The Impact of Inadequate Energy Intake on Readmission Burden of Patients With Heart Failure.

BACKGROUND: Adequate energy intake is essential for good clinical outcomes. The association between energy intake and readmission burden of patients with heart failure (HF) still needs to be clarified. OBJECTIVE: In this study, our aim was to determine the association between energy intake and readmission in patients with HF. METHODS: A total of 311 inpatients with HF were recruited. Demographic and clinical information were collected during hospitalization; the daily diets of the participants were collected in the second week after discharge using the 3-day diet record, and the energy intake was calculated using a standardized nutrition calculator. The inadequate energy intake was defined as <70% × 25 kcal/kg of ideal body weight. The participants were followed up for 12 weeks after discharge. The number, reasons, and length of stay of unplanned readmissions were collected. Regression analyses were used to evaluate the associations between inadequate energy intake, and readmission rate and readmission days. RESULTS: The median of the energy intake of participants was 1032 (interquartile range, 809-1266) kcal/d. The prevalence of inadequate energy intake was 40%. Patients with inadequate energy intake had a higher risk of unplanned readmission (odds ratio, 5.616; 95% confidence interval, 3.015-10.462; P < .001) and more readmission days (incidence rate ratio, 5.226; 95% confidence interval, 3.829-7.134, P < .001) after adjusting for potential confounders. CONCLUSIONS: Patients with HF had a high incidence of inadequate dietary energy intake, and it increases the burden of readmission.

Effects of weight loss in heart failure patients with overweight and obesity: a systematic review and meta-analysis.

AIMS: To perform a systematic review and meta-analysis to evaluate the impact of weight loss (WL) on the prognosis of overweight and obese patients with heart failure (HF). METHODS AND RESULTS: We reviewed the literature up to 1 February 2023 from PubMed, Web of Science, Embase, Cochrane Library, and Chinese databases for cohort studies, and randomized controlled trials (RCTs). Data from eligible studies were extracted, and statistical analyses were performed using Review Manager 5.3. A total of 19 studies (involving 449 882 patients) were included in the systematic review and meta-analyses. The results showed that WL did not reduce the mortality and rehospitalization rates in overweight and obese HF patients, but could improve the quality of life (P = 0.002), cardiac function (P = 0.0001), and exercise capacity (P = 0.03). The subgroup analysis showed that WL from bariatric surgery (BS) reduced the risk of death (P < 0.00001), WL from medication or exercise was not significantly associated with the risk of death (P = 0.18), and WL was associated with a higher mortality in the subgroup with unspecified WL modality or unintentional WL (P < 0.00001). In addition, it did not reduce the risk of short-term rehospitalization (P = 0.11), but reduced the rehospitalization rates over the long-term (P = 0.03). CONCLUSION: WL improves the long-term rehospitalization (>3 months), quality of life, cardiac function, and exercise capacity in overweight and obese HF patients. Although overall WL is not proven effective, subgroup analysis shows that BS can reduce mortality.

We used mortality, rehospitalization rates, quality of life, the New York Heart Association (NYHA), and 6-min walk test (6 MWT) to assess the impact of weight loss (WL) on the prognosis of overweight and obese heart failure (HF) patients. Key findings: WL is associated with improvements in long-term rehospitalization rates, quality of life, cardiac function, and exercise capacity.Bariatric surgery (BS) may reduce mortality in overweight and obese HF patients. Unintentional WL of more than 5% may mean a bad condition and could increase mortality.

The crystal structure of Cry78Aa from Bacillus thuringiensis provides insights into its insecticidal activity.

Genetically modified plants with insecticidal proteins from Bacillus thuringiensis (Bt) have been successfully utilized to control various kinds of pests in crop production and reduce the abuse of pesticides. However, a limited number of genes are available for the protection of crops from rice planthopper. Recently, Cry78Aa protein from Bt strain C9F1 has been found to have high insecticidal activity against Laodelphax striatellus and Nilaparvata lugens. It is the first reported single-component protein in the world to combat rice planthoppers, making it very promising for use in transgenic crops. The ambiguous mechanism of Cry78Aa functions prevented further engineering or application. Here, we report the crystal structure of Cry78Aa, which consists of two domains: a C-terminal ß-pore forming domain belonging to the aerolysin family and an N-terminal trefoil domain resembling the S-type ricin B lectin. Thus, Cry78Aa could represent a distinctive type of ß-pore forming toxin. We also found that Cry78Aa binds carbohydrates such as galactose derivatives and is essential for insecticidal activity against Laodelphax striatellus. Our results suggest a mechanism underlying the function of Cry78Aa against rice planthoppers and pave the way to maximizing the usage of the toxin.

Cryo-EM structures of Escherichia coli Ec86 retron complexes reveal architecture and defence mechanism.

First discovered in the 1980s, retrons are bacterial genetic elements consisting of a reverse transcriptase and a non-coding RNA (ncRNA). Retrons mediate antiphage defence in bacteria but their structure and defence mechanisms are unknown. Here, we investigate the Escherichia coli Ec86 retron and use cryo-electron microscopy to determine the structures of the Ec86 (3.1 Å) and cognate effector-bound Ec86 (2.5 Å) complexes. The Ec86 reverse transcriptase exhibits a characteristic right-hand-like fold consisting of finger, palm and thumb subdomains. Ec86 reverse transcriptase reverse-transcribes part of the ncRNA into satellite, multicopy single-stranded DNA (msDNA, a DNA-RNA hybrid) that we show wraps around the reverse transcriptase electropositive surface. In msDNA, both inverted repeats are present and the 3' sides of the DNA/RNA chains are close to the reverse transcriptase active site. The Ec86 effector adopts a two-lobe fold and directly binds reverse transcriptase and msDNA. These findings offer insights into the structure-function relationship of the retron-effector unit and provide a structural basis for the optimization of retron-based genome editing systems.

The Experimental Exploration of TCM Theory "Treating the Same Disease with Different Approaches" on an Ulcerative Colitis Model.

There is a relationship between lung injury and ulcerative colitis. Currently, traditional Chinese medicine (Huangqi Jiegeng (HQJGD) and Huangqi Huanglian decoctions (HQHLD)) is commonly used for UC-related lung injury; however, the mechanisms of these drugs remain unclear. In this study, UC models were established with the mucous membrane of colon allergize combined with TNBS-alcohol enteroclysis for 4 weeks. The pathological changes in the lung, intestine, liver, and kidney were observed; cytokines, chemokines, and adhesion molecules in lung tissue were detected in order to explore the immunological mechanism of UC-related lung injury and the intervention mechanism of traditional Chinese medicine in treating the lung and intestine in the immune-TNBS-ethanol rat model. Histology examinations demonstrated evident pathological changes in the lungs and intestines of the model groups. Furthermore, all groups treated with TCMs demonstrated reduced expressions of toll-like receptor 4, nuclear factor kappa-B, and macrophage migration inhibitory factor. Additionally, radioimmunoassay and immunohistochemistry showed tumor necrosis factor-α, interleukin-6, and 8 expression downregulation. The results showed that HQJGD and HQHLD could alleviate pulmonary inflammation in UC-related lung injury by obviously improving the pathology and fibrosis of the lung, inhibiting the positive feedback loop of MIF/NF-κB, and reducing lymphocyte homing to bronchial mucosa. This model revealed the immune mechanism of UC-related lung injury and the intervention mechanism of the Chinese medicine, which provided the rationale for treating ulcerative colitis clinically, so as to demonstrate the theory of "the lung and the large intestine being interior-exteriorly related" and "treating the same disease with different approaches."

Structural insights into homotrimeric assembly of cellulose synthase CesA7 from Gossypium hirsutum.

Cellulose is one of the most abundant organic polymers in nature. It contains multiple ß-1,4-glucan chains synthesized by cellulose synthases (CesAs) on the plasma membrane of higher plants. CesA subunits assemble into a pseudo-sixfold symmetric cellulose synthase complex (CSC), known as a 'rosette complex'. The structure of CesA remains enigmatic. Here, we report the cryo-EM structure of the homotrimeric CesA7 from Gossypium hirsutum at 3.5-angstrom resolution. The GhCesA7 homotrimer shows a C3 symmetrical assembly. Each protomer contains seven transmembrane helices (TMs) which form a channel potentially facilitating the release of newly synthesized glucans. The cytoplasmic glycosyltransferase domain (GT domain) of GhCesA7 protrudes from the membrane, and its catalytic pocket is directed towards the TM pore. The homotrimer GhCesA7 is stabilized by the transmembrane helix 7 (TM7) and the plant-conserved region (PCR) domains. It represents the building block of CSCs and facilitates microfibril formation. This structure provides insight into how eukaryotic cellulose synthase assembles and provides a mechanistic basis for the improvement of cotton fibre quality in the future.

Exploration of key regulators driving primary feather follicle induction in goose skin.

The primary feather follicles are universal skin appendages widely distributed in the skin of feathered birds. The morphogenesis and development of the primary feather follicles in goose skin remain largely unknown. Here, the induction of primary feather follicles in goose embryonic skin (pre-induction vs induction) was investigated by de novo transcriptome analyses to reveal 409 differentially expressed genes (DEGs). The DEGs were characterized to potentially regulate the de novo formation of feather follicle primordia consisting of placode (4 genes) and dermal condensate (12 genes), and the thickening of epidermis (5 genes) and dermal fibroblasts (17 genes), respectively. Further analyses enriched DEGs into GO terms represented as cell adhesion and KEGG pathways including Wnt and Hedgehog signaling pathways that are highly correlated with cell communication and molecular regulation. Six selected Wnt pathway genes were detected by qPCR with up-regulation in goose skin during the induction of primary feather follicles. The localization of WNT16, SFRP1 and FRZB by in situ hybridization showed weak expression in the primary feather primordia, whereas FZD1, LEF1 and DKK1 were expressed initially in the inter-follicular skin and feather follicle primordia, then mainly restricted in the feather primordia. The spatial-temporal expression patterns indicate that Wnt pathway genes DKK1, FZD1 and LEF1 are the important regulators functioned in the induction of primary feather follicle in goose skin. The dynamic molecular changes and specific gene expression patterns revealed in this report provide the general knowledge of primary feather follicle and skin development in waterfowl, and contribute to further understand the diversity of hair and feather development beyond the mouse and chicken models.

Expression patterns of three JAK-STAT pathway genes in feather follicle development during chicken embryogenesis.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) (JAK-STAT) pathway is shown to restrain the hair follicles in catagen and telogen and prevent anagen reentry in murine hair follicle cycling. The early roles of JAK-STAT pathway genes in skin development remain uncharacterized in mouse and chicken models. Here, we revealed the expression patterns of three JAK-STAT pathway genes (JAK1, JAK2, and TYK2) in chicken embryonic skin at E6-E10 stages which are key to feather follicle morphogenesis. Multiple sequence alignment of the three genes from chicken and other species all showed a closely related homology with birds like quail and goose. Whole mount in situ hybridization (WISH) revealed weak expression of JAK1, JAK2, and TYK2 in chicken skin at E6 and E7, and followed with the focally restricted signals in the feather follicles of neck and body skin located dorsally at E8 for JAK1, E9 for TYK2 and E10 for JAK2 gene. All three genes displayed stronger expression in feather follicles of neck skin than that of body skin. The expression levels of JAK1 and TYK2 were much stronger than those of JAK2. Quantitative real-time PCR (qRT-PCR) analysis revealed the increased expression tendency for JAK2 both in the neck and body skin from E6 to E10, and the much stronger expression in neck and body skin at later stages (E8-E10) than earlier stages (E6 and E7) for JAK1 and TYK2. Overall, these findings suggest that JAK1 and TYK2, not JAK2 are important to specify the feather follicle primordia, and to arrange the proximal-distal axis of feather follicles, respectively, during the morphogenesis of feather follicles in embryonic chicken skin.

Lactobacillus frumenti improves antioxidant capacity via nitric oxide synthase 1 in intestinal epithelial cells.

Oxidative damages have adverse effects on mammals. Growing studies have focused on exploring new antioxidants. Here, we report that Lactobacillus frumenti increases the total antioxidation capacity activities and decreases the total reactive oxygen species levels in porcine intestinal epithelial cells. Comparative proteomics revealed that expressions of peroxiredoxin 2, isocitrate dehydrogenase 1, NAD(P)H dehydrogenase quinone 1, antioxidant protein 1, and metallothionein-2A, which are associated with antioxidant defense system, were significantly increased with L. frumenti treatment. In germ-free mice, L. frumenti treatment also remarkably improves the intestinal antioxidant capacity. We further illustrated that nitric oxide production-mediated by nitric oxide synthase 1 activation is essential for L. frumenti-induced improvements in intestinal epithelial antioxidant capacity and barrier function. This study suggested that L. frumenti may be a potential probiotic used to prevent oxidative stress-induced aging and diseases in mammals.-Nie, Y., Hu, J., Hou, Q., Zheng, W., Zhang, X., Yang, T., Ma, L., Yan, X. Lactobacillus frumenti improves antioxidant capacity via nitric oxide synthase 1 in intestinal epithelial cells.

A Microbiota-Derived Bacteriocin Targets the Host to Confer Diarrhea Resistance in Early-Weaned Piglets.

Alternatives to antibiotics for preventing diarrhea in early-weaned farm animals are sorely needed. CM piglets (a native Chinese breed) are more resistant to early-weaning stress-induced diarrhea than the commercial crossbred LY piglets. Transferring fecal microbiota, but not saline, from healthy CM into LY piglets by oral administration prior to early weaning conferred diarrhea resistance. By comparing the relative abundance of intestinal microbiota in saline and microbiota transferred LY piglets, we identified and validated Lactobacillus gasseri LA39 and Lactobacillus frumenti as two bacterial species that mediate diarrhea resistance. Diarrhea resistance depended on the bacterial secretory circular peptide gassericin A, a bacteriocin. The binding of gassericin A to Keratin 19 (KRT19) on the plasma membrane of intestinal epithelial cells was essential for enhancement of fluid absorption and decreased secretion. These findings suggest the use of L. gasseri LA39 and L. frumenti as antibiotic alternatives for preventing diarrhea in mammals.

Transcriptome Reveals Long Non-coding RNAs and mRNAs Involved in Primary Wool Follicle Induction in Carpet Sheep Fetal Skin.

Murine primary hair follicle induction is driven by the communication between the mesenchyme and epithelium and mostly governed by signaling pathways including wingless-related integration site (WNT), ectodysplasin A receptor (EDAR), bone morphogenetic protein (BMP), and fibroblast growth factor (FGF), as observed in genetically modified mouse models. Sheep skin may serve as a valuable system for hair research owing to the co-existence of sweat glands with wool follicles in trunk skin and asynchronized wool follicle growth pattern similar to that of human head hair follicles. However, the mechanisms underlying wool follicle development remain largely unknown. To understand how long non-coding RNAs (lncRNAs) and mRNAs function in primary wool follicle induction in carpet wool sheep, we conducted high-throughput RNA sequencing and revealed globally altered lncRNAs (36 upregulated and 26 downregulated), mRNAs (228 elevated and 225 decreased), and 80 differentially expressed novel transcripts. Several key signals in WNT (WNT2B and WNT16), BMP (BMP3, BMP4, and BMP7), EDAR (EDAR and EDARADD), and FGF (FGFR2 and FGF20) pathways, and a series of lncRNAs, including XLOC_539599, XLOC_556463, XLOC_015081, XLOC_1285606, XLOC_297809, and XLOC_764219, were shown to be potentially important for primary wool follicle induction. GO and KEGG analyses of differentially expressed mRNAs and potential targets of altered lncRNAs were both significantly enriched in morphogenesis biological processes and transforming growth factor-ß, Hedgehog, and PI3K-Akt signaling, as well as focal adhesion and extracellular matrix-receptor interactions. The prediction of mRNA-mRNA and lncRNA-mRNA interaction networks further revealed transcripts potentially involved in primary wool follicle induction. The expression patterns of mRNAs and lncRNAs of interest were validated by qRT-PCR. The localization of XLOC_297809 and XLOC_764219 both in placodes and dermal condensations was detected by in situ hybridization, indicating important roles of lncRNAs in primary wool follicle induction and skin development. This is the first report elucidating the gene network of lncRNAs and mRNAs associated with primary wool follicle early development in carpet wool sheep and will shed new light on selective wool sheep breeding.

Lactobacillus gasseri LA39 Activates the Oxidative Phosphorylation Pathway in Porcine Intestinal Epithelial Cells.

Intestinal microbial interactions with the host epithelium have important roles in host health. Our previous data have suggested that Lactobacillus gasseri LA39 is the predominant intestinal Lactobacillus in weaned piglets. However, the regulatory role of L. gasseri LA39 in the intestinal epithelial protein expression in piglets remains unclear. In the present study, we conducted comparative proteomics approach to investigate the intestinal epithelial protein profile alteration caused by L. gasseri LA39 in piglets. The expressions of 15 proteins significantly increased, whereas the expressions of 13 proteins significantly decreased in the IPEC-J2 cells upon L. gasseri LA39 treatment. Bioinformatics analyses, including COG function annotation, GO annotation, and KEGG pathway analysis for the differentially expressed proteins revealed that the oxidative phosphorylation (OXPHOS) pathway in IPEC-J2 cells was significantly activated by L. gasseri LA39 treatment. Further data indicated that two differentially expressed proteins UQCRC2 and TCIRG1, associated with the OXPHOS pathway, and cellular ATP levels in IPEC-J2 cells were significantly up-regulated by L. gasseri LA39 treatment. Importantly, the in vivo data indicated that oral gavage of L. gasseri LA39 significantly increased the expression of UQCRC2 and TCIRG1 and the cellular ATP levels in the intestinal epithelial cells of weaned piglets. Our results, both in vitro and in vivo, reveal that L. gasseri LA39 activates the OXPHOS pathway and increases the energy production in porcine intestinal epithelial cells. These findings suggest that L. gasseri LA39 may be a potential probiotics candidate for intestinal energy production promotion and confers health-promoting functions in mammals.

Defining Key Genes Regulating Morphogenesis of Apocrine Sweat Gland in Sheepskin.

The apocrine sweat gland is a unique skin appendage in humans compared to mouse and chicken models. The absence of apocrine sweat glands in chicken and murine skin largely restrains further understanding of the complexity of human skin biology and skin diseases, like hircismus. Sheep may serve as an additional system for skin appendage investigation owing to the distributions and histological similarities between the apocrine sweat glands of sheep trunk skin and human armpit skin. To understand the molecular mechanisms underlying morphogenesis of apocrine sweat glands in sheepskin, transcriptome analyses were conducted to reveal 1631 differentially expressed genes that were mainly enriched in three functional groups (cellular component, molecular function and biological process), particularly in gland, epithelial, hair follicle and skin development. There were 7 Gene Ontology (GO) terms enriched in epithelial cell migration and morphogenesis of branching epithelium that were potentially correlated with the wool follicle peg elongation. An additional 5 GO terms were enriched in gland morphogenesis (20 genes), gland development (42 genes), salivary gland morphogenesis and development (8 genes), branching involved in salivary gland morphogenesis (6 genes) and mammary gland epithelial cell differentiation (4 genes). The enriched gland-related genes and two Kyoto Encyclopedia of Genes and Genomes pathway genes (WNT and TGF-ß) were potentially involved in the induction of apocrine sweat glands. Genes named BMPR1A, BMP7, SMAD4, TGFB3, WIF1, and WNT10B were selected to validate transcript expression by qRT-PCR. Immunohistochemistry was performed to localize markers for hair follicle (SOX2), skin fibroblast (PDGFRB), stem cells (SOX9) and BMP signaling (SMAD5) in sheepskin. SOX2 and PDGFRB were absent in apocrine sweat glands. SOX9 and SMAD5 were both observed in precursor cells of apocrine sweat glands and later in gland ducts. These results combined with the upregulation of BMP signaling genes indicate that apocrine sweat glands were originated from outer root sheath of primary wool follicle and positively regulated by BMP signaling. This report established the primary network regulating early development of apocrine sweat glands in sheepskin and will facilitate the further understanding of histology and pathology of apocrine sweat glands in human and companion animal skin.

Leucine reduces reactive oxygen species levels via an energy metabolism switch by activation of the mTOR-HIF-1α pathway in porcine intestinal epithelial cells.

Leucine serves not only as a substrate for protein synthesis, but also as a signal molecule involved in protein metabolism. However, whether the levels of cellular reactive oxygen species (ROS), which have damaging effects on cellular DNA, proteins, and lipids, are regulated by leucine is still unclear. Here, we report that leucine supplementation reduces ROS levels in intestinal epithelial cells of weaned piglets. A proteomics analysis revealed that leucine supplementation induces an energy metabolism switch from oxidative phosphorylation (OXPHOS) towards glycolysis. The leucine-induced ROS reduction and the energy metabolism switch were further validated in cultured cells. Mechanistically, our data revealed that leucine-induced ROS reduction actually depends on the energy metabolism switch from OXPHOS towards glycolysis through the mechanistic target of rapamycin (mTOR)- hypoxia-inducible factor-1alpha (HIF-1α) pathway. These findings reveal a vital regulatory role of leucine as the signal molecule involved in an energy metabolism switch in mammals.

Gradual Changes of Gut Microbiota in Weaned Miniature Piglets.

Colonization of gut microbiota in mammals during the early life is vital to host health. The miniature piglet has recently been considered as an optimal infant model. However, less is known about the development of gut microbiota in miniature piglets. Here, this study was conducted to explore how the gut microbiota develops in weaned Congjiang miniature piglets. In contrast to the relatively stabilized gut fungal community, gut bacterial community showed a marked drop in alpha diversity, accompanied by significant alterations in taxonomic compositions. The relative abundances of 24 bacterial genera significantly declined, whereas the relative abundances of 7 bacterial genera (Fibrobacter, Collinsella, Roseburia, Prevotella, Dorea, Howardella, and Blautia) significantly increased with the age of weaned piglets. Fungal taxonomic analysis showed that the relative abundances of two genera (Kazachstania and Aureobasidium) significantly decreased, whereas the relative abundances of four genera (Aspergillus, Cladosporium, Simplicillium, and Candida) significantly increased as the piglets aged. Kazachstania telluris was the signature species predominated in gut fungal communities of weaned miniature piglets. The functional maturation of the gut bacterial community was characterized by the significantly increased digestive system, glycan biosynthesis and metabolism, and vitamin B biosynthesis as the piglets aged. These findings suggest that marked gut microbial changes in Congjiang miniature piglets may contribute to understand the potential gut microbiota development of weaned infants.

The Role of Autophagy in the Gut Pathogens Clearance and Evasion.

The mammalian intestine harbors a mass of microorganisms that is essential to maintain intestinal epithelium homeostasis and health. However, some microbes can damage the epithelial mucosal barrier to utilize nutrients for their survival and growth. Autophagy is a highly conserved cellular process that targets cytoplasmic damaged organelles and some cellular molecules to lysosome for degradation. Accumulating studies have demonstrated that autophagy plays an important role in the innate immune system in response to different gut pathogens. For instance, autophagy can be induced to mediate the process of pathogenic infection during pathogens invasion. In this review, we mainly discuss the steps of autophagy pathway mediated by microbes and the role of autophagy in the gut pathogens clearance and evasion.

Cross-talk between bile acids and intestinal microbiota in host metabolism and health.

Bile acid (BA) is de novo synthesized exclusively in the liver and has direct or indirect antimicrobial effects. On the other hand, the composition and size of the BA pool can be altered by intestinal microbiota via the biotransformation of primary BAs to secondary BAs, and subsequently regulate the nuclear farnesoid X receptor (FXR; NR1H4). The BA-activated FXR plays important roles in BA synthesis and metabolism, glucose and lipid metabolism, and even hepatic autophagy. BAs can also play a role in the interplays among intestinal microbes. In this review, we mainly discuss the interactions between BAs and intestinal microbiota and their roles in regulating host metabolism, and probably the autophagic signaling pathway.