Advancing screening tool for hospice needs and end-of-life decision-making process in the emergency department.

BACKGROUND: Predicting mortality in the emergency department (ED) is imperative to guide palliative care and end-of-life decisions. However, the clinical usefulness of utilizing the existing screening tools still leaves something to be desired. METHODS: We advanced the screening tool with the A-qCPR (Age, qSOFA (quick sepsis-related organ failure assessment), cancer, Performance Status Scale, and DNR (Do-Not-Resuscitate) risk score model for predicting one-year mortality in the emergency department of Taipei City Hospital of Taiwan with the potential of hospice need and evaluated its performance compared with the existing screening model. We adopted a large retrospective cohort in conjunction with in-time (the trained and the holdout validation cohort) for the development of the A-qCPR model and out-of-time validation sample for external validation and model robustness to variation with the calendar year. RESULTS: A total of 10,474 patients were enrolled in the training cohort and 33,182 patients for external validation. Significant risk scores included age (0.05 per year), qSOFA ≥ 2 (4), Cancer (5), Eastern Cooperative Oncology Group (ECOG) Performance Status score ≥ 2 (2), and DNR status (2). One-year mortality rates were 13.6% for low (score ≦ 3 points), 29.9% for medium (3 < Score ≦ 9 points), and 47.1% for high categories (Score > 9 points). The AUROC curve for the in-time validation sample was 0.76 (0.74-0.78). However, the corresponding figure was slightly shrunk to 0.69 (0.69-0.70) based on out-of-time validation. The accuracy with our newly developed A-qCPR model was better than those existing tools including 0.57 (0.56-0.57) by using SQ (surprise question), 0.54 (0.54-0.54) by using qSOFA, and 0.59 (0.59-0.59) by using ECOG performance status score. Applying the A-qCPR model to emergency departments since 2017 has led to a year-on-year increase in the proportion of patients or their families signing DNR documents, which had not been affected by the COVID-19 pandemic. CONCLUSIONS: The A-qCPR model is not only effective in predicting one-year mortality but also in identifying hospice needs. Advancing the screening tool that has been widely used for hospice in various scenarios is particularly helpful for facilitating the end-of-life decision-making process in the ED.

Acidaminococcus homini s sp. nov., Amedibacillus hominis sp. nov., Lientehia hominis gen. nov. sp. nov., Merdimmobilis hominis gen. nov. sp. nov., and Paraeggerthella hominis sp. nov., isolated from human faeces.

The human gastrointestinal tract is inhabited by various microorganisms, including thousands of bacterial taxa that have yet to be cultured and characterized. In this report, we describe the isolation, cultivation, genotypic and phenotypic characterization and taxonomy of five novel anaerobic bacterial strains that were recovered during the massive cultivation and isolation of gut microbes from human faecal samples. On the basis of the polyphasic taxonomic results, we propose two novel genera and five novel species. They are Acidaminococcus hominis sp. nov. (type strain NSJ-142T=CGMCC 1.17903T=KCTC 25346T), Amedibacillus hominis sp. nov. (type strain NSJ-176T=CGMCC 1.17933T=KCTC 25355T), Lientehia hominis gen. nov. sp. nov. (type strain NSJ-141T=CGMCC 1.17902T=KCTC 25345T), Merdimmobilis hominis gen. nov. sp. nov. (type strain NSJ-153T=CGMCC 1.17915T=KCTC 25350T) and Paraeggerthella hominis sp. nov. (type strain NSJ-152T=CGMCC 1.17914T=KCTC 25349T).

The ocular anterior segment examination of perinatal newborns by wide-field digital imaging system: a cross-sectional study.

PURPOSE: The aim of this study was to evaluate and summarize the developmental rules of the ocular anterior segment of neonates by means of wild-field digital imaging system. METHODS: We used the wide-field digital imaging system to sequentially capture images of the neonates' eyes within 42 days after delivery, including the ocular surface, anterior segment, and fundus. At the same time, basic information at the time of birth and examination was collected. RESULTS: Among 248 newborns, 51.21% were male. Abnormalities of the anterior segment such as visualization of anterior chamber angle vessels (79.03%) and iris vessels (51.21%), iris process (42.34%), persistent pupillary membranes (19.35%), albinism, congenital cataracts, corneal leucoma, and subconjunctival hemorrhage were observed in this study. There were significant differences in the appearance of iris vessels among different sex, gestational age and birth weight, postmenstrual age and weight at the time of examination and iris color groups. The iris vessels were more visualized in males relative to females (OR = 6.313, 95% CI 2.529-15.759). The greater the postmenstrual age at the time of examination, the lower the visualization of iris vessels (OR = 0.377, 95% CI 0.247-0.575). In addition, although visualization of anterior chamber angle vessels differed within the birth gestation age and weight at examination groups, there was no significant correlation by regression analysis. CONCLUSIONS: The anterior segment of perinatal neonates can be visualized by the wide-field digital imaging system. The neonatal iris and anterior chamber angle are immature, and the visible vessels at the anterior chamber angle that vanish later than the surface of the iris are characteristic structures.

Pararoseburia lenta gen. nov., sp. nov. isolated from human faeces.

A strictly anaerobic, motile bacterium, designated as strain NSJ-9T, was isolated from human faeces. Cells were Gram-negative, non-spore-forming, non-pigmented, and spiral-shaped or slightly curved rods with flagella. Optimal growth in M2GSC medium was observed at 37 °C (growth range 30-45 °C) and pH 6.5-7.0 (growth range 6.5-7.5) under anaerobic conditions. Phylogenetic analysis of the 16S rRNA gene revealed that strain NSJ-9T formed a distinct phylogenetic lineage that reflects a new genus in the family Lachnospiraceae, with high levels of similarity to Roseburia hominis A2-183T (95.2 %), Roseburia cecicola ATCC 33874T (95.2 %), Pseudobutyrivibrio ruminis DSM 9787T (95.2 %), Pseudobutyrivibrio xylanivorans MZ 5T (94.8%) and Roseburia faecis M72/1T (94.4 %). Genomic similarity (average nucleotide identity and digital DNA-DNA hybridization) values between strain NSJ-9T and its phylogenetic neighbours were below 71 and 31 %, respectively, indicating that strain NSJ-9T represented a novel species. The average amino acid identity and the percentage of conserved proteins between strain NSJ-9T and other related members of the family Lachnospiraceae were below 63 and 50 %, respectively, supporting that strain NSJ-9T was a member of a new genus. The predominant cellular fatty acids of strain NSJ-9T were C16 : 0 and C17 : 0 2-OH, and major polar lipids were glycolipids. The end products of glucose fermentation were acetate, propionate, iso-butyrate, butyrate and valerate. Phylogenetic and phylogenomic lineage, pairwise determined genome identity analysis suggested that strain NSJ-9T represents a novel genus in the family Lachnospiraceae. The genome size of strain NSJ-9T is 2.56 Mbp with 44.9 mol% G+C content. Collectively, the genotypic and phenotypic differences between phylogenetic relatives suggested strain NSJ-9T represented a novel species of a new genus, for which the name Pararoseburia lenta gen. nov., sp. nov. is proposed. The type strain of Pararoseburia lenta is NSJ-9T (=CGMCC 1.32469T=KCTC 15957T).

Bacteroides propionicigenes sp. nov., isolated from human faeces.

An anaerobic bacterial strain, designated as NSJ-90T, was isolated from the faeces of a healthy adult in China. Cells of strain NSJ-90T were Gram-stain-negative, non-motile, non-spore-forming and rod-shaped. Based on 16S rRNA gene sequence analysis, strain NSJ-90T belonged to the genus Bacteroides and was phylogenetically closely related to Bacteroides clarus YIT 12056T (16S rRNA gene identity was 97.04 %). The DNA G+C content of strain NSJ-90T was 44.85 mol% (calculated from the genome). The average nucleotide identity between strain NSJ-90T and B. clarus YIT 12056T was 87.60 %. The major cellular fatty acids (>10 %) of strain NSJ-90T were iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0 3-OH. Menaquinone-10 was detected as the respiratory quinone. The major products of glucose fermentation were acetic, propionic and isovaleric acids. Based on its phylogenetic, phenotypic and chemotaxonomic characteristics, we propose that strain NSJ-90T represents a novel species of the genus Bacteroides, for which the name Bacteroides propionicigenes sp. nov. is proposed. The type strain is NSJ-90T (=CGMCC 1.17886T=KCTC 25305T).

Alkaliphilus flagellatus sp. nov., Butyricicoccus intestinisimiae sp. nov., Clostridium mobile sp. nov., Clostridium simiarum sp. nov., Dysosmobacter acutus sp. nov., Paenibacillus brevis sp. nov., Peptoniphilus ovalis sp. nov. and Tissierella simiarum sp. nov., isolated from monkey faeces.

Non-human primates harbour diverse microbiomes in their guts. As a part of the China Microbiome Initiatives, we cultivated and characterized the gut microbiome of cynomolgus monkeys (Macaca fascicularis). In this report, we communicate the characterization and taxonomy of eight bacterial strains that were obtained from faecal samples of captive cynomolgus monkeys. The results revealed that they represented eight novel bacterial species. The proposed names of the eight novel species are Alkaliphilus flagellatus (type strain MSJ-5T=CGMCC 1.45007T=KCTC 15974T), Butyricicoccus intestinisimiae MSJd-7T (MSJd-7T=CGMCC 1.45013T=KCTC 25112T), Clostridium mobile (MSJ-11T=CGMCC 1.45009T=KCTC 25065T), Clostridium simiarum (MSJ-4T=CGMCC 1.45006T=KCTC 15975T), Dysosmobacter acutus (MSJ-2T=CGMCC 1.32896T=KCTC 15976T), Paenibacillus brevis MSJ-6T (MSJ-6T=CGMCC 1.45008T=KCTC 15973T), Peptoniphilus ovalis (MSJ-1T=CGMCC 1.31770T=KCTC 15977T) and Tissierella simiarum (MSJ-40T=CGMCC 1.45012T=KCTC 25071T).

Mechanism analysis of the immobilization of heavy metal ions with the water-soluble polymer: The influence of resin structure and the further adsorption of chelate.

Polymer materials have become one of the potential materials for remediation of heavy metal (HM) contamination in water and soil. However, the specific advantages of polymers are rarely studied. Water-soluble thiourea formaldehyde resin (WTF) is one of the effective polymer amendments. Through leaching experiments, WTF can stabilize 93.0% of Cd2+ and 99.7% of Cu2+. The results of HM morphology analysis show that after adding WTF, most of the HMs have been transformed into a relatively stable state. For example, in the process of remediation of 6 mg/kg Cd contaminated soil, the proportion of acid-soluble Cd decreased from 56.5% to 12.8%, and the residual state increased from 13.5% to 45.4%. Compared with the resin-free structure, the three-dimensional structure of the resin plays an important role, but the efficiency of precipitation with HMs is doubled. According to the simulation of the adsorption process by Materials Studio, the characterization of the scanning electron microscope-energy dispersive instrument and the results of the adsorption experiment, in the solution, the precipitate formed by WTF and Cd2+ has multilayer adsorption of HMs, and can further adsorb HM by -OH. Soil enzyme activity experiments proved that the risk of secondary pollution by adding WTF is rare, and even WTF can achieve the effect of slow-release nitrogen fertilizer. In the WTF remediation process, the biological toxicity reduction of HMs is result from, on the one hand, the complexation of functional group of WTF; on the other hand, the resin structure of WTF; in addition, multi-layer adsorption and adsorption of end groups in the precipitation formed by WTF and HM. This work provides a theoretical basis for the potential capabilities of water-soluble resins and is beneficial to the design and development of subsequent amendments.

LncRNA GAS5 inhibits miR-579-3p to activate SIRT1/PGC-1α/Nrf2 signaling pathway to reduce cell pyroptosis in sepsis-associated renal injury.

Sepsis is a life-threatening condition that can lead to several organ failures including kidney. In this study, we investigated the roles of GAS5 and miR-579-3p in regulating cell pyroptosis in the sepsis-induced renal injury model. Lipopolysaccharide (LPS) treatment or cecal ligation and puncture (CLP) surgery was used to create the in vitro and in vivo sepsis-induced renal injury model. The interactions between GAS5 and miR-579-3p, and miR-579-3p and SIRT1 were determined by bioinformatic prediction, luciferase reporter assay, and RIP assay. In vitro cell pyroptosis was examined by flow cytometry marked with active caspase-1 and PI. The protein levels of IL-1ß and IL-18 induced by cell pyroptosis were quantified using ELISA assay. In vivo renal injuries were evaluated with HE and TUNEL stainings, bacterial load in serum and creatinine, and blood urea nitrogen content analyses. Expression levels of GAS5, miR-579-3p, pyroptosis, and SIRT1/PGC-1a/Nrf2 pathway-related molecules were evaluated by qRT-PCR or Western blot. GAS5 and SIRT1 were downregulated, whereas miR-579-3p was upregulated in in vitro and in vivo sepsis-induced renal injury models. GAS5 negatively and directly regulated miR-579-3p to reduce cell pyroptosis via the activation of SIRT1/PGC-1a/Nrf2 pathway. In addition, miR-579-3p suppressed PGC-1a/Nrf2 pathway to induce cell pyroptosis by directly targeting SIRT1. What's more, overexpression of GAS5, or knockdown of miR-579-3p, enhanced SIRT1 expression that led to the improved survival rate, reduced the weight loss, and relieved renal injuries in septic mice. Overexpression of GAS5 demonstrated protective effects against sepsis-induced renal injury via downregulating miR-579-3p and activating SIRT1/PGC-1α/Nrf2 pathway to inhibit cell pyroptosis.

Blautia intestinalis sp. nov., isolated from human feces.

A strictly anaerobic bacterial strain (27-44T) was isolated from a stool specimen from an autistic child collected in PR China. The strain was Gram-stain-positive, non-motile, non-pigmented, non-spore-forming, and cells were oval to rod-shaped. Strain 27-44T grew at 20-40 °C (optimal at 37 °C) and at pH 6.0-10 (optimal at 6.0-8.0). The major polar lipids were one phospholipid, two glycolipids, two aminophospholipids and one unidentified lipid. The major cellular fatty acids of strain 27-44T were C16 : 0 and C17 : 0 2-OH. The end product of glucose fermentation was mainly butyric acid. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 27-44T was a member of the genus Blautia and phylogenetically closely related to Blautia obeum ATCC 29174T (with 97.8 % seque nce similarity). The genome of strain 27-44T was 3.5 Mbp with a DNA G+C content of 42.36 mol%. A total of 3436 genes were predicted and, of these, 3133 genes were annotated by KEGG. On the basis of phenotypic, chemotaxonomic and phylogenetic comparisons, strain 27-44T represents a novel species within the genus Blautia, for which the name Blautia intestinalis sp. nov. is proposed. The type strain is 27-44T= CGMCC 1.5285T=NBRC 113774T.

Algibacter pacificus sp. nov., isolated from a deep-sea seamount.

The Gram-stain-negative, rod-shaped, yellow-pigmented and facultative anaerobic bacterial strain, designated H164T, was isolated from seawater collected from the Caroline Seamounts in the Pacific Ocean. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain H164T was related to the genus Algibacter and had highest 16S rRNA gene sequence similarity to Algibacter wandonensis WS-MY22T (97.4 %). The major cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C15 : 1 G, iso-C15 : 0 3-OH and iso-C17 : 0 3-OH. The predominant menaquinone was MK-6. The polar lipid profile contained phosphatidylethanolamine, one unidentified aminolipid and two unidentified lipids. The genomic DNA G+C content of strain H164T was 33.2 mol%. The values of in silico DNA-DNA hybridization (isDDH) and average nucleotide identity (ANI) between strain H164T and A. wandonensis KCTC 32381T were 26.10 and 81.88 %. The isDDH and ANI values between strain H164T and Algibacter lectus DSM 15365T were 25.40 and 81.79 %. Combined data from phenotypic, phylogenetic, isDDH and ANI analyses demonstrated that strain H164T represents a novel species of the genus Algibacter, for which we propose the name Algibacter pacificus sp. nov. (type strain H164T=KCTC 72432T=CGMCC 1.17117T).

Hybrid Two-Component Sensors for Identification of Bacterial Chemoreceptor Function.

Soil bacteria adapt to diverse and rapidly changing environmental conditions by sensing and responding to environmental cues using a variety of sensory systems. Two-component systems are a widespread type of signal transduction system present in all three domains of life and typically are comprised of a sensor kinase and a response regulator. Many two-component systems function by regulating gene expression in response to environmental stimuli. The bacterial chemotaxis system is a modified two-component system with additional protein components and a response that, rather than regulating gene expression, involves behavioral adaptation and results in net movement toward or away from a chemical stimulus. Soil bacteria generally have 20 to 40 or more chemoreceptors encoded in their genomes. To simplify the identification of chemoeffectors (ligands) sensed by bacterial chemoreceptors, we constructed hybrid sensor proteins by fusing the sensor domains of Pseudomonas putida chemoreceptors to the signaling domains of the Escherichia coli NarX/NarQ nitrate sensors. Responses to potential attractants were monitored by ß-galactosidase assays using an E. coli reporter strain in which the nitrate-responsive narG promoter was fused to lacZ Hybrid receptors constructed from PcaY, McfR, and NahY, which are chemoreceptors for aromatic acids, tricarboxylic acid cycle intermediates, and naphthalene, respectively, were sensitive and specific for detecting known attractants, and the ß-galactosidase activities measured in E. coli correlated well with results of chemotaxis assays in the native P. putida strain. In addition, a screen of the hybrid receptors successfully identified new ligands for chemoreceptor proteins and resulted in the identification of six receptors that detect propionate.IMPORTANCE Relatively few of the thousands of chemoreceptors encoded in bacterial genomes have been functionally characterized. More importantly, although methyl-accepting chemotaxis proteins, the major type of chemoreceptors present in bacteria, are easily identified bioinformatically, it is not currently possible to predict what chemicals will bind to a particular chemoreceptor. Chemotaxis is known to play roles in biodegradation as well as in host-pathogen and host-symbiont interactions, but many studies are currently limited by the inability to identify relevant chemoreceptor ligands. The use of hybrid receptors and this simple E. coli reporter system allowed rapid and sensitive screening for potential chemoeffectors. The fusion site chosen for this study resulted in a high percentage of functional hybrids, indicating that it could be used to broadly test chemoreceptor responses from phylogenetically diverse samples. Considering the wide range of chemical attractants detected by soil bacteria, hybrid receptors may also be useful as sensitive biosensors.

Parabacteroides acidifaciens sp. nov., isolated from human faeces.

A polyphasic taxonomic approach was applied to characterize an anaerobic bacterial strain, 426-9T, that was isolated from human faeces. The strain was Gram-stain-negative, non-motile, non-spore-forming, non-pigmented and rod-shaped. Strain 426-9T grew anaerobically at 20-45 °C (optimally at 37-40 °C) and at pH 6.0-10.0 (optimally at pH 6.0-8.0). The major polar lipids were phosphatidylethanolamine, seven amino phospholipids and three phospholipids. The major fatty acids of strain 426-9T were anteiso-C15 : 0 and iso-C17 : 0 3-OH, and the predominant respiratory quinones were menaquinones MK-9 and MK-10. End-products of glucose fermentation were acetate, propionate, iso-butyrate and iso-pentanoate. 16S rRNA gene sequence analysis showed that strain 426-9T was a member of the genus Parabacteroides. The level of 16S rRNA gene sequence similarity of strain 426-9T to the type species of the genus, Parabacteroides distasonis ATCC 8503T, was 91.0 %. Within the genus Parabacteroides, strain 426-9T was phylogenetically closely related to Parabacteroides johnsonii M-165T (96.0 % 16S rRNA gene sequence similarity). The draft genome of strain 426-9T comprised 5.15 Mb with a DNA G+C content of 45.9 mol%. A total of 4088 genes were predicted and, of those, 3744 were annotated. On the basis of phenotypic, chemotaxonomic and phylogenetic characterization, strain 426-9T represents a novel species within the genus Parabacteroides, for which the name Parabacteroides acidifaciens sp. nov. is proposed. The type strain is 426-9T (=CGMCC 1.13558T=NBRC 113433T).

Upregulation of Mitochondrial Transcription Factor A Promotes the Repairment of Renal Tubular Epithelial Cells in Sepsis by Inhibiting Reactive Oxygen Species-Mediated Toll-Like Receptor 4/p38MAPK Signaling.

BACKGROUND: Mitochondrial transcription factor A (TFAM) plays multiple pathophysiologic roles in mitochondrial DNA (mtDNA) maintenance. However, the role of TFAM in sepsis-induced acute kidney injury (AKI) remains largely unknown. METHODS: Lipopolysaccharide (LPS) treatment of HK-2 cells mimics the in vitro model of AKI inflammation. pcDNA3.1 plasmid was used to construct pcDNA3.1-TFAM. sh-TFAM-543, sh-TFAM-717, sh-TFAM-765, sh-TFAM-904 and pcDNA3.1-TFAM were transfected into HK-2 cells using Lipofectamine 2000. MtDNA transcriptional levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay was performed to assess the cell viability. Changes in reactive oxygen species (ROS) and mitochondrial membrane potential in HK-2 cells were detected using the corresponding kits. Immunofluorescence experiment was used to investigate the displacement of TFAM. mRNA and protein expression levels of TFAM and its related genes were measured by qRT-PCR and western blot respectively. Mice in sepsis were administered cecal ligation and puncture surgery. RESULTS: LPS treatment was a non-lethal influencing factor, leading to the upregulation of ROS levels and downregulation of mtDNA copy number and NADH dehydrogenase subunit-1 (ND1) expression, and caused damage to the mitochondria. As the LPS treatment time increased, TFAM was displaced from the periphery of the nucleus to cytoplasm. TFAM reduced ROS and P38MAPK levels by inhibiting toll-like receptor 4 (TLR4) expression, ultimately inhibiting inflammation and repairing mtDNA. CONCLUSIONS: Our results indicate that TFAM repairs mtDNA by blocking the TLR4/ROS/P38MAPK signaling pathway in inflammatory cells, thereby repairing septic tubular epithelial cells, and TFAM may serve as a new target for sepsis therapy.

Effects of Catalytic Action and Ligand Binding on Conformational Ensembles of Adenylate Kinase.

Crystal structures of adenylate kinase (AdK) from Escherichia coli capture two states: an "open" conformation (apo) obtained in the absence of ligands and a "closed" conformation in which ligands are bound. Other AdK crystal structures suggest intermediate conformations that may lie on the transition pathway between these two states. To characterize the transition from open to closed states in solution, X-ray solution scattering data were collected from AdK in the apo form and with progressively increasing concentrations of five different ligands. Scattering data from apo AdK are consistent with scattering predicted from the crystal structure of AdK in the open conformation. In contrast, data from AdK samples saturated with Ap5A do not agree with that calculated from AdK in the closed conformation. Using cluster analysis of available structures, we selected representative structures in five conformational states: open, partially open, intermediate, partially closed, and closed. We used these structures to estimate the relative abundances of these states for each experimental condition. X-ray solution scattering data obtained from AdK with AMP are dominated by scattering from AdK in the open conformation. For AdK in the presence of high concentrations of ATP and ADP, the conformational ensemble shifts to a mixture of partially open and closed states. Even when AdK is saturated with Ap5A, a significant proportion of AdK remains in a partially open conformation. These results are consistent with an induced-fit model in which the transition of AdK from an open state to a closed state is initiated by ATP binding.

Adoptive Regulatory T-cell Therapy Attenuates Perihematomal Inflammation in a Mouse Model of Experimental Intracerebral Hemorrhage.

The CD4+CD25+ regulatory T cells (Tregs), an innate immunomodulator, suppress cerebral inflammation and maintain immune homeostasis in multiple central nervous system injury, but its role in intracerebral hemorrhage (ICH) has not been fully characterized. This study investigated the effect of Tregs on brain injury using the mouse ICH model, which is established by autologous blood infusion. The results showed that tail intravenous injection of Tregs significantly reduced brain water content and Evans blue dye extravasation of perihematoma at day (1, 3 and 7), and improved short- and long-term neurological deficits following ICH in mouse model. Tregs treatment reduced the content of pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and malondialdehyde, while increasing the superoxide dismutase (SOD) enzymatic activity at day (1, 3 and 7) following ICH. Furthermore, Tregs treatment obviously reduced the number of NF-κB+, IL-6+, TUNEL+ and active caspase-3+ cells at day 3 after ICH. These results indicate that adoptive transfer of Tregs may provide neuroprotection following ICH in mouse models.

Wide-field digital imaging system for assessing ocular anterior segment development in very preterm infants.

Purpose: This study aims to longitudinally investigate developments of the anterior segment in very preterm infants who exhibit normal retinal development outcomes by utilizing a wide-field digital imaging system. Methods: Between June 2021 and June 2022, neonates with a birth weight of <1500 g and/or a gestational age (GA) of less than 32 weeks were included in this study. The participants underwent regular ocular examinations, including sequential evaluations of the anterior segment and the retina, at intervals of 2-5 weeks, starting from birth and continuing until they reached a corrected GA of 48 weeks. Term neonates were selected as normal controls for the study. The study recorded the weight and GA of subjects at the time of examination, as well as indicators of abnormal development in the anterior segment. Results: A total of 48 very preterm infants with normal retinal developmental outcomes were enrolled. The control group included 59 full-term infants. Common anterior segment eye abnormalities such as persistent hyperplasia of primary vitreous, persistent pupillary membranes, iris vessels, and anterior chamber angle vessels gradually subsided with the period in very preterm infants. The vascularity of the iris was substantially higher than in term controls (P < 0.05) at term gestation. The imaging of iris vessels and anterior chamber angle vessels in very preterm infants exhibited a decline at 46 and 47 weeks, respectively, which occurred slightly later compared to term infants. Conclusion: In very preterm infant s with normal outcomes, although the developmental process is delayed, they may form a normal anterior segment structure similar to that of full-term infants in the late stages, which is followed up by the wide-field digital imaging system.

Huangshan Floral Mushroom Polysaccharide Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Th17/Treg Balance in a Gut Microbiota-Dependent Manner.

SCOPE: Ulcerative colitis (UC) is a common chronic recurrent inflammatory bowel disease. This study attempts to reveal the improvement mechanism of floral mushroom polysaccharide (FMPS) on UC from the perspective of coordinated interaction between intestinal microbes and intestinal helper T cell 17 (Th17)/regulatory T cell (Treg) balance. METHODS AND RESULTS: Dextran sulfate sodium (DSS)-induced colitis mice model is used for the experiment. The results suggest that FMPS up-regulated the expression of occludin, ZO-1, and MUC2, and down-regulated the secretion of TNF-α, IL-1ß, and IL-6 in colitis mice. Importantly, FMPS restores intestinal Th17/Treg balance. Meanwhile, FMPS can regulate intestinal microorganisms and improve the level of short-chain fatty acids (SCFAs) in colitis mice. Intestinal microbial depletion and fecal microbiota transplantation (FMT) experiments reveal that FMPS ameliorated UC is mediated by intestinal microbiome. Flow cytometry further proves that FMPS restores intestinal Th17/Treg balance in a microbial-dependent manner. CONCLUSION: These results indicate that FMPS has the potential to improve UC, and its mechanism depends on the restoration of Th17/Treg balance mediated by intestinal microorganisms. Therefore, it is suggested that FMPS dietary supplement can be potentially used to intervene UC.

The effects of childhood maltreatment on adolescent non-suicidal self-injury behavior: mediating role of impulsivity.

Background: Non-suicidal self-injury (NSSI) severely challenges mental health in adolescents. Childhood maltreatment experience acts as high-risk factor for adolescents to engage in NSSI behaviors. On the other hand, impulsivity or loss of control sets the threshold for NSSI execution. Here we examined the effects of childhood maltreatment on adolescent NSSI-related clinical outcomes and the potential role of impulsivity. Methods: We assessed the clinical data of 160 hospitalized NSSI adolescents and recruited 64 age-matched healthy subjects as a control group. The clinical symptoms of NSSI are expressed by the NSSI frequency, depression, and anxiety measured by the Ottawa Self-Injury Inventory, the Beck Depression Inventory, and the Beck Anxiety Inventory. Childhood maltreatment and impulsivity were assessed with Childhood Trauma Questionnaire and Barratt Impulsiveness Scale. Results: The results showed that when compared to HC group, NSSI group is more likely to experience childhood maltreatment. Notably, NSSI group with Childhood maltreatment accompanies higher trait impulsivity and exacerbated clinical outcomes, such as NSSI frequency, depression and anxiety symptoms. Mediation analyses indicated that the association between childhood maltreatment and NSSI-related clinical outcomes was partially explained by impulsivity. Conclusion: We found that NSSI adolescents have a higher proportion of childhood maltreatment. Impulsivity plays a mediating role between childhood maltreatment and NSSI behaviors.

Dendrobium fimbriatum polysaccharide ameliorates DSS-induced intestinal mucosal injury by IL-22-regulated intestinal stem cell regeneration.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with unknown etiology and difficult treatment. In this study, the intervention effect of Dendrobium fimbriatum Hook polysaccharide (cDFPW1) on UC was verified by constructing a dextran sulfate sodium (DSS)-induced colitis mouse model, and the protective effect of cDFPW1 on intestinal mucosal integrity in UC was explored by the co-culture system consisting of intestinal organoids and lamina propria lymphocytes (LPLs) combined with the experiment of microbial depletion mice. Results showed that cDFPW1 significantly alleviated UC symptoms in mice and promoted the proliferation of intestinal epithelial cells. Importantly, cDFPW1 could directly improve DSS-induced morphological damage of intestinal organoids and increase the number of epithelial cells, which was validated in mice. During repair, an increase in the number of Lgr5+ cells in intestinal organoids and mouse intestines was promoted by cDFPW1. Meanwhile, cDFPW1 promoted intestinal stem cells (ISCs)-mediated intestinal epithelial regeneration by significantly upregulating IL-22 expression. We further confirmed that the secretion of IL-22 was mediated by LPLs. Together, these findings suggest that cDFPW1 promotes ISCs regeneration by LPLs-mediated up-regulation of IL-22 to protect the intestinal mucosal integrity, thereby playing an important role in improving UC.

Transcriptome-wide identification of altered RNA m6A profiles in cardiac tissue of rats with LPS-induced myocardial injury.

Purpose: Myocardial injury is a common complication in patients with endotoxaemia/sepsis, especially in children. Moreover, it develops through an unclear pathophysiological mechanism, and effective therapies are lacking. Recently, RNA modification, particularly N 6-methyladenosine (m6A) modification, has been found to be involved in various physiological processes and to play important roles in many diseases. However, the role of m6A modification in endotoxaemia/sepsis-induced myocardial injury is still in its infancy. Therefore, we attempted to construct the m6A modification map of myocardial injury in a rat model treated by lipopolysaccharide (LPS) and explore the role of m6A modification in LPS-induced myocardial injury. Method: Myocardial injury adolescent rat model was constructed by intraperitoneal injection of LPS. m6A RNA Methylation Quantification Kit was used to detect overall level of m6A modification in rat cardiac tissue. m6A-specific methylated RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were conducted to identify the altered m6A-modified genes and differentially expressed genes in cardiac tissue of rats treated by LPS and control rats (6 versus. 6). Bioinformatics was used to analyze the functions of differentially m6A modified genes, differentially expressed genes, and genes with both differential m6A modification and differential expression. qPCR was used to detect expression of m6A modification related enzymes. Result: We found that the overall level of m6A modification in cardiac tissue of the LPS group was up-regulated compared with that of the control group. MeRIP-seq and RNA-seq results showed that genes with differential m6A modification, genes with differential expression and genes with both differential m6A modification and differential expression were closely associated with inflammatory responses and apoptosis. In addition, we found that m6A-related enzymes (Mettl16, Rbm15, Fto, Ythdc2 and Hnrnpg) were differentially expressed in the LPS group versus. the control group. Conclusion: m6A modification is involved in the pathogenesis process of LPS-induced myocardial injury, possibly through the regulation of inflammatory response and apoptosis-related pathways. These results provide valuable information regarding the potential pathogenic mechanisms underlying LPS-induced myocardial injury.