Search

We have selected a semi-rigid hexacarboxylic acid ligand H6L enriched with oxygen-active sites with Cd2+ salt, successfully synthesising a 3-D anionic material MOF-1 ([(CH3)2NH2]2[Cd2L]·3DMA·2H2O, H6L = 5,5',5"-(benzene-1,3,5-triyltris(oxy))triisophthalic acid). The structure of this carboxylic acid ligand is triangular in shape, which contributes to the formation of the 3-D framework structure, and its semi-rigidity facilitates entry of dye molecules by slightly adjusting the pore size. The larger pore size of MOF-1 is 1.45 nm x 0.86 nm. The oxygen spacer groups are uniformly distributed throughout the framework, promoting the adsorption of MOF-1 for dyes. Based on these factors, there is a significant advantage in that the anionic material MOF-1 containing [(CH3)2NH2]+ selectively adsorbs cationic organic dyes from aqueous contaminants for recycling. It was discovered that the adsorption process' equilibrium and kinetics followed the Langmuir isothermal model and pseudo-secondary kinetics, respectively. And we measured the adsorption rate of MOF-1' on MB+ to be 1.77 x 10-3 g mg-1 min-1. Its relatively high capacity is ca. 1220 mg g-1. After five cycles of adsorption and desorption, the dye adsorption performance was reduced to ca. 80% and the framework stability remained well. [ABSTRACT FROM AUTHOR]

Most host-microbiota interactions occur within the intestinal barrier, which is essential for separating the intestinal epithelium from toxins, microorganisms, and antigens in the gut lumen. Gut inflammation allows pathogenic bacteria to enter the blood stream, forming immune complexes which may deposit on organs. Despite increased circulating immune complexes (CICs) in patients with inflammatory bowel disease (IBD) and discussions among IBD experts regarding their potential pathogenic role in extra-intestinal manifestations, this phenomenon is overlooked because definitive evidence demonstrating CICinduced extra-intestinal manifestations in IBD animal models is lacking. However, clinical observations of elevated CICs in newly diagnosed, untreated patients with IBD have reignited research into their potential pathogenic implications. Musculoskeletal symptoms are the most prevalent extra-intestinal IBD manifestations. CICs are pivotal in various arthritis forms, including reactive, rheumatoid, and Lyme arthritis and systemic lupus erythematosus. Research indicates that intestinal barrier restoration during the pre-phase of arthritis could inhibit arthritis development. In the absence of animal models supporting extra-intestinal IBD manifestations, this paper aims to comprehensively explore the relationship between CICs and arthritis onset via a multifaceted analysis to offer a fresh perspective for further investigation and provide novel insights into the interplay between CICs and arthritis development in IBD. [ABSTRACT FROM AUTHOR]

Objective: To provide novel insights into the aetiology of non-syndromic cleft lip with or without cleft palate (NSCL/P) by integrating multi-omics data and exploring susceptibility genes associated with NSCL/P. Methods: A two-stage genome-wide association study (GWAS) of NSCL/P was performed, involving a total of 1,069 cases and 1,724 controls. Using promoter capture Hi-C (pCHi-C) datasets in human embryonic stem cells (hESC) and chromatin immunoprecipitation sequencing (ChIP-seq) in craniofacial tissues, we filtered out single nucleotide polymorphisms (SNPs) with active cis-regulation and their target genes. Additionally, we employed expression quantitative trait loci (eQTL) analysis to identify candidate genes. Results: Thirteen SNPs were identified as cis-regulation units associated with the risk of NSCL/P. Five of these were proven to be active in chromatin states in early human craniofacial development (rs7218002: odds ratio [OR] 1.50, P = 8.14E-08; rs835367: OR 0.78, P = 3.48E05; rs77022994: OR 0.55, P = 1.05E-04; rs961470: OR 0.73, P = 1.38E-04; rs17314727: OR 0.73, P = 1.85E-04). Additionally, pCHi-C and eQTL analysis prioritised three candidate genes (rs7218002: NTN1, rs835367: FGGY, LINC01135). NTN1 and FGGY were expressed in mouse orofacial development. Deficiencies in NTN1, FGGY and LINC01135 were associated with cleft palate and cleft lip, abnormal facial shape and bifid uvula, and abnormality of the face, respectively. Conclusion: Our study identified five SNPs (rs7218002, rs835367, rs77022994, rs961470 and rs17314727) and three susceptibility genes (NTN1, FGGY and LINC01135) associated with NSCL/P. These findings contribute to a better understanding of the genetic factors involved. [ABSTRACT FROM AUTHOR]

Phosphorus-solubilizing microbes play key roles in improving phosphorus availability and in alleviating phosphorus nutrient limitation in soils. However, we did not have a comprehensive understanding of the overall research progress and development trend of phosphorus solubilizing microorganisms. In this study, we obtain documents from the Web of Science (WOS) core collection between 2002 and 2022, and a comprehensive review of the progress of global research on soil phosphate solubilizing microorganisms was conducted by using the VOSviewer bibliometric analysis tool. The results showed an increasing trend in the number of published articles from 2002 to 2022. India, accounting for 28% of the total number of published articles, became the most productive country. However, Canada was the country with the highest average citation frequency of articles. Chinese Academy of Sciences (CAS) was the greatest contributor with the most publications. Among the published journals, Frontiers in Microbiology, Applied Soil Ecology and Plant and Soil were the top three core journals in this field. Based on the keyword analysis, the assessment of the mechanisms between phosphorus solubilizing microbes and the soil carbon cycles with the different management practices became the new research trend among the scientific communities. These findings would provide an important reference value for future in-depth research on soil phosphate solubilizing microorganisms. [ABSTRACT FROM AUTHOR]

Reasonable nitrogen fertilizer application is an important strategy to maintain optimal growth of grasslands, thereby enabling them to better fulfil their ecological functions while reducing environmental pollution caused by high nitrogen fertilizer production and application. Optimizing the ammonium (NH4+):nitrate (NO3-) ratio is a common approach for growth promotion in crops and vegetables, but research on this topic in grass plants has not received sufficient attention. Centipedegrass, which is widely used in landscaping and ecological protection, was used as the experimental material. Different NH4+:NO3- ratios (0: 100, 25:75, 50:50, 75:25, 100:0) were used as the experimental treatments under hydroponic conditions. By monitoring the physiological and morphological changes under each treatment, the appropriate NH4+:NO3- ratio for growth and its underlying mechanism were determined. As the proportion of ammonium increased, the growth showed a “bell-shaped” response, with the maximum biomass and total carbon and nitrogen accumulation achieved with the NH4+:NO3- ratio of 50:50 treatment. Compared with the situation where nitrate was supplied alone, increasing the ammonium proportion increased the whole plant biomass by 93.2%, 139.7%, 59.0%, and 30.5%, the whole plant nitrogen accumulation by 44.9%, 94.6%, 32.8%, and 54.8%, and the whole plant carbon accumulation by 90.4%, 139.9%, 58.7%, and 26.6% in order. As a gateway for nitrogen input, the roots treated with an NH4+:NO3- ratio of 50:50 exhibited the highest ammonium and nitrate uptake rate, which may be related to the maximum total root length, root surface area, average root diameter, root volume, and largest root xylem vessel. As a gateway for carbon input, leaves treated with an NH4+:NO3- ratio of 50:50 exhibited the highest stomatal aperture, stomatal conductance, photosynthetic rate, transpiration rate, and photosynthetic products. The NH4+:NO3- ratio of 50:50 treatment had the largest stem xylem vessel area. This structure and force caused by transpiration may synergistically facilitate root-to-shoot nutrient translocation. Notably, the change in stomatal opening occurred in the early stage (4 hours) of the NH4+:NO3- ratio treatments, indicating that stomates are structures that are involved in the response to changes in the root NH4+:NO3- ratio. In summary, we recommend 50:50 as the appropriate NH4+:NO3- ratio for the growth of centipedegrass, which not only improves the nitrogen use efficiency but also enhances the carbon sequestration capacity. [ABSTRACT FROM AUTHOR]

A central question in microbial ecology is how immense microbes are assembled in changing natural environments while executing critical ecosystem functions. Over the past decade, effort has been made to unravel the contribution of stochasticity and determinism to the compositional of microbial communities. However, most studies focus on microbial taxa, ignoring the importance of functional traits. By employing shotgun metagenomic sequencing and state-of-the-art bioinformatics approaches, this study comprehensively investigated the microbially mediated nitrogen (N) cycling processes in two geographically distant coastal locations. Both shotgun and 16S rRNA gene amplicon sequencing demonstrated significantly differed taxonomic compositions between the two sites. The relative abundance of major microbial phyla, such as Pseudomonadota, Thaumarchaeota, and Bacteroidota, significantly differed. In contrast, high homogeneity was observed for N-cycling functional traits. Statistical analyses suggested that N-cycling taxonomic groups were more related to geographic distance, whereas microbial functional traits were more influenced by environmental factors. Multiple community assembly models demonstrated that determinism strongly governed the microbial N-cycling functional traits, whereas their carrying taxonomic groups were highly stochastic. Such discordant patterns between N-cycling functional traits and taxa demonstrated an important mechanism in microbial ecology in which essential ecosystem functions are stably maintained despite geographic distance and stochastic community assembly. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the protective effect of Panax notoginseng rhizomes (PNR) on renal ischemia and reperfusion injury (RIRI) and the underlying molecular network mechanism based on network pharmacology and combined systemic experimental validation. Methods: A bilateral RIRI model was established, and Cr, SCr, and BUN levels were detected. Then, the PNR was pretreated 1 week before the RIRI model was prepared. To determine the effects of the PNR in RIRI, histopathological damage and the effect of PNRs to the kidney was assessed, using TTC, HE, and TUNEL staining. Furthermore, the underlying network pharmacology mechanism was detected by screening drug-disease intersection targets from PPI protein interactions and GO and KEGG analysis, and the hub genes were screened for molecular docking based on the Degree value. Finally, the expression of hub genes in kidney tissues was verified by qPCR, and the protein expression of related genes was further detected by Western blot (WB). Results: PNR pretreatment could effectively increase Cr level, decrease SCr and BUN levels, reduce renal infarct areas and renal tubular cell injury areas, and inhibit renal cell apoptosis. By using network pharmacology combined with bioinformatics, we screened co-targets both Panax notoginseng (Sanchi) and RIRI, acquired ten hub genes, and successfully performed molecular docking. Of these, pretreatment with the PNR reduced the mRNA levels of IL6 and MMP9 at postoperative day 1 and TP53 at postoperative day 7, and the protein expression of MMP9 at postoperative day 1 in IRI rats. These results showed that the PNR could decrease kidney pathological injury in IRI rats and inhibit apoptotic reaction and cell inflammation so as to improve renal injury effectively, and the core network mechanism is involved in the inhibition of MMP9, TP53, and IL-6. Conclusion: The PNR has a marked protective effect for RIRI, and the underlying mechanism is involved in inhibiting the expression of MMP9, TP53, and IL-6. This striking discovery not only provides fruitful evidence for the protective effect of the PNR in RIRI rats but also provides a novel mechanic explanation. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable. [ABSTRACT FROM AUTHOR]

In the context of global food crisis, applying the phytohormone-brassinosteroids (BRs) in combination with the fungicide-pyraclostrobin (Pyr) was beneficial for plant quality and productivity in several field trials. However, in addition to the benefits of disease control due to the innate fungicidal activity of Pyr, it remains to be understood whether the coapplication of BL+ Pyr exerts additional growthpromoting effects. For this purpose, the effects of BL treatment, Pyr treatment, and BL+ Pyr treatment in Arabidopsis thaliana were compared. The results showed that the yield increased at a rate of 25.6% in the BL+Pyr group and 9.7% in the BL group, but no significant change was observed in the Pyr group. Furthermore, the BL+Pyr treatment increased the fresh weight of both the leaves and the inflorescences. In contrast, the Pyr and BL treatments only increased the fresh weight of leaves and inflorescences, respectively. Additionally, the BL + Pyr treatment increased the Pn, Gs, Tr, Vc, max, Jmax, VTPU, ETR, Fv’/Fm’, FPSII, Rd, AYE and Rubisco enzyme activity by 26%, 38%, 40%, 16%, 19%, 15%, 9%, 10%, 17%, 179%, 18% and 32%, respectively. While, these paraments did not change significantly by the BL or Pyr treatments. Treatment with BL + Pyr and Pyr, rather than BL, improved the chlorophyll a and chlorophyll b contents by upregulating genes related to chlorophyll biosynthesis and downregulating genes related to chlorophyll degradation. Additionally, according to transcriptomic and metabolomic analysis, the BL+ Pyr treatment outperformed the individual BL or Pyr treatments in activating the transcription of genes involved in photosynthesis and increasing sugar accumulation. Our results first validated that the combined usage of BL and Pyr exerted striking synergistic effects on enhancing plant biomass and yield by increasing photosynthetic efficiency. These results might provide new understanding for the agricultural effects by the co-application of BL and Pyr, and it might stimulate the efforts to develop new environment-friendly replacement for Pyr to minimize the ecotoxicology of Pyr. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Electrochemistry is the property of Journal of Electrochemistry Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Currently, immune checkpoint inhibitors (ICIs) are the mainstay of treatment for Lynch syndrome patients. However, the tumor regression features in radiology and pathology are inconsistent for patients who are treated with ICIs, which sometimes confuses surgical decision-making. Here, we report a case in which a 36-year-old patient suffering from infertility was diagnosed with Lynch syndrome-associated synchronous endometrial cancer and colon cancer, and persistently enlarged left iliac paravascular lymph nodes were detected after receiving sintilimab treatment, a programmed cell death 1 (PD-1) receptor inhibitor. Fortunately, when she was about to undergo hysterectomy and bilateral salpingo-oophorectomy, intraoperative pathology examination did not reveal any cancer cells in these lymph nodes, and therefore, her reproductive organs were preserved. Later, the patient successfully conceived and gave birth to a healthy male neonate with no immune-related adverse events (irAEs) during an 11-month follow-up. This case indicates that surgeons should carefully inspect the imaging characteristics after immunotherapy and that organ preservation is possible even for patients who fail to achieve complete clinical regression, which is especially important for female patients of childbearing age. [ABSTRACT FROM AUTHOR]

Background: As a recognized highly immunogenic tumor, immune checkpoint blockades (ICB) have been widely used as a systemic treatment option for melanoma. However, only about half of treated patients could benefit from it in Caucasians, and only about 15% in Chinese melanoma patients. Robust predictive biomarkers are needed. HHLA2, a new-found member of B7 family, is generally expressed in kinds of tumors, such as melanoma. This study focuses on illustrating the prognostic value of HHLA2 in melanoma immunotherapy and its association with tumor-infiltrating lymphocytes. Methods: HHLA2 expression in pan-cancer and the association with prognosis and immune microenvironment were identified by analyzing gene expression profiles from TCGA database with selected bioinformatics tools and methods. Tumor tissues from 81 cases with advanced and unresectable melanoma were collected for detecting HHLA2 and CD8 levels by immunohistochemistry. Results: HHLA2 was found to be ubiquitously expressed in pan-cancer with high level and correlate with the prognosis of patients. Further comprehensive analysis from TCGA database demonstrated that the highly expressed HHLA2 was remarkably correlated with better prognosis, high infiltration status of various immune-active cells and immune activated pathways in skin cutaneous melanoma (SKCM). Moreover, immunohistochemistry (IHC) analyses of FFPE tissue from melanoma patients revealed that HHLA2 high expression was strongly related to improved response to ICB and indicated a longer progression-free survival (PFS) and overall survival (OS). Besides, HHLA2 expression was found to have a positive association with the density of CD8+ TILs. Conclusion: Our findings revealed that high expression of HHLA2 has important values in predicting the response to ICB and indicating improved PFS and OS in patients with advanced and unresectable melanoma, suggesting that HHLA2 may serve as a costimulatory ligand in melanoma, which renders it as an ideal biomarker for immunotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD). METHODS This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE. RESULTS In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C = 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C = 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group (P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250). CONCLUSIONS In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study. [ABSTRACT FROM AUTHOR]

This paper aimed to research the function and in-depth mechanism of GPR37 in lung adenocarcinoma (LUAD). Herein, based on TCGA and Oncomine databases, we revealed that GPR37 was expressed at high levels in LUAD, and upregulation of GPR37 was related to the poor outcomes. Furthermore, biological function experiments in vitro were utilized to assess whether GPR37 impacts malignant phenotype of LUAD cells. Gain- or loss-of-function assays indicated that the upregulation of GPR37 contributed to improving the proliferation, migration, and invasion of LUAD cells in vitro, while knockdown of GPR37 can inhibit the malignant biological behaviors. Then, we found that depletion of GPR37 resulted in a decrease in the expression of TGF-β1 as well as the extents of Smad2 and Smad3 phosphorylation, while overexpression of GPR37 presented opposite outcomes. Altogether, our findings indicated that GPR37 is a potential oncogene of LUAD, and its promoting effects on the malignant progression of LUAD may be realized via TGF-β/Smad pathway. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of Qishen decoction on dedifferentiation and autophagy of liver sinusoid endothelial cells (LSEC); Methods: LSEC were randomly divided into the control group, model group, Qishen Decoction low, medium, high dose group, and inhibitor group. The model was induced by 100µg/ml oxidized low-density lipoprotein (oxLDL) for 24 hours, and the corresponding drugs or medicated serum were given for intervention. The expression levels of VEGFR2 and ET1 were detected by RT-qPCR and immunofluorescence staining, the ultrastructure of LSEC was detected by transmission electron microscopy, the content of NO was detected by ELISA, the expression levels of autophagy related proteins (LC3BI, LC3BII and p62) and endothelial function related proteins (eNOS and p- eNOS) were detected by western blot; Results: The results of transmission electron microscopy showed that Qishen decoction medicated serum could increase the number of fenestra and autophagy in LSEC cells, and inhibit the formation of basement membrane under endothelium. Compared with the model group, Qishen decoction medicated serum could significantly up-regulate the expression level of VEGFR2 mRNA and protein in LSEC, down regulate the expression level of ET1 mRNA and protein, the difference was statistically significant (P<0.05). In addition, Qishen decoction medicated serum could significantly increase the expression of LC3BII, p- eNOS, eNOS protein and the ratio of LC3BII/LC3BI, p- eNOS/eNOS, and reduce the expression of LC3BI and p62 protein in LSEC, which is statistically significant compared with the model group (P<0.05). Conclusion: Qishen decoction can inhibit the dedifferentiation of LSEC by promoting the autophagy level of LSEC, and then play an anti-fibrosis role. [ABSTRACT FROM AUTHOR]

Objective: To screen the main active components of Qishen decoction by network pharmacology and predict the target of its treatment for nonalcoholic fatty liver disease (NAFLD), and to verify it by experiments. Methods: The main active components of Qishen decoction and the disease target of NAFLD were screened through the database; the drug disease target network and PPI were constructed by the software of Cytoscape and string database; the enrichment of go and KEGG were analyzed by the database of DAVID; HE staining, red oil O staining, serum biochemical index and Western blot were used to verify the effect mechanism of Qishen Decoction on NAFLD. Results: A total of 207 active compounds and 95 drug- disease-targets of Qishen Decoction were selected in this study. The results of KEGG enrichment analysis showed that the mechanism of Qishen decoction in the treatment of NAFLD involved adipocytokines, insulin signaling pathway, fatty acid biosynthesis, etc. The results showed that Qishen decoction could significantly reduce the liver NAS score and oil red O staining area of NAFLD rats (P<0.05). At meanwhile, Qishen decoction significantly reduced the levels of serum glucose, insulin, HOMA-IR, TC, TG, AST and ALT in NAFLD rats (P<0.05). In addition, Qishen decoction can significantly up regulate the expression of p-INSR ß in liver tissue, down regulate the expression of SREBP-1c, Fas and p-ACC (P<0.05). Conclusion: Qishen decoction can improve the insulin resistance of NAFLD rats through insulin signaling pathway, so as to improve NAFLD fat deposition and liver injury. In addition, Qishen decoction can also achieve the therapeutic effect of NAFLD through multiple channels and targets. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of Qishen decoction on PI3K/Akt/mTOR signal pathway in rats with liver fibrosis; Methods: 40 SD rats were randomly divided into four groups: the control group, the model group, Qishen decoction group, and Colchicine group. Except the control group, the remaining three groups were used to establish liver fibrosis model by intraperitoneal injection of carbon tetrachloride. At the end of modeling, Qishen decoction and colchicine group were given corresponding drug gavage treatment, rats in the model group and the control group were treated with equal volume distilled water for 8 weeks. At the end of the treatment, the blood and liver tissues of rats in each group were collected, the liver function indexes and hydroxyproline content were detected by ELISA, the pathological morphology of liver tissue was detected by HE and Masson staining. Immunohistochemical method was used to detect a-SMA protein expression and Western blot was used to detect the expression of -SMA, Col-I, Col-III and key proteins in PI3K/Akt/mTOR signaling pathway. Results: Compared with the model group, Qishen decoction significantly reduced the levels of AST, ALT, and TBIL in serum, and reduced Hyp content, inflammatory score, fibrosis score, and collagen staining area in liver tissue, differences were statistically significant (P<0.05). At meanwhile, Qishen decoction significantly reduce the expression level of -SMA, CoL-I and Col-III in liver tissue(P<0.05). In addition, compared with the model group, Qishen decoction significantly down-regulated the expressions of p-PI3K, p-Akt and p-mTOR in liver tissue, difference were statistically significant (P<0.05). Conclusion: Qishen decoction suppresses liver fibrosis and inhibits the deposition of collagen in liver tissue by down-regulating PI3K/Akt/mTOR signal pathway. [ABSTRACT FROM AUTHOR]

Objective: To explore the mechanism of Qishen Decoction in the treatment of nonalcoholic fatty liver fibrosis (NAFLF) by 16S rRNA technology. Methods: NAFLF rat model was established by intraperitoneal injection of carbon tetrachloride combined with high fat diet. During the modeling period, each group was given corresponding drug intervention treatment for 8 weeks. The changes of liver histopathology, serum liver function, lipid and liver fibrosis were analyzed and compared after treatment in each group. The contents of cecum end were collected and the intestinal flora was sequenced by Illumina Miseq platform. Results: Compared with the model group, Qishen Decoction could significantly improve the pathological changes of liver tissue in NALFL rats, and reduce the NAS score, oil red staining area, collagen staining area, ALT, AST, TC, TG, HA, LN, PIIINP and C-IV levels, with significant differences (P<0.05). In addition, compared with the control group, the intestinal flora abundance and diversity of the rats in the model group were significantly reduced (P<0.05), Qishen decoction could significantly increase the abundance and diversity of the intestinal flora of NAFLF rats (P<0.05), and upregulated the abundance of Bacteroidales_ S24-7_group_unclassified, Bifidobacterium, Lactobacillu s, Turicibacter, Parabacteroides, Phascolarctobacterium, Lachnospiraceae_NK4A13 6_group, Coriobacteriaceae_UCG-002, Parasutterella, Odoribacter, Anaerostipes, Ruminococcaceae_unclassified, Allobaculum, Romboutsia, Holdemanella, and Haem ophilus, the difference was statistically significant (P<0.05). Conclusion: Qishen Decoction inhibits liver fibrosis in NAFLF rats by restore the diversity of intestinal flora and increase the abundance of probiotics in intestinal tract. [ABSTRACT FROM AUTHOR]

Objectives: Colorectal cancer is one of the most common malignancies both in men and women. Owing to metastasis and resistance, the prognosis of colorectal cancer-CRC patients remains extremely poor with chemotherapy. A disintegrin and metalloproteinase 17 (ADAM17) induces the activation of Notch pathway and contributes to the chemoresistance. This study aimed to discover a novel ADAM17 inhibitor and investigate the chemosensitization effect. Materials and methods: Pharmacophore model, western blot and enzymatic assay were used to discover ZLDI-8. Cell proliferation was determined by MTT and colony formation assay. Cell migratory and invasive ability were determined by wound healing scratch and transwell assay. Immunofluorescence images and western blot analysed the expression of Notch or epithelial-mesenchymal transition (EMT) pathway markers. Xenografts were employed to evaluate the chemosensitization effect of ZLDI-8 in vivo. Results: We found that ZLDI-8 cell-specifically inhibited the proliferation of CRC, and this effect was due to abrogation of ADAM17 and Notch pathway. Meanwhile, we reported for the first time that ZLDI-8 synergistically improved the anti-tumour and anti-metastasis activity of 5-fluorouracil or irinotecan by reversing Notch and EMT pathways. Interestingly, in vivo studies further demonstrated that ZLDI-8 promoted the anti-tumour effect of 5-fluorouracil through Notch and EMT reversal. Conclusions: A novel ADAM17 inhibitor ZLDI-8 may be a potential chemosensitizer which sensitized CRC cells to 5-fluorouracil or irinotecan by reversing Notch and EMT pathways. [ABSTRACT FROM AUTHOR]

Cytokine-induced killer (CIK) cells that are stimulated using mature dendritic cells (DCs), referred to as (DC-CIK cells) exhibit superior anti-tumor potency. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. This phase I study aimed to assess the safety and clinical activity of immunotherapy with PD-1 blockade (pembrolizumab)-activated autologous DC-CIK cells in patients with advanced solid tumors. Patients with selected types of advanced solid tumors received a single intravenous infusion of activated autologous DC-CIK cells weekly for the first month and every 2 weeks thereafter. The primary end points were safety and adverse event (AE) profiles. Antitumor responses, overall survival (OS), progression-free survival (PFS) and cytolytic activity were secondary end points. Treatment-related AEs occurred in 20/31 patients. Grade 3 or 4 toxicities, including fever and chills, were observed in two patients. All treatment-related AEs were reversible or controllable. The cytotoxicity of DC-CIK cells induced up-regulation of PD-L1 expression on autologous tumor cells. When activated using pembrolizumab ex vivo, DC-CIK cells exerted superior antitumor properties and elevated IFN-γ secretion. Objective responses (complete or partial responses) were observed in 7 of the 31patients.These responses were durable, with 6 of 7 responses lasting more than 5 months. The overall disease control rate in the patients was 64.5%. At the time of this report, the median OS and PFS were 270 and 162 days, respectively. In conclusions, treatment with pembrolizumab-activated autologous DC-CIK cells was safe and exerted encouraging antitumor activity in advanced solid tumors. A larger phase II trial is warranted. [ABSTRACT FROM AUTHOR]

Wheat stem rust, caused by Puccinia granimis f. sp. tritici, severely affects wheat production, but it has been effectively controlled in China since the 1970s. However, the appearance and spread of wheat stem rust races Ug99 (TTKSK, virulence to Sr31), TKTTF (virulence to SrTmp) and TTTTF (virulence to the cultivars carrying Sr9e and Sr13) have received attention. It is important to clarify the effectiveness of resistance genes in a timely manner, especially for the purpose of using new resistance genes in wheat cultivars for durable-resistance. However, little is known about the stem rust resistance genes present in widely used wheat cultivars from Gansu. This study aimed to determine the resistance level at the seedling stage of the main wheat cultivars in Gansu Province. A secondary objective was to assess the prevalence of Sr2, Sr24, Sr25, Sr26, Sr31, and Sr38 using molecular markers. The results of the present study indicated that 38 (50.7%) wheat varieties displayed resistance to all the tested races of Puccinia graminis f. sp. tritici. The molecular marker analysis showed that 13 out of 75 major wheat cultivars likely carried Sr2; 25 wheat cultivars likely carried Sr31; and nine wheat cultivars likely carried Sr38. No cultivar was found to have Sr25 and Sr26, as expected. Surprisingly, no wheat cultivars carried Sr24. The wheat lines with known stem rust resistance genes could be used as donor parent for further breeding programs. [ABSTRACT FROM AUTHOR]

Autophagy is a degradative pathway that delivers cellular components to the lysosome for degradation. The role of autophagy in cell differentiation is poorly understood. Here we show that CaMKII can directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy. Meanwhile, CaMKII can also promote K63-linked ubiquitination of inhibitor of differentiation 1/2 (Id-1/2) by catalyzing phosphorylation of Id proteins and recruiting TRAF-6. Ubiquitinated Id-1/Id-2 can then bind to p62 and be transported to autolysosomes for degradation. Id degradation promotes the differentiation of neuroblastoma cells and reduces the proportion of stem-like cells. Our study proposes a mechanism by which autophagic degradation of Id proteins can regulate cell differentiation. This suggests that targeting of CaMKII and the regulation of autophagic degradation of Id may be an effective therapeutic strategy to induce cell differentiation in neuroblastoma. [ABSTRACT FROM AUTHOR]

Background: Many publications have investigated the association between metal ions and the risk of Alzheimer's disease (AD), but the results were ambiguous. Aims: The objective of this study was to assess the association between the serum levels of metals (copper/zinc/iron) and the risk of AD via meta-analysis of case-control studies. Methods: We screened literatures published after 1978 in the Pubmed, Embase, Cochrane library, Web of Science and ClinicalTrials.gov. Electronic databases. By using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the 407 publications, there are 44 of these publications met all inclusion criteria. The Review Manager 5.3 software was used to calculate available data from each study. Results: Consistent with the conclusions of other meta-analysis, our results demonstrated serum copper levels were significantly higher [MD = 9.27, 95% CI (5.02-13.52); p < 0.0001], and the serum zinc levels were significantly lower in AD patients than in healthy controls [MD = -6.12, 95% CI (-9.55, -2.69); p = 0.0005]. Serum iron levels were significantly lower in AD patients than in healthy controls after excluded two studies [MD = -13.01, 95% CI (-20.75, -5.27); p = 0.001]. Conclusion: The results of our meta-analysis provided rigorous statistical support for the association of the serum levels of metals and the risk of AD, suggesting a positive relationship between the serum copper levels and AD risk, and a negative relationship between the serum zinc/iron levels and AD risk. [ABSTRACT FROM AUTHOR]

In flowering plants, male gametophyte development occurs in the anther. Tapetum, the innermost of the four anther somatic layers, surrounds the developing reproductive cells to provide materials for pollen development. A genetic pathway of DYT1-TDF1- AMS-MS188 in regulating tapetum development has been proven. Here we used laser microdissection and pressure catapulting to capture and analyze the transcriptome data for the Arabidopsis tapetum at two stages. With a comprehensive analysis by the microarray data of dyt1, tdf1, ams, and ms188 mutants, we identified possible downstream genes for each transcription factor. These transcription factors regulate many biological processes in addition to activating the expression of the other transcription factor. Briefly, DYT1 may also regulate early tapetum development via E3 ubiquitin ligases and many other transcription factors. TDF1 is likely involved in redox and cell degradation. AMS probably regulates lipid transfer proteins, which are involved in pollen wall formation, and other E3 ubiquitin ligases, functioning in degradating proteins produced in previous processes. MS188 is responsible for most cell wall-related genes, functioning both in tapetum cell wall degradation and pollen wall formation. These results propose a more complex gene regulatory network for tapetum development and function. [ABSTRACT FROM AUTHOR]

PURPOSE: To investigate the correlation between quantitative parameters on contrast-enhanced ultrasound (CEUS) and pathological prognostic factors in patients with breast invasive ductal carcinomas (IDCs). MATERIALS AND METHODS: 102 patients with pathologically proven IDCs were retrospectively enrolled and all were preoperatively evaluated by CEUS. Quantitative analysis was conducted using the SonoLiver® software. On the parametric imaging, the data of rise time (RT), time to peak (TTP), mean transit time (mTT) and maximum intensity (IMAX) were recorded. Pathological prognostic factors, including histological grade, tumor diameter, lymph node status, estrogen receptor (ER), progesterone receptor (PR), C-erb-B2 and Ki-67 expression were evaluated. Correlation of enhancement parameters with pathological prognostic factors was analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance and operator consistency was evaluated. RESULTS: The RTs and TTPs for lower grade IDCs (grade I or II) and higher histological grade IDCs (grade III) were 9.3 s±3.9 vs. 11.4 s±5.4 (p = 0.016), 11.6 s±6.1 vs. 14.7 s±7.7 (p = 0.028), respectively. The RTs for positive-C-erbB- 2 expression and negative-C-erbB-2 expression IDCs were 10.1 s±4.5 vs. 11.9 s±6.0 (p = 0.047). The IMAX showed statistical difference between IDCs with negative-ER and those with positive-ER (p = 0.003), as well as IDCs with negative- PR and those with positive-PR (p = 0.019). The ROC analysis showed that, for the differentiation ER expression, the cut-off point for IMAX was 648.8% with an Az value of 0.718 (95% CI: 0.599-0.836), and the sensitivity and specificity were 63.6% and 70.2% respectively. The intra-operator consistency of the RT, TTP, mTT and IMAX were excellent with an overall ICC of 0.893, 0.858, 0.984 and 0.800, respectively (all p < 0.001). CONCLUSIONS: Quantitative analysis of CEUS may be a useful and objective method in predicting pathological prognostic factors in breast IDCs. [ABSTRACT FROM AUTHOR]

Background: Magnesium influences hepatic lipid deposition in vertebrates, but the underlying mechanism is unknown.Objective: We used yellow catfish and their isolated hepatocytes to test the hypothesis that magnesium influences lipid deposition by modulating lipogenesis and lipolysis.Methods: Juvenile yellow catfish (mean ± SEM weight: 3.43 ± 0.02 g, 3 mo old, mixed sex) were fed a 0.14- (low), 0.87- (intermediate) or 2.11- (high) g Mg/kg diet for 56 d. Primary hepatocytes were incubated for 48 h in control or MgSO4-containing medium with or without 2-h pretreatment with an inhibitor (AG490, GW6471, or Compound C). Growth performance, cell viability, triglyceride (TG) concentrations, and expression of enzymes and genes involved in lipid metabolism were measured. Results: Compared with fish fed low magnesium, those fed intermediate or high magnesium had lower hepatic lipids (18%, 22%) and 6-phosphogluconate dehydrogenase (6PGD; 3.7%, 3.8%) and malic enzyme (ME; 35%, 48%) activities and greater mRNA levels of the lipolytic genes adipose triacylglyceride lipase (atgl; 82% and 1.7-fold) and peroxisome proliferator-activated receptor (ppara; 18% and 1.0-fold), respectively (P < 0.05). Relative mRNA levels of AMP-activated protein kinase (ampk) a1, ampka2, ampkb1, ampkb2, ampkg1a, ampkg1b, Janus kinase (jak) 2a, jak2b, and signal transducers and activators of transcription (stat) 3 in fish fed high magnesium were higher (24% to 3.1-fold, P < 0.05) than in those fed low or intermediate magnesium. Compared with cells incubated with MgSO4 alone, those incubated with MgSO4 and pretreated with AG490, GW6471, or Compound C had greater TG concentrations (42%, 31%, or 56%), g6pd (98%, 59%, or 51%), 6pgd (68%, 73%, or 32%) mRNA expression, and activities of G6PD (35%, 45%, or 16%) and ME (1.5-fold, 1.3-fold, or 13%), and reduced upregulation (61%, 25%, or 45%) of the lipolytic gene, atgl (P < 0.05).Conclusions: Magnesium reduced hepatic lipid accumulation in yellow catfish and the variation might be attributed to inhibited lipogenesis and increased lipolysis. PPARA, JAK-STAT, and AMPK pathways mediated the magnesium-induced changes in lipid deposition and metabolism. These results offer new insight into magnesium nutrition in vertebrates. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the diagnostic performance of two different shear wave elastography (SWE) techniques in distinguishing malignant breast lesions from benign ones. MATERIALS AND METHODS: From March 2016 to May 2016, a total of 153 breast lesions (mean diameter, 16.8mm±10.5; range 4.1-90.0 mm) in 153 patients (mean age, 46.4 years±15.1; age range 20-86 years) were separately performed by two different SWE techniques (i.e. T-SWE, Aplio500, Toshiba Medical System, Tochigi, Japan; and S-SWE, the Aixplorer US system, SuperSonic Imagine, Provence, France). The maximum (Emax), mean (Emean) and standard deviation (ESD) of elasticity modulus values in T-SWE and S-SWE were analyzed. All the lesions were confirmed by ultrasound (US)-guided core needle biopsy (n = 26), surgery (n = 122), or both (n = 5), with pathological results as the gold standard. The areas under the receiver operating characteristic curves (AUROCs) were calculated. Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV) were calculated to assess the diagnostic performance between T-SWE and S-SWE. Operator consistency was also evaluated. RESULTS: Among the 153 lesions, 41 (26.8%) were malignant and 112 (73.2%) were benign. Emax (T-SWE: 40.10± 37.14 kPa vs. 118.78±34.41 kPa; S-SWE: 41.22±22.54 kPa vs. 134.77±60.51 kPa), Emean (T-SWE: 19.75±16.31 kPa vs. 52.93±25.75 kPa; S-SWE: 20.95±10.98 kPa vs. 55.95±22.42 kPa) and ESD (T-SWE: 9.00±8.55 kPa vs. 38.44± 12.30 kPa; S-SWE: 8.17±6.14 kPa vs. 29.34±13.88 kPa) showed statistical differences in distinguishing malignant lesions from benign ones both in T-SWE and S-SWE (all p < 0.05). In T-SWE, the diagnostic performance of ESD was the highest (AUROC= 0.958), followed by Emax (AUROC= 0.909; p = 0.001 in comparison with ESD) and Emean (AUROC= 0.892; p < 0.001 in comparison with ESD), while in S-SWE, the diagnostic performance of Emax was the highest (AUROC= 0.967), followed by ESD (AUROC= 0.962, p > 0.05 in comparison with Emax) and Emean (AUROC= 0.930, p = 0.034 in comparison with Emax).AUROC-max (T-SWE: 0.909 vs. S-SWE: 0.967),AUROC-mean (T-SWE: 0.892 vs. S-SWE: 0.930) and AUROCSD (T-SWE: 0.958 vs. S-SWE: 0.962) showed no significant difference between T-SWE and S-SWE (all p > 0.05). The intra-class correlation coefficients (ICC) of the intra-operator consistency and inter-operator consistency respectively were 0.961 and 0.898 in T-SWE, while 0.954 and 0.897 in S-SWE. CONCLUSION: T-SWE and S-SWE are equivalent for distinguishing the breast lesions. In T-SWE, ESD had the best diagnostic performance, while in S-SWE, Emax had the best diagnostic performance. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to compare the diagnostic performance of two different 2D shear wave speed imaging techniques of Virtual Touch Tissue Imaging&Quantification (VTIQ) and Toshiba shear wave elastography (T-SWE) in predicting malignant thyroid nodules (TNs). MATERIALS AND METHODS: 75 TNs in 75 patients which were subject to both VTIQ and T-SWE examinations were enrolled and analyzed. Shear wave speed (SWS) values on VTIQ and T-SWE were computed (SWS max, min, mean and median). Area under the receiver operating characteristic (AUROC) curve was obtained to assess the diagnostic performance. RESULTS: The AUROC for VTIQ was the highest with SWS min whereas for T-SWE was SWS max (0.774 versus 0.851; p > 0.05). The AUROC, sensitivity and negative predictive value (NPV) corresponding to SWS max for VTIQ were significantly lower than those for T-SWE (0.717 versus 0.851, 61.5% versus 92.3% and 78.7% versus 94.3%; all p < 0.05). However, no significant differences were found between AUROC with SWS min, SWS mean, or SWS median for VTIQ and SWS max for T-SWE (all p > 0.05). CONCLUSION: In general, VTIQ is equal to T-SWE for diagnosis of TNs. In the clinical practice, the selection of SWS max should be avoided in VTIQ whereas should be selected in T-SWE. [ABSTRACT FROM AUTHOR]

BACKGROUND: Non-calcified thyroid nodules are relatively difficult to diagnose only relying on features of at conventional US images. OBJECTIVE: To investigate the diagnostic performances of conventional strain elastography (SE), acoustic radiation force impulse (ARFI) SE and point shear-wave speed (pSWS) measurement for non-calcified thyroid nodules. METHODS:Atotal of 201 non-calcified thyroid nodules in 195 patients were studied. They were examined with conventional ultrasound (US), conventional SE, ARFISEandpSWSmeasurement. Their diagnostic performances and multivariable models were assessed with receiver operating characteristic (ROC) curve and logistic regression analyses respectively. RESULTS: There were 156 benign and 45 malignant non-calcified nodules proven by histopathology or cystology. The mean diameters of the nodules were 21.2±10.8 mm. Areas under receiver operating characteristic curve (AUCs) of elastography features (ranged, 0.488-0.745) were all greater than that of US (ranged, 0.111-0.332). At multivariate analysis, there were three predictors of malignancy for non-calcified nodules, including pSWS of nodule (odds ratio [OR], 34.960; 95% CI, 11.582-105.529), marked hypoechogenicity (OR, 16.223; 95% CI, 1.761-149.454) and ARFI SE grade (OR, 10.900; 95% CI, 3.567-33.310). US+SE+pSWS owned the largest AUC (0.936; 95% CI, 0.887-0.985; P < 0.05), followed by US+pSWS (0.889; 95% CI, 0.823-0.955), and the poorest was US (0.727; 95% CI, 0.635-0.819). CONCLUSIONS: ARFI SE and pSWS measurement had better diagnostic performances than conventional SE and US. When US combined with SE and pSWS measurement, it could achieve an excellent diagnostic performance and might contribute a better decision-making of FNA for non-calcified thyroid nodules. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the usefulness of thyroid imaging reporting and data system (TI-RADS) for cytological Bethesda Category III thyroid nodules (TNs). METHODS: This retrospective study included 121 patients with 121 TNs classified as Bethesda Category III at fine needle aspiration (FNA) cytology and thereafter underwent surgery. The TNs were classified according to US TI-RADS category and the malignancy risk of each category was calculated. RESULTS: Surgical pathology confirmed 43 (35.5%) malignant and 78 (64.5%) benign TNs. The malignancy risks of categories 3, 4a, 4b, 4c, and 5 TNs were 0%, 4.0%, 12.5%, 62.2%, and 100%, respectively. For those >10mm (n = 55), the malignancy risks were 0%, 6.2%, 12.5%, 73.3%, and 100%, respectively, whereas for those ≤10 mm (n = 66), the risks were 0%, 0%, 12.5%, 56.7%, and 100%, respectively. CONCLUSION: Bethesda Category III TNs without suspicious US features or those ≤10mm with only one suspicious US feature can be followed up with US. [ABSTRACT FROM AUTHOR]

Objective: To investigate the usefulness of fusion imaging of contrast-enhanced ultrasound (CEUS) and CECT/CEMRI before percutaneous ultrasound-guided radiofrequency ablation (RFA) for liver cancers. Methods: 45 consecutive patients with 70 liver lesions were included between March 2013 and October 2015, and all the lesions were identified on CEMRI/CECT prior to inclusion in the study. Planning ultrasound for percutaneous RFA was performed using conventional ultrasound, ultrasound-CECT/CEMRI and CEUS and CECT/CEMRI fusion imaging during the same session. The numbers of the conspicuous lesions on ultrasound and fusion imaging were recorded. RFA was performed according to the results of fusion imaging. Complete response (CR) rate was calculated and the complications were recorded. Results: On conventional ultrasound, 25 (35.7%) of the 70 lesions were conspicuous, whereas 45 (64.3%) were inconspicuous. Ultrasound-CECT/CEMRI fusion imaging detected additional 24 lesions thus increased the number of the conspicuous lesions to 49 (70.0%) (70.0% vs 35.7%; p < 0.001 in comparison with conventional ultrasound). With the use of CEUS and CECT/CEMRI fusion imaging, the number of the conspicuous lesions further increased to 67 (95.7%, 67/70) (95.7% vs 70.0%, 95.7% vs 35.7%; both p < 0.001 in comparison with ultrasound and ultrasound-CECT/CEMRI fusion imaging, respectively). With the assistance of CEUS and CECT/CEMRI fusion imaging, the confidence level of the operator for performing RFA improved significantly with regard to visualization of the target lesions (p = 0.001). The CR rate for RFA was 97.0% (64/66) in accordance to the CECT/CEMRI results 1 month later. No procedure-related deaths and major complications occurred during and after RFA. Conclusion: Fusion of CEUS and CECT/CEMRI improves the visualization of those inconspicuous lesions on conventional ultrasound. It also facilitates improvement in the RFA operators' confidence and CR of RFA. Advances in knowledge: CEUS and CECT/CEMRI fusion imaging is better than both conventional ultrasound and ultrasound-CECT/CEMRI fusion imaging for lesion visualization and improves the operator confidence, thus it should be recommended to be used as a routine in ultrasound-guided percutaneous RFA procedures for liver cancer. [ABSTRACT FROM AUTHOR]

Background: What patients expect to happen during treatment or benefit from the treatment might influence the subsequent factors such as treatment outcome, patient satisfaction, patient's cooperation as well as compliance. The aim of this systematic review is to assess the role of patients' expectations from orthodontic treatment. Methods: A systematic literature search of four databases Pubmed, Cochrane, Web of Science and PsychINFO was conducted following PRISMA guidelines. Studies reporting expectations regarding orthodontic treatment were selected and a narrative review was conducted. The quality of study was rated according to STROBE statements and the methodology as well as key findings were summarized. Results: Thirteen studies (14 papers) were finally included for analysis. Among them, only one was a randomized control trial, while the rest included one cohort study, two questionnaire-developments and ten cross-sectional studies. The STROBE quality of reporting scores of the studies ranged from 12 to 18. Seven papers described expectations of the treatment experiences, along with seven talking about benefit expectations from the treatment. Dental appearance and function improvement were most expected in studies relate to the treatment benefits. Conclusions: Orthodontics appears to have adopted various standardized questionnaires. However, most of them are poor in the quality of methodology and results analyses, which prohibit synthesizing sufficient evidence to help identify which factors influence patient expectations. The evidence of "expectations" affecting treatment outcomes is not found in current research. Future studies are needed to better understand the impact of "expectation" on the treatment both theoretically and experimentally. [ABSTRACT FROM AUTHOR]

Background: Chronic stable angina is a leading cause of death worldwide. Danhong injection, a complementary alternative medicine for chronic stable angina, has been demonstrated to be effective in numerous studies and is widely prescribed to patients. However, the methodological quality of most prior studies was found to be, in general, low. Therefore, we designed this randomized controlled trial to evaluate the efficacy and safety of using Danhong injection to treat chronic stable angina.Methods/design: This is a randomized multicentre, double-blind, placebo-controlled, adaptive clinical trial. A total of 870 patients meeting the eligibility criteria will be randomly assigned into either the Danhong injection or the placebo group in a 2:1 ratio. Participants will then undergo a 2-week treatment regimen and a 76-day follow-up period. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. Based on the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire, which will be administered on day 30. Other secondary efficacy and safety outcomes will also be assessed.Discussion: This trial will provide high-quality evidence regarding the use of Danhong injection to treat chronic stable angina.Trial Registration: ClinicalTrials.gov: NCT01681316 . [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have emerged as important regulators of cancer-cell biological processes. Previous studies have shown that mi-766 plays an important role in a variety of biological processes in various human cancers. However, the underlying mechanism of mi-766 in colorectal cancer (CRC) cells remains unclear. In this study, we investigated mi-766's role in CRC cell proliferation. Polymerase chain reaction results showed that mi- 766 expression was significantly upregulated in CRC tissues and cells. Ectopic expression of mi-766 promoted cell growth and anchorage-independent growth in CRC cells. Bioinformatic analysis predicted SOX6, a potential target of mi-766, acting as a tumor suppressor. Luciferase reporter assay results demonstrated that mi-766 directly bound to the 3'-untranslated region of SOX6. Overexpression of mi-766 suppressed SOX6 expression, resulting in the downregulation of p21 and upregulation of cyclin D1. In a further experiment, SOX6-silenced SW480 cells transfected with mi-766 promoted cell growth, suggesting that downregulation of SOX6 was required for mi-766-induced CRC cell proliferation. Taken together, these results suggested that mi-766 represents an onco-miRNA and participates in the development of CRC by modulating SOX6 expression. [ABSTRACT FROM AUTHOR]

The aim of this study was to construct an expression vector carrying the hypoxia/radiation dual-sensitive chimeric hypoxia response element (HRE)/early growth response 1 (Egr-1) promoter in order to overexpress the therapeutic second mitochondria-derived activator of caspases (Smac). Using this expression vector, the present study aimed to explore the molecular mechanism underlying radiotherapy-induced A549 human lung adenocarcinoma cell death and apoptosis under hypoxia. The plasmids, pcDNA3.1-Egr1-Smac (pE-Smac) and pcDNA3.1-HRE/Egr-1-Smac (pH/E-Smac), were constructed and transfected into A549 human lung adenocarcinoma cells using the liposome method. CoCl2 was used to chemically simulate hypoxia, followed by the administration of 2 Gy X-ray irradiation. An MTT assay was performed to detect cell proliferation and an Annexin V-fluorescein isothiocyanate apoptosis detection kit was used to detect apoptosis. Quantitative polymerase chain reaction and western blot analyses were used for the detection of mRNA and protein expression, respectively. Infection with the pE-Smac and pH/E-Smac plasmids in combination with radiation and/or hypoxia was observed to enhance the expression of Smac. Furthermore, Smac overexpression was found to enhance the radiation-induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis. The cytochrome c/caspase-9/caspase-3 pathway was identified to be involved in this regulation of apoptosis. Plasmid infection in combination with X-ray irradiation was found to markedly induce cell death under hypoxia. In conclusion, the hypoxia/radiation dual-sensitive chimeric HRE/Egr-1 promoter was observed to enhance the expression of the therapeutic Smac, as well as enhance the radiation-induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis under hypoxia. This apoptosis was found to involve the mitochondrial pathway. [ABSTRACT FROM AUTHOR]

We investigate the synchronization problem of two colored networks via discrete control based on the Lyapunov stability theory. First, intermittent control is adopted to synchronize two edge-colored networks, and the sufficient condition connecting the control width, control period and the network topology is established for reaching synchronization. Then, an impulsive controller is designed to ensure two general colored networks in synchronization, and the relation among the impulsive interval, impulsive gain and the network topology for synchronization is also discovered. Finally, two numerical examples are provided to demonstrate and verify the theoretical results. [ABSTRACT FROM AUTHOR]

Background: Hirsutanol A is a novel sesquiterpene compound purified from fungus Chondrostereum sp. in Sarcophyton tortuosum. Our previous studies had demonstrated that hirsutanol A exhibited potent cytotoxic effect on many kinds of cancer cell lines. In the current study, the antitumor activity of hirsutanol A and its molecular mechanisms were investigated. Methods: Hirsutanol A induced growth inhibition and apoptotic cell death of human colon cancer SW620 cells and human breast cancer MDA-MB-231 cells were determined using MTT assay and flow cytometry assay, respectively. The effect of hirsutanol A on intrinsic ROS level and change in mitochondrial membrane potential (ΔΨm) of different cell lines were also measured by flow cytometry assay. The function of JNK was compromised by JNK siRNA or JNK inhibitor SP600125. The expression of cytochrome c, p-JNK, p-c-Jun after treatment with hirsutanol A were detected by Western blot analysis. Finally, the in vivo anti-tumor effect of hirsutanol A was examined in human cancer cell SW620 xenograft model. Results: The results showed that hirsutanol A significantly induced apoptosis, mitochondrial-independent increase of Reactive Oxygen Species (ROS) level, change of mitochondrial membrane potential, release of cytochrome c in human cancer cells. Preventing increase of ROS level using the potent antioxidant N-acetyl-L-cysteine (NAC) markedly decreased hirsutanol A-induced apoptosis. In addition, JNK signaling pathway was activated by hirsutanol A through elevating ROS level. Blockade of JNK signaling pathway by JNK specific inhibitor SP600125 enhanced apoptosis and hirsutanol A-induced ROS accumulation. Also, hirsutanol A exhibited antitumor activity in human cancer cell SW620 xenograft model. Conclusion: These data suggested that hirsutanol A inhibited tumor growth through triggering ROS production and apoptosis. [ABSTRACT FROM AUTHOR]

Background: Topotecan produces DNA damage that induces autophagy in cancer cells. In this study, sensitising topotecan to colon cancer cells with different P53 status via modulation of autophagy was examined. Methodology/Principal Findings: The DNA damage induced by topotecan treatment resulted in cytoprotective autophagy in colon cancer cells with wild-type p53. However, in cells with mutant p53 or p53 knockout, treatment with topotecan induced autophagy-associated cell death. In wild-type p53 colon cancer cells, topotecan treatment activated p53, upregulated the expression of sestrin 2, induced the phosphorylation of the AMPKα subunit at Thr172, and inhibited the mTORC1 pathway. Furthermore, the inhibition of autophagy enhanced the anti-tumour effect of topotecan treatment in wild-type p53 colon cancer cells but alleviated the anti-tumour effect of topotecan treatment in p53 knockout cells in vivo. Conclusions/Significance: These results imply that the wild-type p53-dependent induction of cytoprotective autophagy is one of the cellular responses that determines the cellular sensitivity to the DNA-damaging drug topotecan. Therefore, our study provides a potential therapeutic strategy that utilises a combination of DNA-damaging agents and autophagy inhibitors for the treatment of colon cancer with wild-type p53. [ABSTRACT FROM AUTHOR]

Background: Autophagy is an evolutionarily conserved protein degradation pathway. A defect in autophagy may contribute to tumorigenesis. Autophagy inducers could have a potential function in tumor prevention and treatment. Methodology/Principal Findings: Our results showed that Rhabdastrellic acid-A, an isomalabaricane triterpenoid isolated from the sponge Rhabdastrella globostellata, inhibited proliferation of human cancer cell lines Hep3B and A549 and induced caspase-independent cell death in both the cell lines. Further investigation showed that Rhabdastrellic acid-A induced autophagy of cancer cells determined by YFP-LC3 punctation and increased LC3-II. The pretreatment with autophagy inhibitor 3-MA inhibited Rhabdastrellic acid-A-induced cell death. Knockdown of autophagy-related gene Atg5 inhibited Rhabdastrellic acid-A-induced cell death in A549 cells. Also, phospho-Akt and its downstream targets significantly decreased after treatment with Rhabdastrellic acid-A in both cancer cell lines. Transfection of constitutive active Akt plasmid abrogated autophagy and cell death induced by Rhabdastrellic acid-A. Conclusions/Significance: These results suggest that Rhabdastrellic acid-A could induce autophagy-associated cell death through blocking Akt pathway in cancer cells. It also provides the evidence that Rhabdastrellic acid-A deserves further investigation as a potential anticancer or cancer preventive agent. [ABSTRACT FROM AUTHOR]