Four New Species and One New Record of Thelephora from China.

Species of the genus Thelephora (Thelephorales, Thelephoraceae) are ectomycorrhizal symbionts of coniferous and broad-leaved plants, and some of them are well-known edible mushrooms, making it an exceptionally important group ecologically and economically. However, the diversity of the species from China has not been fully elucidated. In this study, we conducted a phylogenetic analysis based on the internal transcribed spacer (ITS) regions, using Maximum Likelihood and Bayesian analyses, along with morphological observations of this genus. Four new species from China are proposed, viz., T. dactyliophora, T. lacunosa, T. petaloides, and T. pinnatifida. In addition, T. sikkimensis originally described from India is reported for the first time from China. Thelephora dactyliophora, T. pinnatifida, and T. sikkimensis are distributed in subtropical forests and mainly associated with plants of the families Fagaceae and Pinaceae. Thelephora lacunosa and T. petaloides are distributed in tropical to subtropical forests. Thelephora lacunosa is mainly associated with plants of the families Fagaceae and Pinaceae, while T. petaloides is mainly associated with plants of the family Fagaceae. Line drawings of microstructures, color pictures of fresh basidiomes, and detailed descriptions of these five species are provided.

Exploring the interplay of liquid crystal orientation and spherical elastic shell deformation in spatial confinement.

The application of liquid crystal technology typically relies on the precise control of molecular orientation at a surface or interface. This control can be achieved through a combination of morphological and chemical methods. Consequently, variations in constrained boundary flexibility can result in a diverse range of phase behaviors. In this study, we delve into the self-assembly of liquid crystals within elastic spatial confinement by using the Gay-Berne model with the aid of molecular dynamics simulations. Our findings reveal that a spherical elastic shell promotes a more regular and orderly alignment of liquid crystals compared to a hard shell. Moreover, during the cooling process, the hard-shell confined system undergoes an isotropic-smectic phase transition. In contrast, the phase behavior within the spherical elastic shell closely mirrors the isotropic-nematic-smectic phase transition observed in bulk systems. This indicates that the orientational arrangement of liquid crystals and the deformations induced by a flexible interface engage in a competitive interplay during the self-assembly process. Importantly, we found that phase behavior could be manipulated by altering the flexibility of the confined boundaries. This insight offers a fresh perspective for the design of innovative materials, particularly in the realm of liquid crystal/polymer composites.

Enhanced Electrical Properties and Impact Strength of Phenolic Formaldehyde Resin Using Silanized Graphene and Ionic Liquid.

In this study, to improve the electrical properties and impact strength of phenolic formaldehyde (PF) resin, PF-based composites were prepared by mixing graphene and the ionic liquid 3-decyl-bis(1-vinyl-1H-imidazole-3-ium-bromide) (C10[VImBr]2) via hot blending and compression-curing processes. The graphene surface was modified using a silane coupling agent. The synergistic effect of graphene and C10[VImBr]2 on the electrical properties, electromagnetic shielding efficiency, thermal stability, impact strength, and morphology of PF/graphene and PF/graphene/C10[VImBr]2 composites was then investigated. It was found that the electrical conductivity of the composites significantly increased from 2.3 × 10-10 to 4.14 × 10-3 S/m with an increase in the graphene content from 0 to 15 wt %, increasing further to 0.145 S/m with the addition of 5 wt % C10[VImBr]2. The electromagnetic shielding efficiency of the composite increased from 4.70 to 28.64 dB with the addition of 15 wt % graphene, while the impact strength of the composites rose significantly from 0.59 to 1.13 kJ/m2 with an increase in the graphene content from 0 to 15 wt %, reaching 1.53 kJ/m2 with the addition of 5 wt % C10[VImBr]2. Scanning electron microscopy images of the PF/GNP/C10[VImBr]2 composites revealed a rough morphology with numerous microcracks.

Nitrogen Fixation by Benzene into Pyridine and Aniline in Water/Nitrogen Plasma.

We demonstrated direct conversion of benzene into pyridine and aniline, assisted through exact mass measurements (m/z 80.0494, 93.0574, and 94.0651, respectively), through the interaction of benzene with water/nitrogen vapor plasma produced by corona discharge. Systematic analysis using a series of isotopic standards indicated that formation of pyridine and aniline occurred through the reaction between neutral benzene and reactive N+(OH2)2 in water/nitrogen plasma; exact mass measurements of products and intermediates supported this hypothesis. As the proportion of water vapor in plasma increased over time, the reaction proceeded from exclusive formation of protonated pyridine to formation of protonated aniline as the main product; theoretical simulations indicated that the presence of water vapor promoted proton migration to elicit formation of protonated aniline. The reactions we discovered suggest a new mechanism for direct nitrogen fixation.

Pillar[5]arene-based supramolecular pseudorotaxane polymer material for ultra-sensitive detection of Fe3+ and F.

Recent advancements in ultra-sensitive detection, particularly the Aggregation Induced Emission (AIE) materials, have demonstrated a promising detection method due to their low cost, real-time detection, and simplicity of operation. Here, coumarin functionalized pillar[5]arene (P5C) and bis-bromohexyl pillar[5]arene (DP5) were successfully combined to create a linear AIE supramolecular pseudorotaxane polymer (PCDP-G). The use of PCDP-G as a supramolecular AIE polymer material for recyclable ultra-sensitive Fe3+ and F- detection is an interesting application of the materials. According to measurements, the low detection limits of PCDP-G for Fe3+ and F- are 4.16 × 10-10 M and 6.8 × 10-10 M, respectively. The PCDP-G is also a very effective logic gate and a material for luminous displays.

Clinical characteristics of children with omicron SARS-CoV-2 infection in Changchun, China from march to april 2022: A retrospective study.

Background: Recently, there was an outbreak in China of the Omicron (B.1.1.529) variant, the corresponding clinical characteristics of Chinese children with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were then reviewed and summarized retrospectively. Methods: From March to April 2022, a total of 134 children infected with the Omicron variant were included in the study. Data such as sex, age, clinical symptoms, laboratory examinations, and imaging features were collected for further analyses. Results: Half of the children were male and the median age was 5.67 years. The most SARS-CoV-2 Omicron variant was identified in mild (122, 91%), and the most three frequent symptoms were as cough (108, 80.6%), fever (75, 56%), and sore throat (38, 28.4%). Among age groups, no significant difference was observed in the distribution of symptoms, and no statistical difference was found in different clinical types among sex or age groups. Laboratory examinations revealed that white blood cells, neutrophils, and hemoglobin decreased; and monocytes, C-reactive protein (CRP), and aspartate aminotransferase (AST) increased. Further analyses showed that neutrophils, hemoglobin, CRP, and AST exhibited significant differences among age groups. Radiological abnormalities were found in nine cases, with small patchy high-density shadows. Of the 76 cured cases discharged from the hospital, the median hospital stay was 13 days (mean, 12 days). Conclusions: In China, most children with Omicron SARS-CoV-2 infection have mild presentation. The findings of this study may help other districts improve the management of children with Omicron SARS-CoV-2 infection in China.

N6-adenomethylation of GsdmC is essential for Lgr5+ stem cell survival to maintain normal colonic epithelial morphogenesis.

Gut epithelial morphogenesis is maintained by intestinal stem cells. Here, we report that depletion of N6-adenosine methyltransferase subunit Mettl14 from gut epithelial cells in mice impaired colon mucosal morphogenesis, leading to increased mucosal permeability, severe inflammation, growth retardation, and premature death. Mettl14 ablation triggered apoptosis that depleted Lgr5+ stem cells and disrupted colonic organoid growth and differentiation, whereas the inhibition of apoptosis rescued Mettl14-deleted mice and organoids. Mettl14 depletion disrupted N6-adenomethylation on GsdmC transcripts and abolished GsdmC expression. Reconstitution of Mettl14-deleted organoids or mice with GSDMC rescued Lgr5 expression and prevented apoptosis and mouse premature death, whereas GSDMC silence eliminated LGR5 and triggered apoptosis in human colonic organoids and epithelial cells. Mechanistically, Mettl14 depletion eliminated mitochondrial GsdmC, disrupted mitochondrial membrane potential, and triggered cytochrome c release that activates the pro-apoptotic pathway. In conclusion, GsdmC N6-adenomethylation protects mitochondrial homeostasis and is essential for Lgr5+ cell survival to maintain normal colonic epithelial regeneration.

Baseline serum uric acid level is associated with progression-free survival, disease control rate, and safety in postoperative patients with colorectal cancer treated by FOLFOX, FOLFIRI, or XELOX.

Background: High serum uric acid (SUA) levels increase the risk of overall cancer morbidity and mortality, particularly for digestive malignancies. Nevertheless, the correlation between SUA level and clinical outcomes of the postoperative patients with colorectal cancer (CRC) treated by chemotherapy is unclear. This study aimed at exploring the relationship between baseline SUA level and progression-free survival (PFS), disease control rate (DCR), and safety in postoperative CRC patients receiving chemotherapy. Patients and Methods: We conducted a retrospective study to evaluate the relationship between baseline SUA level and PFS, DCR, and incidence of serious adverse events of 736 postoperative CRC patients treated with FOLFOX, FOLFIRI or XELOX at our center. Results: Data from our center suggested that high baseline SUA level is linked to poor PFS in non-metastatic CRC patients using FOLFOX (HR=2.59, 95%CI: 1.29-11.31, p=0.018) and in male patients using FOLFIRI (HR=3.77, 95%CI: 1.57-39.49, p=0.012). In patients treated by FOLFIRI, a high SUA is also linked to a low DCR (p=0.035). In patients using FOLFOX, high baseline SUA level is also linked to a high incidence of neutropenia (p=0.0037). For patients using XELOX, there is no significant correlation between SUA level and PFS, effectiveness, or safety. Conclusions: These findings imply that a high SUA level is a promising biomarker associated with poor PFS, DCR and safety of postoperative CRC patients when treated with FOLFOX or FOLFIRI.

Generation of Phenol and Molecular Hydrogen through Catalyst-Free C-H Activation of Benzene by Water Radical Cations.

Here, we report on the abundant formation of phenol and molecular hydrogen when benzene vapor was exposed to gas plasma generated by +5.5 kV corona discharge of water vapor in argon in the absence of oxygen. Systematic analysis using a series of isotopic standards (d6-benzene, D2O, and H218O) and benzene derivatives (mono-, di-, trichlorobenzene, and N,N-dimethylaniline) indicated that the formation of phenol occurred through the reaction between neutral benzene and the radical cation of water dimer, (H2O)2+•. A two-step reaction mechanism was proposed based on the results of experiments and DFT calculations: (1) the formation of (C6H6...H2O)+• intermediate through electrophilic addition; (2) the formation of C6H5OH+• through the release of H2 from the (C6H6...H2O)+• intermediate. Our findings offer a novel catalyst-free method to prepare phenol from benzene with phenol selectivity >90%.

NMDA receptor-mediated synaptic transmission in prefrontal neurons underlies social memory retrieval in female mice.

Social memory is the ability to discriminate familiar conspecific from the unknown ones. Prefrontal neurons are essentially required for social memory, but the mechanism associated with this regulation remains unknown. It is also unclear to what extent the neuronal representations of social memory formation and retrieval events overlap in the prefrontal cortex (PFC) and which event drives social memory strength. Here we asked these questions by using a repeated social training paradigm for social recognition in FosTRAP mice. We found that after 4 days' repeated social training, female mice developed stable social memory. Specifically, repeated social training activated more cells that were labeled with tdTomato during memory retrieval compared with the first day of memory encoding. Besides, combining TRAP with c-Fos immunostaining, we found about 30% of the FosTRAPed cells were reactivated during retrieval. Moreover, the number of retrieval-induced but not first-day encoding-induced tdTomato neurons correlates with the social recognition ratio in the prelimbic but not other subregions. The activated cells during the retrieval session also showed increased NMDA receptor-mediated synaptic transmission compared with that in non-labeled pyramidal neurons. Blocking NMDA receptors by MK-801 impaired social memory but not sociability. Therefore, our results reveal that repetitive training elevates mPFC involvement in social memory retrieval via enhancing NMDA receptor-mediated synaptic transmission, thus rendering stable social memory.

A protocol for macrophage depletion and reconstitution in a mouse model of sepsis.

Macrophages are key innate immune cells involved in a broad spectrum of physiological and pathological processes. Macrophage depletion with clodronate-liposomes is commonly used to investigate in vivo functions of macrophages in mice. Here, we describe a protocol that combines the depletion of resident macrophages with the reconstitution of the mice with in vitro differentiated, lentivirus-transduced bone marrow-derived macrophages (BMDMs) in the context of an experimental sepsis model. This experimental strategy is easily adapted to other experimental designs. For complete details on the use and execution of this protocol, please refer to Du et al. (2020).

The Genus Leccinum (Boletaceae, Boletales) from China Based on Morphological and Molecular Data.

Leccinum is one of the most important groups of boletes. Most species in this genus are ectomycorrhizal symbionts of various plants, and some of them are well-known edible mushrooms, making it an exceptionally important group ecologically and economically. The scientific problems related to this genus include that the identification of species in this genus from China need to be verified, especially those referring to European or North American species, and knowledge of the phylogeny and diversity of the species from China is limited. In this study, we conducted multi-locus (nrLSU, tef1-α, rpb2) and single-locus (ITS) phylogenetic investigations and morphological observisions of Leccinum from China, Europe and North America. Nine Leccinum species from China, including three new species, namely L. album, L.parascabrum and L.pseudoborneense, were revealed and described. Leccinum album is morphologically characterized by the white basidioma, the white hymenophore staining indistinct greenish blue when injured, and the white context not changing color in pileus but staining distinct greenish blue in the base of the stipe when injured. Leccinumparascabrum is characterized by the initially reddish brown to chestnut-brown and then pale brownish to brown pileus, the white to pallid and then light brown hymenophore lacking color change when injured, and the white context lacking color change in pileus but staining greenish blue in the base of the stipe when injured. Leccinumpseudoborneense is characterized by the pale brown to dark brown pileus, the initially white and then brown hymenophore lacking color change when injured, and the white context in pileus and stipe lacking color change in pileus but staining blue in stipe when bruised. Color photos of fresh basidiomata, line drawings of microscopic features and detailed descriptions of the new species are presented.

Cyanescent Gyroporus (Gyroporaceae, Boletales) from China.

Gyroporus species with cyanescent oxidation reactions were investigated, based on morphology and phylogenetic analysis of DNA sequences from the nuclear ribosomal large subunit (nrLSU), the nuclear ribosomal internal transcribed spacer (ITS) and the mitochondrial adenosine triphosphate ATP synthase subunit 6 (atp6). Three species, including two new species, namely G. alpinus and G. flavocyanescens and one previously-described species, namely G. brunneofloccosus, are revealed from China. Collections formerly reported from China as "G. cyanescens" are either G. alpinus or G. flavocyanescens. The new species are documented and illustrated in detail, while the concept of G. brunneofloccosus is refined with additional recently-collected materials. Additionally, the cyanescent species G. pseudomicrosporus, previously described from China, is shown to be a member of the genus Gyrodon, based on re-examination of the type specimen. A key to the cyanescent Gyroporus species from China is provided.

Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin-angiotensin system in the lung.

Idiopathic pulmonary fibrosis (IPF) is a severe disorder leading to progressive and irreversible loss of pulmonary function. In this study we investigated the anti-fibrotic effect of vitamin D using a mouse model of IPF. Lung fibrosis was induced with bleomycin in vitamin D-sufficient and vitamin D-deficient C57BL/6 mice. We found that treatment with active vitamin D analog paricalcitol prevented mouse body weight loss and alleviated lung fibrosis, whereas vitamin D deficiency severely aggravated lung injury. At the molecular level, paricalcitol treatment suppressed the induction of fibrotic inducer TGF-ß and extracellular matrix proteins α-SMA, collagen type I and fibronectin in the lung, whereas vitamin D deficiency exacerbated the induction of these proteins. Interestingly, bleomycin treatment activated the local renin-angiotensin system (RAS) in the lung, manifested by the induction of renin, angiotensinogen, angiotensin II and angiotensin receptor type 1 (AT1R). Paricalcitol treatment suppressed the induction of these RAS components, whereas vitamin D deficiency enhanced the activation of the lung RAS. We also showed that treatment of bleomycin-induced vitamin D-deficient mice with AT1R antagonist losartan relieved weight loss, substantially ameliorated lung fibrosis and markedly blocked TGF-ß induction in the lung. Moreover, we demonstrated that in lung fibroblast cultures, TGF-ß and angiotensin II synergistically induced TGF-ß, AT1R, α-SMA, collagen type I and fibronectin, whereas 1,25-dihydroxyvitamin D markedly suppressed the induction of these fibrotic markers. Collectively, these observations strongly suggest that vitamin D mitigates lung fibrosis by blocking the activation of the lung RAS in this mouse model of IPF.

Prevalence and clinical characteristics of septicemia in children with Mycoplasma pneumoniae pneumonia.

BACKGROUND: Mycoplasma pneumoniae (MP) pneumonia in children can be challenging to treat, and the impact of MP blood infection is unclear. The present study aims to determine the prevalence and clinical characteristics of MP septicemia among pediatric patients. METHODS: Children hospitalized at our center for MP pneumonia between October 2017 and June 2018 were included. Healthy controls visiting our outpatient clinic for regular physical examinations were also enrolled. MP was detected by real-time polymerase chain reaction (qPCR) analysis of plasma and peripheral blood mononuclear cell (PBMC) samples. RESULTS: Sixty-one children with MP pneumonia and 30 healthy children were included. Among children with MP infection, 31 (50.8%) were positive for MP by qPCR (19 in plasma samples, 8 in PBMC samples, and 4 in both). All healthy controls were negative for MP by qPCR. CONCLUSIONS: The prevalence of MP septicemia in children with MP pneumonia is moderate. However, detection of MP in blood samples may have limited clinical value for guiding treatment.

Prediction of microvascular invasion in solitary hepatocellular carcinoma ≤ 5 cm based on computed tomography radiomics.

BACKGROUND: Liver cancer is one of the most common malignant tumors, and ranks as the fourth leading cause of cancer death worldwide. Microvascular invasion (MVI) is considered one of the most important factors for recurrence and poor prognosis of liver cancer. Thus, accurately identifying MVI before surgery is of great importance in making treatment strategies and predicting the prognosis of patients with hepatocellular carcinoma (HCC). Radiomics as an emerging field, aims to utilize artificial intelligence software to develop methods that may contribute to cancer diagnosis, treatment improvement and evaluation, and better prediction. AIM: To investigate the predictive value of computed tomography radiomics for MVI in solitary HCC ≤ 5 cm. METHODS: A total of 185 HCC patients, including 122 MVI negative and 63 MVI positive patients, were retrospectively analyzed. All patients were randomly assigned to the training group (n = 124) and validation group (n = 61). A total of 1351 radiomic features were extracted based on three-dimensional images. The diagnostic performance of the radiomics model was verified in the validation group, and the Delong test was applied to compare the radiomics and MVI-related imaging features (two-trait predictor of venous invasion and radiogenomic invasion). RESULTS: A total of ten radiomics features were finally obtained after screening 1531 features. According to the weighting coefficient that corresponded to the features, the radiomics score (RS) calculation formula was obtained, and the RS score of each patient was calculated. The radiomics model exhibited a better correction and identification ability in the training and validation groups [area under the curve: 0.72 (95% confidence interval: 0.58-0.86) and 0.74 (95% confidence interval: 0.66-0.83), respectively]. Its prediction performance was significantly higher than that of the image features (P < 0.05). CONCLUSION: Computed tomography radiomics has certain predictive value for MVI in solitary HCC ≤ 5 cm, and the predictive ability is higher than that of image features.

MicroRNA-122 contributes to lipopolysaccharide-induced acute kidney injury via down-regulating the vitamin D receptor in the kidney.

BACKGROUND: Our previous studies showed that vitamin D receptor (VDR) depletion promotes lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in mice, and renal VDR is down-regulated in AKI, but the mechanism of VDR down-regulation is unclear. METHODS: Nutritional vitamin D deficiency was induced by feeding mice a vitamin D-deficient (VD-D) diet. Mice were injected intraperitoneally with LPS (20 mg/kg) to establish LPS-induced AKI. Levels of VDR and miR-122 were measured both in vivo and in vitro. The associations between VDR and miR-122 were analysed by dual-luciferase reporter assays. RESULTS: Compared with vitamin D-sufficient (VD-S) mice, VD-D mice developed more severe renal injury following LPS challenge. LPS induced a dramatic decrease in VDR expression and marked induction of miR-122 both in vivo and in vitro. Furthermore, miR-122 hairpin inhibitor alleviated LPS-induced VDR down-regulation whereas miR-122 mimic directly suppressed VDR expression in HK-2 cells. In luciferase reporter assays, miR-122 mimic was able to suppress luciferase activity in 293T cells co-transfected with a luciferase reporter that contains a putative miR-122 target site from 3'UTR of the VDR transcript, but not when this site was mutated. Moreover, miR-122 mimic significantly blocked paricalcitol-induced luciferase activity in 293T cells co-transfected with a VDRE-driven luciferase reporter, whereas miR-122 hairpin inhibitor enhanced paricalcitol's activity to suppress PUMA and caspase 3 activation induced by LPS in HK-2 cells. CONCLUSIONS: Collectively, these studies provide evidence that miR-122 directly targets VDR in renal tubular cells, which strongly suggest that miR-122 up-regulation in the kidney under LPS challenge contributes to kidney injury by down-regulating VDR expression.

Vitamin D Deficiency Exacerbates Colonic Inflammation Due to Activation of the Local Renin-Angiotensin System in the Colon.

BACKGROUND: The renin-angiotensin system (RAS) is activated in inflammatory bowel disease (IBD), and vitamin D deficiency aggravates the development of colitis, but the relationship between the local colonic RAS and vitamin D is unclear with regard to the pathogenesis of IBD. AIMS: To investigate whether vitamin D suppresses the local colonic RAS to prevent colonic mucosal inflammation in a mouse model of experimental colitis. METHODS: C57BL/6 mice fed vitamin D-deficient (VDD) diet for 8 weeks were induced to colitis by 2,4,6-trinitrobenzenesulfonic acid (TNBS), with mice fed vitamin D-sufficient (VDS) diet as controls. Colitis severity was assessed by histology, and pro-inflammatory cytokines, RAS components, and signaling pathways were quantified by real-time RT-PCR and Western blotting. RESULTS: C57BL/6 mice fed the VDD diet for 8 weeks exhibited significantly lower serum 25(OH)D3 concentrations compared to mice fed the VDS diet. When these VDD mice were induced to colitis by TNBS, they exhibited more severe colonic inflammation and developed more severe colitis compared to the VDS counterparts. VDD diet feeding resulted in higher production of mucosal pro-inflammatory cytokines, higher activation of the myosin light chain kinase-tight junction regulatory pathway, and greater increases in mucosal permeability. VDD diet feeding also enhanced colonic RAS activation. Treatment with angiotensin II receptor blocker losartan markedly alleviated colitis in TNBS-induced VDD mice. CONCLUSION: Vitamin D deficiency promotes colonic inflammation at least in part due to over activation of the local RAS in the colon.

A Subpopulation of Prefrontal Cortical Neurons Is Required for Social Memory.

BACKGROUND: The medial prefrontal cortex (mPFC) is essential for social behaviors, yet whether and how it encodes social memory remains unclear. METHODS: We combined whole-cell patch recording, morphological analysis, optogenetic/chemogenetic manipulation, and the TRAP (targeted recombination in active populations) transgenic mouse tool to study the social-associated neural populations in the mPFC. RESULTS: Fos-TRAPed prefrontal social-associated neurons are excitatory pyramidal neurons with relatively small soma sizes and thin-tufted apical dendrite. These cells exhibit intrinsic firing features of dopamine D1 receptor-like neurons, show persisting firing pattern after social investigation, and project dense axons to nucleus accumbens. In behaving TRAP mice, selective inhibition of prefrontal social-associated neurons does not affect social investigation but does impair subsequent social recognition, whereas optogenetic reactivation of their projections to the nucleus accumbens enables recall of a previously encountered but "forgotten" mouse. Moreover, chemogenetic activation of mPFC-to-nucleus accumbens projections ameliorates MK-801-induced social memory impairments. CONCLUSIONS: Our results characterize the electrophysiological and morphological features of social-associated neurons in the mPFC and indicate that these Fos-labeled, social-activated prefrontal neurons are necessary and sufficient for social memory.

Upregulation of polycistronic microRNA-143 and microRNA-145 in colonocytes suppresses colitis and inflammation-associated colon cancer.

Because ADAM17 promotes colonic tumorigenesis, we investigated potential miRNAs regulating ADAM17; and examined effects of diet and tumorigenesis on these miRNAs. We also examined pre-miRNA processing and tumour suppressor roles of several of these miRNAs in experimental colon cancer. Using TargetScan, miR-145, miR-148a, and miR-152 were predicted to regulate ADAM17. miR-143 was also investigated as miR-143 and miR-145 are co-transcribed and associated with decreased tumour growth. HCT116 colon cancer cells (CCC) were co-transfected with predicted ADAM17-regulating miRNAs and luciferase reporters controlled by ADAM17-3'UTR. Separately, pre-miR-143 processing by colonic cells was measured. miRNAs were quantified by RT-PCR. Tumours were induced with AOM/DSS in WT and transgenic mice (Tg) expressing pre-miR-143/miR-145 under villin promoter. HCT116 transfection with miR-145, -148a or -152, but not scrambled miRNA inhibited ADAM17 expression and luciferase activity. The latter was suppressed by mutations in ADAM17-3'UTR. Lysates from colonocytes, but not CCC, processed pre-miR-143 and mixing experiments suggested CCC lacked a competency factor. Colonic miR-143, miR-145, miR-148a, and miR-152 were downregulated in tumours and more moderately by feeding mice a Western diet. Tg mice were resistant to DSS colitis and had significantly lower cancer incidence and tumour multiplicity. Tg expression blocked up-regulation of putative targets of miR-143 and miR-145, including ADAM17, K-Ras, XPO5, and SET. miR-145, miR-148a, and miR-152 directly suppress colonocyte ADAM17 and are down-regulated in colon cancer. This is the first direct demonstration of tumour suppressor roles for miR-143 and miR-145 in an in vivo model of colonic tumorigenesis.