A genomic compendium of cultivated human gut fungi characterizes the gut mycobiome and its relevance to common diseases.

The gut fungal community represents an essential element of human health, yet its functional and metabolic potential remains insufficiently elucidated, largely due to the limited availability of reference genomes. To address this gap, we presented the cultivated gut fungi (CGF) catalog, encompassing 760 fungal genomes derived from the feces of healthy individuals. This catalog comprises 206 species spanning 48 families, including 69 species previously unidentified. We explored the functional and metabolic attributes of the CGF species and utilized this catalog to construct a phylogenetic representation of the gut mycobiome by analyzing over 11,000 fecal metagenomes from Chinese and non-Chinese populations. Moreover, we identified significant common disease-related variations in gut mycobiome composition and corroborated the associations between fungal signatures and inflammatory bowel disease (IBD) through animal experimentation. These resources and findings substantially enrich our understanding of the biological diversity and disease relevance of the human gut mycobiome.

Evaluation of characteristic metabolites of aromatic amino acids in patients with HIV infection at different stages of disease.

BACKGROUND: Acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV) infection, and antiretroviral therapy are usually associated with metabolic disorders. Screening for biomarkers to evaluate the progression of metabolic disorders is important for the diagnosis and treatment of HIV infection. This study aimed to establish and validate a method to quantify serum aromatic amino acid (AAA) metabolites as biomarkers of metabolic disorders in patients with HIV. METHODS: The AAAs and metabolites were analyzed using high-performance liquid chromatography-tandem mass spectrometry. Pearson's correlation, heatmap, and receiver operating characteristic curve analyses were used for statistical analysis. RESULTS: Under optimal detection conditions, the lower limits of phenylalanine (Phe), tryptophan (Trp), kynurenine (Kyn), tyrosine, phenylacetylglutamine (PAGln), and 5-hydroxytryptamine quantification reached 0.02, 0.02, 0.01, 0.02, 0.01, and 0.002 µg/ml, respectively, and the precision of intra- and inter-day was stay below 10.30%. Serum samples were stable for at least 6 months when stored at -80°C. The inter-group differences and associations between the biomarkers exhibited a particular volatility trend in PAGln, Trp, and Kyn metabolism in HIV-infected patients with metabolic syndrome. CONCLUSIONS: The developed method can be used for rapid and sensitive quantification of the AAA metabolism profile in vivo to further appraise the process of HIV infection, evaluate intervening measures, conduct mechanistic investigations, and further study the utility of PAGln, a characteristic metabolite of AAA, as a biomarker of HIV infection coupled with metabolic syndrome.

The clinicopathological and prognostic significances of IGF-1R and Livin expression in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. However, limited effective biomarkers are associated with the tumorigenesis and prognosis of CRC. METHODS: The present study identified potential signatures from The Cancer Genome Atlas (TCGA) database and further validated the identified biomarkers in CRC tissues by immunohistochemistry (IHC). RESULTS: The expression of insulin-like growth factor 1 receptor (IGF-1R) and Livin gene was significantly upregulated in CRC samples compared to the adjacent normal samples in the TCGA dataset. IHC indicated that IGF-1R and Livin protein levels are increased in CRC and adenoma tissues compared to normal tissues. Notably, the IGF-1R protein levels differed significantly between adenoma and CRC. The elevated IGF-1R and Livin expression was associated with CRC clinicopathological features, including age, gender, histological subtype, individual cancer stages, nodal metastasis, and TP53-mutant in TCGA. Additionally, the IGF-1R promoter methylation level was closely related to CRC. Consistent with the TCGA study, IHC indicated that overexpressed IGF-1R and Livin proteins were independent risk factors for stage and metastasis. A marked correlation was established between IGF-1R and Livin expression in CRC, while the survival map showed no significant correlation with CRC. Kaplan-Meier survival curves showed that CRC patients with high IGF-1R or Livin expression had a prolonged overall disease-free survival than those with low expression in TCGA. CONCLUSION: IGF-1R and Livin are associated with CRC tumorigenesis and might be valuable for novel biomarker identification and targeted therapeutic strategy development.

Student Experiences in Practice-Based Small Animal Clerkships.

Practice-based clerkships provide a way for students to experience the types of cases, clients, and procedures that they can expect to see in a general practice setting. These clerkships are typically quite different from those offered in teaching hospitals. Forty-seven (65.28%) of the 72 invited veterinary medicine students from three cohorts participated in pre- and post-test surveys designed to compare their expectations to their actual experiences. Students reported significant positive changes in terms of adequate supervision, approachability of practitioner, and comfort level when asking questions, as well as seeing different cases than they see at the teaching hospital. Students reported significant negative changes in terms of their ability to interact with clients as much as they expected with respect to the practice of communication skills, history-taking skills, preventative therapy discussions with clients, and treatment. These findings were supported by written survey comments regarding the most and least helpful portions of the clerkship. We suggest further research to study student experiences over time and to survey practitioners before and following placement with veterinary students; the aim would be to obtain more information about the expectations and success of practice-based clerkships.

Exploring the role of cellular senescence in cancer prognosis across multiple tumor types.

Background: Cellular senescence is a common biological process with a well-established link to cancer. However, the impact of cellular senescence on tumor progression remains unclear. To investigate this relationship, we utilized transcriptomic data from a senescence gene set to explore the connection between senescence and cancer prognosis. Methods: We developed the senescence score by the Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. We obtained transcriptomic information of the senescence gene set from The Cancer Genome Atlas (TCGA) program. Additionally, we created a nomogram that integrates these senescence scores with clinical characteristics, providing a more comprehensive tool for prognosis evaluation. Results: We calculated the senescence score based on the expression level of 42 senescence-related genes. We established the nomogram based on the senescence score and clinical characteristics. The senescence score showed a positive correlation with epithelial-to-mesenchymal transition, cell cycle, and glycolysis, and a negative correlation with autophagy. Furthermore, we carried out Gene Ontology (GO) analysis to explore the signaling pathways and biological process in different senescence score groups. Conclusions: The senescence score, a novel tool constructed in this study, shows promise in predicting survival outcomes across various cancer types. These findings not only highlight the complex interplay between senescence and cancer but also indicate that cellular senescence might serve as a biomarker for tumor prognosis.

Isoquercitrin attenuates the progression of non-alcoholic steatohepatitis in mice by modulating galectin-3-mediated insulin resistance and lipid metabolism.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a global health problem with no effective treatment. Isoquercitrin (IQ) alters hepatic lipid metabolism and inhibits adipocyte differentiation. The underlying regulatory mechanisms of IQ in regulating insulin resistance (IR) and lipid metabolism remain unclear. PURPOSE: This study was aimed at investigating the effects of IQ on NASH and deciphering whether the underlying mechanisms are via modulation of galectin-3 mediated IR and lipid metabolism. METHODS: IR-HepG2 cell lines were used to demonstrate the ability of IQ to modulate galectin-3-mediated glucose disposal and lipid metabolism. A 20-week high-fat diet (HFD)-induced NASH model was established in C57BL/6J mice, and the protective effect of IQ on lipid disposal in the liver was verified. Further, the mRNA and protein levels of glucose and lipid metabolism were investigated, and lysophosphatidylcholine (LPC) and acylcarnitine (AC) profiling were performed to characterize the changes in endogenous substances associated with mitochondrial function and lipid metabolism in serum and cells. Furthermore, the pharmacokinetic features of IQ were explored in a rat model of NASH. RESULTS: IQ restored liver function and ameliorated inflammation and lipid accumulationin NASH model mice. Notably, significant regulation of the proteins included fatty acid-generating and transporting, cholesterol metabolism enzymes, nuclear transcription factors, mitochondrial metabolism, and IR-related enzymes was noted to be responsible for the therapeutic mechanisms of IQ against experimental NASH. Serum lipid metabolism-related metabolomic assay confirmed that LPC and AC biosynthesis mostly accounted for the therapeutic effect of IQ in mice with NASH and that IQ maintained the homeostasis of LPC and AC levels. CONCLUSION: This is the first study showing that IQ protects against of NASH by modulating galectin-3-mediated IR and lipid metabolism. The mechanisms responsible for liver protection and improved lipid metabolic disorder by IQ may be related to the suppression of IR and regulation of mitochondrial function and lipid metabolism. Galectin-3 down-regulation represents a potentially novel approach for the treatment and prevention of NASH.

Nanoscale-controlled organicinorganic hybrid spheres for comprehensive enrichment of ultratrace chlorobenzenes in marine and fresh water.

The size of the adsorbent has the potential to influence extraction performance, but the size effect at the nanoscale is still poorly understood. In this study, organic-inorganic hybrid nanospheres (OIHNs) with controllable nanoscale sizes of 30, 50, and 100 nm were successfully prepared. These materials were further fabricated as solid phase microextraction (SPME) coatings with similar thicknesses, and coupled with gas chromatography-mass spectrometry (GC-MS) to investigate their extraction performance. The results showed that the extraction capacities of OIHNs for chlorobenzenes (CBs) and polycyclic aromatic hydrocarbons (PAHs) were much better than those of their corresponding derived carbon materials, despite the smaller specific surface areas and lower porosities of them. In addition, the enrichment performance increased significantly with decreasing particle size, and the OIHN-30 coating demonstrated the best performance, with enrichment factors ranging from 1098 to 6853 for CBs. Finally, a highly sensitive and practical analytical method was established with a wide linear range of 0.5-5000 ng·L-1, and the limits of quantification (LOQs) were 0.43-1.7 ng·L-1. The determinations of ultratrace CBs in five marine water samples and five fresh water samples were realized successfully. This study is expected to contribute to a deep understanding of the environmental effects of nanoparticles and the design of high-performance adsorbents.

Gut virome-wide association analysis identifies cross-population viral signatures for inflammatory bowel disease.

BACKGROUND: The gut virome has been implicated in inflammatory bowel disease (IBD), yet a full understanding of the gut virome in IBD patients, especially across diverse geographic populations, is lacking. RESULTS: In this study, we conducted a comprehensive gut virome-wide association study in a Chinese cohort of 71 IBD patients (15 with Crohn's disease and 56 with ulcerative colitis) and 77 healthy controls via viral-like particle (VLP) and bulk virome sequencing of their feces. By utilizing an integrated gut virus catalog tailored to the IBD virome, we revealed fundamental alterations in the gut virome in IBD patients. These characterized 139 differentially abundant viral signatures, including elevated phages predicted to infect Escherichia, Klebsiella, Enterococcus_B, Streptococcus, and Veillonella species, as well as IBD-depleted phages targeting Prevotella, Ruminococcus_E, Bifidobacterium, and Blautia species. Remarkably, these viral signatures demonstrated high consistency across diverse populations such as those in Europe and the USA, emphasizing their significance and broad relevance in the disease context. Furthermore, fecal virome transplantation experiments verified that the colonization of these IBD-characterized viruses can modulate experimental colitis in mouse models. CONCLUSIONS: Building upon these insights into the IBD gut virome, we identified potential biomarkers for prognosis and therapy in IBD patients, laying the foundation for further exploration of viromes in related conditions. Video Abstract.

Nitrogen-rich covalent organic framework as a practical coating for effective determinations of polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are high-profile organic pollutants to be poisonous, carcinogenic, and mutagenic, and widely distributed at trace levels in the environment. In order to effectively enrich PAHs, two stable covalent organic frameworks (COFs, TAPT-OMe-PDA and TPB-DMTP) were prepared by combining 2,4,6-tri(4-aminophenyl)-1,3,5-triazine (TAPT) and 1,3,5-tri(4-aminophenyl) benzene (TAPB) with 2,5-dimethoxy-phenyl-1,4-diformaldehyde (OMe-PDA), respectively. Even though the surface area of TAPT-OMe-PDA was much lower than that of TPB-DMTP, it still demonstrated much better extraction efficiencies towards PAHs as the solid phase microextraction (SPME) coating. Therefore, the TAPT-OMe-PDA coated fiber was coupled with gas chromatography-mass spectrometry (GC-MS) to establish a practical and sensitive method, after the extraction parameters (extraction time, extraction temperature, desorption temperature, desorption time, salt concentration and pH) were optimized. This developed analytical method showed wide linear ranges, low limits of detection, good repeatability and reproducibility. Finally, five PAHs in three water samples were detected and quantified precisely (2.72-38.7 ng·L-1) with satisfactory recoveries (88.3%-118%).

Selective S-Arylation of Sulfenamides with Arynes: Access to Sulfilimines.

Sulfilimines, the aza analogues of sulfoxides, are of increasing interest in medicinal and agrochemical research programs. However, the development of efficient routes for their synthesis has remained relatively unexplored. In this study, we report a transition metal-free, selective S-arylation reaction between sulfenamides and arynes, enabling the facile preparation of structurally diverse sulfilimines under mild and redox-neutral conditions in good yields. The application value of our method was further demonstrated by scale-up synthesis, downstream derivatization, and robustness screen.

Structure of the Newcastle Disease Virus L protein in complex with tetrameric phosphoprotein.

Newcastle disease virus (NDV) belongs to Paramyxoviridae, which contains lethal human and animal pathogens. NDV RNA genome is replicated and transcribed by a multifunctional 250 kDa RNA-dependent RNA polymerase (L protein). To date, high-resolution structure of NDV L protein complexed with P protein remains to be elucidated, limiting our understanding of the molecular mechanisms of Paramyxoviridae replication/transcription. Here, we used cryo-EM and enzymatic assays to investigate the structure-function relationship of L-P complex. We found that C-terminal of CD-MTase-CTD module of the atomic-resolution L-P complex conformationally rearranges, and the priming/intrusion loops are likely in RNA elongation conformations different from previous structures. The P protein adopts a unique tetrameric organization and interacts with L protein. Our findings indicate that NDV L-P complex represents elongation state distinct from previous structures. Our work greatly advances the understanding of Paramyxoviridae RNA synthesis, revealing how initiation/elongation alternates, providing clues for identifying therapeutic targets against Paramyxoviridae.

RSM, ANN-GA and ANN-PSO modeling of SDBS removal from greywater in rural areas via Fe2O3-coated volcanic rocks.

Decontamination and reuse of greywater in rural areas has attracted increasing attention. Typical contaminants in grey water are SDBS, which has a stubborn molecular structure. In this study, Fe2O3-coated volcanic rocks (Fe2O3-VR) prepared from FeCl3 solution by a heating evaporation method can reach 95% removal of SDBS, which is 80% higher than before. The effect of contact time, pH, initial concentration, FeCl3 solution concentration, adsorbent dosage and calcination temperature on the removal rate was researched and modeled by response methodology (RSM) and artificial neural network (ANN). Based on the univariate test, the Box-Behnken design method was used to establish the data sample, which represented a quadratic polynomial model with p-value <0.001, R 2 = 0.9872, while the ANN model has the better performance with R 2 = 0.9961. The weights of the BP-ANN model were further analyzed using the Garson equation, and the results showed that the validity ranking of the variables was as follows: contact time (37.31%) > calcination temperature (29.43%) > dosage (24.44%) > initial concentration (17.18%) > FeCl3 solution concentration (17.18%) > pH (11.56%). Genetic algorithm (GA) and particle swarm optimization (PSO) were selected to optimize the process parameters. The results showed that ANN-PSO methodology presented a satisfactory alternative and the predicted removal efficiency was 99.9982% with relative error = 0.2230. The optimum level of contact time, pH, initial SDBS concentration, FeCl3 solution concentration, adsorbent dosage and calcination temperature is 136.45 min, 5.64, 22.4 mg L-1, 0.3 mol L-1, 83.21 g L-1, 274.02 °C, respectively. Moreover, Fe2O3-VR was characterized via instrumental analyses (SEM-EDS, FTIR, XRD, BET).

Patient-derived organoids as a model for tumor research.

Cancer represents a leading cause of death, despite the rapid progress of cancer research, leading to urgent need for accurate preclinical model to further study of tumor mechanism and accelerate translational applications. Cancer cell lines cannot fully recapitulate tumors of different patients due to the lack of tumor complexity and specification, while the high technical difficulty, long time, and substantial cost of patient-derived xenograft model makes it unable to be used extensively for all types of tumors and large-scale drug screening. Patient-derived organoids can be established rapidly with a high success rate from many tumors, and precisely replicate the key histopathological, genetic, and phenotypic features, as well as therapeutic response of patient tumor. Therefore, they are extensively used in cancer basic research, biobanking, disease modeling and precision medicine. The combinations of cancer organoids with other advanced technologies, such as 3D bio-printing, organ-on-a-chip, and CRISPR-Cas9, contributes to the more complete replication of complex tumor microenvironment and tumorigenesis. In this review, we discuss the various methods of the establishment and the application of patient-derived organoids in diverse tumors as well as the limitations and future prospects of these models. Further advances of tumor organoids are expected to bridge the huge gap between bench and bedside and provide the unprecedented opportunities to advance cancer research.

PCSK9 inhibitor inclisiran for treating atherosclerosis via regulation of endothelial cell pyroptosis.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) belongs to an intracellular invertase or decarboxylase and is an independent risk factor for atherosclerosis (AS). This study aimed to investigate the therapeutic potential of the PCSK9 inhibitor, inclisiran, and its underlying mechanism in AS. Methods: ApoE-/- mice were fed with a high-fat diet (HFD) and intraperitoneally injected with 1, 5, or 10 mg/kg inclisiran. Low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels were determined using commercially available kits. Oil Red O staining was applied to detect the aortic plaque area and oil formation. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to induce cell injuries. Cell death was determined using a Hoechst 33342/propidium iodide (PI) dual-staining assay. Cytotoxicity was measured by lactate dehydrogenase (LDH) activity analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were performed to examine the pyroptosis-related factors. Results: Inclisiran inhibited the levels of LDL-C, TC, and TG, but increased the HDL-C level in the AS animal model. It also significantly inhibited plaque and oil droplet formation in a dose-dependent manner. Moreover, inclisiran markedly inhibited pyroptosis, as evidenced by the decreased levels of cleaved-caspase-1, NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC), gasdermin-D (GSDMD)-N, interleukin (IL)-1ß, and IL-18. Furthermore, inclisiran substantially inhibited cell death and cytotoxicity induced by ox-LDL in HUVECs. Conclusions: Inclisiran exerted an anti-atherosclerotic effect by inhibiting pyroptosis. This study provides a theoretical basis for the therapeutic potential of inclisiran in AS.

Adsorption and Fenton-like Degradation of Ciprofloxacin Using Corncob Biochar-Based Magnetic Iron-Copper Bimetallic Nanomaterial in Aqueous Solutions.

An economical corncob biochar-based magnetic iron-copper bimetallic nanomaterial (marked as MBC) was successfully synthesized and optimized through a co-precipitation and pyrolysis method. It was successfully used to activate H2O2 to remove ciprofloxacin (CIP) from aqueous solutions. This material had high catalytic activity and structural stability. Additionally, it had good magnetic properties, which can be easily separated from solutions. In MBC/H2O2, the removal efficiency of CIP was 93.6% within 360 min at optimal reaction conditions. The conversion of total organic carbon (TOC) reached 51.0% under the same situation. The desorption experiments concluded that adsorption and catalytic oxidation accounted for 34% and 66% on the removal efficiency of CIP, respectively. The influences of several reaction parameters were systematically evaluated on the catalytic activity of MBC. OH was proved to play a significant role in the removal of CIP through electron paramagnetic resonance (EPR) analysis and a free radical quenching experiment. Additionally, such outstanding removal efficiency can be attributed to the excellent electronic conductivity of MBC, as well as the redox cycle reaction between iron and copper ions, which achieved the continuous generation of hydroxyl radicals. Integrating HPLC-MS, ion chromatography and density functional theory (DFT) calculation results, and possible degradation of the pathways of the removal of CIP were also thoroughly discussed. These results provided a theoretical basis and technical support for the removal of CIP in water.

The combination of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair alleviated inflammation in liver fibrosis.

Objective: To explore the active components and epigenetic regulation mechanism underlying the anti-inflammatory effects of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair (LFP) in carbon tetrachloride (CCl4)-induced rat liver fibrosis. Methods: The main active ingredients and disease-related gene targets of LFP were determined using TCMSP and UniProt, and liver fibrosis disease targets were screened in the GeneCards database. A network was constructed with Cytoscape 3.8.0 and the STRING database, and potential protein functions were analyzed using bioinformatics analysis. Based on these analyses, we determined the main active ingredients of LFP and evaluated their effects in a CCl4-induced rat liver fibrosis model. Serum biochemical indices were measured using commercial kits, hepatocyte tissue damage and collagen deposition were evaluated by histopathological studies, and myofibroblast activation and inflammation were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. High-performance liquid chromatography-mass spectrometry was performed to determine the levels of homocysteine, reduced glutathione, and oxidized glutathione, which are involved in inflammation and oxidative stress. Results: The main active components of LFP were quercetin, kaempferol, and luteolin, and its main targets were α-smooth muscle actin, cyclooxygenase-2, formyl-peptide receptor-2, prostaglandin-endoperoxide synthase 1, nuclear receptor coactivator-2, interleukinß, tumor necrosis factor α, CXC motif chemokine ligand 14, and transforming growth factor ß1. A combination of quercetin, kaempferol, and luteolin alleviated the symptoms of liver fibrosis. Conclusion: The results of this study support the role of LFP in the treatment of liver fibrosis, and reveal that LFP reduces collagen formation, inflammation, and oxidative stress. This study suggests a potential mechanism of action of LFP in the treatment of liver fibrosis.

Quercetin 7-rhamnoside protects against alpha-naphthylisothiocyanate (ANIT)-induced in cholestatic hepatitis rats by improving biliary excretion and inhibiting inflammatory responses.

Objective: To explore the pharmacological effects and molecular mechanism of quercetin 7-rhamnoside (Q7R) in the treatment of cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT). Methods: ANIT-induced cholestatic hepatitis rat model was used to investigate the hepatoprotective effects of three different doses of Q7R (1.25 mg/kg; 2.5 mg/kg; 5 mg/kg). Serum biochemical indices were detected using commercial kits. H&E and masson staining were used to observe hepatic tissue damage and collagen deposition in hepatocytes. The metabolism of bile acid-related substances was detected via HPLC-MS/MS by 5-(diisopropylamino) amylamine (DIAAA) derivative method. Hepatocyte injury, cholestasis, and inflammation were detected at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, respectively. Results: Q7R can decrease the level of CYP7A1, and increase FXR, CYP27A1 so then improving abnormal bile acid secretion. Furthermore, Q7R can also ameliorating inflammation by reduce TNF-α, IL-1ß, PTGS1, PTGS2, NCOA2, NF-κB level. Therefore, Q7R had an effective therapeutic effect on ANIT-induced cholestatic hepatitis, improving abnormal bile acid secretion, and inhibiting inflammatory responses. Conclusion: The results demonstrated that Q7R treat cholestatic hepatitis by regulating bile acid secretion and alleviating inflammation.

Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line.

Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34(+)CD41a(+) and CD41a(+)CD42b(+) cells. LAIR-1 is also detectable in a fraction of human cord blood CD34(+) cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34(+) cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.

The effect of leachate seepage on the mechanical properties and microstructure of solidified sludge when used as a landfill temporary cover material.

In this study, the effect of leachate seepage on the strength properties of a landfill temporary cover material: sewage sludge solidified with soda residue, ground granulated blast furnace slag, and quicklime, was investigated using small-scale column tests. The strength of the solidified sludge was reflected by penetration resistance with a micro penetrometer. The results showed that the penetration resistance increased at first, but then decreased with the increase in duration. The peak value for penetration resistance appeared at around the 75th day under the effect of leachate seepage. In contrast, without leachate seepage, penetration resistance increased at first as duration increased and then remained stable. The main hydration products were calcium silicate hydrate, ettringite and hydrocalumite. Some pollutants, such as copper, chromium, and arsenic, were also stabilized by the solidified sludge. The nuclear magnetic resonance results showed that the sample with highest penetration resistance had a reduced pore volume, especially macropore volume. Furthermore, leachate corrosion and the removal of some substances contributed to the decrease in penetration resistance after long-term seepage. The strength performance of temporary cover in laboratory short-term seepage and leachate soaking environments might be different from that in a landfill leachate seepage environment. This study improves understanding about the performance of temporary cover materials in landfill.

Exploring the genes involved in biosynthesis of dihydroquercetin and dihydromyricetin in Ampelopsis grossedentata.

Dihydroquercetin (DHQ), an extremely low content compound (less than 3%) in plants, is an important component of dietary supplements and used as functional food for its antioxidant activity. Moreover, as downstream metabolites of DHQ, an extremely high content of dihydromyricetin (DHM) is up to 38.5% in Ampelopsis grossedentata. However, the mechanisms involved in the biosynthesis and regulation from DHQ to DHM in A. grossedentata remain unclear. In this study, a comparative transcriptome analysis of A. grossedentata containing extreme amounts of DHM was performed on the Illumina HiSeq 2000 sequencing platform. A total of 167,415,597 high-quality clean reads were obtained and assembled into 100,584 unigenes having an N50 value of 1489. Among these contigs, 57,016 (56.68%) were successfully annotated in seven public protein databases. From the differentially expressed gene (DEG) analysis, 926 DEGs were identified between the B group (low DHM: 210.31 mg/g) and D group (high DHM: 359.12 mg/g) libraries, including 446 up-regulated genes and 480 down-regulated genes (B vs. D). Flavonoids (DHQ, DHM)-related DEGs of ten structural enzyme genes, three myeloblastosis transcription factors (MYB TFs), one basic helix-loop-helix (bHLH) TF, and one WD40 domain-containing protein were obtained. The enzyme genes comprised three PALs, two CLs, two CHSs, one F3'H, one F3'5'H (directly converts DHQ to DHM), and one ANS. The expression profiles of randomly selected genes were consistent with the RNA-seq results. Our findings thus provide comprehensive gene expression resources for revealing the molecular mechanism from DHQ to DHM in A. grossedentata. Importantly, this work will spur further genetic studies about A. grossedentata and may eventually lead to genetic improvements of the DHQ content in this plant.