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Abstract Background Colony stimulating factor 1 (CSF1) is generally expressed by immune cells in response to pro-inflammatory stimuli. The CSF1 receptor (CSFR) is activated by CSF1, and plays a key role in macrophage homeostasis. Furthermore, the CSF1R+ macrophages maintain homeostasis in the intestinal epithelium. The aim of this study was to explore the functions of CSF1-expressing and CSF1R+ macrophages in necrotizing enterocolitis (NEC), which commonly affects the ileum of neonates. Methods In-situ CSF1 expression in the intestines of neonates with NEC or intestinal atresia (n = 4 each) was detected by immunofluorescence staining. The CSF1 levels in the intestinal crypt-derived organoid cultures were measured by ELISA. Peripheral blood monocyte-derived Mφ macrophages were co-cultured with the organoids and stimulated with lipopolysaccharide (LPS) to mimic the inflamed state of the ileum in NEC patients. Results CSF1 was expressed in the intestinal epithelial cells of the fetal and neonatal samples, but suppressed in the NEC samples. Furthermore, CSF1 expression was downregulated in the intestinal crypt-derived organoids by LPS. CSF1R+ macrophages were detected near the intestinal crypts in the non-inflamed intestines but were absent in tissues obtained from pediatric NEC patients. Peripheral blood monocyte-derived macrophages promoted intestinal organoid proliferation in vitro following CSF1 stimulation. Finally, low concentrations of LPS slightly enhanced the proliferation of organoids co-cultured with the macrophages, whereas higher doses had a significant inhibitory effect. Conclusions Intestinal epithelial cells express CSF1 to regulate the resident macrophages, maintain epithelial homeostasis, and resist infection. The abundant CSF1R+ macrophages in the fetal intestine may overexpress TNF-α upon activation of the TLR4/NF-κB pathway, resulting in epithelial damage and NEC induction.

Abstract Necrotizing enterocolitis (NEC) involves intestinal epithelial damage and inflammatory response and is associated with high morbidity and mortality in infants. To improve therapeutic prospects, elucidating underlying molecular mechanisms of intestinal epithelial damage during NEC is of the essence. Poly (ADP-ribose) polymerase 1 (PARP1)-dependent parthanatos is a programmed inflammatory cell death. In the present study, the presence of parthanatos-associated proteins PARP1 and poly (ADP-ribose) (PAR), along with high expression of DNA damage-associated biomarkers, 8-hydroxy-2’-deoxyguanosine (8-OHdG) and phosphorylation of histone H2AX (γH2AX), were discovered in the intestinal tissues of NEC infants. Additionally, the upregulated expression of PARP1 and PAR in NEC intestinal tissues correlated distinctly with clinical indices indicative of NEC incidence and severity. Furthermore, we demonstrated that inhibiting the expression of parthanatos-associated proteins, by either pharmacological blockage using 3-aminobenzamide (3-AB), an inhibitor of PARP1, or genetic knockout using Parp1-deficient mice, resulted in substantial improvements in both histopathological severity scores associated with intestinal injury and inflammatory reactions. Moreover, in an in vitro NEC model, reactive oxygen species (ROS)-induced DNA damage promoted the formation of PAR and nuclear translocation of apoptosis-inducing factor (AIF), thus activating PARP1-dependent parthanatos in Caco-2 cells and human intestinal organoids. Our work verifies a previously unexplored role for parthanatos in intestinal epithelial damage during NEC and suggests that inhibition of parthanatos may serve as a potential therapeutic strategy for intervention of NEC.

Objective: To analyse the research history, development trends and current status of relevant literature in the field of Kawasaki disease, and to provide the basis for future directions in Kawasaki disease (KD) research. Methods: Literature on Kawasaki disease published between January 1974 and December 2022 was searched for in the Web of Science database, and CiteSpace was used to perform visual analyses. Results: The search yielded a total of 6950 articles. The number of publications related to Kawasaki disease showed an increasing trend. A collaborative network analysis revealed that the United States, Japan and mainland China were the most influential countries in this field. The University of California system contributed the most publications and the journal with the most publications was Circulation. JW Newburger was an authoritative author in this field. “Coronary artery lesion”, “Intravenous immunoglobulin” (IVIG) and “Risk factor” were three prominent keywords. Keyword bursts changed from “TNF” and “IVIG”, which focused on aetiology and treatment, to “Long term management”, which emphasized the recovery period, and to “Kawasaki-like disease” and “Multisystem inflammatory syndrome” during the novel coronavirus pandemic. Trends of highly cited references indicated that landmark articles in different periods focused on Kawasaki disease guidelines, gene polymorphisms and multisystem inflammatory syndrome caused by the novel coronavirus. Conclusion: The aetiology of Kawasaki disease remains unclear, but viral infection is likely to play an important role. The combination of evolving sequencing technologies, large-scale epidemiological investigations and prospective cohort studies is likely to be important in exploring Kawasaki disease and improving its prognosis in future.

ABSTRACT The pivotal roles of gut microbiota in severe acute pancreatitis-associated acute lung injury (SAP-ALI) are increasingly revealed, and recent discoveries in the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used in clinical to treat SAP-ALI. However, the underlying mechanisms remain to be fully elucidated. Herein, by using a caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model and antibiotics (Abx) cocktail-induced pseudogermfree mice model, we tried to uncover the roles of the gut microbiota by administration of QYD and explored its possible mechanisms. Immunohistochemical results showed that the severity of SAP-ALI and intestinal barrier functions could be affected by the relative depletion of intestinal bacteria. The composition of gut microbiota was partially recovered after QYD treatment with decreased Firmicutes/Bacteroidetes ratio and increased relative abundance in short-chain fatty acids (SCFAs)-producing bacteria. Correspondingly increased levels of SCFAs (especially propionate and butyrate) in feces, gut, serum, and lungs were observed, generally consistent with changes in microbes. Western-blot analysis and RT-qPCR results indicated that the AMPK/NF-κB/NLRP3 signaling pathway was activated after oral administration of QYD, which was found to be possibly related to the regulatory effects on SCFAs in the intestine and lungs. In conclusion, our study provides new insights into treating SAP-ALI through modulating the gut microbiota and has prospective practical value for clinical use in the future. IMPORTANCE Gut microbiota affects the severity of SAP-ALI and intestinal barrier function. During SAP, a significant increase in the relative abundance of gut pathogens (Escherichia, Enterococcus, Enterobacter, Peptostreptococcus, Helicobacter) was observed. At the same time, QYD treatment decreased pathogenic bacteria and increased the relative abundance of SCFAs-producing bacteria (Bacteroides, Roseburia, Parabacteroides, Prevotella, Akkermansia). In addition, The AMPK/NF-κB/NLRP3 pathway mediated by SCFAs along the gut-lung axis may play an essential role in preventing the pathogenesis of SAP-ALI, which allows for reduced systemic inflammation and restoration of the intestinal barrier.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. The in-depth study of genes and metabolites related to nucleotide metabolism will provide new ideas for predicting the prognosis of HCC patients. This study integrated the transcriptome data of different cancer types to explore the characteristics and significance of nucleotide metabolism-related genes (NMGRs) in different cancer types. Then, we constructed a new HCC classifier and prognosis model based on HCC samples from TCGA and GEO, and detected the gene expression level in the model through molecular biology experiments. Finally, nucleotide metabolism-related products in serum of HCC patients were examined using untargeted metabolomics. A total of 97 NMRGs were obtained based on bioinformatics techniques. In addition, a clinical model that could accurately predict the prognostic outcome of HCC was constructed, which contained 11 NMRGs. The results of PCR experiments showed that the expression levels of these genes were basically consistent with the predicted trends. Meanwhile, the results of untargeted metabolomics also proved that there was a significant nucleotide metabolism disorder in the development of HCC. Our results provide a promising insight into nucleotide metabolism in HCC, as well as a tailored prognostic and chemotherapy sensitivity prediction tool for patients.

The woody plant gender difference may lead to alteration in rhizosphere microbial communities and soil physicochemical properties. In this study, we investigated the differences in rhizosphere soil properties and microbial community structures of S. linearistipularis. Rhizosphere microorganisms were analyzed by high-throughput sequencing technology. The results showed that there were significant differences in rhizosphere soil nutrition between male and female S. linearistipularis plants in saline–alkali soil. The female S. linearistipularis plants significantly reduce soil pH values and significantly increase the soil water content (SWC), available total nitrogen (TN), soil organic matter (SOM), and soil urease activity (S-UE) compared to the male plant. The ACE, Chao, and Shannon index of the female plant was significantly higher than that of the male strain. At the level of Bacteriophyta, the relative abundance of Actinobacteriota in male and female S. linearistipularis was the highest, with 34.26% and 31.03%, respectively. Among the named bacterial genera, the relative abundance of Defluviicoccus of male and female plants was the highest, with 2.67% and 5.27%, respectively. At the level of Eumycophyta, the relative abundance of Ascomycetes in male and female plants was the highest, with 54.93% and 52.10%, respectively. Among the named fungi genera, the relative abundance of male and female plants of Mortierella was the highest, with 6.18% and 9.31%, respectively. In addition, soil pH, SOM, SWC, and S-UE activities were the main driving factors of soil microbial community structures. In the process of restoring saline–alkali land in the Songnen Plain, we may prioritise the planting of female S. linearistipularis, which also provides a theoretical basis for the microorganisms restoration of saline–alkali land in the Songnen plain.

Abstract Background Late-onset sepsis (LOS) is a systemic inflammatory response syndrome in neonates, and the molecular mechanism of LOS is incompletely characterized. The purpose of this study was to explore the potential value of receptor interacting protein 3 (RIP3) in LOS. Methods 63 neonates with LOS supported by positive culture and 79 neonates without sepsis were enrolled in this study from September 2019 to March 2021. Plasma RIP3 was detected by enzyme-linked immunosorbent assay (ELISA) and assessed along with the whole blood hypersensitive C-reactive protein (hs-CRP) level and platelet count (PLT). Differences in RIP3, hs-CRP and PLT between the two groups were compared. Changes in the three indicators in sepsis were also observed after treatment. The diagnostic value of indicators for LOS was evaluated by receiver operating characteristic (ROC) curve analysis. Results In the sepsis group, RIP3 and hs-CRP levels were significantly higher than those in the control group (RIP3, p 15,845.19 pg/mL, hs-CRP > 5.00 mg/L, and PLT

ObjectiveTo review and critically appraise articles on prediction models for coronary artery lesions (CALs) in Kawasaki disease included in PubMed, Embase, and Web of Science databases from January 1, 1980, to December 23, 2021.Materials and methodsStudy screening, data extraction, and quality assessment were performed by two independent reviewers, with a statistics expert resolving discrepancies. Articles that developed or validated a prediction model for CALs in Kawasaki disease were included. The Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies checklist was used to extract data from different articles, and Prediction Model Risk-of-Bias Assessment Tool (PROBAST) was used to assess the bias risk in different prediction models. We screened 19 studies from a pool of 881 articles.ResultsThe studies included 73–5,151 patients. In most studies, univariable logistic regression was used to develop prediction models. In two studies, external data were used to validate the developing model. The most commonly included predictors were C-reactive protein (CRP) level, male sex, and fever duration. All studies had a high bias risk, mostly because of small sample size, improper handling of missing data, and inappropriate descriptions of model performance and the evaluation model.ConclusionThe prediction models were suitable for the subjects included in the studies, but were poorly effective in other populations. The phenomenon may partly be due to the bias risk in prediction models. Future models should address these problems and PROBAST should be used to guide study design.

Autophagy has dual roles in cancer, resulting in cellular adaptation to promote either cell survival or cell death. Modulating autophagy can enhance the cytotoxicity of many chemotherapeutic and targeted drugs and is increasingly considered to be a promising cancer treatment approach. Cynaropicrin (CYN) is a natural compound that was isolated from an edible plant (artichoke). Previous studies have shown that CYN exhibits antitumor effects in several cancer cell lines. However, it anticancer effects against neuroblastoma (NB) and the underlying mechanisms have not yet been investigated. More specifically, the regulation of autophagy in NB cells by CYN has never been reported before. In this study, we demonstrated that CYN induced apoptosis and protective autophagy. Further mechanistic studies suggested that ER stress-induced autophagy inhibited apoptosis by activating the p62/Keap1/Nrf2 pathways. Finally, in vivo data showed that CYN inhibited tumour growth in xenografted nude mice. Overall, our findings suggested that CYN may be a promising candidate for the treatment of NB, and the combination of pharmacological inhibitors of autophagy may hold novel therapeutic potential for the treatment of NB. Our paper will contribute to the rational utility and pharmacological studies of CYN in future anticancer research.

The gut microbiota plays an important role in regulating the pharmacokinetics and pharmacodynamics of many drugs. FLZ, a novel squamosamide derivative, has been shown to have neuroprotective effects on experimental Parkinson's disease (PD) models. FLZ is under phase Ⅰ clinical trial now, while the underlying mechanisms contributing to the absorption of FLZ are still not fully elucidated. Due to the main metabolite of FLZ was abundant in feces but rare in urine and bile of mice, we focused on the gut microbiota to address how FLZ was metabolized and absorbed. In vitro studies revealed that FLZ could be exclusively metabolized to its major metabolite M1 by the lanosterol 14 alpha-demethylase (CYP51) in the gut microbiota, but was almost not metabolized by any other metabolism-related organs, such as liver, kidney, and small intestine. M1 was quickly absorbed into the blood and then remethylated to FLZ by catechol O-methyltransferase (COMT). Notably, dysbacteriosis reduced the therapeutic efficacy of FLZ on the PD mouse model by inhibiting its absorption. The results show that the gut microbiota mediate the absorption of FLZ through a FLZ–M1–FLZ circulation. Our research elucidates the vital role of the gut microbiota in the absorption of FLZ and provides a theoretical basis for clinical pharmacokinetic studies and clinical application of FLZ in the treatment of PD.

Severe acute pancreatitis (SAP), one of the most serious abdominal emergencies in general surgery, is characterized by acute and rapid onset as well as high mortality, which often leads to multiple organ failure (MOF). Acute lung injury (ALI), the earliest accompanied organ dysfunction, is the most common cause of death in patients following the SAP onset. The exact pathogenesis of ALI during SAP, however, remains unclear. In recent years, advances in the microbiota-gut-lung axis have led to a better understanding of SAP-associated lung injury (PALI). In addition, the bidirectional communications between intestinal microbes and the lung are becoming more apparent. This paper aims to review the mechanisms of an imbalanced intestinal microbiota contributing to the development of PALI, which is mediated by the disruption of physical, chemical, and immune barriers in the intestine, promotes bacterial translocation, and results in the activation of abnormal immune responses in severe pancreatitis. The pathogen-associated molecular patterns (PAMPs) mediated immunol mechanisms in the occurrence of PALI via binding with pattern recognition receptors (PRRs) through the microbiota-gut-lung axis are focused in this study. Moreover, the potential therapeutic strategies for alleviating PALI by regulating the composition or the function of the intestinal microbiota are discussed in this review. The aim of this study is to provide new ideas and therapeutic tools for PALI patients.

The progression of hyperuricemia disease is often accompanied by damage to renal function. However, there are few studies on hyperuricemia nephropathy, especially its association with intestinal flora. This study combines metabolomics and gut microbiota diversity analysis to explore metabolic changes using a rat model as well as the changes in intestinal flora composition. The results showed that amino acid metabolism was disturbed with serine, glutamate and glutamine being downregulated whilst glycine, hydroxyproline and alanine being upregulated. The combined glycine, serine and glutamate could predict hyperuricemia nephropathy with an area under the curve of 1.00. Imbalanced intestinal flora was also observed. Flavobacterium, Myroides, Corynebacterium, Alcaligenaceae, Oligella and other conditional pathogens increased significantly in the model group, while Blautia and Roseburia, the short-chain fatty acid producing bacteria, declined greatly. At phylum, family and genus levels, disordered nitrogen circulation in gut microbiota was detected. In the model group, the uric acid decomposition pathway was enhanced with reinforced urea liver-intestine circulation. The results implied that the intestinal flora play a vital role in the pathogenesis of hyperuricemia nephropathy. Hence, modulation of gut microbiota or targeting at metabolic enzymes, i.e., urease, could assist the treatment and prevention of this disease. KEY WORDS: Hyperuricemia, Renal function, Gut microbiota, Metabolomics, Urease

Willow (Salix), a dioecious plant, is an important ornamental tree species in the world. Salix linearistipularis, a perennial woody plant species naturally distributed on the Songnen Plain saline-alkali land in northeast China, has a high saline condition. To study the sexual differences of S. linearistipularis in salinity tolerance, the physiological and transcriptional responses to salinity were compared between female and male cuttings. Under salinity stress, the female leaves exhibited higher superoxide dismutase and peroxidase activities and photosynthetic capacity, and lower H2O2 contents than those of male leaves. Under salinity stress, sodium (Na+) accumulation in female leaves was lower than that in the male leaves. The non-invasive micro-test showed that the net Na+ efflux in the salt-treated female roots was higher than that in male roots. Physiological responses revealed that female cuttings were more tolerant than males, which may be mainly due to females having lower leaf Na+ accumulation and higher root Na+ efflux capacity than males. Transcriptional analyses showed that 108 differentially expressed salt-responsive genes were identified in both female and male roots; most of these showed sexual differences in expression patterns under salinity stress. RNA-seq combined with qPCR analysis showed that the salt-induced expression of four Na+/H+ antiporter (NHX) genes (SlNHX3, 5, 6, 7) in female roots was higher than that in male roots. Transcriptional analyses revealed that the higher Na+ efflux capacity in female roots than in male roots may be closely related to the differential expression of salt-responsive genes, especially NHX genes.

This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005–2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded.

BACKGROUND: The epicuticular waxy layer of plant leaves enhances the extreme environmental stress tolerance. However, the relationship between waxy layer and saline tolerance was not established well. The epicuticular waxy layer of rice (Oryza sativa L.) was studied under the NaHCO3 stresses. In addition, strong saline tolerance Puccinellia tenuiflora was chosen for comparative studies. RESULTS: Scanning electron microscope (SEM) images showed that there were significant changes in waxy morphologies of the rice epicuticular surfaces, while no remarkable changes in those of P. tenuiflora epicuticular surfaces. The NaHCO3-induced morphological changes of the rice epicuticular surfaces appeared as enlarged silica cells, swollen corns-shapes and leaked salt columns under high stress. Energy dispersive X-ray (EDX) spectroscopic profiles supported that the changes were caused by significant increment and localization of [Na+] and [Cl-] in the shoot. Atomic absorption spectra showed that [Na+]shoot/[Na+]root for P. tenuiflora maintained stable as the saline stress increased, but that for rice increased significantly. CONCLUSION: In rice, NaHCO3 stress induced localization and accumulation of [Na+] and [Cl-] appeared as the enlarged silica cells (MSC), the swollen corns (S-C), and the leaked columns (C), while no significant changes in P. tenuiflora.

Poplar is a model organism for high in vitro regeneration in woody plants. We have chosen a hybrid poplar Populus davidiana Dode × Populus bollena Lauche. By optimizing the Murashige and Skoog medium with (0.3 mg/L) 6-benzylaminopurine and (0.08 mg/L) naphthaleneacetic acid, we have achieved the highest frequency (90%) for shoot regeneration from poplar leaves. It was also important to improve the transformation efficiency of poplar for genetic breeding and other applications. In this study, we found a significant improvement of the transformation frequency by controlling the leaf age. Transformation efficiency was enhanced by optimizing the Agrobacterium concentration (OD600 = 0.8–1.0) and an infection time (20–30 min). According to transmission electron microscopy observations, there were more Agrobacterium invasions in the 30-day-old leaf explants than in 60-day-old and 90-day-old explants. Using the green fluorescent protein (GFP) marker, the expression of MD–GFP fusion proteins in the leaf, shoot, and root of hybrid poplar P. davidiana Dode × P. bollena Lauche was visualized for confirmation of transgene integration. Southern and Northern blot analysis also showed the integration of T-DNA into the genome and gene expression of transgenic plants. Our results suggest that younger leaves had higher transformation efficiency (~30%) than older leaves (10%).

Abstract  Alkaline-saline soil is widespread in arid and semiarid regions of the world and causes severe environmental and agricultural problems. To advance our understanding of the adaptation of ectomycorrhizal fungi (EMF) to alkaline-saline soil, we investigated EMF communities on Mongolian willow (Salix linearistipularis) growing in alkaline-saline soil (up to pH 9.2) in northeastern China. In total, 75 root samples were collected from 25 willow individuals over 4.7 ha. To identify fungal species in ectomycorrhizal root tips, we used terminal restriction fragment length polymorphism and sequencing analyses of the internal transcribed spacer region of ribosomal DNA. We detected 11 EMF species, including species of Inocybe, Hebeloma, and Tomentella of the Basidiomycota and three Ascomycota species. The EMF richness of the study site was estimated to be 15–17 using major estimators. The most abundant species was Geopora sp. 1, while no Geopora-dominated EMF communities have been reported so far. Phylogenetic analysis showed that the phylogroup including Geopora sp. 1 has been found mostly in alkaline soil habitats, indicating its adaptation to high soil pH. Because EMF are indispensable for host plant growth, the EMF species detected in this study may be useful for restoration of alkaline-saline areas. [ABSTRACT FROM AUTHOR]

The photosynthesis and transpiration characteristics of Adenophora lobophylla and A. potaninii, as well as stomatal behavior such as stomatal size, stomatal density, stomatal open and stomatal conductivity were measured at different altitudes. The relationship between the photosynthesis and transpiration characteristics and the stomatal behavior was analysed by correlation coefficient and path coefficient analysis with altitude changes. The results showed that the influences of stomatal behavior were not evident on the photosynthesis and transpiration characteristics of A. Lobophylla, but evident on that of A. potaninii. [ABSTRACT FROM AUTHOR]