Calcium-sensing receptor-mediated macrophage polarization improves myocardial remodeling in spontaneously hypertensive rats.

Chronic inflammation is a key element in the progression of essential hypertension (EH). Calcium plays a key role in inflammation, so its receptor, the calcium-sensing receptor (CaSR), is an essential mediator of the inflammatory process. Compelling evidence suggests that CaSR mediates inflammation in tissues and immune cells, where it mediates their activity and chemotaxis. Macrophages (Mφs) play a major role in the inflammatory response process. This study provided convincing evidence that R568, a positive regulator of CaSR, was effective in lowering blood pressure in spontaneously hypertensive rats (SHRs), improving cardiac function by alleviating cardiac hypertrophy and fibrosis. R568 can increase the content of CaSR and M2 macrophages (M2Mφs, exert an anti-inflammatory effect) in myocardial tissue, reduce M1 macrophages (M1Mφs), which have a pro-inflammatory effect in this process. In contrast, NPS2143, a negative state regulator of CaSR, exerted the opposite effect in all of the above experiments. Following this study, R568 increased CaSR content in SHR myocardial tissue, lowered blood pressure, promoted macrophages to M2Mφs and improved myocardial fibrosis, but interestingly, both M1Mφs and M2Mφs were increased in the peritoneal cavity of SHRs, the number of M2Mφs remained lower than M1Mφs. In vitro, R568 increased CaSR content in RAW264.7 cells (a macrophage cell line), regulating intracellular Ca2+ ([Ca2+]i) inhibited NOD-like receptor family protein 3 (NLRP3) inflammasome activation and ultimately prevented its conversion to M1Mφs. The results showed that a decrease in CaSR in hypertensive rats causes further development of hypertension and cardiac damage. EH myocardial remodeling can be improved by CaSR overexpression by suppressing NLRP3 inflammasome activation and macrophage polarization toward M1Mφs and increasing M2Mφs.

Effects of yak rumen anaerobic fungus Orpinomyces sp. YF3 fermented on in vitro wheat straw fermentation and microbial communities in dairy goat rumen fluid, with and without fungal flora.

Rumen fungi play an essential role in the breakdown of dietary fibrous components, facilitating the provision of nutrients and energy to the host animals. This study investigated the fermentation characteristics and effects on rumen microbiota of yak rumen anaerobic fungus Orpinomyces sp. YF3 in goat rumen fluid, both with and without fungal flora, utilizing anaerobic fermentation bottles. Crushed and air-dried wheat straw served as the fermentation substrate, and cycloheximide was used to eradicate microorganisms from the rumen fluid of dairy goats. The experiment compromised four treatment groups (2×2 factorial design): control (C); yak fungus group (CF, Orpinomyces sp. YF3); goat fungi eliminated group (CA, antibiotic: 0.25 mg/mL cycloheximide); goat fungi eliminated+yak fungus group (CAF). Each treatment had six replicates. Fermentation characteristics and microbial composition of the fermentation media were analyzed using one-way analysis of variance and high-throughput sequencing technology. The findings revealed that in the Orpinomyces sp. YF3 addition group (CF and CAF groups), there were significant increases in ammonia nitrogen concentration by 70%, total volatile fatty acids (VFA) by 53%, as well as acetate, isobutyrate, and valerate concentrations, and the ratio of acetate to propionate (p < 0.05), while the propionate proportion declined by 13%, alongside a reduction of butyrate concentration (p < 0.05). Similarly, in the CF and CAF groups, there were a notable increase in the relative abundance of Bacteroidota, Synergistota, Desulfobacterota, Actinobacteria, and Fusobacteriota, alongside a decrease in the relative abundance of Fibrobacterota and Proteobacteria (p < 0.05). Bacteria exhibiting increased relative abundance were positively correlated with the activity of carboxymethyl cellulase and avicelase, total VFA concentration, and acetate proportion, while showing a negatively correlation with propionate proportion. In conclusion, supplementing rumen fermentation media with yak rumen anaerobic fungus Orpinomyces sp. YF3 led to an increase in bacteria associated with fibre degradation and acetic acid production, a decrease in propionate-producing bacteria, enhanced the activity of plant cell wall degrading enzymes, and promoted cellulose degradation, ultimately elevating total VAF concentration and acetate proportion. This presents a novel approach to enhance roughage utilization in ruminants.

Transcriptome in Liver of Periparturient Dairy Cows Differs between Supplementation of Rumen-Protected Niacin and Rumen-Protected Nicotinamide.

To investigate the difference between rumen-protected niacin (RPN) and rumen-protected nicotinamide (RPM) in the transcriptome of genes relating to the lipid metabolism of the liver of periparturient dairy cows, 10 healthy Chinese Holstein cows were randomly divided into two groups and fed diets supplemented with 18.4 g/d RPN or 18.7 g/d RPM, respectively. The experiment lasted from 14 days before to 21 days after parturition. Liver biopsies were taken 21 days postpartum for transcriptomic sequencing. In addition, human LO2 cells were cultured in a medium containing 1.6 mmol/L of non-esterified fatty acids and 1 mmol/L niacin (NA) or 2 mmol/L nicotinamide (NAM) to verify the expression of the 10 genes selected from the transcriptomic analysis of the liver biopsies. The expression of a total of 9837 genes was detected in the liver biopsies, among which 1210 differentially expressed genes (DEGs) were identified, with 579 upregulated and 631 downregulated genes. These DEGs were associated mainly with lipid metabolism, oxidative stress, and some inflammatory pathways. Gene ontology (GO) enrichment analysis showed that 355 DEGs were enriched in 38 GO terms. The differences in the expression of these DEGs between RPN and RPM were predominantly related to the processes of steroid catabolism, steroid hydroxylase, monooxygenase activity, oxidoreductase activity, hemoglobin binding, and ferric iron binding, which are involved mainly in lipid anabolism and redox processes. The expressions of FADS2, SLC27A6, ARHGAP24, and THRSP in LO2 cells were significantly higher (p < 0.05) while the expressions of BCO2, MARS1, GARS1, S100A12, AGMO, and OSBPL11 were significantly lower (p < 0.05) on the NA treatment compared to the NAM treatment, indicating that NA played a role in liver metabolism by directly regulating fatty acid anabolism and transport, inflammatory factor expression, and oxidative stress; and NAM functioned more as a precursor of nicotinamide adenine dinucleotide (NAD, coenzyme I) and nicotinamide adenine dinucleotide phosphate (NADP, coenzyme II) to participate indirectly in biological processes such as ether lipid metabolism, cholesterol metabolism, energy metabolism, and other processes.

Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes.

It is unclear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to the strong but ineffective inflammatory response that characterizes severe Coronavirus disease 2019 (COVID-19), with amplified immune activation in diverse cell types, including cells without angiotensin-converting enzyme 2 receptors necessary for infection. Proteolytic degradation of SARS-CoV-2 virions is a milestone in host viral clearance, but the impact of remnant viral peptide fragments from high viral loads is not known. Here, we examine the inflammatory capacity of fragmented viral components from the perspective of supramolecular self-organization in the infected host environment. Interestingly, a machine learning analysis to SARS-CoV-2 proteome reveals sequence motifs that mimic host antimicrobial peptides (xenoAMPs), especially highly cationic human cathelicidin LL-37 capable of augmenting inflammation. Such xenoAMPs are strongly enriched in SARS-CoV-2 relative to low-pathogenicity coronaviruses. Moreover, xenoAMPs from SARS-CoV-2 but not low-pathogenicity homologs assemble double-stranded RNA (dsRNA) into nanocrystalline complexes with lattice constants commensurate with the steric size of Toll-like receptor (TLR)-3 and therefore capable of multivalent binding. Such complexes amplify cytokine secretion in diverse uninfected cell types in culture (epithelial cells, endothelial cells, keratinocytes, monocytes, and macrophages), similar to cathelicidin's role in rheumatoid arthritis and lupus. The induced transcriptome matches well with the global gene expression pattern in COVID-19, despite using <0.3% of the viral proteome. Delivery of these complexes to uninfected mice boosts plasma interleukin-6 and CXCL1 levels as observed in COVID-19 patients.

The role of gut fungi in Clostridioides difficile infection.

Clostridioides difficile, the etiological agent of C. difficile infection (CDI), elicits a spectrum of diarrheal symptoms with varying severity and the potential to result in severe complications such as colonic perforation, pseudomembranous colitis, and toxic megacolon. The perturbation of gut microbiome, often triggered by antibiotic usage, represents the primary factor augmenting the risk of CDI. This underscores the significance of interactions between C. difficile and the microbiome in determining pathogen adaptability. In recent years, researchers have increasingly recognized the pivotal role played by intestinal microbiota in host health and its therapeutic potential as a target for medical interventions. While extensive evidence has been established regarding the involvement of gut bacteria in CDI, our understanding of symbiotic interactions between hosts and fungi within intestinal microbiota remains limited. Herein, we aim to comprehensively elucidate both composition and key characteristics of gut fungal communities that significantly contribute to CDI, thereby enhancing our comprehension from pharmacological and biomarker perspectives while exploring their prospective therapeutic applications for CDI.

[Enzyme production mechanism of anaerobic fungus Orpinomyces sp. YF3 in yak rumen induced by different carbon source].

In order to investigate the enzyme production mechanism of yak rumen-derived anaerobic fungus Orpinomyces sp. YF3 under the induction of different carbon sources, anaerobic culture tubes were used for in vitro fermentation. 8 g/L of glucose (Glu), filter paper (Flp) and avicel (Avi) were respectively added to 10 mL of basic culture medium as the sole carbon source. The activity of fiber-degrading enzyme and the concentration of volatile fatty acid in the fermentation liquid were detected, and the enzyme producing mechanism of Orpinomyces sp. YF3 was explored by transcriptomics. It was found that, in glucose-induced fermentation solution, the activities of carboxymethyl cellulase, microcrystalline cellulase, filter paper enzyme, xylanase and the proportion of acetate were significantly increased (P < 0.05), the proportion of propionate, butyrate, isobutyrate were significantly decreased (P < 0.05). The results of transcriptome analysis showed that there were 5 949 differentially expressed genes (DEGs) between the Glu group and the Flp group, 10 970 DEGs between the Glu group and the Avi group, and 6 057 DEGs between the Flp group and the Avi group. It was found that the DEGs associated with fiber degrading enzymes were significantly up-regulated in the Glu group. Gene ontology (GO) function enrichment analysis identified that DEGs were mainly associated with the xylan catabolic process, hemicellulose metabolic process, ß-glucan metabolic process, cellulase activity, endo-1,4-ß-xylanase activity, cell wall polysaccharide metabolic process, carbohydrate catabolic process, glucan catabolic process and carbohydrate metabolic process. Moreover, the differentially expressed pathways associated with fiber degrading enzymes enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were mainly starch and sucrose metabolic pathways and other glycan degradation pathways. In conclusion, Orpinomyces sp. YF3 with glucose as carbon source substrate significantly increased the activity of cellulose degrading enzyme and the proportion of acetate, decreased the proportion of propionate, butyrate and isobutyrate. Furthermore, the degradation ability and energy utilization efficiency of fungus in the presence of glucose were improved by means of regulating the expression of cellulose degrading enzyme gene and participating in starch and sucrose metabolism pathway, and other glycan degradation pathways, which provides a theoretical basis for the application of Orpinomyces sp. YF3 in practical production and facilitates the application of Orpinomyces sp. YF3 in the future.

The Effects of Rumen-Protected Choline and Rumen-Protected Nicotinamide on Liver Transcriptomics in Periparturient Dairy Cows.

To investigate the effects of rumen-protected choline (RPC) and rumen-protected nicotinamide (RPM) on liver metabolic function based on transcriptome in periparturient dairy cows, 10 healthy Holstein dairy cows with similar parity were allocated to RPC and RPM groups (n = 5). The cows were fed experimental diets between 14 days before and 21 days after parturition. The RPC diet contained 60 g RPC per day, and the RPM diet contained 18.7 g RPM per day. Liver biopsies were taken 21 days after calving for the transcriptome analysis. A model of fat deposition hepatocytes was constructed using the LO2 cell line with the addition of NEFA (1.6 mmol/L), and the expression level of genes closely related to liver metabolism was validated and divided into a CHO group (75 µmol/L) and a NAM group (2 mmol/L). The results showed that the expression of a total of 11,023 genes was detected and clustered obviously between the RPC and RPM groups. These genes were assigned to 852 Gene Ontology terms, the majority of which were associated with biological process and molecular function. A total of 1123 differentially expressed genes (DEGs), 640 up-regulated and 483 down-regulated, were identified between the RPC and RPM groups. These DEGs were mainly correlated with fat metabolism, oxidative stress and some inflammatory pathways. In addition, compared with the NAM group, the gene expression level of FGF21, CYP26A1, SLC13A5, SLCO1B3, FBP2, MARS1 and CDH11 in the CHO group increased significantly (p < 0.05). We proposed that that RPC could play a prominent role in the liver metabolism of periparturient dairy cows by regulating metabolic processes such as fatty acid synthesis and metabolism and glucose metabolism; yet, RPM was more involved in biological processes such as the TCA cycle, ATP generation and inflammatory signaling.

Murine Cytomegalovirus Infection Induced miR-1929-3p Down-Regulation Promotes the Proliferation and Apoptosis of Vascular Smooth Muscle Cells in Mice by Targeting Endothelin A Receptor and Downstream NLRP3 Activation Pathway.

Our previous study demonstrated in vivo that mouse cytomegalovirus (MCMV) infection promoted vascular remodeling after downregulation of miR-1929-3p. This study aimed to investigate the role of miR-1929-3p/ETAR/NLRP3 pathway in mouse vascular smooth muscle cells (MOVAS) after MCMV infection. First, PCR was used to detect the success of the infection. Second, MOVAS were transfected with the miR-1929-3p mimic, inhibitor, and ETAR overexpressed adenovirus vector. Cell proliferation was detected using EdU, whereas apoptosis was detected using flow cytometry. The expression of miR-1929-3p and ETAR were detected using qRT-PCR. Western blot detected proteins of cell proliferation, apoptosis, and the NLRP3 inflammasome. Interleukin-1ß and interleukin-18 were determined using ELISA. The results revealed that after 48 h, MCMV infection promoted the proliferation of MOVAS when the MOI was 0.01. MCMV infection increased ETAR by downregulating miR-1929-3p. The miR-1929-3p mimic reversed the proliferation and apoptosis, whereas the miR-1929-3p inhibitor promoted this effect. ETAR overexpression further promoted MCMV infection by downregulating miR-1929-3p-mediated proliferation and apoptosis. MCMV infection mediates the downregulation of miR-1929-3p and the upregulation of ETAR, which activates NLRP3 inflammasome. In conclusion, MCMV infection promoted the proliferation of MOVAS, possibly by downregulating miR-1929-3p, promoting the upregulation of the target gene ETAR and activating NLRP3 inflammasome.

Low expression of miR-1929-3p mediates murine cytomegalovirus-induced fibrosis in cardiac fibroblasts via targeting endothelin a receptor/NLRP3 inflammasome pathway.

MicroRNAs are crucial in the development of myocardial remodeling in hypertension. Low miR-1929-3p expression induced by murine cytomegalovirus (MCMV) infection is closely related to hypertensive myocardial remodeling. This study investigated the molecular mechanism of miR-1929-3p-induced myocardial remodeling after MCMV infection. We modeled MCMV-infected mouse cardiac fibroblasts (MMCFs) as the primary cell model. First, MCMV infection reduced the expression of miR-1929-3p and increased the mRNA and protein expression of its target gene endothelin receptor type A (ETAR) in mouse cardiac fibroblasts (MCFs), which demonstrated an internal relationship with myocardial fibrosis (MF) based on high proliferation, phenotypic transformation (α-SMA), and collagen expression in MMCFs. The transfection of the miR-1929-3p mimic downregulated the high expression of ETAR and alleviated these adverse effects in MMCFs. Inversely, these effects were exacerbated by the miR-1929-3p inhibitor. Second, the transfection of endothelin receptor type A over-expressed adenovirus (adETAR) reversed these positive effects of the miR-1929-3p mimic on MF improvement. Third, the transfection of adETAR exhibited a strong inflammatory response in MMCFs with increased expression of NOD-like receptors pyrin domain containing 3 (NLRP3) and increased secretion of interleukin-18. However, we found that the ETAR antagonist BQ123 and the selected NLRP3 inflammasome inhibitor MCC950 effectively eliminated the inflammatory response induced by both MCMV infection and miR-1929-3p inhibitor. Moreover, the MCF supernatant was related to cardiomyocyte hypertrophy. Our findings suggest that MCMV infection promotes MF by inducing the downregulation of miR-1929-3p and the high expression of ETAR, which activates NLRP3 inflammasomes in MCFs.

Does parental autonomy support mediate the relation between parent and infant executive function? A study of mothers and fathers in the Netherlands and China.

Parenting skills, such as Autonomy Support (AS), have been proposed as a potential mechanism explaining the intergenerational contiguity of Executive Function (EF). However, few studies have focused on mothers and fathers among non-Western families. The current study investigated the role of maternal and paternal AS in the relation between parental EF and infant EF at 14 months of age among 123 Dutch and 63 Chinese first-time mothers and fathers and their infants. Multiple-group structural equation models were built for mothers and fathers separately with country as a grouping variable. Results showed that parental AS did not mediate the relation between parent EF and infant EF at 14 months. Mean-level differences were found in parental AS, maternal EF, and infant inhibition across countries, while no country differences were found in the relation between parent EF, AS and infant EF. Our findings suggested that individual differences in early EF may not be stable enough to be reliably predicted from parental factors across the Netherlands and China.

Preservation of the Innate Immune Response to Clostridioides difficile Infection in Hospitalized Immunocompromised Patients.

Background: Clostridioides difficile infection (CDI) immune response is influenced by the innate and adaptive (humoral) immune systems. Our prior research found attenuated humoral responses to C difficile in immunocompromised hosts (ICHs) with CDI. We sought to evaluate whether the innate immune response to CDI was influenced by ICH status. Methods: We conducted a prospective study of hospitalized adults with CDI (acute diarrhea, positive C difficile stool nucleic acid amplification testing [NAAT], and decision to treat), with and without immunosuppression and measured a panel of cytokines (granulocyte colony-stimulating factor [G-CSF], interleukin [IL]-10, IL-15, IL-1ß, IL-4, IL-6, IL-8, and tumor necrosis factor-α) in blood and stool at CDI diagnosis. Results were compared with measurements from a cohort of asymptomatic carrier patients (ASCs) (NAAT positive, without diarrhea) with and without immunocompromise. Results: One hundred twenty-three subjects (42 ICHs, 50 non-ICHs, 31 ASCs) were included. Median values for blood and stool cytokines were similar in ICH versus non-ICH CDI subjects. In blood, G-CSF, IL-10, IL-15, IL-6, and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). In stool, IL-1ß and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). Median stool concentrations of IL-1ß demonstrated significant differences between the groups (ICHs, 10.97 pg/mL; non-ICHs, 9.71 pg/mL; and ASCs, 0.56 pg/mL) (P < .0001). Conclusions: In this small exploratory analysis, ICH status did not significantly impact blood and fecal patterns of cytokines in humans at the diagnosis of CDI, suggesting that the innate immune response to C difficile may be conserved in immunocompromised patients.

Stool Interleukin-1ß Differentiates Clostridioides difficile Infection (CDI) From Asymptomatic Carriage and Non-CDI Diarrhea.

BACKGROUND: Despite advances in the understanding and diagnosis of Clostridioides difficile infection (CDI), clinical distinction within the colonization-infection continuum remains an unmet need. METHODS: By measuring stool cytokines and antitoxin antibodies in well-characterized cohorts of CDI (diarrhea, nucleic acid amplification test [NAAT] positive), non-CDI diarrhea (NCD; diarrhea, NAAT negative), asymptomatic carriers (ASC; no diarrhea, NAAT positive) and hospital controls (CON; no diarrhea, NAAT negative), we aim to discover novel biological markers to distinguish between these cohorts. We also explore the relationship of these stool cytokines and antitoxin antibody with stool toxin concentrations and disease severity. RESULTS: Stool interleukin (IL) 1ß, stool immunoglobulin A (IgA), and immunoglobulin G (IgG) anti-toxin A had higher (P < .0001) concentrations in CDI (n = 120) vs ASC (n = 43), whereas toxins A, B, and fecal calprotectin did not. Areas under the receiver operating characteristic curve (ROC-AUCs) for IL-1ß, IgA, and IgG anti-toxin A were 0.88, 0.83, and 0.83, respectively. A multipredictor model including IL-1ß and IgA anti-toxin A achieved an ROC-AUC of 0.93. Stool IL-1ß concentrations were higher in CDI compared to NCD (n = 75) (P < .0001) and NCD + ASC+ CON (CON, n = 75) (P < .0001), with ROC-AUCs of 0.83 and 0.86, respectively. Stool IL-1ß had positive correlations with toxins A (ρA = +0.55) and B (ρB = +0.49) in CDI (P < .0001) but not in ASC (P > .05). CONCLUSIONS: Stool concentrations of the inflammasome pathway, proinflammatory cytokine IL-1ß, can accurately differentiate CDI from asymptomatic carriage and NCD, making it a promising biomarker for CDI diagnosis. Significant positive correlations exist between stool toxins and stool IL-1ß in CDI but not in asymptomatic carriers.

On becoming socially anxious: Toddlers' attention bias to fearful faces.

Early attention bias to threat-related negative emotions may lead children to overestimate dangers in social situations. This study examined its emergence and how it might develop in tandem with a known predictor namely temperamental shyness for toddlers' fear of strangers in 168 Chinese toddlers. Measurable individual differences in such attention bias to fearful faces were found and remained stable from age 12 to 18 months. When shown photos of paired happy versus fearful or happy versus angry faces, toddlers initially gazed more and had longer initial fixation and total fixation at fearful faces compared with happy faces consistently. However, they initially gazed more at happy faces compared with angry faces consistently and had a longer total fixation at angry faces only at 18 months. Stranger anxiety at 12 months predicted attention bias to fearful faces at 18 months. Temperamentally shyer 12-month-olds went on to show stronger attention bias to fearful faces at 18 months, and their fear of strangers also increased more from 12 to 18 months. Together with prior research suggesting attention bias to angry or fearful faces foretelling social anxiety, the present findings point to likely positive feedback loops among attention bias to fearful faces, temperamental shyness, and stranger anxiety in early childhood. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Yak rumen microbiome elevates fiber degradation ability and alters rumen fermentation pattern to increase feed efficiency.

Rumen microbes play an important role in ruminant energy supply and animal performance. Previous studies showed that yak (Bos grunniens) rumen microbiome and fermentation differ from other ruminants. However, little is understood about the features of the rumen microbiome that make yak adapted to their unique environmental and dietary conditions. This study was to investigate the rumen microbiome and metabolome to understand how yak adapt to the coarse forage and harsh environment in the Qinghai-Tibetan plateau. Nine female Qaidam yellow cattle (Bos taurus), 9 dzomo (hybrids of cattle and yak) and 9 female plateau yak (B. grunniens), about 5 to 6 years old, were used in this study. Rumen fermentation parameters, fibrolytic enzyme activities, and rumen metataxonomic were determined. Then 18 (6 samples per group) were selected for rumen metagenomic and metabolome analysis. Metataxonomic analysis revealed that the rumen microbiota was significantly different among plateau yak, Qaidam yellow cattle, and dzomo (P < 0.05). Metagenomic analysis displayed a larger gene pool encoding a richer repertoire of carbohydrate-active enzymes in the rumen microbiome of plateau yak and dzomo than Qaidam yellow cattle (P < 0.05). Some of the genes encoding glycoside hydrolases that mediate the digestion of cellulose and hemicellulose were significantly enriched in the rumen of plateau yak than Qaidam yellow cattle, but glycoside hydrolase 57 that primarily includes amylases was abundant in Qaidam yellow cattle (P < 0.05). The rumen fermentation profile differed also, Qaidam yellow cattle having a higher molar proportion of acetate but a lower molar proportion of propionate than dzomo and plateau yak (P < 0.05). Based on metabolomic analysis, rumen microbial metabolic pathways and metabolites were different. Differential metabolites are mainly amino acids, carboxylic acids, sugars, and bile acids. Changes in rumen microbial composition could explain the above results. The present study showed that the rumen microbiome of plateau yak helps its host to adapt to the Qinghai-Tibetan plateau. In particular, the plateau yak rumen microbiome has more enzymes genes involved in cellulase and hemicellulase than that of cattle, resulting higher fibrolytic enzyme activities in yak, further providing stronger fiber degradation function.

Analysis of Intestinal Mycobiota of Patients with Clostridioides difficile Infection among a Prospective Inpatient Cohort.

Clostridioides difficile infection (CDI) is a burden to health care systems worldwide. Gut microbiota dysbiosis associated with CDI has been well accepted. However, contribution of fungal mycobiota to CDI has recently gained research interest. Here, we report the gut mycobiota composition of 149 uniquely well characterized participants from a prospective clinical cohort and evaluate the discriminating ability of gut mycobiota to classify CDI and non-CDI patients. Fecal samples were divided into two groups: (i) CDI (inpatients who had clinically significant diarrhea and positive nucleic acid amplification testing [NAAT] and received subsequent CDI therapy, n = 58) and (ii) non-CDI, which can be further divided into three subgroups: (a) carrier (inpatients with positive stool NAAT but without diarrhea; n = 28); (b) diarrhea (inpatients with negative stool NAAT; n = 31); and (c) control (inpatients with negative stool NAAT and without diarrhea; n = 32). Fecal mycobiota composition was analyzed by internal transcribed spacer 2 (ITS2) sequencing. In comparison to non-CDI patients, CDI patients tend to have gut mycobiota with lower biodiversity, weaker fungi correlations, and weaker correlations between fungi and host immune factors. Notably, 11 genera (Saccharomyces, Penicillium, Aspergillus, Cystobasidium, Cladosporium, and so on) were significantly enriched in non-CDI patients, and Pichia and Suhomyces were enriched in patients with CDI, while 1 two genera, Cystobasidium and Exophiala, had higher abundance in patients with diarrhea compared with CDI (linear discriminant analysis [LDA] > 3.0; P < 0.05). Ascomycota and Basidiomycota (or Candida and Saccharomyces) exhibited a strong negative correlation (r ≤ -0.714 or r ≤ -0.387; P < 0.05), and the ratios of Ascomycota to Basidiomycota or genera Candida to Saccharomyces were dramatically higher in CDI patients than in non-CDI patients (P < 0.05). A disease-specific pattern with much weaker fungal abundance correlations was observed in the CDI group compared to that in the non-CDI and diarrhea groups, suggesting that these correlations may contribute to the development of CDI. Our findings provided specific markers of stool fungi that distinguish CDI from all non-CDI hospitalized patients. This study's potential clinical utility for better CDI diagnosis warrants further investigation. IMPORTANCE Clostridioides difficile is an opportunistic bacterial pathogen that causes a serious and potentially life-threatening infection of the human gut. It remains an existing challenge to distinguish active infection of CDI from diarrhea with non-CDI causes. A few large prospective studies from recent years suggest that there is no single optimal test for the diagnosis of CDI. Previous research has concentrated on the relationship between bacteria and CDI, while the roles of fungi, as a significant proportion of the gut microbial ecosystem, remain understudied. In this study, we report a series of fungal markers that may add diagnostic values for the development of a more systematic approach to accurate CDI diagnosis. These results help open the door for better understanding of the relationship between host immune factors and the fungal community in the context of CDI pathogenesis.

Iopromide and Iodixanol in the Development of Postoperative Contrast Nephropathy in Patients with Renal Insufficiency: A Meta-Analysis.

In order to compare the effects of iopromide and isoxazole on postoperative contrast-induced nephropathy in patients with renal insufficiency, the paper searches for randomized controlled trials and retrospective cohort studies comparing the effects of iopromide and iodixanol on renal function in patients with renal insufficiency after surgery. The data are extracted from eligible studies. We tried to assess the incidence of contrast-agent nephropathy, preoperative and postoperative serum creatinine indicators, and mortality. This paper includes 8 studies with a total of 1243 patients. The incidence of contrast-induced nephropathy in the iopromide group is higher than that in the iodixanol group, and there is no significant difference between the two groups in postoperative mortality and preoperative serum creatinine expression. Sensitivity analysis and funnel chart show that our research is robust and has low publication bias. Our research shows that in patients with renal insufficiency, the incidence of contrast-medium nephropathy in the iopromide group is higher than that in the iodixanol group. Iodixanol is safer and has less effect on patients' serum creatinine levels.

[Corrigendum] MicroRNA­1929­3p participates in murine cytomegalovirus­induced hypertensive vascular remodeling through Ednra/NLRP3 inflammasome activation.

Following the publication of this article, the authors have realized that the images selected for the 'MCMV+miR­NC' and 'MCMV+miR­1929­3p' data panels (15 months), as featured in the lower of the two rows of data shown in Fig. 4A on p. 726, were derived from the same experimental group. The authors re­examined their original data, and discovered that an error had inadvertently been made on account of the similar file names of the two images. The corrected version of Fig. 4, featuring the correct data for the 'MCMV+miR­NC' experiment, is shown on the next page. The authors regret that this error was not picked up upon before the paper was sent to press, and thank the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish a corrigendum. Note that the error did not affect either the results or the conclusions reported in the study, and all the authors agree to this corrigendum. Furthermore, the authors regret any inconvenience caused to the readership. [the original article was published in International Journal of Molecular Medicine 47: 719-731, 2021; DOI: 10.3892/ijmm.2020.4829].

The role of infant attention and parental sensitivity in infant cognitive development in the Netherlands and China.

Infant attention and parental sensitivity are important predictors of later child executive function (EF). However, most studies have investigated infant and parent factors in relation to child EF separately and included only mothers from Western samples. The current study examined whether both infant attention at 4 months and parental sensitivity at 4 and 14 months were related to infant EF (i.e., inhibition, working memory, and cognitive flexibility) at 14 months among 124 Dutch and 63 Chinese first-time mothers and fathers and their infants. Findings revealed that parental sensitivity at 4 months was not correlated with infant EF abilities at 14 months. However, infant attention at 4 months was significantly related to 14-month working memory, but not to inhibition and cognitive flexibility. Maternal sensitivity at 14 months was significantly related to 14-month inhibition, but not to working memory and cognitive flexibility. No country differences were found in the relation among 4-month infant attention, parental sensitivity, and EF outcomes. Results show that both infant and parent factors are associated with early EF development and that these correlates of early EF skills may be similar in Western and non-Western samples.

Analysis of bacterial diversity and functional differences of Jiang-flavored Daqu produced in different seasons.

High-temperature Daqu is an important saccharifying fermenting starter for brewing Jiang-flavored Baijiu. This paper analyzed the diversity characteristics of bacterial communities of Jiang-flavored Daqu (JFDQ) with seasonal changes through Illumina HiSeq sequencing and multivariate statistical methods. Results showed that 21 phyla, 529 genera, and 47 core bacterial genera were identified from the 48 composite samples. Among them, eight functional genera were only found in the summer-produced Daqu (Propionigenium, etc.). Pantoea, Bacillus, Lentibacillus, and Oceanobacillus, respectively, served as the representative functional bacterial genera of the four seasons. Functional prediction analysis showed that Amino acid metabolism Carbohydrate metabolism, Lipid metabolism, Metabolism of cofactors and vitamins, and Nucleotide metabolism (relative abundance > 1%) were the most critical microbial functions in JFDQ, and these key enzymes involved in acetoin biosynthesis, and acetyl-CoA biosynthesis were more abundant in the summer than in the winter. The functional microorganisms community in this paper would provide valuable suggestions about the seasonal production of JFDQ, guiding the Baijiu brewing processes.