spinal deformity surgery: a study protocol for a randomised controlled trial

Introduction Postoperative anaemia is prevalent in adult spinal deformity (ASD) surgery in association with unfavourable outcomes. Ferric derisomaltose, a novel iron supplement, offers a promising solution in rapidly treating postoperative anaemia. However, the clinical evidence of its effect on patients receiving spinal surgery remains inadequate. This randomised controlled trial aims to evaluate the safety and efficacy of ferric derisomaltose on postoperative anaemia in ASD patients.Methods and analysis This single-centre, phase 4, randomised controlled trial will be conducted at Department of Orthopaedics at Peking Union Medical College Hospital and aims to recruit adult patients who received ASD surgery with postoperative anaemia. Eligible participants will be randomly assigned to receive ferric derisomaltose infusion or oral ferrous succinate. The primary outcome is the change in haemoglobin concentrations from postoperative days 1–14. Secondary outcomes include changes in iron parameters, reticulocyte parameters, postoperative complications, allogeneic red blood cell infusion rates, length of hospital stay, functional assessment and quality-of-life evaluation.Ethics and dissemination This study has been approved by the Research Ethics Committee of Peking Union Medical College Hospital and registered at ClinicalTrials.gov. Informed consent will be obtained from all participants prior to enrolment and the study will be conducted in accordance with the principles of the Declaration of Helsinki. The results of this study are expected to be disseminated through peer-reviewed journals and academic conferences.Trial registration number NCT05714007

Host-microbiota interaction in intestinal stem cell homeostasis

Intestinal stem cells (ISCs) play a pivotal role in gut physiology by governing intestinal epithelium renewal through the precise regulation of proliferation and differentiation. The gut microbiota interacts closely with the epithelium through myriad of actions, including immune and metabolic interactions, which translate into tight connections between microbial activity and ISC function. Given the diverse functions of the gut microbiota in affecting the metabolism of macronutrients and micronutrients, dietary nutrients exert pronounced effects on host-microbiota interactions and, consequently, the ISC fate. Therefore, understanding the intricate host-microbiota interaction in regulating ISC homeostasis is imperative for improving gut health. Here, we review recent advances in understanding host-microbiota immune and metabolic interactions that shape ISC function, such as the role of pattern-recognition receptors and microbial metabolites, including lactate and indole metabolites. Additionally, the diverse regulatory effects of the microbiota on dietary nutrients, including proteins, carbohydrates, vitamins, and minerals (e.g. iron and zinc), are thoroughly explored in relation to their impact on ISCs. Thus, we highlight the multifaceted mechanisms governing host–microbiota interactions in ISC homeostasis. Insights gained from this review provide strategies for the development of dietary or microbiota-based interventions to foster gut health

Stimulation of Gastric Transit Function Driven by Hydrolyzed Casein Increases Small Intestinal Carbohydrate Availability and Its Microbial Metabolism

Gastrointestinal (GI) functions affect gut nutrient flow and microbial metabolism. Dietary peptides modulate GI functions and improve small intestinal health, but the mechanism remains elusive. This study aims to investigate whether dietary peptides affect small intestinal microbial metabolism, and the underlying mechanisms. An ileal-cannulated pig model is adopted to explore the relationship between gut nutrient flow and microbial metabolism after treatment with hydrolyzed casein (peptides) or intact casein (Control)-based diet. The results demonstrate that hydrolyzed casein enhances microbial carbohydrate metabolism with higher Streptococcus abundance and higher lactate level in the ileum. Meanwhile, hydrolyzed casein increases ileal flows of nutrients, especially carbohydrate, leading to a higher carbohydrate availability in ileal digesta. To unveil the mechanisms, it is found that the hydrolyzed casein enhances the ghrelin signal and improves development of interstitial cells of Cajal and muscular layer in gastric corpus, indicating the enhanced upper GI transit function. In addition, hydrolyzed casein improves small intestinal health, as indicated by higher villus heights and luminal lactate concentrations in the jejunum and ileum. In conclusion, hydrolyzed casein stimulates upper GI transit function, enhances gut nutrient flow, and increases small intestinal carbohydrate availability and its microbial metabolism, which favor the small intestinal health.</p

How do orphan disease patients live during the pandemic of Omicron variant? A nationwide survey of spinal muscular atrophy patients in China

Objectives: To investigate the challenges of patients with spinal muscular atrophy (SMA) during the Omicron variant COVID-19 pandemic. Design: A cross-sectional survey was conducted in China from January 02, 2023, to January 12, 2023, using a questionnaire that covered three aspects: (1) Demographic information; (2) SMA-related information; and (3) COVID-19-related information. We recruited patients with SMA from 33 provinces. The prevalence, course, and clinical manifestations of COVID-19 were calculated. The relationships between independent and outcome variables were investigated. Results: In total, 677 patients (male: 349; female: 328) were included in this study (average age = 11.40 years); 534 (78.88%) suffered from COVID-19. The most common symptoms were fever (95.51%), cough (57.87%), and sputum (49.44%). Of the infected patients, 91.57% recovered with at-home care, and 8.43% were hospitalized; 1.31% were admitted to the intensive care unit (ICU). A positive correlation was observed between the SMA severity and hospitalization rate. The ICU stay rate in patients with SMA type I was significantly higher than that in other SMA types. Conclusion: This is the first large sample survey to timely reveal the living situation of patients with SMA during the COVID-19 pandemic's Omicron variant. Patients with SMA type I should be paid more attention in terms of hospitalization and ICU stay

Assessment Tools for Health Literacy among the General Population: A Systematic Review

Health literacy is an important determinant of health, and is one of the key indicators of a healthy city. Developing and improving methods to measure health literacy is prudent and necessary. This review summarizes the findings of published tools for assessing health literacy among the general population to provide a reference for establishing health literacy assessment tools in the future. In this systematic review, PubMed, Embase, and Web of Science were used to search articles regarding tools for assessing health literacy among the general population published up to 10 January 2018. Two researchers independently conducted literature screening, quality assessment of methodology, and data extraction according to preset inclusion and exclusion criteria. The quality assessment of the research was examined with the use of the specifications of the reporting guidelines for survey research (SURGE). Eleven articles met the inclusion criteria. All included instruments in monitoring the health literacy of the general population were presented through the form of questionnaires. The multistage process of making all the scales generally involved the following steps: item development, pre-testing, and evaluation of readability. However, the specific methods were different. Internal consistency for all the instruments was acceptable but with weak consistency among the subscales for some instruments. Most of the identified instruments derived from the definition of health literacy or were based on existing health literacy theory. Approximately 30% of the performed studies provided no description of the important features specified in the SURGE. This review indicates a trend in the increasing tools for assessing the health literacy of the general population by using multidimensional structures and comprehensive measurement approaches. However, no clear &ldquo;consensus&rdquo; was observed in the dimensions of health literacy tools