CaSTH2 disables CaWRKY40 from activating pepper thermotolerance and immunity against Ralstonia solanacearum via physical interaction.

CaWRKY40 coordinately activates pepper immunity against Ralstonia solanacearum infection (RSI) and high temperature stress (HTS), forms positive feedback loops with other positive regulators and is promoted by CaWRKY27b/CaWRKY28 through physical interactions; however, whether and how it is regulated by negative regulators to function appropriately remain unclear. Herein, we provide evidence that CaWRKY40 is repressed by a SALT TOLERANCE HOMOLOG2 in pepper (CaSTH2). Our data from gene silencing and transient overexpression in pepper and epoptic overexpression in Nicotiana benthamiana plants showed that CaSTH2 acted as negative regulator in immunity against RSI and thermotolerance. Our data from BiFC, CoIP, pull down, and MST indicate that CaSTH2 interacted with CaWRKY40, by which CaWRKY40 was prevented from activating immunity or thermotolerance-related genes. It was also found that CaSTH2 repressed CaWRKY40 at least partially through blocking interaction of CaWRKY40 with CaWRKY27b/CaWRKY28, but not through directly repressing binding of CaWRKY40 to its target genes. The results of study provide new insight into the mechanisms underlying the coordination of pepper immunity and thermotolerance.

Open reduction after failed closed reduction following failed Pavlik harness treatment in developmental dysplasia of the hip: One- or two-stage?

INTRODUCTION: The current published evidence for the treatment of developmental dysplasia of the hip (DDH) with failed closed reduction (CR) following failed Pavlik harness (PH) treatment is still limited. This study aimed to determine whether an one-stage open reduction (OR) would lead to a similar outcome to a two-stage OR in these patients. Meanwhile, the occurrence of femoral head avascular necrosis (AVN) and further surgery (pelvic osteotomy, PO) within the follow-up period was investigated. MATERIALS AND METHODS: A consecutive series of DDH patients who failed CR following failed PH treatment and received OR finally between January 2008 and December 2020 were studied. The patients were divided into two groups. One group of which received OR immediately after failed CR (one-stage OR group, Group A), and the other received a delayed OR (two-stage OR group, Group B). The McKay's criteria, acetabular index (AI) and the degree of dislocation of the hips were evaluated for the final outcomes. RESULTS: At the last follow-up, 54 (84.4%) of the 64 hips in Group A and 26 (83.9%) of 31 hips in Group B were in excellent or good condition. Comparison between the two groups revealed that there were no differences in terms of McKay grading (P = 0.950), AI (P = 0.783), incidence of AVN (P = 0.745), and also incidence of PO (P = 1.000). However, a significant lower mean AI was found in Group A, when the OR was performed in Group B (31.06 ± 4.45° vs. 33.87 ± 4.12°, P = 0.004). CONCLUSION: Both of the one- and two-stage OR may acheive favorable outcomes. Moreover, one-stage OR is of without the general anesthesia risk associated with two-stage OR. We therefore advocate that an OR should be performed in appropriate DDH patients during the same session once a failed CR is detected.

MADS-box protein AGL8 interacts with chromatin-remodelling component SWC4 to activate thermotolerance and environment-dependent immunity in pepper.

Pepper (Capsicum annuum) employs distinct defence responses against Ralstonia solanacearum infection (RSI); however, the mechanisms by which pepper activates these defence responses in a context-dependent manner is unclear. Here we study pepper plants defence response to RSI under room temperature-high humidity (RSRT, 28 °C / 90%) and high temperature-high humidity (RSHT, 37 °C / 90%) conditions, and non-infected plants under high temperature-high humidity (HTHH, 42 °C / 90%) stress. Herein, we found that the MADS-box transcription factor CaAGL8 was up-regulated by HTHH stress and RSRT or RSHT, and its silencing significantly reduced pepper thermotolerance and susceptibility to infection under both room and high temperature-high humidity (RSRT and RSHT). This was coupled with down-regulation of CaSTH2 and CaDEF1 upon RSRT, down-regulation of CaMgst3 and CaPRP1 upon RSHT, and down-regulation of CaHSP24 upon HTHH. In contrast, the ectopic overexpression of CaAGL8 significantly increased the resistance of Nicotiana benthamiana plants to RSRT, RSHT, and HTHH. In addition, CaAGL8 was found to interact with CaSWC4, which acted as a positive regulator of the pepper response to RSRT, RSHT, and HTHH. Silencing of either CaAGL8 or CaSWC4 blocked the hypersensitive response (HR) cell death and context-dependent up-regulation of defence-related genes triggered by the other. Importantly, enrichment of H4K5Ac, H3K9Ac, H3K4me3, and H3K9me2 on the tested defence-related genes was context- and gene-specifically regulated through synergistic interaction between CaSWC4 and CaAGL8. Our results indicate that pepper employs CaAGL8 to modulate chromatin remodelling by interacting with CaSWC4, thereby activating defence responses to RSRT, RSHT, and HTHH.

The identification and preliminary study of lncRNA TUG1 and its related genes in hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is a common malignant tumour of the digestive system, which is a threat to public health. The purpose of this study was to investigate the featured genes and pathways of HCC from a bioinformatics database, and verify their correlation with diagnosis and prognosis of HCC. Material and methods: We downloaded the gene expression profile on HCC from the Gene Expression Omnibus (GEO), and software R was used to identify differentially expressed lncRNA (DEL). The target genes of the lncRNA were further predicted by using a cluster database and molecular interaction database. Subsequently, a combined interaction network of target genes was constructed using the Cytoscape platform with preliminary verification at the level of different databases, cell lines, and tissues. Finally, we explored the effectiveness of TUG1 and its target genes on the diagnosis and prognosis of HCC by univariate Cox analysis and survival analysis. Results: A total of four DELs were identified and the most remarkably up-regulated lncRNA was TUG1, which included 12 high-confidence target genes. Moreover, we found that the expression changes of TUG1 and its target genes in different databases, cell lines, and liver cancer tissues were consistent with the prediction. The high expression of TUG1 and its target genes could significantly predict the shorter survival time of HCC patients, among which NCAPG, MCM6, PIGC, PEA15, and RACGAP1 have significant diagnostic value for HCC (AUC > 0.9). Conclusions: This study provides a starting point for the screening of therapeutically relevant targets in HCC. Further experiment should be conducted to verify our findings.

Impact of Failed Pavlik Harness Treatment on the Outcomes Following Closed or Open Reduction in Developmental Dysplasia of the Hip.

Purpose: To investigate the impact of failed Pavlik harness (PH) treatment on the outcomes following closed reduction (CR) or open reduction (OR) in developmental dysplasia of the hip (DDH). Methods: Ninety-three DDH patients treated with CR or OR were enrolled. One group of which received previous PH treatment (F group) and the other (L group) not. The clinical outcomes were evaluated according to McKay's criteria. Radiographs were evaluated for acetabular index (AI) and the degree of dislocation of the hips. Results: A higher rate of CR was found in F group (P = 0.034). Before CR/OR, the mean AI in F group was significantly lower than that in L group (P = 0.000), while at the last follow-up, the AIs in both groups were all improved. In F group, there were 7 (16.67%), 18 (42.86%) and 17 (40.48%) hips were classified as Graf type II, III and IV pathologic changes, respectively, when PH treatment started, while the corresponding data were 17 (40.48%), 17 (40.48%) and 8 (19.05%) after PH treatment (P = 0.024). At the last follow-up, no significant difference was found concerning the complications between the two groups (P > 0.05). Conclusions: PH treatment, even if failed, may have the ability of accelerating the development of the acetabulum and increasing the rate of successful CR. Thus we advocate a trial of PH treatment for all DDH patients less than 6 months of age. Meanwhile, a close monitoring by dynamic ultrasonography is required due to the risk of AVN.

[RBM38 Mediates the Proliferation of Acute Myeloid Leukemia Cells HL-60 by Regulating FZD1 mRNA Stability].

OBJECTIVE: To explore the regulatory function of RNA binding motif protein 38 (RBM38) in human acute myeloid leukemia cells HL-60 and its mechanism. METHODS: The lentivirus carriers of overexpressed and knockdown RBM38 were constructed. After HL-60 cells were transfected, Western blot was used to analyze the expression level of RBM38 in HL-60 cells. The cell proliferation and cycle of HL-60 were detected by CCK-8 assay and flow cytometry assay, respectively. RNA immunoprecipitation coupled real-time PCR (RIP-qPCR) was used to detect the combination of RBM38 with mRNAs. Actinomycin D treatment followed by real-time PCR (AcD-qPCR) was used to detect the effect of RBM38 on the stability of target mRNAs. RESULTS: RBM38 in HL-60 cells was overexpressed or inhibited by lentivirus transduction. Overexpressed RBM38 promoted the cell cycle and proliferation of HL-60, while RBM38 knockdown repressed the two processes. RBM38 showed an interaction with FZD1 mRNA and enhancement of its stability. CONCLUSION: RBM38 can regulate cell proliferation of HL-60 by improving the stability of FZD1 mRNA.

Iron metabolism in Pseudomonas aeruginosa biofilm and the involved iron-targeted anti-biofilm strategies.

Pseudomonas aeruginosa is a gram-negative bacterium that exists in various ecosystems, causing severe infections in patients with AIDS or cystic fibrosis. P. aeruginosa can form biofilm on a variety of surfaces, whereby the bacteria produce defensive substances and enhance antibiotic-resistance, making themselves more adaptable to hostile environments. P. aeruginosa resistance represents one of the main causes of infection-related morbidity and mortality at a global level. Iron is required for the growth of P. aeruginosa biofilm. This review summarises how the iron metabolism contributes to develop biofilm, and more importantly, it may provide some references for the clinic to achieve novel anti-biofilm therapeutics by targeting iron activities.

Iron oxide magnetic nanoparticles based low-field MR thermometry.

This paper reports on a highly accurate approach of magnetic resonance (MR) thermometry using iron oxide magnetic nanoparticles (MNPs) as temperature sensors. An empirical model for the description of the temperature dependent R 2 relaxation rate is proposed by taking into account the temperature sensitivity of the MNP magnetization. The temperature sensitivity of the MNP magnetization (η) and the temperature sensitivity of the R 2 relaxation rate (κ) are simulated with the proposed empirical models to investigate their dependence on the magnetic field and the particle size. Simulation results show the existence of optimal magnetic fields Hoη and Hoκ that maximize the temperature sensitivities η and κ. Furthermore, simulations and experiments demonstrate that the optimal magnetic field Hoη (Hoκ ) decreases with increasing the particle size. Experiments on temperature dependent R 2 relaxation rate are performed at different magnetic fields for MNP samples with different iron concentrations. Experimental results show that the proposed MR thermometry using MNPs as temperature sensors allows a temperature estimation accuracy of about 0.05 °C. We believe that the achieved approach of highly accurate MR thermometry is of great interest and significance to biomedicine and biology.

Evidence Base of Clinical Studies on Qi Gong: A Bibliometric Analysis.

OBJECTIVE: This bibliometric study aimed to systematically and comprehensively summarize the volume, breadth and evidence for clinical research on Qigong. And this bibliometric analysis also can provide the evidence of this field. DESIGN: Bibliometric analysis. METHODS: All types of primary and secondary studies on humans were included: systematic reviews, randomized clinical trials, non-randomized controlled clinical studies, case series and case reports. Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Chinese Academic Conference Papers Database and Chinese Dissertation Database, PubMed and the Cochrane Library were searched from the date of inception to December 10, 2018. Bibliometric information, such as publication information, disease/condition, Qigong intervention and research results were extracted and analyzed. RESULTS: A total of 886 clinical studies were identified: including 47 systematic reviews, 705 randomized clinical trials, 116 non-randomized controlled clinical studies, 12 case series and 6 case reports. The studies were conducted in 14 countries. The top 15 diseases/conditions studied were: diabetes, chronic obstructive pulmonary disease, hypertension, stroke, cervical spondylosis, lumbar disc herniation, insomnia, knee osteoarthritis, low back pain, and osteoporosis, Coronary heart disease, breast cancer, periarthritis of shoulder, depression, metabolic syndrome. Of the various Qigong exercises reported in these 886 clinical studies, Ba Duan Jin was the most frequently researched in 492 (55.5%) studies, followed by Health Qigong 107 (12.1%), Dao Yin Shu 85 (9.6%), Wu Qin Xi 67 (7.6%) and Yi Jin Jing 66 (7.4%). The most frequently used comparisons in randomized trials were maintaining normal way of life unchanged 149 (18.1%), the remaining controls included conventional treatment, mainly western medicine, Chinese herbal medicine, acupuncture, health education, psychological therapy, Yoga, Tai Chi and other non-drug therapy. The most frequently reported outcomes were physical function, quality of life, symptoms, pain and mental health indicators. Beneficial results from practicing Qigong were reported in 97% of studies. CONCLUSIONS: Qigong research publications have been increasing gradually. Reports on study types, participants, Qigong Intervention, and outcomes are diverse and inconsistent. There is an urgent need to develop a set of reporting standards for various interventions of Qigong. Further trials of high methodological quality with sufficient sample size and real world studies are needed to verify the effects of Qigong in health and disease management.

Diagnosing chronic atrophic gastritis by gastroscopy using artificial intelligence.

BACKGROUND: The sensitivity of endoscopy in diagnosing chronic atrophic gastritis is only 42%, and multipoint biopsy, despite being more accurate, is not always available. AIMS: This study aimed to construct a convolutional neural network to improve the diagnostic rate of chronic atrophic gastritis. METHODS: We collected 5470 images of the gastric antrums of 1699 patients and labeled them with their pathological findings. Of these, 3042 images depicted atrophic gastritis and 2428 did not. We designed and trained a convolutional neural network-chronic atrophic gastritis model to diagnose atrophic gastritis accurately, verified by five-fold cross-validation. Moreover, the diagnoses of the deep learning model were compared with those of three experts. RESULTS: The diagnostic accuracy, sensitivity, and specificity of the convolutional neural network-chronic atrophic gastritis model in diagnosing atrophic gastritis were 0.942, 0.945, and 0.940, respectively, which were higher than those of the experts. The detection rates of mild, moderate, and severe atrophic gastritis were 93%, 95%, and 99%, respectively. CONCLUSION: Chronic atrophic gastritis could be diagnosed by gastroscopic images using the convolutional neural network-chronic atrophic gastritis model. This may greatly reduce the burden on endoscopy physicians, simplify diagnostic routines, and reduce costs for doctors and patients.

The Potential Effects and Use of Chinese Herbal Medicine Pine Pollen (Pinus pollen): A Bibliometric Analysis of Pharmacological and Clinical Studies.

The objectives of this study are to conduct a comprehensive literature search and bibliometric analysis to identify the breadth and volume of pharmacological and clinical studies on pine pollen (Pinus pollen) and to identify the potential effects and the use of pine pollen. Three Chinese electronic databases and two English electronic databases were searched for pharmacological and clinical studies on pine pollen. Data were extracted and analyzed and included publication year, authors, study type, pharmacological research topics or clinical diseases/conditions, usage and type of preparation, authors' conclusions, and adverse effects. Of 239 publications identified, 180 were pharmacological studies, 37 were clinical trials, and 22 were reviews. Numbers of publications increased particularly from 2004 onward. The top 10 most frequent topics in pharmacological studies were immune regulation, antisenility, antioxidation, liver protection, inhibiting prostate hyperplasia, inhibiting tumor cell proliferation, lowering blood glucose, lowering blood lipids, antifatigue, and improving intestinal function. The top 10 most frequent clinical diseases treated or where pine pollen was used as an adjuvant were bedsores, diaper dermatitis, hyperlipidemia, oral mucositis, eczema, hyperplasia of prostate, hypertension, prostatitis, type 2 diabetes mellitus, and radiodermatitis. Eight trials reported no adverse events associated with pine pollen, one reported mild gastrointestinal reactions, but symptoms disappeared without special management. There have been an increasing number of publications on pine pollen during the past 20 years. Pharmacological studies have shown many potential benefits, and clinical studies have indicated some positive effects when it is either used as a single herb or as an adjuvant to treat disease. Its use as a topical agent, especially for skin diseases, was notable.

The mechanism study of miR-125b in occurrence and progression of multiple myeloma.

Although many efforts have contributed to improve our knowledge of molecular pathogenesis about multiple myeloma (MM), the role and significance of microRNAs and long noncoding RNAs in MM cells, along with the core mechanism remains virtually absent. The mRNA levels of miR-125b and MALAT1 in MM cell lines were detected by qRT-PCR. The influence of Lenti-Sh-miR-125b on cell viability and the Notch-1 pathway-related proteins were assessed by MTT method and western blot, respectively. We also investigated the regulation effect between MALAT1 and Notch1 pathway. Moreover, the connection between Notch1 signaling and MM cell growth was discussed in-depth. The reverse effect of pcDNA-Notch1 on the cell viability and Notch-1 pathway proteins induced by Si-MALAT1 was also studied. Furthermore, miR-125b overexpressing MM cell lines were injected subcutaneously into nude mice. MiR-125b and MALAT1 were inversely expressed in MM cell lines. Lenti-Sh-miR-125b inhibited the expression of MALAT1 and Notch-1 protein. Binding sites were confirmed between miR-125b and MALAT1, and silencing MALAT1 did not alter the expression of Notch-1. The apoptosis rate was increased and the survival rate was decreased obviously in GSI XII (targeted cleavage of Notch-1 receptor) group, along with the inhibited Notch1 and HES1 proteins. Moreover, the decreased cell viability and Notch-1 pathway proteins induced by Si-MALAT1 could be reversed by pcDNA-Notch1. Lenti-Sh-miR-125b promoted survival and decreased Notch1 and HES1 proteins levels, while this effect was reversed by si -MALAT1. MiR-125b regulated MALAT1 expression via Notch1 signaling pathway to regulate cell growth, thus participating in the occurrence and progression of MM, which functioned as a therapeutic target for tracking MM.

LncRNA MALAT-1 Elevates HMGB1 to Promote Autophagy Resulting in Inhibition of Tumor Cell Apoptosis in Multiple Myeloma.

Long non-coding RNAs (lncRNAs) can participate in the pathological process of multiple myeloma (MM) via regulation of specific gene expression and function. This research aimed to study the role of MALAT-1 and the underlying mechanism in MM. In this study, the expression of MALAT-1 and HMGB1 protein in the bone marrow mononuclear cells from MM patients at different stages and in MM cell lines was determined by qRT-PCR and western blot, respectively. The endogenous expression of MALAT-1 and HMGB1 was modulated using lentivirus vectors transfection. CHX chase assay and RIP analyses were performed to explore the interaction between MALAT-1 and HMGB1 in MM. Nude mouse xenograft was made and used for in vivo experiment study. The expression of MALAT-1 and HMGB1 in the bone marrow mononuclear cells from patients with untreated multiple myeloma was dramatically increased, as well as in MM cell lines, KM3 and U266; while MALAT-1 expression and HMGB1 protein level both decreased significantly in complete remission patients. Furthermore, MALAT-1 knockdown facilitated the degradation of HMGB1 at the post-translational level via increase of the ubiquitination of HMGB1 in MM cells. MALAT-1 was shown to promote autophagy in MM through upregulation of HMGB1. In vivo, MALAT-1 knockdown could inhibit tumor growth significantly in tumor-bearing mice and reduced the protein expressions of HMGB1, Beclin-1, and LC3B in tumor tissues. LncRNA MALAT-1 increases the expression level of HMGB1 in MM thereby promotes autophagy resulting in the inhibition of apoptosis. J. Cell. Biochem. 118: 3341-3348, 2017. © 2017 Wiley Periodicals, Inc.

2-Hydroxydiplopterol, a new cytotoxic pentacyclic triterpenoid from the halotolerant fungus Aspergillus variecolor B-17.

A new hopane type pentacyclic triterpenoid, 2-hydroxydiplopterol (1) has been isolated from the metabolites produced by the halotolerant fungal strain Aspergillus variecolor B-17. The structure of 1 was determined by spectroscopic methods and single crystal X-Ray diffraction analysis. 2-Hydroxydiplopterol (1) exhibited cytotoxicity against K562 cells with an IC50 value of 22 microM.

Carbonarones A and B, new bioactive gamma-Pyrone and alpha-Pyridone derivatives from the marine-derived fungus Aspergillus carbonarius.

Two new secondary metabolites, carbonarones A (1) and B (2), were obtained from the culture of the marine-derived fungus Aspergillus carbonarius isolated from the marine sediment collected at Weizhou island of China. Based on ESIMS, 1D and 2D NMR data, and the X-ray crystallographic analysis, their structures were elucidated as 6-benzyl-4-oxo-4H-pyran-3-carboxamide and 6-benzyl-4-hydroxy-2-oxo-1, 2-dihydropyridine-3-carbaldehyde, respectively. 1 and 2 showed moderate cytotoxicity against K562 cells with IC(50) values of 56.0 and 27.8 mug/ml, respectively.

A new diphenyl ether from marine-derived fungus Aspergillus sp. B-F-2.

A new diphenyl ether dimethyl 2,3'-dimethylosoate (1) together with three known compounds monomethylsulochrin (2), emodin (3), and questin (4) were isolated through bioassay-guided fractionations from the culture of a marine-derived fungus Aspergillus sp. B-F-2. The structures of these compounds were determined by spectroscopic methods. Cytotoxicities of compounds 1 and 2 against K562 cell line were preliminarily evaluated by the MTT method and flow cytometry.