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Figure S1: Experimental design, Figure S2: LyzM-Cre-mediated RBPj cKO suppressed the growth of subcutaneous LLC tumors, Figure S3: LyzM-Cre-mediated RBPj cKO promoted the growth of orthotopic HCC tumors, Figure S4: kclTAMs dominated TAM populations promoting HCC growth, Figure S5: RBPj cKO led to increased proliferation of kclTAMs without influencing apoptosis in hepatic Hepa1-6 tumors, Figure S6: RBPj cKO did not affect the proliferation capacity of monocytes in vitro, Figure S7: RBPj cKO promoted the growth of hepatic Hepa1-6 tumors independent of CCR2,Figure S8: Notch signaling negatively regulated the activation of Wnt/β-catenin signaling and the proliferation of kclTAMs, Figure S9: Blocking Wnt signaling inhibited the growth of hepatic Hepa1-6 tumors, Figure S10: Knockdown of β-catenin repressed the proliferation of RBPj-deficient KCs, Figure S11: RBPj cKO promoted kclTAM proliferation and hepatic tumor growth through β-catenin-dependent Wnt signaling, Figure S12: RBPj cKO promoted the hepatic metastasis but suppressed lung metastasis, Figure S13: A model depicting the role of Notch signaling in TAM subsets regulating hepatic tumor growth and metastasis in liver, Table S1: Clinical data of 44 HCC patients involved in this study, Table S2: Antibodies used in this study, Table S3: Primers and oligonucleotides used in this study

Tumor-associated macrophages (TAM) play pivotal roles in tumor progression and metastasis, but the contribution and regulation of different macrophage populations remain unclear. Here we show that Notch signaling plays distinct roles in regulating different TAM subsets in hepatocellular carcinoma (HCC). Myeloid-specific NOTCH blockade by conditional disruption of recombination signal binding protein Jκ (RBPj cKO) significantly delayed the growth of subcutaneously inoculated Lewis lung carcinoma (LLC), but accelerated orthotopically inoculated hepatic Hepa1-6 tumors in mice. In contrast to subcutaneous LLC, RBPj cKO significantly increased the number of TAMs in hepatic Hepa1-6 tumors despite impeded differentiation of monocyte-derived TAMs (moTAM). The dominating TAMs in orthotopic HCC manifested properties of Kupffer cells (KC) and hence are tentatively named KC-like TAMs (kclTAM). The increased proliferation of RBPj cKO kclTAMs was maintained even in Ccr2−/− mice, in which moTAMs were genetically blocked. NOTCH signaling blockade accelerated proliferation of kclTAMs via enhanced β-catenin–dependent WNT signaling, which also downregulated IL12 and upregulated IL10 expression by kclTAMs likely through c-MYC. In addition, myeloid-specific RBPj cKO facilitated hepatic metastasis of colorectal cancer but suppressed lung metastasis in mice, suggesting that the phenotype of RBPj cKO in promoting tumor growth was liver-specific. In patient-derived HCC biopsies, NOTCH signaling negatively correlated with WNT activation in CD68+ macrophages, which positively correlated with advanced HCC stages. Therefore, NOTCH blockade impedes the differentiation of moTAMs, but upregulates Wnt/β-catenin signaling to promote the proliferation and protumor cytokine production of kclTAMs, facilitating HCC progression and hepatic metastasis of colorectal cancer.Significance:These findings highlight the role of NOTCH and WNT signaling in regulating TAMs in hepatocellular carcinoma.

Background/Objectives: Gut microbiota dysbiosis is a complication of acute pancreatitis (AP). However, the composition of the pancreatic and ileal microbiota and their relationship during acute pancreatitis remain unknown. Methods: AP was induced in mice using three modeling methods, Caerulein (CAE), Caerulein+lipopolysaccharide (CAE+LPS) and L-arginine (ARG). Pancreas and ileum were collected for histological study and bacterial 16S rRNA gene sequencing to investigate the changes in the pancreatic and ileal flora under different inductions and their relationships. Blood samples were tested for amylase, lipase, and inflammatory markers, and histological investigations were done to assess pancreatic and ileal pathological damage. Results: All three modeling techniques led to inflammation and AP and ileal damage. Rarefaction and Shannon indices revealed that the pancreas and ileum of AP mice had higher levels of microbial diversity. Principal coordinate analysis (PCoA) and non-metric multidimensional scaling (NMDS) analysis showed microbial structural segregation in both the AP and control groups in the pancreas and ileum. In the three AP groups, there was microbial structural segregation between the ARG and the two CAE groups (CAE, CAE+LPS). Taxonomic analysis at the genus level showed a significant increase in the relative abundance of Muribaculaceae and a decrease in the relative abundance of Dietzia in the pancreas and ileum of AP mice. The same finding was found for linear discriminant analysis of effect size (LEfSe) at the operational taxonomic unit (OTU) level. In addition, the pancreas and ileum of both CAE groups were enriched with Roseburia, whereas the pancreas of the ARG group was enriched with Escherichia-Shigella. The abundance of Muribaculaceae and Dietzia in the pancreas is associated with that in the ileum, according to Spearman correlation analysis of the pancreatic and ileal microbiota. Conclusions: These results showed that when AP was induced, caerulein and L-arginine differentially affected the pancreatic and ileal microbiota.

OBJECTIVE To investigate the potential therapeutic role of porous SiO2 -coated ultrasmall selenium particles nanospheres (Se@SiO2 nanospheres) pretreatment in acute pancreatitis (AP) and to investigate the related mechanism. METHODS C57BL/6 mice were randomized to the normal control (CON) group, the AP (induced by cerulein injection) (CAE) group, and AP pretreated with Se@SiO2 nanocomposites at 1 and 2 mg/kg (CAE + 1 or 2 mg/kg Se@SiO2 ) groups, respectively. Serum levels of amylase and lipase, inflammatory cytokines (interleukin [IL]-6, IL-1β and tumor necrosis factor [TNF]-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were measured, and histopathology was performed to examine the tissue samples of the pancreas, lungs, kidneys and liver. Immunofluorescence assay of reactive oxygen species (ROS), myeloperoxidase (MPO) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling were conducted, and levels of MPO, malondialdehyde, superoxide dismutase and glutathione were evaluated. Finally, Western blot analysis was used to evaluate protein expressions of Nrf2, HO-1, NQO1, TLR4, MyD88 and p-p65 in pancreatic tissue. RESULTS Se@SiO2 nanospheres alleviated pathological damage to the pancreas, and reduced pancreatic enzymes and inflammatory cytokines. Injury to other organs such as the liver, lungs and kidneys was also alleviated, as indicated by decreased ALT, AST, BUN, and Cr levels as well as improved histopathology. Moreover, Se@SiO2 nanospheres reduced oxidative stress, and ultimately inhibited TLR4/ MyD88/p-p65 pathway and increased the protein expressions of NQO1, Nrf2, and HO-1. CONCLUSION Se@SiO2 nanospheres may alleviate AP by relieving oxidative stress and targeting the TLR4/Myd88/p-p65 and NQO1/Nrf2/HO-1 pathways.

Based on molecular dynamic method, densities, mechanical behavior and mechanical performance of P(BAMO/ AMMO) (Polymer 1) and two novel modified P(BAMO/AMMO) (Polymer 2: containing amino group, Polymer 3: containing nitro group), and their effects on mechanical properties of four energetic materials are investigated, the main results are as follow: Polymer 2 (1.235 g/cm3, 240 ± 5 K) and Polymer 3: 1.281 g/cm3, 181 ± 3 K) possess higher densities and lower glass transition temperatures than Polymer 1 (1.229 g/cm3, 247 ± 4 K). The modification makes Polymer 1 difficult to expand, improves its mechanical properties, but has few effect on its diffusion coefficient at same temperature and state. In addition, three binders are compatible with TNT, HMX and CL-20, and may react with DNTF. All polymers particularly improve rigidity of four energetic materials, and enhance their ductility except Polymer 2 on TNT. The ability of Polymer 2 and Polymer 3 improving rigidity (except Polymer 3 on HMX) and ductility of TNT and HMX is inferior to that of Polymer 1, but it is contrary for CL-20 and DNTF (except Polymer 2 on rigidity of DNTF). Moreover, Polymer 2-based interfacial crystals exhibit higher rigidity than Polymer 3-based interfacial crystals.

One new meroterpenoid, antroquinonol Y (1), a new ergostane-type sterol, antcamphin Y (2), and a new ergostane-type triterpenoid, antcamphin Z (3), together with 10 known ones (4–13), were isolated...

Leukemia is a broad term for blood cell cancer. Leukemia is divided into acute or chronic, depending on cell differentiation. Leukemia patients are prone to adverse reactions during chemotherapy, such as anxiety, depression, and even suicide, affecting prognosis. As a nursing model developed by three well-known cognitive psychologists, empathetic nursing with mindfulness cognitive therapy (ENMCT) can effectively reduce anxiety and depression and improve the quality of life in patients with chronic disease.To explore the effect of ENMCT on cancer-induced fatigue, hope level, and negative emotions in patients with long-term leukemia chemotherapy.A total of 103 patients with long-term leukemia chemotherapy diagnosed and treated in our hospital from July 2017 to October 2019 were enrolled and randomly assigned to observation and control groups using the random number table approach. Fifty-one patients in the control group received routine nursing, while 52 patients in the observation group received empathic nursing with mindfulness cognitive therapy. After three months of nursing care, cancer-induced fatigue was measured with the Piper Fatigue Scale (PFS), hope level with the Herth Hope Index (HHI), and negative emotion with the Hamilton Anxiety Scale (HAMA)/Hamilton Depression Scale (HAMD). Self-management (Chinese Strategies Used by People to Promote Health) was also recorded.The observation group's total scores in behavior, cognition, emotion, feeling, and PFS were lower than the control group after the intervention (Empathetic nursing with cognitive mindfulness therapy is beneficial in improving cancer-related fatigue, negative emotions, expectation level, and self-management ability in patients with long-term leukemia chemotherapy.

Background Bone metastases are high prevalence in advanced prostate cancer and breast cancer patients, which have a serious impact on the quality of life and survival time of patients. Abnormal expression of microRNAs (miRNAs) has been reported in different types of cancer and metastasis. However, the underlying miRNAs associated with prostate and breast cancer bone metastasis remains unknown. Methods We performed bioinformatics analysis for TCGA cohort to identify differentially expressed miRNAs (DE-miRNAs) and their targets in the metastatic process. Results QPCR confirmed that miR-524-5p expression was down-regulated in prostate and breast cancer cell. And miR-524-5p over-expression restrained cell proliferation, invasion and metastasis ability in prostate and breast cancer. Meanwhile, miR-524-5p specifically targeting MEF2C was verified by luciferase assay. Conclusions In conclusion, our data strongly suggests down-regulation of miR-524-5p appears as a precocious event in prostate and breast cancer, and MEF2C emerges as a new player in prostate and breast cancer bone metastasis.

Nodular lymphoid hyperplasia (NLH) in the small intestine is a rare benign lesion characterized by multiple small nodules on the intestinal surface. Patients with terminal ileal NLH may experience long-term abdominal pain, diarrhea, and abdominal distension, among other symptoms. Supplementation with probiotics could mitigate these symptoms. NLH is linked to the immune system, and it may result from accumulation of plasma-cell precursors due to a maturational defect during the development of B lymphocytes. The intestinal microbiome plays an essential role in the immune system. Thus, we speculate that the gut flora plays a key role in terminal ileal NLH.To explore the correlation between intestinal flora and terminal ileal NLH.We collected mucosal biopsy samples that were obtainedCompared with the control group, the terminal ileal NLH group showed an increased alpha diversity (Maintaining the microbial balance and supplementing targeted protective bacteria could improve symptoms and potentially reduce the risk of lymphoma transformation in patients with terminal ileal NLH.

Tumor-associated macrophages (TAM) play pivotal roles in tumor progression and metastasis, but the contribution and regulation of different macrophage populations remain unclear. Here we show that Notch signaling plays distinct roles in regulating different TAM subsets in hepatocellular carcinoma (HCC). Myeloid-specific NOTCH blockade by conditional disruption of recombination signal binding protein Jκ (RBPj cKO) significantly delayed the growth of subcutaneously inoculated Lewis lung carcinoma (LLC), but accelerated orthotopically inoculated hepatic Hepa1-6 tumors in mice. In contrast to subcutaneous LLC, RBPj cKO significantly increased the number of TAMs in hepatic Hepa1-6 tumors despite impeded differentiation of monocyte-derived TAMs (moTAM). The dominating TAMs in orthotopic HCC manifested properties of Kupffer cells (KC) and hence are tentatively named KC-like TAMs (kclTAM). The increased proliferation of RBPj cKO kclTAMs was maintained even in Ccr2−/− mice, in which moTAMs were genetically blocked. NOTCH signaling blockade accelerated proliferation of kclTAMs via enhanced β-catenin–dependent WNT signaling, which also downregulated IL12 and upregulated IL10 expression by kclTAMs likely through c-MYC. In addition, myeloid-specific RBPj cKO facilitated hepatic metastasis of colorectal cancer but suppressed lung metastasis in mice, suggesting that the phenotype of RBPj cKO in promoting tumor growth was liver-specific. In patient-derived HCC biopsies, NOTCH signaling negatively correlated with WNT activation in CD68+ macrophages, which positively correlated with advanced HCC stages. Therefore, NOTCH blockade impedes the differentiation of moTAMs, but upregulates Wnt/β-catenin signaling to promote the proliferation and protumor cytokine production of kclTAMs, facilitating HCC progression and hepatic metastasis of colorectal cancer. Significance: These findings highlight the role of NOTCH and WNT signaling in regulating TAMs in hepatocellular carcinoma.

To investigate the potential therapeutic role of porous SiOC57BL/6 mice were randomized to the normal control (CON) group, the AP (induced by cerulein injection) (CAE) group, and AP pretreated with Se@SiOSe@SiOSe@SiO

One new meroterpenoid, antroquinonol Y (

Dynamic assessment has been recognized as a nonbiased approach to evaluating language learning potential among children who do not have equal access to the target language. However, it remains to be determined whether the graduated prompting approach of dynamic assessment is feasible in foreign language (FL) learning contexts as FL learners may not benefit from the small number of prompts administered in a single test session. The study explored the feasibility of a dynamic assessment of phonological awareness by examining its predictability of spelling performance in young FL learners and its potential to reveal learners’ modifiability in phonological awareness. Fourth-grade learners of English as a FL (N = 50) took two phonological awareness measures (dynamic and static) and two FL spelling tests (real words and pseudowords), along with a questionnaire of prior FL learning experience. Results showed that dynamic phonological awareness uniquely predicted performance in both spelling tests after controlling for static phonological awareness and FL learning experience. Performance on phonological awareness improved from the first to the second half of the dynamic measure but not in the static measure. These findings suggest that a dynamic measure holds promise for enhancing prediction of spelling performance and evaluating modifiability of phonological awareness in young FL learners.

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2+ macrophages infiltration. In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease. Electronic supplementary material The online version of this article (10.1007/s13238-018-0527-6) contains supplementary material, which is available to authorized users.

The high mortality rate of ovarian cancer is connected with the development of acquired resistance to multiple cancer drugs, especially cisplatin. Activation of cytoprotective autophagy has been implicated as a contributing mechanism for acquired cisplatin resistance in ovarian cancer cells. Hexokinase 2 (HK2) phosphorylates glucose to generate glucose-6-phosphate, the rate-limiting step in glycolysis. Higher HK2 expression has been associated with chemoresistance in ovarian cancer. However, whether HK2 functionally contributes to cisplatin resistance in ovarian cancer is unclear. In this study, we investigated the role of HK2 in regulating ovarian cancer cisplatin resistance. Increased HK2 levels were detected in drug-resistant human ovarian cancer cells and tissues. Cisplatin downregulated HK2 in cisplatin-sensitive but not in resistant ovarian cancer cells. HK2 knockdown sensitized resistant ovarian cancer cells to cisplatin-induced cell death and apoptosis. Conversely, HK2 overexpression in cisplatin-sensitive cells induced cisplatin resistance. Mechanistically, cisplatin increased ERK1/2 phosphorylation as well as autophagic activity. Blocking autophagy with the autophagy inhibitor 3-MA sensitized resistant ovarian cancer cells to cisplatin. HK2 overexpression enhanced cisplatin-induced ERK1/2 phosphorylation and autophagy while HK2 knockdown showed the opposite effects. Blocking the MEK/ERK pathway using the MEK inhibitor U0126 prevented cisplatin-induced autophagy enhanced by HK2 overexpression. Furthermore, HK2 knockdown sensitized resistance ovarian tumor xenografts to cisplatin in vivo. In conclusion, our data supported that HK2 promotes cisplatin resistance in ovarian cancer by enhancing drug-induced, ERK-mediated autophagy. Therefore, targeting HK2 may be a new therapeutic strategy to combat chemoresistance in ovarian cancer.

Turmeric (Curcuma longa L.) is a popular herbal medicine worldwide. Curcuminoids and volatile constituents are its major bioactive components. To improve the quality control of turmeric, we determined the contents of three main curcuminoids in 160 batches of turmeric samples collected from five major production areas of China by HPLC, and analyzed the volatile components by GC/MS. The results indicated that samples with red cross sections (2.75 ± 0.82 mg/g) contained significantly higher amounts of curcuminoids than samples with yellow sections (1.23 ± 0.60 mg/g) (p 0.001). This result was consistent with empirical standard of TCM pharmacists. The contents of curcuminoids in samples from Hainan (4.51±0.25%), Guizhou (3.17±0.41%), and Sichuan (2.25±0.54%) were relatively high and consistent. Moreover, the GC/MS profiles of turmeric may be affected by storage and processing. This study sets a good example for comprehensive quality control of herbal medicines.

We construct a self-directed replication system for label-free and real-time sensing of repair glycosylases with zero background., Genomic DNA damage and repair are involved in multiple fundamental biological processes, including metabolism, disease, and aging. Inspired by the natural repair mechanism in vivo, we demonstrate for the first time the construction of a self-directed replication system for label-free and real-time sensing of repair glycosylases with zero background. The presence of DNA glycosylase can catalyze the excision repair of the damaged base, successively autostarting the self-directed replication through recycling polymerization extension and strand-displacement DNA synthesis for the generation of exponentially amplified dsDNAs. The resultant dsDNA products can be label-free and real-time monitored with SYBR Green I as the fluorescent indicator. Owing to the high efficiency of self-directed exponential replication and the absolute zero background resulting from the efficient inhibition of nonspecific amplification induced by multiple primer-dependent amplification, this strategy exhibits high sensitivity with a detection limit of 1 × 10–8 U μL–1in vitro and 1 cell in vivo, and it can be further used to screen inhibitors, quantify DNA glycosylase from diverse cancer cells, and even monitor various repair enzymes by simply changing the specific damaged base in the DNA template. Importantly, this assay can be performed in a label-free, real-time and isothermal manner with the involvement of only a single type of polymerase, providing a simple, robust and universal platform for repair enzyme-related biomedical research and clinical therapeutics.

The present work aimed to investigate the role of Paneth cells in small intestinal injury during acute necrotizing pancreatitis (ANP) using rat models established by injection of dithizone, a metal chelator of zinc with the ability to selectively ablate Paneth cells. Sprague-Dawley rats were randomly divided into four groups: Sham-operated group, ANP group (3.5% sodium taurocholate solution, 1 ml/kg body weight), dithizone group (100 mg/kg of body weight) and ANP + dithizone group (sodium taurocholate solution was administered 6 h after dithizone injection). Each group was further divided into five subgroups (6, 12, 24, 36 and 48 h) based on the time period between induction of the model and sample collection. The present results suggested the number of Paneth cells was gradually decreased in the ANP group in a time-dependent manner. Most of the Paneth cells were ablated in the ANP + dithizone group at 6 h, but a subset of Paneth cells recovered after 24–48 h. Compared with the ANP group, combination of dithizone and ANP significantly induced more severe histopathological injuries in the pancreas and distal ileum, with higher Schmidt and Chiu's scores, respectively. Additionally, increased expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-17A were detected in the ileum, causing an increase in intestinal permeability, as assessed by a decrease in the expression level of the intestinal tight junction protein occludin and high plasma levels of diamine oxidase and D-lactate. The increase in intestinal permeability led to the translocation of bacteria to the bloodstream, triggering systemic inflammation, as assessed by the increased plasma levels of TNF-α, IL-1β and IL-17A, reducing the survival rates of rats, which was 66.7% and 83.3% in the ANP + dithizone and the ANP group, respectively. The increase in intestinal endoplasmic reticulum stress, as assessed by high expression levels of binding-immunoglobulin protein and activating transcription factor 6, may be one mechanism associated with Paneth cells loss and intestinal barrier impairment during ANP. Collectively, the present study suggested that the absence of Paneth cells may be an important factor involved in intestinal injury, promoting the progression of ANP.

To evaluate safety and efficacy of fluoroscopy-guided percutaneous vertebroplasty (PVP) for painful osteoblastic spinal metastases.PVP was performed in 39 consecutive patients (median age, 60.1 y ± 9.5) with 51 osteoblastic metastatic spinal lesions; 14 patients had pathologic fractures. The patients were followed for 3-30 months (average, 14.5 mo ± 7.4). Visual analog scale (VAS), Oswestry Disability Index (ODI), and Karnofsky performance scale (KPS) were used to evaluate pain, quality of life, and performance status before the procedure and at 3 days and 1, 3, 6, 12, and 18 months after the procedure.Technical success was achieved in all patients. Minimal follow-up time was 3 months. Mean VAS scores declined significantly from 7.4 ± 1.1 before the procedure to 2.5 ± 0.9 by day 3 after the procedure and were 2.1 ± 1.1 at 1 month, 2.0 ± 1.1 at 3 months, 1.9 ± 1.1 at 6 months, 1.8 ± 0.9 at 12 months, and 1.7 ± 0.7 at 18 months after the procedure (P.001). ODI and KPS scores also changed after the procedure, with significant differences between baseline scores and at each follow-up examination (P.001). Extraosseous cement leakage occurred in 15 cases without causing any clinical complications.PVP is a safe and effective treatment for painful osteoblastic spinal metastases. It can relieve pain, reduce disability, and improve function.

Patients with ovarian cancer frequently develop acquired drug resistance after the long-term chemotherapy, leading to disease progression. Enhanced epithelial-mesenchymal transition (EMT) has been implicated in chemoresistance of ovarian cancer cells; however, the molecular mechanisms involved are largely undefined. Pyruvate dehydrogenase kinase 1 (PDK1), a key regulatory enzyme in glucose metabolism, has been recognized as a gatekeeper of the Warburg effect, a hallmark of cancer. In this study, the function of PDK1 in cisplatin resistance of ovarian cancer in terms of growth and EMT was investigated. PDK1 was upregulated in cisplatin-resistant ovarian cancer cells. PDK1 knockdown in resistant cells led to increased sensitivity to cisplatin-induced cell death and apoptosis. PDK1 downregulation also reversed the EMT and cell motility in cisplatin-resistant cells. In a mouse xenograft model, tumors derived from PDK1-silenced ovarian cancer cells exhibited decreased tumor growth and EMT compared with control after the cisplatin treatment. Mechanistically, PDK1 overexpression led to increased phosphorylation of EGFR, and blocking EGFR kinase activity by erlotinib reversed cisplatin resistance induced by PDK1 overexpression. Furthermore, in patients with ovarian cancer, higher PDK1 and p-EGFR levels were associated with chemoresistance. These results supported that PDK1 contributes to chemoresistance of ovarian cancer by activating EGFR. Therefore, PDK1 may serve as a promising target to combat chemoresistance of ovarian cancer.

To investigate the effect of miR-183 on the cell proliferation in SW1990 pancreatic cancer cell line by targeting programmed cell death factor 4(PDCD4).The SW1990 pancreatic cancer cells were transfected with miR-183 mimics and inhibitors at different concentrations, the alteration of PDCD4 levels was observed at specific concentrations by qPCR and Western blot. The cellular proliferation of transfected cells was determined by MTT assay. The distribution of cell cycle and apoptosis was examined by flow cytometry (FCM) and Hoechst 33258 staining. The expression of B-cell lymphoma(bcl-2) was evaluated by Western blot.The miR-183 mimic and inhibitor (at concentrations of 50 nmol/L or 150 nmol/L) showed significantly increasing or decreasing effects on the levels ofThe miR-183 inhibitors could restrain cell proliferation, promote cell apoptosis and increase G₀/G₁ arrest in SW1990 pancreatic cancer cells, which may be possibly through targeting PDCD4.

Treatment of symptomatic lumbar disc herniation with Modic type I endplate changes is complex and challenging, requiring systemic and local therapies which include conservative therapy, epidural infiltrations, percutaneous therapeutic techniques, and surgical options. The clinical management of symptomatic lumbar disc herniation involving Modic type I endplate changes is uniquely challenging because it requires alleviating pain caused by both the herniated disc and the endplate osteochondritis. Through different approaches, percutaneous lumbar discectomy (PLD) and percutaneous cementoplasty (PCP) have been introduced into clinical practice as alternatives to traditional surgical and radiotherapy treatments of symptomatic lumbar disc herniation and other spine diseases.To evaluate the feasibility of PLD and PCP for symptomatic lumbar disc herniation with Modic type I endplate changes.PLD and PCP in 7 patients with symptomatic lumbar disc herniation with Modic type I endplate changes and its clinical effects were retrospectively evaluated.This study was conducted by an interventional therapy group at a medical center in a major Chinese city.Seven consecutive patients (2 men, 5 women; median age, 74.14 ± 5.34 years; age range, 68 - 82 years) who underwent percutaneous lumbar discectomy and cementoplasty for the treatment of symptomatic lumbar disc herniation with Modic type I changes between May 2013 and August 2015 were retrospectively analyzed. The MacNab Criteria, visual analog scale (VAS), and Oswestry Disability Index (ODI) for pain were assessed before and one week, 6 months, and one year after the procedure. Furthermore, the procedure duration, hospital stay length, and complications were assessed.The VAS of the back and leg decreased from 6.14 ± 0.69 (range, 5 - 7) and 7.29 ± 0.76 (range, 6 - 8) preoperatively to 2.29 ± 1.38 (range, 1 - 5) and 2.71 ± 0.60 (range, 1 - 6) one week, 1.86 ± 0.69 (range, 1 - 3) and 2.00 ± 0.58 (range, 1 - 3) 6 months, and 1.71 ± 0.76 (range, 1 - 3) and 1.85 ± 0.69 (range, 1 - 3) one year postoperatively. The ODI dropped from 76.86 ± 7.45 (range, 70 - 82) preoperatively to 26.29 ± 19.47 (range, 16 - 70) one week, 19.14 ± 2.79 (range, 16 - 24) 6 months, and 18.57 ± 2.99 (range, 16 - 24) one year postoperatively. The mean procedure duration was 55.71 ± 6.07 minutes (range, 50 - 65 minutes). The average length of hospital stay was 7.57 ± 1.27 days (range, 6 - 10 days). No obvious complications were noted.This was a retrospective study with a relatively small sample size.PLD plus PCP is a feasible technique for symptomatic lumbar disc herniation with Modic type I endplate changes.

To establish a culture system for mouse intestinal organoids and investigate the effect of deoxycholic acid (DCA) on organoids growth.The terminal ileum was collected from 8-month-old C57BL6 mice. The tissue blocks were treated with EDTA and the crypts were collected and embedded in Matrigel Matrix. Orgnoids growth and buddings were observed in the control group, anhydrous alcohol group, short-term (2 days) 100 µmolL DCA treatment group, and long-term (10 days) 10 µmolL DCA treatment group; the orgnoids were further cultured for 10 days after removal of DCA from the medium and observed for orgnoids growth and buddings.Short-term treatment with high-concentration DCA resulted in significantly reduced enterosphere formation, enteroids formation, progression from enterospheres to enteroids and number of crypt buds per enteroid (P0.05), which remained unchanged even after removal of DCA for a short time (P0.05); long after DCA removal, the enteroids formation rate and number of the crypt buds still remained lower than those in normal organoids (P0.05). Short-term treatment with low-concentration DCA only resulted in reduced enteroids formation rate and number of crypt buds (P0.05), and prolonged treatment caused reduced enterospheres formation rate, enteroids formation rate and number of crypt buds (P0.05). After DCA removal, enteroids formation rate and the number of crypt buds still remained lower than those in the normal group (P0.05).We successfully established an organoids culture system. The presence of DCA in the culture system affects the growth of the organoids, which can partly recover following a prolonged period after the removal of DCA.

Turmeric, derived from the rhizomes of Curcuma longa L. (Zingiberaceae), is one of the most popular herbal medicines. Its main bioactive constituents include curcuminoids, sesquiterpenes, and terpecurcumins. It exhibits antitumor, anti-inflammatory, antioxidant, antibacterial, and antiviral activities. With the rapid development of analytical technologies, remarkable progress has been made in studies of turmeric. This review article summarizes research advances in chemical analysis and quality control of turmeric from 2009 to 2018.

Rapid and correct authentication of commercial strains is still important in today’s mushroom industry. Here for the first time we reported the using of sequence characterized amplified region (SCAR) marker developed from inter-retrotransposon amplified polymorphism (IRAP) marker to identify Lentinula edodes strain. Genomic polymorphism among 44 shiitake cultivars in China were surveyed by 24 IRAP primer combinations, from which primer combination LTR1L/MarY1R could generate a unique and reproducible 1712 bp fragment to distinguish strain No. 4 from other 43 strains. Based on this strain-specific fragment, a SCAR primer pair was designed and its validity was verified by correctly amplifying a single strain-specific fragment from DNA samples of 100 L. edodes strains. Our study lays the foundation for developing strain-specific SCAR marker by retrotransposon-based marker technique in fungi.

The C-Jun N-terminal Kinase (JNK) inhibitor SP600125 is widely used to inhibit the JNK-mediated Bax activation and cell apoptosis. However, this report demonstrates that SP600125 synergistically enhances the dihydroartemisinin (DHA)-induced human lung adenocarcinoma cell apoptosis by accelerating Bax translocation and subsequent intrinsic apoptotic pathway involving mitochondrial membrane depolarization, cytochrome c release, caspase-9 and caspase-3 activation. The dynamical analysis of GFP-Bax mobility inside single living cells using fluorescence recovery after photobleaching revealed that SP600125 aggravated the DHA-induced decrease of Bax mobility and Bax translocation. These results for the first time present a novel pro-apoptotic action of SP600125 in DHA-induced apoptosis.

A fully automated system was developed for the depth of anesthesia estimation and control with the intravenous anesthetic, Propofol. The system determines the anesthesia depth by assessing the characteristics of the mid-latency auditory evoked potentials (MLAEP). The discrete time wavelet transformation was used for compacting the MLAEP which localizes the time and the frequency of the waveform. Feature reduction utilizing step discriminant analysis selected those wavelet coefficients which best distinguish the waveforms of those responders from the nonresponders. A total of four features chosen by such analysis coupled with the Propofol effect-site concentration were used to train a four-layer artificial neural network for classifying between the responders and the nonresponders. The Propofol is delivered by a mechanical syringe infusion pump controlled by Stanpump which also estimates the Propofol effect-site and plasma concentrations using a three-compartment pharmacokinetic model with the Tackley parameter set. In the animal experiments on dogs, the system achieved a 89.2% accuracy rate for classifying anesthesia depth. This result was further improved when running in real-time with a confidence level estimator which evaluates the reliability of each neural network output. The anesthesia level is adjusted by scheduled incrementation and a fuzzy-logic based controller which assesses the mean arterial pressure and/or the heart rate for decrementation as necessary. Various safety mechanisms are implemented to safeguard the patient from erratic controller actions caused by external disturbances. This system completed with a friendly interface has shown satisfactory performance in estimating and controlling the depth of anesthesia.

The most saturated linkage map for Lentinula edodes to date was constructed based on a mono-. karyotic population of 146 single spore isolates (SSIs) using sequence-related amplified polymorphism (SRAP), target region amplification polymorphism (TRAP), insertion deletion (InDel) markers, and the mating-type loci. Five hundred and twenty-four markers were located on 13 linkage groups (LGs). The map spanned a total length of 1006.1 cM, with an average marker spacing of 2.0 cM. Quantitative trait loci (QTLs) mapping was utilized to uncover the loci regulating and controlling the vegetative mycelium growth rate on various synthetic media, and complex medium for commercial cultivation of L. edodes. Two and 13 putative QTLs, identified respectively in the monokaryotic population and two testcross dikaryotic populations, were mapped on seven different LGs. Several vegetative mycelium growth rate-related QTLs uncovered here were clustered on LG4 (Qmgr1, Qdgr1, Qdgr2 and Qdgr9) and LG6 (Qdgr3, Qdgr4 and Qdgr5), implying the presence of main genomic areas responsible for growth rate regulation and control. The QTL hotspot region on LG4 was found to be in close proximity to:the region containing the mating-type A (MAT-A) locus. Moreover, Qdgr2 on LG4 was detected on different media, contributing 8.07%-23.71% of the phenotypic variation. The present study provides essential information for QTL mapping and marker-assisted selection (MAS) in L. edodes. (C) 2014 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary syndrome known to predispose subjects to endocrine neoplasms in a variety of tissues such as the parathyroid glands, pituitary gland, pancreas and gastrointestinal tract. We herein report a patient with a past history of pituitary adenoma, presenting with symptoms of chronic diarrhea for nearly one year and a sudden upper gastrointestinal hemorrhage as well as perforation without signs. Nodules in the duodenum and in the uncinate process and tail of pancreas and enlargement of the parathyroid glands were detected on preoperative imaging. Gastroscopy revealed significant ulceration and esophageal reflux diseases. The patient underwent subtotal parathyroidectomy and autotransplantation, pylorus-preserving pancreaticoduodenectomy and pancreatic tail resection and recovered well. The results observed in our patient suggest that perforation and bleeding of intestine might be symptoms of Zollinger-Ellison Syndrome in patients with MEN1.

The major concern limiting the industrial application of organo-bentonite in powder form (P-Bent) for wastewater treatment is that it is difficult to separate it from treated water by settlement. To address this problem, a novel approach for synthesizing immobilized organo-bentonite in globular form (G-Bent) is proposed. The G-Bent is modified using the cationic surfactant cetylpyridinium chloride (CPC) and immobilized by polyvinyl alcohol (PVA). The removal of 2-naphthol by G-Bent was compared with removal by P-Bent for solid/liquid separation, removal efficiency and desorption of the modifier used in its preparation. Results indicated that G-Bent was easy to recover from treated wastewater, and was effective and reusable in removing 2-naphthol. The percentage of 2-naphthol removed by G-Bent exceeded 90% with the cationic exchange capacity (CEC) loadings ranging from 100% to 150%. This was almost equivalent to the results obtained using P-Bent. In the five rounds of reuse examined, the percentage of 2-naphthol removed was maintained above 50% for 150%-G-Bent. The percentage of CPC desorption was less than 0.75% after five rounds of reuse and no PVA was detected. The results of this work provide novel information for using G-Bent in the treatment of wastewater containing organic contaminants.

To investigate the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in human gastric cancer and it's mechanism in apoptosis and cell cycle arrest.Expression of 15-PGDH mRNA and protein was examined by immunohistochemistry, immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting in tissue from human gastric cancer, gastric precancerous state (gastric polyps and atrophic gastritis), normal stomach, and gastric cancer cell lines. The relationship between gastric cancer, gastric precancerous state and 15-PGDH expression was determined. The association between expression of 15-PGDH and various clinicopathological parameters in gastric cancer was evaluated. Human gastric cancer cell line SGC-7901 was transfected with 15-PGDH expression plasmids. The effect of 15-PGDH on the cell cycle was examined by flow cytometry. The effect of 15-PGDH on apoptosis was examined by transmission electron microscopy, flow cytometry and transferase mediated nick end labeling (TUNEL) assay. Expression of cell cycle (p21, p27, p16 and p53) and apoptosis (Survivin, BCL-2, BCL-X(L), BAK and BAX) genes was analyzed by RT-PCR.Expression of 15-PGDH mRNA and protein in human gastric cancer tissues was significantly lower than in normal gastric tissues (P0.01). Expression in human gastric cancer cell lines MKN-28 and MKN-45 was reduced, and absent in SGC-7901 cells (P0.05). Reduction of 15-PGDH expression was also found in precancerous tissues, such as gastric polyps and atrophic gastritis (P0.01). There was a significant difference in expression of 15-PGDH among various gastric cancer pathological types (P0.05), with or without distant metastasis (P0.05) and different TNM stage (P0.01). Flow cytometry demonstrated a significant increase in apoptotic cells in SGC-7901 cells transfected with pcDNA3/15-PGDH plasmid for 24 h and 48 h (P0.01), and an increased fraction of sub-G1 phase after transfection (P0.05). TUNEL assay showed an increased apoptotic index in cells overexpressing 15-PGDH (P0.01). After transfection, expression of proapoptotic genes, such as BAK (P0.05), BAX and p53 (P0.01), was increased. Expression of antiapoptotic genes was decreased, such as Survivin, BCL-2 and BCL-X(L) (P0.01). Expression of cyclin-dependent kinase inhibitors p21 and p16 (P0.01) was significantly upregulated in cells overexpressing 15-PGDH.Reduction of 15-PGDH is associated with carcinogenesis and development of gastric carcinoma. 15-PGDH induces apoptosis and cell cycle arrest in SGC-7901 cells.

Dihydroartemisinin (DHA), a first-line anti-malarial drug with low toxicity, has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathway, but the molecular mechanisms are not well understood. In this paper, we focus on whether Bad, a BH3-only pro-apoptotic protein, is involved in apoptotic cell death in DHA-treated human lung adenocarcinoma (ASTC-a-1) cells. Confocal fluorescence microscope imaging was used to monitor the temporal and spatial distribution of Bad in single living cells. Our results indicate that Bad is still located in cytoplasm and does not translocate to mitochondria after treatment with DHA for 24 h, while only a small proportion of Bad located in cytoplasm in the STS-treated cells for 6 h. These results show for the first time that Bad is not involved in DHA-induced apoptosis in ASTC-a-1 cells, which could give more evidence for the molecular mechanisms of apoptosis induced by DHA.

Live and let dye: Three coumarin-cyclooctyne conjugates have been used to label proteins tagged with azidohomoalanine in Rat-1 fibroblasts. All three fluorophores labeled intracellular proteins with fluorescence enhancements ranging from eight- to 20-fold. These conjugates are powerful tools for visualizing biomolecule dynamics in living cells.

The target region amplification polymorphism (TRAP) technique was utilized for assessing the genetic diversity of 55 wild strains and one cultivated strain of Lentinula edodes in China. From these strains, 932 DNA fragments were amplified using 12 primer combinations, 929 fragments (99.68%) of which were polymorphic between two or more strains. The average coefficient of pairwise genetic similarity was 0.696, within a range from 0.503 to 0.947. Cluster analysis and principal coordinate analysis separated the tested strains of L. edodes into two major groups. Group A was further divided into seven subgroups. In most cases, the strains from the same or adjoining regions could be preferentially clustered into small groups. The results from the average genetic similarity and the weighted average value of Shannon's Information Index among the tested strains of L. edodes from the same region revealed a vast genetic diversity in the natural germplasm found in China. Compared with the L. edodes strains from other regions, those found on the Yunnan Plateau, in the Hengduanshan Mountains, in Taiwan, South China, and Northeast China showed greater genetic diversity. The results of the present study indicated that the wild strains of L. edodes in China possessed abundant genetic variation, and the genetic relationships among them were highly associated with the geographic distribution. This is the first report demonstrating that TRAP markers were powerful for analyzing the genetic diversity of L. edodes, and the study lays the foundation for a further application of this remarkable technique to other fungi. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Background Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, isolated from the traditional Chinese herb Artemisia annua, is recommended as the first-line anti-malarial drug with low toxicity. DHA has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathways, although the molecular mechanisms are not well understood. Methods In this study, cell counting kit (CCK-8) assay was employed to evaluate the survival of DHA-treated ASTC-a-1 cells. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. Collapse of mitochondrial transmembrane potential (ΔΨm) was measured by dynamic detection under a laser scanning confocal microscope and flow cytometry analysis using Rhodamine123. Caspase-3 activities measured with or without Z-VAD-fmk (a broad spectrum caspase inhibitor) pretreatment by FRET techniques, caspase-3 activity measurement, and western blotting analysis. Results Our results indicated that DHA induced apoptotic cell death in a dose- and time-dependent manner, which was accompanied by mitochondrial morphology changes, the loss of ΔΨm and the activation of caspase-3. Conclusion These results show for the first time that DHA can inhibit proliferation and induce apoptosis via caspase-3-dependent mitochondrial death pathway in ASTC-a-1 cells. Our work may provide evidence for further studies of DHA as a possible anticancer drug in the clinical treatment of lung adenocarcinoma.