Functional Changes Research Articles

Characterization of the MT-2 Treg-like cell line in the presence and absence of forkhead box P3 (FOXP3).

CD4+ forkhead box P3 (FOXP3)+ regulatory T cells (Tregs) are essential in maintaining immune tolerance and suppressing excessive immune responses. Tregs also contribute to tissue repair processes distinct from their roles in immune suppression. For these reasons, Tregs are candidates for targeted therapies for inflammatory and autoimmune diseases, and in diseases where tissue damage occurs. MT-2 cells, an immortalized Treg-like cell line, offer a model to study Treg biology and their therapeutic potential. In the present study, we use clustered regularly interspaced palindromic repeats (CRISPR)-mediated knockdown of FOXP3 in MT-2 cells to understand the transcriptional and functional changes that occur when FOXP3 is lost and to compare MT-2 cells with primary human Tregs. We demonstrate that loss of FOXP3 affects the transcriptome of MT-2 cells and that FOXP3's potential downstream targets include a wide range of transcripts that participate in the cell cycle, promote growth and contribute to inflammatory processes, but do not wholly simulate previously reported human primary Treg transcriptional changes in the absence of FOXP3. We also demonstrate that FOXP3 regulates cell cycling and proliferation, expression of molecules crucial to Treg function and MT-2 cell-suppressive activities. Thus, MT-2 cells offer opportunities to address regulatory T-cell functions in vitro.

Changes in Milk Protein Functionality at Low Temperatures and Rennet Concentrations

This study aimed to evaluate the influence of low-concentration rennet on the chemical, rheological characteristics, and protein fractions of skim milk (SM) at 4 ± 1 °C. Skimmed milk (SM) was divided into four lots of 500 mL, and diluted rennet (1:10,000) was added at different levels at 4 ± 1 °C. The treatments included control (no rennet), T1 (0.001 mL/rennet), T2 (0.01 mL rennet), and T3 (0.1 mL rennet) treatments, which were incubated for 24 h. The sampling was performed at 0, 1, 2, 6, 12, and 24 h, and the SM after incubation time was heated to 73 °C/16 s to denature the rennet enzyme. Skim milk samples (SMS) (control and rennet-added samples) were evaluated for proximate composition, capillary gel electrophoresis (CGE), hydrodynamic diameter, zeta potential, and rheology at 0, 1, 2, 6, 12, and 24 h. Foaming ability, foaming stability, water-holding capacity (WHC), oil emulsifying activity (OEA), and emulsion stability (ES) were performed at 0, 12, and 24 h of incubation time. There was a significant (p < 0.05) increase in non-proteins by 0.50% and in non-casein nitrogen by 0.81% as incubation progressed. The results showed that aggregation or curd was not formed during storage time. The CGE data indicated that increasing the rennet concentration had a significant (p < 0.05) effect on decreasing κ-CN, and breakdown increased at higher levels of rennet usage. There was a significant (p < 0.05) increase in the hydrodynamic diameter and a decrease in the zeta potential values in rennet-added samples at the end of the incubation time (24 h). The rheological results showed no changes in the storage modulus (G′), loss modulus (G″), or viscosity values. Increasing the rennet amount and storage time led to a significant (p < 0.05) decrease in the foaming ability and foaming stability and a significant (p < 0.05) increase in the oil emulsifying activity and emulsion stability of rennet-added SMS. This study concluded that milk protein functionality can be changed without aggregating or curd formation, and rennet milk can be processed.

Multiscale characterization of the UV aging resistance and mechanism of light stabilizer-modified asphalt

Abstract To clarify the effect and mechanism of hindered amine light stabilizer (HALS) on the UV aging behavior of asphalt binder, T622-HALS was selected as the modifier for UV aging resistance of asphalt. The physicochemical properties and microstructure of T622 light stabilizer were comprehensively analyzed. The light stabilizer-modified asphalt was prepared and placed in the UV radiation chamber for UV aging treatment. Scanning electron microscope and atomic force microscope were used to analyze the microscopic morphology evolution of light stabilizer-modified asphalt induced by UV radiation. The thermal properties and functional group composition changes in light stabilizer-modified asphalt during UV aging were studied by using the thermogravimetric and infrared spectroscopy combined testing system. The decay laws of the physical and rheological performances of light stabilizer-modified asphalt were studied during UV aging process, and the effect of light stabilizer on the UV aging behavior of asphalt binder was clarified. The research results indicated that HALSs could alleviate the microcracks and roughness change on the surface of asphalt and reduce the content of functional groups such as carbonyl and sulfoxide in asphalt. Furthermore, HALS could reduce the value difference of physical and rheological properties of asphalt before and after UV aging, significantly improving the UV aging resistance of asphalt binder.

Single nucleotide polymorphisms and Zn transport by ZIP11 shape functional phenotypes of HeLa cells.

Zinc (Zn) is a vital micronutrient with essential roles in biological processes like enzyme function, gene expression, and cell signaling. Disruptions in the cellular regulation of Zn2+ ions often lead to pathological states. Mammalian Zn transporters, such as ZIP11, play a key role in homeostasis of this ion. ZIP11 resides predominately in the nucleus and Golgi apparatus. Our laboratory reported a function of ZIP11 in maintaining nuclear Zn levels in HeLa cervical cancer cells. Analyses of cervical and ovarian cancer patients' datasets identified four coding, single nucleotide polymorphisms (SNPs) in SLC39A11, the gene that encodes ZIP11, correlating with disease severity. We hypothesized that these SNPs might translate to functional changes in the ZIP11 protein by modifying access to substrate availability. We also proposed that a metal-binding site (MBS) in ZIP11 is crucial for transmembrane Zn2+ transport and required for maintenance of various pathogenic phenotypes observed in HeLa cells. Here, we investigated these claims by re-introducing single the SLC39A11 gene encoding for mutant residues associated with the SNPs, as well as MBS mutations into HeLa cells knocked down for the transporter. Some SNPs-encoding ZIP11 variants rescued Zn levels, proliferation, migration, and invasiveness of knockdown (KD) cells. Conversely, single MBS mutations mimicked the traits of KD cells, confirming the transporter's role in establishing and maintaining proliferative, migratory, and invasive traits. Overall, the intricate role of Zn in cellular dynamics and cancer progression underscores the significance of Zn transporters like ZIP11 in potential therapeutic interventions.

Investigating the Mechanism of Arsenic-induced Ferroptosis in the Skin

Background: Ferroptosis, an oxidative and iron-dependent cell death, is a new type of regulated cell death. There are few studies on the mechanisms of ferroptosis in the skin and related diseases. Arsenic is shown to induce ferroptosis cell death. This study aimed to decipher the relationship between arsenic exposure and ferroptosis cell death in the skin. Methods: Arsenic-gene interactions were obtained. Then, skin-specific arsenic-gene interactions were screened. Ferroptosis-related genes were identified. Analysis of functional and biological interactions was performed to identify possible mechanisms. Results: The arsenic-gene interactions and the ferroptosis-related genes showed an overlap of 59 genes. Functional enrichment, protein-protein interaction, and transcription factor (TF)/miRNA target gene interaction analyses were used to look into the mechanism of arsenic-induced ferroptosis in the skin. ACTB, CTNNB1, HSPA8, SRC, RACK1, CD44, and SQSTM1 were identified as key proteins. Gene ontology analysis of these proteins indicated the mitochondrial morphology and functionality changes following arsenic-induced ferroptosis in the skin. HIF1A and SP1 TFs regulate a large number of genes compared to other TFs. Ten miRNAs with high interaction with ferroptosis-associated genes were identified. Conclusion: This work investigated the mechanism of arsenic-induced ferroptosis in the skin and identified key genes and regulators, and functional analysis highlighted the role of mitochondria in this skin exposure.

Portal hypertension in patients with nonalcoholic fatty liver disease: Current knowledge and challenges.

Portal hypertension (PH) has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease (NAFLD). However, recent studies have provided evidence that PH may develop in earlier stages of NAFLD, suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis. The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning, leading to the compression of liver sinusoids. External compression and intra-luminal obstacles cause mechanical forces such as strain, shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways, resulting in endothelial dysfunction and the development of fibrosis. The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD. Thus, current diagnostic methods such as hepatic venous pressure gradient (HVPG) measurement tend to underestimate portal pressure (PP) in NAFLD patients, who might decompensate below the HVPG threshold of 10 mmHg, which is traditionally considered the most relevant indicator of clinically significant portal hypertension (CSPH). This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients. In theory, the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component, but more investigations are needed to test its clinical utility for this indication. Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment. Lifestyle change remains the cornerstone of the treatment of PH in NAFLD, together with correcting the components of metabolic syndrome, using nonselective beta blockers, whereas emerging candidate drugs require more robust confirmation from clinical trials.

On the question of choosing the most valid methods for diagnostics of pulpal hyperemia

The choice of the most optimal methods for the diagnosis and treatment of reversible forms of pulpitis is an urgent issue of modern practical endodontics. The dental pulp is unique in its histological structure, innervation and microcirculation. Reversible forms of pulpitis (including pulp hyperemia) are associated with a number of morphological and functional changes in the neurovascular bundle, which, at their early stages, are not fully detected during clinical examination, and require the inclusion of additional functional diagnostic methods, which include not only in the assessment of the nerve elements of the pulp (EOD), but also the study of the state of microcirculation (LDF), a change in which can become a predictor of the inflammatory response. In order to determine the most valid method for assessing the condition of the pulp in reversible forms of pulpitis, 43 young people with a diagnosis of K04.00 (pulp hyperemia) deep caries were examined and treated. Each patient was assessed carious and intact (symmetrical) teeth. At the same time, in addition to clinical diagnostic methods, EOD and LDF were used (M and σ were evaluated). Within two weeks, after the treatment, in 2 patients with the highest values of EOD (19 and 21 μA at the time of the initial examination) and LDF (M: 21.14 and 23.56 arb. units and σ: 0.82 and 0.85 conventional units) was diagnosed with irreversible pulpitis, which required a different treatment strategy. Therefore, when diagnosing reversible forms of pulpitis, it is necessary to be guided not only by the data of a clinical examination (which is undoubtedly the main and determining one), but also to assess the state of the vascular and nervous elements of the pulp, changes in which often anticipate the clinical manifestations of the pathology of the pulp of the tooth.

Cutaneous nerve biopsy in patients with symptoms of small fiber neuropathy: a retrospective study.

We aimed to investigate to what extent small fiber tests were abnormal in an unselected retrospective patient material with symptoms suggesting that small fiber neuropathy (SFN) could be present, and to evaluate possible gender differences. Nerve conduction studies (NCS), skin biopsy for determination of intraepidermal nerve fiber density (IENFD) and quantitative sensory testing (QST) were performed. Z-scores were calculated from reference materials to adjust for the effects of age and gender/height. Two hundred and three patients, 148 females and 55 males had normal NCS and were considered to have possible SFN. 45.3 % had reduced IENFD, 43.2 % of the females and 50.9 % of the males. Mean IENFD was 7.3±2.6 fibers/mm in females and 6.1±2.3 in males (p<0.001), but the difference was not significant when adopting Z-scores. Comparison of gender differences between those with normal and abnormal IENFD were not significant when Z-scores were applied. QST was abnormal in 50 % of the patients (48.9 % in females and 52.9 % in males). In the low IENFD group 45 cases out of 90 (50 %) were recorded with abnormal QST. In those with normal IENFD 51 of 102 (50 %) showed abnormal QST. Less than half of these patients had reduced IENFD, and 50 % had abnormal QST. There were no gender differences. A more strict selection of patients might have increased the sensitivity, but functional changes in unmyelinated nerve fibers are also known to occur with normal IENFD. Approval to collect data was given by the Norwegian data protection authority at University Hospital of North Norway (Project no. 02028).

Trait-related functional changes in understory forest community after invasion are driven by complementarity rather than displacement

Forests support a variety of functions essential for the provisioning of ecosystem services. However, invasive plants can disrupt forest functioning, particularly in temperate forest understories that commonly experience invasive plant encroachment, by altering community-level trait distributions. Invasive plants, frequently characterized by acquisitive traits such as higher specific leaf area and nitrogen content, may either outcompete native species with different trait values (displacement), or add trait values to the existing community (complementarity). Therefore, complementarity may still allow restoration of the original community function by removing invasive species, and consequently the added provision of function when compared to the natives, but displacement may not. While understanding which process occurs is critical in managing ecosystem functionality, little is known about the impact of invasion on the co-occurring native community trait distributions. To address this knowledge gap, we leveraged survey data on temperate forest understories that varied in their degree of invasion (i.e., gradient of invasion). We calculated the community-weighted mean of three leaf traits: leaf nitrogen, specific leaf area, and leaf dry matter content – traits strongly linked to invasion, sensitive to environmental changes, and that affect ecosystem functions. Our findings show that increasing invasion had a significant positive effect on total (native and invasive) community leaf nitrogen, but did not alter native community trait distributions. This suggests that potential impacts on ecosystem functions, such as increased primary productivity and nitrogen cycling, would be primarily driven by trait complementarity and not displacement. We did not find any significant differences in the total or native communities with respect to specific leaf area or leaf dry matter content. Differentiating trait displacement from trait complementarity contributes to our understanding of how invasion affects functionality of understory plant communities in forests. Additionally, it provides a valuable framework to facilitate evidence-based decisions for the management of ecosystem functionality.

Does Hypertension Affect the Recovery of Renal Functions after Reversal of Unilateral Ureteric Obstruction?

Research has demonstrated that hypertension can lead to an exaggeration in the renal functional and histological changes caused by ureteral obstruction. These changes were particularly observed shortly after the release of a relatively brief period of unilateral ureteral obstruction (UUO). However, the long-term impact of hypertension on the recovery of renal functions has not been investigated beyond the immediate period after UUO reversal. In order to investigate this effect, a group of spontaneously hypertensive rats (G-SHR, n = 11) and a group of normotensive Wistar Kyoto rats (G-NTR, n = 11) were subjected to a 48 h reversible left UUO. The impact of UUO was then examined 45 days after the reversal of obstruction. The glomerular filtration rate, renal blood flow, and the fractional excretion of sodium in the post-obstructed left kidney (POK) showed similarities to the non-obstructed right kidney (NOK) in both groups. However, the changes in the albumin creatinine ratio, renal injury markers, pro-apoptotic markers, and histological changes in the G-SHR were much more pronounced compared to the G-NTR. We conclude that hypertension continues to have a significant impact on various aspects of renal injury and function, even several weeks after UUO reversal.

Effectiveness of Different Neurocognitive Intervention Approaches on Functionality in Healthy Older Adults: A Systematic Review.

Subtle loss of functionality in healthy older adults is considered one of the most important predictors of cognitive decline. Neurocognitive interventions are increasingly being used, from a preventive maintenance approach to functional capacity. This study evaluates the effectiveness of different neurocognitive approaches on the functionality of healthy older adults. In this systematic review (CRD42023473944), an extensive search was conducted for articles published in the last 10 years (2013-2023) in the following databases: Medline, Scopus, and Web of Science. A total of 809 trials were identified, of which 18 were considered to be eligible for inclusion in the review. The data revealed heterogeneity in sample size, measures of functional assessment, neurocognitive interventions used, number of sessions, session duration, and time. Traditional cognitive stimulation is shown to have no significant functional benefit, while other less commonly used neurocognitive interventions, such as those based on everyday cognition, are associated with more significant benefits. Moreover, it is demonstrated that although the Instrumental Activities of Daily Living scale (IADL) is the most used test in similar studies, it is not sensitive enough to detect changes in functionality in healthy elderly individuals, with other tests such as the Timed Instrumental Activities of Daily Living (TIADL) being more advantageous. Therefore, a new guideline is proposed for its use in clinical practice and research, using homogeneous study protocols and neurocognitive interventions that allow for the transfer and generalization of results in daily life.

Prostanoids in Cardiac and Vascular Remodeling.

Prostanoids are biologically active lipids generated from arachidonic acid by the action of the COX (cyclooxygenase) isozymes. NSAIDs, which reduce the biosynthesis of prostanoids by inhibiting COX activity, are effective anti-inflammatory, antipyretic, and analgesic drugs. However, their use is limited by cardiovascular adverse effects, including myocardial infarction, stroke, hypertension, and heart failure. While it is well established that NSAIDs increase the risk of atherothrombotic events and hypertension by suppressing vasoprotective prostanoids, less is known about the link between NSAIDs and heart failure risk. Current evidence indicates that NSAIDs may increase the risk for heart failure by promoting adverse myocardial and vascular remodeling. Indeed, prostanoids play an important role in modulating structural and functional changes occurring in the myocardium and in the vasculature in response to physiological and pathological stimuli. This review will summarize current knowledge of the role of the different prostanoids in myocardial and vascular remodeling and explore how maladaptive remodeling can be counteracted by targeting specific prostanoids.

Alterations and correlations in dental plaque microbial communities and metabolome characteristics in patients with caries, periodontitis, and comorbid diseases

BackgroundsThe pathogenic microorganisms and clinical manifestations of caries and periodontitis are different, caries and periodontitis are usually discussed separately, and the relationship between them is ignored. Clinically, patients prone to dental caries generally have a healthier periodontal status, whereas patients with periodontitis generally have a lower incidence of dental caries. The relationship between dental caries and periodontitis remains unclear.ObjectivesThis study aimed to explain the clinical phenomenon of antagonism between dental caries and periodontitis by exploring the ecological chain and bacterial interactions in dental caries, periodontitis, and other comorbid diseases.MethodsThe dental plaque microbiomes of 30 patients with oral diseases (10 each with caries, periodontitis, and comorbid diseases) were sequenced and analysed using 16 S rRNA gene sequencing. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) database was used for a differential functional analysis of dental plaque microbial communities in caries, periodontitis, and comorbid diseases.ResultsThe coinfection group had the greatest bacterial richness in dental plaque. The principal coordinate analysis showed that caries and periodontitis were separate from each other, and comorbid diseases were located at the overlap of caries and periodontitis, with most of them being periodontitis. Simultaneously, we compared the microbiomes with significant differences among the three groups and the correlations between the microbiome samples. In addition, KEGG pathway analysis revealed significant differences in functional changes among the three groups.ConclusionsThis study revealed the composition of the dental plaque microbial communities in caries, periodontitis, and comorbidities and the differences among the three. Additionally, we identified a possible antagonism between periodontitis and caries. We identified a new treatment strategy for the prediction and diagnosis of caries and periodontitis.

Effect of changes in metabolic enzymes and transporters on drug metabolism in the context of liver disease: Impact on pharmacokinetics and drug-drug interactions.

Changes in the pharmacokinetic and resulting pharmacodynamic properties of drugs are common in many chronic liver diseases, leading to adverse effects, drug interactions and increased risk of over- or underdosing of medications. Structural and functional hepatic impairment can have major effects on drug metabolism and transport. This review summarizes research on the functional changes in phase I and II metabolic enzymes and in transport proteins in patients with metabolic diseases such as type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis and cirrhosis, providing a clinical perspective on how these changes affect drug uptake and metabolism. Generally, a decrease in expression and/or activity of many enzymes of the cytochrome P450 family (e.g. CYP2E1 and CYP3A4), and of influx and efflux transporters (e.g. organic anion-transporting polypeptide [OATP]1B1, OATP2B1, OAT2 and bile salt export pump), has been recently documented in patients with liver disease. Decreased enzyme levels often correlate with increased severity of chronic liver disease. In subjects with hepatic impairment, there is potential for strong alterations of drug pharmacokinetics due to reduced absorption, increased volume of distribution, metabolism and extraction. Due to the altered pharmacokinetics, specific drug-drug interactions are also a potential issue to consider in patients with liver disease. Given the huge burden of liver disease in western societies, there is a need to improve awareness among all healthcare professionals and patients with liver disease to ensure appropriate drug prescriptions.

Multiparametric Cardiovascular Magnetic Resonance in Nonhospitalized COVID-19 Infection Subjects: An Intraindividual Comparison Study.

To investigate intraindividual cardiac structural and functional changes before and after COVID-19 infection in a previously healthy population with a 3T cardiac magnetic resonance (CMR). A total of 39 unhospitalized patients with COVID-19 were recruited. They participated in our previous study as non-COVID-19 healthy volunteers undergoing baseline CMR examination and were recruited to perform a repeated CMR examination after confirmed COVID-19 infection in December 2022. The CMR parameters were measured and compared between before and after COVID-19 infection with paired t tests. The laboratory measures including myocardial enzymes and inflammatory indicators were also collected when performing repeated CMR. The median duration was 393 days from the first to second CMR and 26 days from clinical symptoms onset to the second CMR. Four patients (10.3%, 4/39) had the same late gadolinium enhancement pattern at baseline and repeated CMR and 5 female patients (12.8%, 5/39) had myocardial T2 ratio >2 (2.07 to 2.27) but with normal T2 value in post-COVID-19 CMR. All other CMR parameters were in normal ranges before and after COVID-19 infection. Between before and after the COVID-19 infection, there were no significant differences in cardiac structure, function, and tissue characterization, no matter with or without symptoms (fatigue, chest discomfort, palpitations, shortness of breath, and insomnia/sleep disorders) (all P >0.05). The laboratory measures at repeated CMR were in normal ranges in all participants. These intraindividual CMR studies showed unhospitalized patients with COVID-19 with normal myocardial enzymes had no measurable CMR abnormalities, which can help alleviate wide social concerns about COVID-19-related myocarditis.

Late Cenozoic Faunal and Ecological Change in Africa

Africa's fossil record of late Cenozoic mammals documents considerable ecological and evolutionary changes through time. Here, we synthesize those changes in the context of the mechanisms proposed to account for them, including bottom-up (e.g., climate change) and top-down (e.g., hominin impacts) processes. In doing so, we (a) examine how the incompleteness of the fossil record and the varied spatiotemporal scales of the evidence complicate efforts to establish cause-effect relationships; (b) evaluate hypothesized drivers of long-term ecological and evolutionary change, highlighting key unknowns; and (c) synthesize major taxonomic and functional trends through time (e.g., downsizing of faunal communities) considering the proposed drivers. Throughout our review, we point to unresolved questions and highlight research avenues that have potential to inform on the processes that have shaped the history of what are today the most diverse remaining large mammal communities on Earth.▪The study of late Cenozoic African mammal communities is intertwined with questions about the context, causes, and consequences of hominin evolution.▪The fossil record documents major functional (e.g., loss of megaherbivores) and taxonomic (e.g., rise of the Bovidae) changes over the past ∼7 Myr.▪Complexities inherent to the fossil record have made it difficult to identify the processes that drove ecological and evolutionary changes.▪Unanswered questions about the drivers of faunal change and the functioning of past ecosystems represent promising future research directions.

P1230 Integrated analysis of microbiome and metabolome reveals disease-specific profiles in inflammatory bowel disease and intestinal Behcet’s disease

Abstract Background Gut microbial and metabolic characteristics in intestinal Behcet’s disease (BD), a condition sharing many clinical similarites with ulcerative colitis (UC) and Crohn’s disease (CD), are largely unexplored. This study aimed to investigate the gut microbial and metabolic characteristics, as well as potential biomarkers in intestinal BD, comparing them with UC and CD, along with healthy controls. Methods Patients with UC, CD, and intestinal BD, along with healthy volunteers undergoing diagnostic endoscopies, were enrolled. Colon tissue and stool samples were analyzed using 16S ribosomal RNA sequencing, assessing microbial diversity, taxonomic composition, and functional profiling by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). Plasma metabolomic analysis was performed using gas chromatography and ultra-performance liquid chromatography-time-of-flight mass spectrometry, and quantitative enrichment analysis (QEA) was performed. Results In total, 100 patients (35 UC, 30 CD, and 35 BD) and 41 healthy volunteers were enrolled. While CD exhibited reduced microbial diversity in colon tissue, BD showed no significant decrease. The taxonomic profile of intestinal BD resembled healthy controls more than UC or CD but exhibited specific distinct features. Common changes across all conditions included a decrease in five beneficial bacteria producing short-chain fatty acids (Fusicatenibacter saccharivorans, Coprococcus comes, Blautia obeum, Dorea formicigenerans, and Roseburai ceciola). Additional changes in intestinal BD included a decreased abundance of Subdoligranulum variable and Blautia wexlerae, which were shared features with either UC or CD. Intestinal BD-specific alterations involved decreased abundance of certain bacteria, including Bacteroides fragilis. Metabolomic profiles of intestinal BD by QEA showed similarity to CD and distinction from UC and controls, with pronounced functional changes in energy metabolism and genetic information processing, correlating with microbial functional analysis by PICRUSt. Conclusion This integrative analysis unveiled both common and distinctive profiles in intestinal BD when compared to UC, CD, and controls. The study identified potential biomarkers, contributing to a deeper comprehension of the unique features in these diseases, which could serve as key elements for elucidating their pathogenesis.

Altered resting-state brain functional activities and networks in Crohn’s disease: a systematic review

BackgroundCrohn’s disease (CD) is a non-specific chronic inflammatory disease of the gastrointestinal tract and is a phenotype of inflammatory bowel disease (IBD). The current study sought to compile the resting-state functional differences in the brain between CD patients and healthy controls.MethodsThe online databases PubMed, Web of Science Core, and EMBASE were used to find the published neuroimage studies. The search period was from the beginning through December 15, 2023. The predetermined inclusion and exclusion criteria allowed for the identification of the studies. The studies were assembled by two impartial reviewers, who also assessed their quality and bias.ResultsThis review comprised 16 resting-state fMRI studies in total. The included studies generally had modest levels of bias. According to the research, emotional processing and pain processing were largely linked to increased or decreased brain activity in patients with CD. The DMN, CEN, and limbic systems may have abnormalities in patients with CD, according to research on brain networks. Several brain regions showed functional changes in the active CD group compared to the inactive CD group and the healthy control group, respectively. The abnormalities in brain areas were linked to changes in mood fluctuations (anxiety, melancholy) in patients with CD.ConclusionFunctional neuroimaging helps provide a better understanding of the underlying neuropathological processes in patients with CD. In this review, we summarize as follows: First, these findings indicate alterations in brain function in patients with CD, specifically affecting brain regions associated with pain, emotion, cognition, and visceral sensation; second, disease activity may have an impact on brain functions in patients with CD; and third, psychological factors may be associated with altered brain functions in patients with CD.

The salt-tolerance of perennial ryegrass is linked with root exudate profiles and microflora recruitment

Salinity poses a significant threat to plant growth and development. The root microbiota plays a key role in plant adaptation to saline environments. Nevertheless, it remains poorly understood whether and how perennial grass plants accumulate specific root-derived bacteria when exposed to salinity. Here, we systematically analyzed the composition and variation of rhizosphere and endophytic bacteria, as well as root exudates in perennial ryegrass differing in salt tolerance grown in unsterilized soils with and without salt. Both salt-sensitive (P1) and salt-tolerant (P2) perennial ryegrass genotypes grew better in unsterilized soils compared to sterilized soils under salt stress. The rhizosphere and endophytic bacteria of both P1 and P2 had lower alpha-diversity under salt treatment compared to control. The reduction of alpha-diversity was more pronounced for P1 than for P2. The specific root-derived bacteria, particularly the genus Pseudomonas, were enriched in rhizosphere and endophytic bacteria under salt stress. Changes in bacterial functionality induced by salt stress differed in P1 and P2. Additionally, more root exudates were altered under salt stress in P2 than in P1. The content of important root exudates, mainly including phenylpropanoids, benzenoids, organic acids, had a significantly positive correlation with the abundance of rhizosphere and endophytic bacteria under salt stress. The results indicate that the interactions between root-derived bacteria and root exudates are crucial for the salt tolerance of perennial ryegrass, which provides a potential strategy to manipulate root microbiome for improved stress tolerance of perennial grass species.

The impact of a tDCS and cognitive training intervention on task-based functional connectivity.

Declines in several cognitive domains, most notably processing speed, occur in non-pathological aging. Given the exponential growth of the older adult population, declines in cognition serve as a significant public health issue that must be addressed. Promising studies have shown that cognitive training in older adults, particularly using the useful field of view (UFOV) paradigm, can improve cognition with moderate to large effect sizes. Additionally, meta-analyses have found that transcranial direct current stimulation (tDCS), a non-invasive form of brain stimulation, can improve cognition in attention/processing speed and working memory. However, only a handful of studies have looked at concomitant tDCS and cognitive training, usually with short interventions and small sample sizes. The current study assessed the effect of a tDCS (active versus sham) and a 3-month cognitive training intervention on task-based functional connectivity during completion of the UFOV task in a large older adult sample (N = 153). We found significant increased functional connectivity between the left and right pars triangularis (the ROIs closest to the electrodes) following active, but not sham tDCS. Additionally, we see trending behavioral improvements associated with these functional connectivity changes in the active tDCS group, but not sham. Collectively, these findings suggest that tDCS and cognitive training can be an effective modulator of task-based functional connectivity above and beyond a cognitive training intervention alone.