Characterization of the MIKCC-type MADS-box gene family in blueberry and its possible mechanism for regulating flowering in response to the chilling requirement.

MAIN CONCLUSION: The expression peak of VcAP1.4, VcAP1.6, VcAP3.1, VcAP3.2, VcAG3, VcFLC2, and VcSVP9 coincided with the endo-dormancy release of flower buds. Additionally, GA4+7 not only increased the expression of these genes but also promoted flower bud endo-dormancy release. The MIKCC-type MADS-box gene family is involved in the regulation of flower development. A total of 109 members of the MIKCC-type MADS-box gene family were identified in blueberry. According to the phylogenetic tree, these 109 MIKCC-type MADS-box proteins were divided into 13 subfamilies, which were distributed across 40 Scaffolds. The results of the conserved motif analysis showed that among 20 motifs, motifs 1, 3, and 9 formed the MADS-box structural domain, while motifs 2, 4, and 6 formed the K-box structural domain. The presence of 66 pairs of fragment duplication events in blueberry suggested that gene duplication events contributed to gene expansion and functional differentiation. Additionally, the presence of cis-acting elements revealed that VcFLC2, VcAG3, and VcSVP9 might have significant roles in the endo-dormancy release of flower buds. Meanwhile, under chilling conditions, VcAP3.1 and VcAG7 might facilitate flower bud dormancy release. VcSEP11 might promote flowering following the release of endo-dormancy, while the elevated expression of VcAP1.7 (DAM) could impede the endo-dormancy release of flower buds. The effect of gibberellin (GA4+7) treatment on the expression pattern of MIKCC-type MADS-box genes revealed that VcAP1.4, VcAP1.6, VcAP3.1, VcAG3, and VcFLC2 might promote flower bud endo-dormancy release, while VcAP3.2, VcSEP11, and VcSVP9 might inhibit its endo-dormancy release. These results indicated that VcAP1.4, VcAP1.6, VcAP1.7 (DAM), VcAP3.1, VcAG3, VcAG7, VcFLC2, and VcSVP9 could be selected as key regulatory promoting genes for controlling the endo-dormancy of blueberry flower buds.

Relationships between circulating metabolites and facial skin aging: a Mendelian randomization study.

BACKGROUND: Blood metabolites are important to various aspects of our health. However, currently, there is little evidence about the role of circulating metabolites in the process of skin aging. OBJECTIVES: To examine the potential effects of circulating metabolites on the process of skin aging. METHOD: In the primary analyses, we applied several MR methods to study the associations between 249 metabolites and facial skin aging risk. In the secondary analyses, we replicated the analyses with another array of datasets including 123 metabolites. MR Bayesian model averaging (MR-BMA) method was further used to prioritize the metabolites for the identification of predominant metabolites that are associated with skin aging. RESULTS: In the primary analyses, only the unsaturation degree of fatty acids was found significantly associated with skin aging with the IVW method after multiple testing (odds ratio = 1.084, 95% confidence interval = 1.049-1.120, p = 1.737 × 10-06). Additionally, 11 out of 17 unsaturation-related biomarkers showed a significant or suggestively significant causal effect [p < 0.05 and > 2 × 10-4 (0.05/249 metabolites)]. In the secondary analyses, seven metabolic biomarkers were found significantly associated with skin aging [p < 4 × 10-4 (0.05/123)], while six of them were related to the unsaturation degree. MR-BMA method validated that the unsaturation degree of fatty acids plays a dominant role in facial skin aging. CONCLUSIONS: Our study used systemic MR analyses and provided a comprehensive atlas for the associations between circulating metabolites and the risk of facial skin aging. Genetically proxied unsaturation degree of fatty acids was highlighted as a dominant factor correlated with the risk of facial skin aging.

Assessment of the role of false-positive alerts in computer-aided polyp detection for assistance capabilities.

BACKGROUND AND AIM: False positives (FPs) pose a significant challenge in the application of artificial intelligence (AI) for polyp detection during colonoscopy. The study aimed to quantitatively evaluate the impact of computer-aided polyp detection (CADe) systems' FPs on endoscopists. METHODS: The model's FPs were categorized into four gradients: 0-5, 5-10, 10-15, and 15-20 FPs per minute (FPPM). Fifty-six colonoscopy videos were collected for a crossover study involving 10 endoscopists. Polyp missed rate (PMR) was set as primary outcome. Subsequently, to further verify the impact of FPPM on the assistance capability of AI in clinical environments, a secondary analysis was conducted on a prospective randomized controlled trial (RCT) from Renmin Hospital of Wuhan University in China from July 1 to October 15, 2020, with the adenoma detection rate (ADR) as primary outcome. RESULTS: Compared with routine group, CADe reduced PMR when FPPM was less than 5. However, with the continuous increase of FPPM, the beneficial effect of CADe gradually weakens. For secondary analysis of RCT, a total of 956 patients were enrolled. In AI-assisted group, ADR is higher when FPPM ≤ 5 compared with FPPM > 5 (CADe group: 27.78% vs 11.90%; P = 0.014; odds ratio [OR], 0.351; 95% confidence interval [CI], 0.152-0.812; COMBO group: 38.40% vs 23.46%, P = 0.029; OR, 0.427; 95% CI, 0.199-0.916). After AI intervention, ADR increased when FPPM ≤ 5 (27.78% vs 14.76%; P = 0.001; OR, 0.399; 95% CI, 0.231-0.690), but no statistically significant difference was found when FPPM > 5 (11.90% vs 14.76%, P = 0.788; OR, 1.111; 95% CI, 0.514-2.403). CONCLUSION: The level of FPs of CADe does affect its effectiveness as an aid to endoscopists, with its best effect when FPPM is less than 5.

Regulatory mechanism of the Glabrene against non-small cell lung cancer by suppressing FGFR3.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a highly malignant tumor with limited effective treatment options. This study aimed to investigate the regulatory mechanism of Glabrene on NSCLC through its interaction with FGFR3. METHODS: HCC827 cells were implanted into nude mice and treated with Glabrene. Tumor volume was monitored at 0, 3, 6, and 9 days after medical treatment. Tissue analysis included Hematoxylin and Eosin (HE) and Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) staining, as well as immunohistochemistry for Ki67, ERK1/2, and p-ERK1/2 expression. Cell viability was determined with the CCK8 method. We utilized immunofluorescence techniques to observe apoptosis, as well as the levels of E-cadherin and Vimentin expression. Cellular proliferation was determined via plate cloning assay and cellular mobility was determined via scratch assay. Cellular invasion ability was assessed via a transwell assay. mRNA and protein levels of FGFR3, MMP1, MMP9, vimentin, E-cadherin, ERK1/2, and p-ERK1/2 were detected via qPCR and Western blot. IGF-1, VEGF, and Estradiol (E2) levels were measured through Enzyme linked immunosorbent assay (ELISA). RESULTS: This study verified that Glabrene was capable of suppressing tumor growth in NSCLC mice, reversing tumor tissue's pathological morphology, attenuating the capacities of cancerous cells' proliferation, migration, and invasion, and leading to apoptosis. Besides, Glabrene could reduce the FGFR3 expression in HCC827 cells. Over-expression of FGFR3 promotes the proliferation of HCC827 cells, increase both contents of IGF-1, VEGF, and E2, and expressions of MMP1, MMP9, vimentin, and p-ERK1/2, while Glabrene inhibited FGFR3. Glabrene, and inhibition of FGFR3 expression were capable of decreasing FGFR3, MMP1, MMP9, vimentin, and p-ERK1/2 expression, as well as contents of IGF-1, VEGF, and E2 in model mice and HCC827 cells, and promoting the expression of E-cadherin. CONCLUSION: Glabrene has the potential as a therapeutic agent for NSCLC by reducing cancer invasion and migration through the inhibition of ERK1/2 phosphorylation and suppression of epithelial-mesenchymal transition (EMT).

Characteristics and effects on daily lives of pelvic girdle pain during early postpartum in Beijing women, China.

Pelvic girdle pain (PGP) is a common problem during pregnancy and postpartum and negatively affects women's well-being. Yet it is not well known in China. This study assessed PGP's intensity, location, and quality and the status of daily activities on postpartum women with pain, and explored the relationship between pain and the prevalence of depressive symptoms. A cross-sectional study recruiting 1,038 eligible women at 6 weeks postpartum from the obstetric clinic of a hospital was conducted in Beijing, China. Data were collected using self-reported questionnaires, including Introductory information form, Body chart, Number Rating Scale, McGill Pain Questionnaire-2, Pelvic Girdle Questionnaire, and Edinburgh Postnatal Depression Scale. In this study, 32.2 percent women experienced pain. The mean (SD) pain intensity score was 3.07 ± 1.60. About 50.6 percent women experienced sacroiliac joint pain, and 25.5 percent women experienced pain in a combination of locations. About 73.1 percent women experienced aching pain, and 57.5 percent experienced more than one kind of pain quality. The mean total score, which assesses activity and symptom limitations, was 21.93 ± 17.35 (percent), of which a normal sex life (1.29 ± 0.94) was made more challenging due to pain. In mental health, the prevalence of depressive symptoms coincided with the prevalence of pain (p = 0.008). Postpartum PGP still needs to be taken seriously, and women with pain require further support. The above knowledge offers information to manage pain, daily lives and depressive symptoms, contributes to think about strategies to better promote postpartum women physical and mental health in the future.

Molecular characterization of SPL gene family during flower morphogenesis and regulation in blueberry.

The SPL gene is a plant-specific transcription factor involved in the regulation of plant growth and development, which have been identified in woody plants. The process of floral bud differentiation affects the timing of flowering and fruit set and regulates plant growth, however, the mechanism of regulation of flower development by SPL genes is less studied. In this study, 56 VcSPL genes were identified in the tetraploid blueberry. The VcSPL gene family was classified into six subfamilies, and analysis of cis-elements showed that VcSPL genes were regulated by light, phytohormones (abscisic acid, MeJA), and low temperature. In the evolutionary analysis, segmental replication may play an important role in VcSPL gene amplification. Interestingly, we also studied diploid blueberry (Bilberry), in which 24 SPL genes were identified, and 36 homologous pairs were found, suggesting a high degree of convergence in the syntenic relationship between blueberry (Vaccinium corymbosum L) and bilberry (Vaccinium darrowii). Based on the expression profile, VcSPL genes were expressed at high levels in flowers, shoots, and roots, indicating a diversity of gene functions. Then we selected 20 differentially-expressed SPL genes to further investigate the role of VcSPL in floral induction and initiation. It showed that the genes VcSPL40, VcSPL35, VcSPL45, and VcSPL53 may play a crucial role in the blueberry floral transition phase (from vegetative growth to flower initiation). These results provided important information for understanding and exploring the role of VcSPLs in flower morphogenesis and plant growth.

Onset of p53/NF-κB signaling crosstalk in human melanoma cells in response to anti-cancer theabrownin.

As a major tea component, theabrownin represents a promising anti-cancer candidate. However, its effect on the melanoma is unknown. To evaluate the in vitro and in vivo anti-melanoma efficacy of TB, we conducted cell viability, immunostaining, comet, and TUNEL assays on human A375 melanoma cells, and employed a zebrafish xenograft model of A375 cells. Real-time PCR (qPCR) and western blot were conducted to explore the molecular mechanisms of TB. In vitro, TB significantly inhibited the proliferation of A375 cells, and A375 cells showed the highest inhibitory rate among the other melanoma cell line (A875) and human dermal fibroblasts. TB triggered DNA damage and induced apoptosis of A375 cells and significantly inhibited the growth of A375 xenograft tumors in zebrafishes. Several key molecular events were activated by TB, including DNA damage-associated p53 and NF-κB pathways, through up-regulation of GADD45α, γ-H2A.X, phospho-ATM(p-ATM), phospho-ATR (p-ATR), phospho-p53 (p-p53), phospho-IKKα/ß (p-IKKα/ß), phospho-p65 (p-p65), etc. However, the TB-activated molecular events were counteracted by either knockdown of p53 or p65, and only dual knockdown of both p53 and p65 completed counteracted the anti-melanoma efficacy of TB. In conclusion, TB triggered DNA damage and thereby inhibited proliferation and induced cellular senescence and apoptosis of melanoma cells through mechanisms mediated by p53/NF-κB signaling crosstalk. This is the first report on the efficacy and mechanisms of TB on melanoma cells, making TB a promising candidate for anti-melanoma agent development.

Association between KRAS gene polymorphisms and genetic susceptibility to breast cancer in a Chinese population.

OBJECTIVE: The KRAS gene has a pathophysiological role in the development of many cancers. This study aims to investigate the relationship between KRAS polymorphisms and genetic susceptibility to breast cancer. METHOD: The rs712, rs12587 and rs9266 gene loci in the KRAS gene of 421 subjects (141 breast cancer patients, 141 benign breast tumours and 139 healthy controls) were analysed by the polymerase chain reaction and SNaPshot sequencing. Transcriptomic information on KRAS and corresponding clinical information was downloaded from the TCGA and GTEx databases. Differences in KRAS expression between breast cancer tissues and control tissues were analysed. RESULTS: We found no significant association between KRAS rs712 and rs12587 locus gene polymorphisms and an increased risk of developing benign breast tumours and breast cancer (p > 0.05). The KRAS rs9266 locus mutation heterozygous model CT and dominant model CT + TT were significantly associated with an increased risk of breast cancer (both p < 0.05). In addition, the TAT haplotype was expressed at an increased frequency, and the GAC haplotype was expressed at a reduced frequency in breast cancer compared with controls (both p < 0.05). We found that KRAS was over expressed in breast cancer tumour tissues compared with the control tissues (p < 0.0001). CONCLUSION: The KRAS rs9266 gene polymorphism and the TAT haplotype may be associated with an increased risk of breast cancer in Chinese women. The GAC haplotype may be a protective factor against breast cancer.

Classification of normal and abnormal fetal heart ultrasound images and identification of ventricular septal defects based on deep learning.

OBJECTIVES: Congenital heart defects (CHDs) are the most common birth defects. Recently, artificial intelligence (AI) was used to assist in CHD diagnosis. No comparison has been made among the various types of algorithms that can assist in the prenatal diagnosis. METHODS: Normal and abnormal fetal ultrasound heart images, including five standard views, were collected according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) Practice guidelines. You Only Look Once version 5 (YOLOv5) models were trained and tested. An excellent model was screened out after comparing YOLOv5 with other classic detection methods. RESULTS: On the training set, YOLOv5n performed slightly better than the others. On the validation set, YOLOv5n attained the highest overall accuracy (90.67 %). On the CHD test set, YOLOv5n, which only needed 0.007 s to recognize each image, had the highest overall accuracy (82.93 %), and YOLOv5l achieved the best accuracy on the abnormal dataset (71.93 %). On the VSD test set, YOLOv5l had the best performance, with a 92.79 % overall accuracy rate and 92.59 % accuracy on the abnormal dataset. The YOLOv5 models achieved better performance than the Fast region-based convolutional neural network (RCNN) & ResNet50 model and the Fast RCNN & MobileNetv2 model on the CHD test set (p<0.05) and VSD test set (p<0.01). CONCLUSIONS: YOLOv5 models are able to accurately distinguish normal and abnormal fetal heart ultrasound images, especially with respect to the identification of VSD, which have the potential to assist ultrasound in prenatal diagnosis.

Interleukin-33 Exacerbates IgA Glomerulonephritis in Transgenic Mice Overexpressing B Cell Activating Factor.

BACKGROUND: The cytokine IL-33 is an activator of innate lymphoid cells 2 (ILC2s) in innate immunity and allergic inflammation. B cell activating factor (BAFF) plays a central role in B cell proliferation and differentiation, and high levels of this protein cause excess antibody production, including IgA. BAFF-transgenic mice overexpress BAFF and spontaneously develop glomerulonephritis that resembles human IgA nephropathy. METHODS: We administered IL-33 or PBS to wild-type and BAFF-transgenic mice. After treating Rag1-deficient mice with IL-33, with or without anti-CD90.2 to preferentially deplete ILC2s, we isolated splenocytes, which were adoptively transferred into BAFF-transgenic mice. RESULTS: BAFF-transgenic mice treated with IL-33 developed more severe kidney dysfunction and proteinuria, glomerular sclerosis, tubulointerstitial damage, and glomerular deposition of IgA and C3. Compared with wild-type mice, BAFF-transgenic mice exhibited increases of CD19+ B cells in spleen and kidney and ILC2s in kidney and intestine, which were further increased by administration of IL-33. Administering IL-33 to wild-type mice had no effect on kidney function or histology, nor did it alter the number of ILC2s in spleen, kidney, or intestine. To understand the role of ILC2s, splenocytes were transferred from IL-33-treated Rag1-deficient mice into BAFF-transgenic mice. Glomerulonephritis and IgA deposition were exacerbated by transfer of IL-33-stimulated Rag1-deficient splenocytes, but not by ILC2 (anti-CD90.2)-depleted splenocytes. Wild-type mice infused with IL-33-treated Rag1-deficient splenocytes showed no change in kidney function or ILC2 numbers or distribution. CONCLUSIONS: IL-33-expanded ILC2s exacerbated IgA glomerulonephritis in a mouse model. These findings indicate that IL-33 and ILC2s warrant evaluation as possible mediators of human IgA nephropathy.

Development and validation of an artificial intelligence-based system for predicting colorectal cancer invasion depth using multi-modal data.

OBJECTIVES: Accurate endoscopic optical prediction of the depth of cancer invasion is critical for guiding an optimal treatment approach of large sessile colorectal polyps but was hindered by insufficient endoscopists expertise and inter-observer variability. We aimed to construct a clinically applicable artificial intelligence (AI) system for the identification of presence of cancer invasion in large sessile colorectal polyps. METHODS: A deep learning-based colorectal cancer invasion calculation (CCIC) system was constructed. Multi-modal data including clinical information, white light (WL) and image-enhanced endoscopy (IEE) were included for training. The system was trained using 339 lesions and tested on 198 lesions across three hospitals. Man-machine contest, reader study and video validation were further conducted to evaluate the performance of CCIC. RESULTS: The overall accuracy of CCIC system using image and video validation was 90.4% and 89.7%, respectively. In comparison with 14 endoscopists, the accuracy of CCIC was comparable with expert endoscopists but superior to all the participating senior and junior endoscopists in both image and video validation set. With CCIC augmentation, the average accuracy of junior endoscopists improved significantly from 75.4% to 85.3% (P = 0.002). CONCLUSIONS: This deep learning-based CCIC system may play an important role in predicting the depth of cancer invasion in colorectal polyps, thus determining treatment strategies for these large sessile colorectal polyps.

Targeting inflammatory monocytes by immune-modifying nanoparticles prevents acute kidney allograft rejection.

Inflammatory monocytes are a major component of the cellular infiltrate in acutely rejecting human kidney allografts. Since immune-modifying nanoparticles (IMPs) bind to circulating inflammatory monocytes via the specific scavenger receptor MARCO, causing diversion to the spleen and subsequent apoptosis, we investigated the therapeutic potential of negatively charged, 500-nm diameter polystyrene IMPs to prevent kidney allograft rejection. Kidney transplants were performed from BALB/c (H2d) to C57BL/6 (H2b) mice in two groups: controls (allo) and allo mice infused with IMPs. Groups were studied for 14 (acute rejection) or 100 (chronic rejection) days. Allo mice receiving IMPs exhibited superior survival and markedly less acute rejection, with better kidney function, less tubulitis, and diminished inflammatory cell density, cytokine and cytotoxic molecule expression in the allograft and lower titers of donor-specific IgG2c antibody in serum at day 14, as compared to allo mice. Cells isolated from kidneys from allo mice receiving IMPs showed reduced Ly6Chi monocytes, CD11b+ cells and NKT+ cells compared to allo mice. IMPs predominantly bound CD11b+ cells in the bloodstream and CD11b+ and CD11c-B220+ marginal zone B cells in the spleen. In the spleen, IMPs were found predominantly in red pulp, colocalized with MARCO and expression of cleaved caspase-3. At day 100, allo mice receiving IMPs exhibited reduced macrophage M1 responses but were not protected from chronic rejection. IMPs afforded significant protection from acute rejection, inhibiting both innate and adaptive alloimmunity. Thus, our current experimental findings, coupled with our earlier demonstration of IMP-induced protection in kidney ischemia-reperfusion injury, identify IMPs as a potential induction agent in kidney transplantation.

Use of catalytic wet air oxidation (CWAO) for pretreatment of high-salinity high-organic wastewater.

Catalytic wet air oxidation (CWAO) coupled desalination technology provides a possibility for the effective and economic degradation of high salinity and high organic wastewater. Chloride widely occurs in natural and wastewaters, and its high content jeopardizes the efficacy of Advanced oxidation process (AOPs). Thus, a novel chlorine ion resistant catalyst B-site Ru doped LaFe1-xRuxO3-δ in CWAO treatment of chlorine ion wastewater was examined. Especially, LaFe0.85Ru0.15O3-δ was 45.5% better than that of the 6%RuO2@TiO2 (commercial carrier) on total organic carbon (TOC) removal. Also, doped catalysts LaFe1-xRuxO3-δ showed better activity than supported catalysts RuO2@LaFeO3 and RuO2@TiO2 with the same Ru content. Moreover, LaFe0.85Ru0.15O3-δ has novel chlorine ion resistance no matter the concentration of Cl- and no Ru dissolves after the reaction. X-ray diffraction (XRD) refinement, X-ray photoelectron spectroscopy (XPS), transmission electron microscope (TEM), and X-ray absorption fine structure (XAFS) measurements verified the structure of LaFe0.85Ru0.15O3-δ. Kinetic data and density functional theory (DFT) proved that Fe is the site of acetic acid oxidation and adsorption of chloride ions. The existence of Fe in LaFe0.85Ru0.15O3-δ could adsorb chlorine ion (catalytic activity inhibitor), which can protect the Ru site and other active oxygen species to exert catalytic activity. This work is essential for the development of chloride-resistant catalyst in CWAO.

Aberrant brain network topology in the frontoparietal-limbic circuit in bipolar disorder: a graph-theory study.

Characterizing the properties of brain networks across mood states seen in bipolar disorder (BP) can provide a deeper insight into the mechanisms involved in this type of affective disorder. In this study, graph theoretical methods were used to examine global, modular and nodal brain network topology in the resting state using functional magnetic resonance imaging data acquired from 95 participants, including those with bipolar depression (BPD; n = 30) and bipolar mania (BPM; n = 39) and healthy control (HC) subjects (n = 26). The threshold value of the individual subjects' connectivity matrix varied from 0.15 to 0.30 with steps of 0.01. We found that: (1) at the global level, BP patients showed a significantly increased global efficiency and synchronization and a decreased path length; (2) at the nodal level, BP patients showed impaired nodal parameters, predominantly within the frontoparietal and limbic sub-network; (3) at the module level, BP patients were characterized by denser FCs (edges) between Module III (the front-parietal system) and Module V (limbic/paralimbic systems); (4) at the nodal level, the BPD and BPM groups showed state-specific differences in the orbital part of the left superior-frontal gyrus, right putamen, right parahippocampal gyrus and left fusiform gyrus. These results revealed abnormalities in topological organization in the whole brain, especially in the frontoparietal-limbic circuit in both BPD and BPM. These deficits may reflect the pathophysiological processes occurring in BP. In addition, state-specific regional nodal alterations in BP could potentially provide biomarkers of conversion across different mood states.

Biocontrol Potential of Trichoderma afroharzianum TM24 Against Grey Mould on Tomato Plants.

Grey mould caused by Botrytis cinerea leads to severe economic loss on commercial tomato production. Application of beneficial microorganism offers an eco-friendly alternative for mitigation of tomato fungal disease damage, considering negative influences of fungicides. In the present study, an antagonistic Trichoderma afroharzianum isolate TM24 was evaluated for its biocontrol potential on tomato grey mould. The isolate TM24 showed obviously antagonistic effect on B. cinerea mycelium growth and production of glucanase and chitinase. Leaf spraying with spore suspension of isolate TM24 showed a biocontrol efficiency of over 54% against tomato grey mould in greenhouse pot experiment. The activities of plant defense-related enzymes including polyphenol oxidase, phenylalanine ammonialyase, superoxide dismutase, and peroxidase were all increased to varying degrees in tomato leaves after isolate TM24 treatment. Transcriptome analysis showed that, a total of 1941, 1753 and 38 differentially expressed genes (DEGs) were obtained at 24, 48 and 72 hpi, respectively, in tomato leaves pretreated with T. afroharzianum TM24, and then challenged with B. cinerea inoculation. The DEGs were mainly enriched in MAPK signaling pathway and plant hormones signal transduction pathway. Multiple genes that regulated crucial nodes of defense-related pathways, like flavonoid, phenylpropanoid, jasmonic acid and ethylene metabolisms were also identified, which may have positive correlations with the biocontrol potential of isolate TM24 in tomato plants. These promising results provided valuable information on using T. afroharzianum TM24 as a beneficial biocontrol agent in tomato grey mould management.

Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid-Mediated Activation of G Protein-Coupled Receptors GPR43 and GPR109A.

BACKGROUND: Studies have reported "dysbiotic" changes to gut microbiota, such as depletion of gut bacteria that produce short-chain fatty acids (SCFAs) through gut fermentation of fiber, in CKD and diabetes. Dietary fiber is associated with decreased inflammation and mortality in CKD, and SCFAs have been proposed to mediate this effect. METHODS: To explore dietary fiber's effect on development of experimental diabetic nephropathy, we used streptozotocin to induce diabetes in wild-type C57BL/6 and knockout mice lacking the genes encoding G protein-coupled receptors GPR43 or GPR109A. Diabetic mice were randomized to high-fiber, normal chow, or zero-fiber diets, or SCFAs in drinking water. We used proton nuclear magnetic resonance spectroscopy for metabolic profiling and 16S ribosomal RNA sequencing to assess the gut microbiome. RESULTS: Diabetic mice fed a high-fiber diet were significantly less likely to develop diabetic nephropathy, exhibiting less albuminuria, glomerular hypertrophy, podocyte injury, and interstitial fibrosis compared with diabetic controls fed normal chow or a zero-fiber diet. Fiber beneficially reshaped gut microbial ecology and improved dysbiosis, promoting expansion of SCFA-producing bacteria of the genera Prevotella and Bifidobacterium, which increased fecal and systemic SCFA concentrations. Fiber reduced expression of genes encoding inflammatory cytokines, chemokines, and fibrosis-promoting proteins in diabetic kidneys. SCFA-treated diabetic mice were protected from nephropathy, but not in the absence of GPR43 or GPR109A. In vitro, SCFAs modulated inflammation in renal tubular cells and podocytes under hyperglycemic conditions. CONCLUSIONS: Dietary fiber protects against diabetic nephropathy through modulation of the gut microbiota, enrichment of SCFA-producing bacteria, and increased SCFA production. GPR43 and GPR109A are critical to SCFA-mediated protection against this condition. Interventions targeting the gut microbiota warrant further investigation as a novel renoprotective therapy in diabetic nephropathy.

Gut Microbial Metabolites Induce Donor-Specific Tolerance of Kidney Allografts through Induction of T Regulatory Cells by Short-Chain Fatty Acids.

BACKGROUND: Short-chain fatty acids derived from gut microbial fermentation of dietary fiber have been shown to suppress autoimmunity through mechanisms that include enhanced regulation by T regulatory cells (Tregs). METHODS: Using a murine kidney transplantation model, we examined the effects on alloimmunity of a high-fiber diet or supplementation with the short-chain fatty acid acetate. Kidney transplants were performed from BALB/c(H2d) to B6(H2b) mice as allografts in wild-type and recipient mice lacking the G protein-coupled receptor GPR43 (the metabolite-sensing receptor of acetate). Allograft mice received normal chow, a high-fiber diet, or normal chow supplemented with sodium acetate. We assessed rejection at days 14 (acute) and 100 (chronic), and used 16S rRNA sequencing to determine gut microbiota composition pretransplantation and post-transplantation. RESULTS: Wild-type mice fed normal chow exhibited dysbiosis after receiving a kidney allograft but not an isograft, despite the avoidance of antibiotics and immunosuppression for the latter. A high-fiber diet prevented dysbiosis in allograft recipients, who demonstrated prolonged survival and reduced evidence of rejection compared with mice fed normal chow. Allograft mice receiving supplemental sodium acetate exhibited similar protection from rejection, and subsequently demonstrated donor-specific tolerance. Depletion of CD25+ Tregs or absence of the short-chain fatty acid receptor GPR43 abolished this survival advantage. CONCLUSIONS: Manipulation of the microbiome by a high-fiber diet or supplementation with sodium acetate modified alloimmunity in a kidney transplant model, generating tolerance dependent on Tregs and GPR43. Diet-based therapy to induce changes in the gut microbiome can alter systemic alloimmunity in mice, in part through the production of short-chain fatty acids leading to Treg cell development, and merits study as a potential clinical strategy to facilitate transplant acceptance.

First Report of Anthracnose Caused by Colletotrichum siamense and C. fructicola of Camellia chrysantha in China.

Camellia chrysantha (Hu) Tuyama, belonging to the Theaceae family, is famous for its large size and golden yellow flowers, which has high ornamental and health care functions (Mo et al. 2013). Anthracnose is one of the most important fungal diseases worldwide, causing serious economic losses to many plants. In October 2019, severe anthracnose symptoms were observed on the leaves of C. chrysantha in a 0.6 hectare field with 15-20% disease incidence in Fangchenggang city, Guangxi Zhuang Autonomous Region of China. Diseased leaves initially appeared irregular chlorotic spots, which afterwards enlarged and coalesced. Finally, the spots became dark brown or black, sunken lesions (8-22 mm in diameter), and covered with plenty of acervuli. For pathogen isolation, the leaf lesions were cut into small tissue pieces (5 mm×5 mm), disinfected by 0.3% sodium hypochlorite for 2 min and 70% ethanol for 40 s, rinsed in sterile distilled water, and then incubated at 28°C on potato dextrose agar (PDA) plates. A total of 7 fungal isolates with whitish to light grey, dense colonies were recovered at 5 days. These isolates were tentatively identified as belonging to Colletotrichum gloeosporioides species complex through morphological and cultural characters (Weir et al. 2012). The conidia were nonseptate, cylindrical with obtuse to rounded ends, 13.9 to 18.3 (average 16.1) µm × 4.5 to 6.2 (average 5.4) µm (n = 50). For further precise identification, the 7 Colletotrichum isolates were analyzed using partial sequences of genomic loci including the internal transcribed spacer (ITS), ß-tubulin (TUB), calmodulin (CAL), actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glutamine synthetase (GS), and the mating type locus MAT1-2 (ApMat) genes (Liu et al. 2015). The amplification sequences were compared with the sequences registered in the GenBank database based on nucleotide similarity. The above sequences of 4 isolates (JZB-PF4232, JZB-PF2231, JZB-PF42 and JZB-PF22) had 99-100% identity to the sequences of Colletotrichum siamense strains retrieved from GenBank, while the sequences of the other 3 isolates (JZB-PF3231, JZB-PF32 and JZB-PF41) showed over 99% identity with those of the C. fructicola strains. All the sequences were deposited in GenBank with accession number MT708987 to MT709007, MW149430 to MW149433, and MW142259 to MW142282. A multi-loci phylogenetic analysis of the concatenated sequences of ITS, TUB, CAL, ACT, GAPDH, GS and ApMat genes placed the 4 isolates described above in the C. siamense clade, while the other 3 isolates was attribute to the C. fructicola clade. Pathogenicity tests were conducted on 7 healthy 2-year-old C. chrysantha seedlings (cv. Fangpu), consisted of 21 wounded leaves made by a sterile needle, with 3 leaves per seedling. Artificial inoculations were performed by treating each seedling with 20 µl of spore suspension (106 conidia/ml) of each isolate. Leaves of seedlings treated with sterilized water under the same conditions served as controls. The experiment was repeated three times. All the seedlings were covered with plastic bags to maintain high humidity (90% RH) and placed in a greenhouse kept at 25°C with a 16 h light / 8 h dark photoperiod. After 8 days, the inoculated leaves of C. chrysantha plants developed typical dark brown or black lesions, similar to the symptoms in the field, whereas controls remained symptomless. Koch's postulates were fulfilled by re-isolation of the same fungi from symptomatic inoculated leaves, identification confirmed by morphological and molecular characteristics, respectively. C. siamense and C. fructicola have been found to cause anthracnose on Camellia sinensis (Wang et al. 2016; Shi et al. 2018). C. fructicola has also been reported to cause anthracnose on Citrus sinensis in China (Hu et al. 2019). To our knowledge, this is the first report of C. siamense and C. fructicola causing anthracnose on C. chrysantha in China.

Efficient removal of acetic acid by a regenerable resin-based spherical activated carbon.

Carboxylic acids are the main pollutant of industrial wastewater during the advanced oxidation process (AOPs). In this study, a resin-based spherical activated carbon (RSAC, AF5) as an adsorbent was examined and acetic acid was used as a model substrate for adsorption investigation. The pH = 3, temperature = 298 K were fixed by batch technique. The pseudo-second-order kinetic model, the intraparticle and external models are fitted well, and it was found that the adsorption of acetic acid onto AF5 was controlled by liquid film diffusion. A Freundlich model indicated that the adsorption process was heterogeneous multimolecular layer adsorption on the surface. AF5 shows good regenerative ability; the recovery rate of adsorption capacity was ∼88% after five cycles. Chemical oxygen demand (COD) adsorption removal rate could be maintained at 100% for over 35 h in an actual AOPs effluent, and could be eluted for 100% after 8 h by 0.8wt% NaOH. Characterizations, including XRF, XRD, TG/DSC,FTIR, SEM and N2 adsorption, showed that the excellent adsorption performance was mainly due to the microporous structure and large specific surface area (1,512.88 m2/g), the adsorption mechanism mainly included pore filling effect and electrostatic attraction. After five adsorption recycles, AF5's pore characteristic did not change significantly. This study provides a scientific basis for the wastewater standard discharge process of AOPs coupled adsorption.

Deep learning-based pancreas segmentation and station recognition system in EUS: development and validation of a useful training tool (with video).

BACKGROUND AND AIMS: EUS is considered one of the most sensitive modalities for pancreatic cancer detection, but it is highly operator-dependent and the learning curve is steep. In this study, we constructed a system named BP MASTER (pancreaticobiliary master) for EUS training and quality control. METHODS: The standard procedure of pancreatic EUS was divided into 6 stations. We developed a station classification model and a pancreas/abdominal aorta/portal confluence segmentation model with 19,486 images and 2207 images, respectively. Then, we used 1920 images and 700 images for classification and segmentation internal validation, respectively. To test station recognition we used 396 videos clips. An independent data set containing 180 images was applied for comparing the performance between models and EUS experts. Seven hundred sixty-eight images from 2 other hospitals were used for external validation. A crossover study was conducted to test the system effect on reducing difficulty in ultrasonographics interpretation among trainees. RESULTS: The models achieved 94.2% accuracy in station classification and .836 dice in segmentation at internal validation. At external validation, the models achieved 82.4% accuracy in station classification and .715 dice in segmentation. For the video test, the station classification model achieved a per-frame accuracy of 86.2%. Compared with EUS experts, the models achieved 90.0% accuracy in classification and .77 and .813 dice in blood vessel and pancreas segmentation, which is comparable with that of experts. In the crossover study, trainee station recognition accuracy improved from 67.2% to 78.4% (95% confidence interval, .058-1.663; P < .01). CONCLUSIONS: The BP MASTER system has the potential to play an important role in shortening the pancreatic EUS learning curve and improving EUS quality control in the future.