MethMarkerDB: a comprehensive cancer DNA methylation biomarker database.

DNA methylation plays a crucial role in tumorigenesis and tumor progression, sparking substantial interest in the clinical applications of cancer DNA methylation biomarkers. Cancer-related whole-genome bisulfite sequencing (WGBS) data offers a promising approach to precisely identify these biomarkers with differentially methylated regions (DMRs). However, currently there is no dedicated resource for cancer DNA methylation biomarkers with WGBS data. Here, we developed a comprehensive cancer DNA methylation biomarker database (MethMarkerDB, https://methmarkerdb.hzau.edu.cn/), which integrated 658 WGBS datasets, incorporating 724 curated DNA methylation biomarker genes from 1425 PubMed published articles. Based on WGBS data, we documented 5.4 million DMRs from 13 common types of cancer as candidate DNA methylation biomarkers. We provided search and annotation functions for these DMRs with different resources, such as enhancers and SNPs, and developed diagnostic and prognostic models for further biomarker evaluation. With the database, we not only identified known DNA methylation biomarkers, but also identified 781 hypermethylated and 5245 hypomethylated pan-cancer DMRs, corresponding to 693 and 2172 genes, respectively. These novel potential pan-cancer DNA methylation biomarkers hold significant clinical translational value. We hope that MethMarkerDB will help identify novel cancer DNA methylation biomarkers and propel the clinical application of these biomarkers.

[Short-term efficacy of digitally-assisted traditional Chinese medicine manual reduction combined with 3D printed splint in the treatment of AO type-A distal radius fractures].

Objective To explore the short-term efficacy of digitally-assisted traditional Chinese medicine manual reduction combined with 3D printed splint in the treatment of AO type-A distal radius fractures, and explore the quantification of traditional Chinese medicine manual reduction and personalized improvement of splinting. Methods The clinical data of 50 patients with AO type-A distal radius fractures, who received treatment at the outpatient department of Cangzhou Integrated Traditional Chinese and Western Medicine Hospital in Hebei Province, were retrospective analyzed. The patient cohort included 22 females and 28 males, with ages ranging from 25 to 75 years old. Among them, 27 cases presented with distal radius fractures on the left side, and 24 cases on the right side. The patients were categorized into two groups: treatment group (n=25) and control group(n=25). There were 13 males and 12 females in the treatment group, with an average age of (56.2±5.5) years old. Treatment approach for this group involved several steps. Initially, Mimics Research software was used to conduct comprehensive analysis of complete CT data from the affected limb, resulting in the creation of a three-dimensional model. Subsequently, 3D models of the bones and skin contours, stored as STL format files, were imported into the Materialise Magics 23.0 software for model processing and repair. This facilitated the simulation of reduction and recording of displacement data, effectively generating a "digital prescription" to guide and quantify traditional Chinese medicine manipulation procedures. Finally, a personalized 3D printed splint was applied for fixation treatment. There were 15 males and 10 females in the control group, with an average age of (53.32±5.28) years old. These patients were treated with manualreduction combined with traditional splinting. The clinical efficacy of the two groups was assessed in terms of fracture reduction quality, fracture healing time, Gartland-Werley wrist joint score and X-ray parameters (palminclination angle, ulnar deviation angle, radius height) at 6 weeks post-operatively. Results The treatment group exhibited a shorter duration for achieving clinical healing compared to the control group (P<0.05). Six weeks post-operatively, the treatment group demonstrated higher wrist joint function scores, and a higher proportion of excellent and good outcomes than the control group(P<0.05). The treatment group was superior to the control group in terms of imaging parameters 6 weeks post-operatively (P<0.05). Conclusion By quantifying skin contours through digital simulation prescription reduction, a personalized 3D printed splint is developed to effectively stabilize fractures, enhancing localized fixation while ensuring greater adherence, stability, and comfort. This innovative approach offers personalized treatment for AO type-A distal radius fractures and presents a novel, precise treatment strategy for consideration.

Genome Sequence Resource of Pectobacterium polaris QK413-1 that Causes Blackleg on Potato in Fujian Province, China.

The Pectobacterium pathogens cause soft rot and blackleg diseases on many plants and crops, including potatoes. Here, we first report a high-quality genome assembly and announcement of the P. polaris strain QK413-1, which causes blackleg disease in potatoes in China. The QK413-1 genome was sequenced and assembled using the PacBio Sequel II and Illumina sequencing platform. The assembled genome has a total size of 5,005,507 bp with a GC content of 51.81%, encoding 4,782 open reading frames, including 639 virulence genes, 273 drug resistance genes, and 416 secreted proteins. The QK413-1 genome sequence provides a valuable resource for the control of potato blackleg and research into its mechanism.

Genetic Dissection of Phosphorus Use Efficiency and Genotype-by-Environment Interaction in Maize.

Genotype-by-environment interaction (G-by-E) is a common but potentially problematic phenomenon in plant breeding. In this study, we investigated the genotypic performance and two measures of plasticity on a phenotypic and genetic level by assessing 234 maize doubled haploid lines from six populations for 15 traits in seven macro-environments with a focus on varying soil phosphorus levels. It was found intergenic regions contributed the most to the variation of phenotypic linear plasticity. For 15 traits, 124 and 31 quantitative trait loci (QTL) were identified for genotypic performance and phenotypic plasticity, respectively. Further, some genes associated with phosphorus use efficiency, such as Zm00001eb117170, Zm00001eb258520, and Zm00001eb265410, encode small ubiquitin-like modifier E3 ligase were identified. By significantly testing the main effect and G-by-E effect, 38 main QTL and 17 interaction QTL were identified, respectively, in which MQTL38 contained the gene Zm00001eb374120, and its effect was related to phosphorus concentration in the soil, the lower the concentration, the greater the effect. Differences in the size and sign of the QTL effect in multiple environments could account for G-by-E. At last, the superiority of G-by-E in genomic selection was observed. In summary, our findings will provide theoretical guidance for breeding P-efficient and broadly adaptable varieties.

Metabolomics-based evidence of the hypoglycemic effect and alleviation of diabetic complications by Ficus racemosa fruit in diabetic mice.

The hypoglycemic and metabolic effects of Ficus racemosa fruit were studied in diabetic mice, and its potential mechanisms of hypoglycemic activity and its alleviation of diabetic complications were explored using a metabolomics approach. The histopathological effect of Ficus racemosa fruit was characterized by hematoxylin and eosin histological staining. Dynamic fasting blood glucose (FBG), postprandial glucose (PPG), body weight, and biochemical parameters, including hepatic-renal function and lipid levels, were monitored to confirm the hypoglycemic activity and attenuation effect. The metabolomics analysis was performed using the established platform, combining liquid chromatography-tandem mass spectrometry with statistical analysis to identify the metabolites internally regulated by Ficus racemosa fruit. Desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was employed to explore the presence and spatial distribution patterns of differential molecules further. An inhibition of blood glucose levels and improvements in tissue lesions were observed after Ficus racemosa fruit treatment, especially with high-dose treatment. Ficus racemosa fruit primarily induced metabolomic alterations in amino acids, organic acids and nucleotides, and displayed a systematic effect, which involved the mediation of amino acid metabolism, glucose metabolism, energy metabolism and lipid accumulation. The effect of Ficus racemosa fruit on the liver was primarily discussed in this study, and it regulated purine metabolism, glycolysis/gluconeogenesis, arginine biosynthesis, histidine metabolism, alanine, aspartate and glutamate metabolism, and the citrate cycle. Through the mediation of related pathways or single molecules that could affect insulin resistance, insulin secretion or FBG, e.g., the amino acid histidine or the organic acid uric acid in the liver, Ficus racemosa fruit achieved its hypoglycemic effect and alleviated diabetic complications in the liver. The results of the tissue metabolomic analysis, histopathological analysis, plasma biochemical parameters, plasma metabolite analysis and tissue DESI-MSI analysis were consistent with one another. The present study provides the evidence of the hypoglycemic effect and its alleviation of diabetic complications for Ficus racemosa fruit as well as the scientific support for its traditional use.

Genetic Dissection of Phosphorus Use Efficiency in a Maize Association Population under Two P Levels in the Field.

Phosphorus (P) deficiency is an important challenge the world faces while having to increase crop yields. It is therefore necessary to select maize (Zea may L.) genotypes with high phosphorus use efficiency (PUE). Here, we extensively analyzed the biomass, grain yield, and PUE-related traits of 359 maize inbred lines grown under both low-P and normal-P conditions. A significant decrease in grain yield per plant and biomass, an increase in PUE under low-P condition, as well as significant correlations between the two treatments were observed. In a genome-wide association study, 49, 53, and 48 candidate genes were identified for eleven traits under low-P, normal-P conditions, and in low-P tolerance index (phenotype under low-P divided by phenotype under normal-P condition) datasets, respectively. Several gene ontology pathways were enriched for the genes identified under low-P condition. In addition, seven key genes related to phosphate transporter or stress response were molecularly characterized. Further analyses uncovered the favorable haplotype for several core genes, which is less prevalent in modern lines but often enriched in a specific subpopulation. Collectively, our research provides progress in the genetic dissection and molecular characterization of PUE in maize.

Transient complete atrioventricular block and ST-segment elevation induced by coronary vasospasm due to iatrogenic hyperkalemia: a case report.

BACKGROUND: Hyperkalemia and acute coronary syndrome are not only all responsible for syncope related to complete atrioventricular block, but also share parts of electrocardiogram manifestations. Additionally, they influence each other. CASE PRESENTATION: A 32-year-old Chinese man presented with severe hypokalemia (1.63 mmol/l) at midnight in the emergency room. He developed unexpected rebound hyperkalemia (7.76 mmol/l) after 18 hours of oral and intravenous potassium chloride supplementation at a concentration of about 10 g/day and a rate of 10 mmol/hour. Subsequently, the patient complained of chest discomfort and dyspnea, followed by syncope for several minutes, approximately 2 hours after potassium reduction treatment had been started. The instant electrocardiogram showed complete atrioventricular block and elevated ST segment in the inferolateral leads, which resolved 15 minutes later, before hyperkalemia was corrected. Combined with mild coronary stenosis and negative myocardial injury markers, transient complete atrioventricular block induced by coronary vasospasm due to iatrogenic hyperkalemia was diagnosed. Normal urine potassium excretion, acid-base state, and other examinations made the diagnosis of hypokalemic periodic paralysis possible. CONCLUSIONS: Hyperkalemia may provoke acute coronary syndrome, and early coronary angiography is an effective strategy for identifying the direct cause of acute complete atrioventricular block.

Clinical study of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen in the treatment of advanced esophageal cancer.

OBJECTIVE: this study aimed to investigate the clinical efficacy and feasibility of the treatment of advanced esophageal cancer with a combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen. METHODS: forty-five patients with advanced esophageal cancer were enrolled and were randomly divided into two groups: a treatment group and a control group. Patients in the treatment group were treated with a 125I particle-integrated esophageal covered stent and hyperbaric oxygen, while patients in the control group were treated with a 125I particle-integrated esophageal covered stent. The clinical effects and long-term survival time of the two groups were observed. RESULTS: in the treatment group, the complete remission (CR) rate and partial remission (PR) rate of local lesions were 19.2 % and 61.5 %, respectively, and the total effective rate was 80.7 %. In the control group, the CR rate and PR rate of local lesions were 10.5 % and 52.6 %, respectively, and the total effective rate was 63.1 %. The total effective rate was higher in the treatment group than in the control group, which was statistically significant (p < 0.05). CONCLUSION: the combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen shows a good short- and long-term efficacy in the treatment of advanced esophageal cancer.

Emerging strategies for the activity assay and inhibitor screening of alpha-glucosidase.

The high incidence of diabetes mellitus has caused widespread concern around the world, and has quickly become one of the most prevalent and costly chronic diseases. Alpha-glucosidase has been considered as the main target enzyme in the prevention and treatment of type 2 diabetes, and the inhibition of alpha-glucosidase activity can control postprandial blood glucose levels of diabetics and keep blood glucose levels normal. However, most of the current antidiabetic drugs in the clinic have many side effects. Recently, the screening of alpha-glucosidase inhibitors, from natural products, with excellent activity and less side effects has been successfully achieved, which also proposes more requirements and challenges for the approaches of alpha-glucosidase inhibitor (AGI) screening because of the trace level of active compounds in natural products, large-scale sample screening, and complex matrix of natural products. In this review, we comprehensively summarized the available strategies for the assay of alpha-glucosidase activity and AGI screening for the first time, including classic strategies such as high throughput screening methods (e.g. capillary electrophoresis strategies, HPLC/LC-MS strategies), emerging sensing strategies (e.g. colorimetric sensing, fluorescence sensing, electrochemical sensing, and surface plasmon resonance sensing) and other strategies. Finally, future opportunities and challenges in future research are tentatively proposed.

Fragmented endocardial signals and early afterdepolarizations during torsades de pointes tachycardia.

BACKGROUND: Bradycardia-induced torsade de pointes (TdP) tachycardia in patients with spontaneous high-degree atrioventricular block (AVB) is common. The aim of this study was to analyze endocardial recordings during TdP in spontaneous high-degree AVB in humans to better understand the electrophysiological mechanisms underlying this phenomenon. METHODS: The study group consisted of 5 patients with typical episodes of TdP during spontaneous high-degree AVB. A standard (USCI) temporary bipolar endocardial catheter positioned at the apex of the right ventricle (RV) and bipolar chest leads from two precordial leads V1 and V4 were used to record the tracings during TdP. RESULTS: The presence of a wide spectrum of fragmentations was noted on endocardial electrograms (EGMs), which were invisible on the surface electrocardiogram (ECG) tracing. Endocardial signals indicated that TdP started in the proximity of the RV apex, since the local EGM began prior to the QRS complex on the surface ECG. Early afterdepolarizations (EADs) were observed in 2 out of 5 cases confirming a common opinion about the mechanism of TdP. However, this phenomenon was not observed in 3 other patients suggesting that the arrhythmia was the result of a different mechanism originating in proximity to the RV apex. CONCLUSIONS: This work demonstrated early endocardial signals in the RV apex during TdP associated with high-degree AVB in humans, and exhibits a spectrum of fragmented signals in this area occurring on a single or multiple beats. These fragmentations indicate areas of poor conduction and various degrees of intramyocardial block, and therefore a new mechanism of TdP tachycardia in some patients with spontaneous high-degree AVB.

An advanced and universal method to high-efficiently deproteinize plant polysaccharides by dual-functional tannic acid-feIII complex.

Deproteinization is a crucial step for the purification of polysaccharides from natural biomass. However, traditional deproteinization technologies often suffer from complicated operating processes and the usage of toxic chemical reagents. Herein, an advanced and universal deproteinization method based on dual-functional adsorbent consisted of preferential protein adsorption coating of tannic acid-FeIII (TA-FeIII) and magnetic Fe3O4 (Fe3O4@TA-FeIII, abbreviated as FTF NPs) was developed. The proposed FTF NPs showed remarkable efficiency to remove protein from Lycium barbarum L. polysaccharides (LBPs) with deproteinization ratio of 96%, higher than the typical Sevag method (85%). Detailed adsorption kinetics studies demonstrated deproteinization process reached equilibrium after 10 min, faster than other reported deproteinization adsorbents. Furthermore, FTF NPs are structurally and functionally nondestructive as regards LBPs without using organic reagents. Also, it exhibited widespread-use deproteinization performance to several common plant species. Therefore, the proposed nano-separation based on TA-FeIII complex is an advanced and universal tool to high-efficiently deproteinize plant polysaccharides.

Biologically synthesized green gold nanoparticles from Siberian ginseng induce growth-inhibitory effect on melanoma cells (B16).

Siberian ginseng, perennial herb belongs to Araliaceae family used in traditional medicines to treat hypertension, thrombus, inflammation and cancer. In the present study, we biosynthesized goldnanoparticles using Siberian ginseng aqeous extract in a cost effective manner. The synthesized Siberian ginseng gold nanoparticle (SG-GNPs) were characterized using UV-Vis spec, HR-TEM, XRD, FTIR, SAED analysis. UV-Vis spectroscopic analysis showed a surface Plasmon resonance peak at 538 nm which does not reduce till 30 days of incubation. The results of HR-TEM, XRD and SAED confirm the spherical shape, crystalline nature and the size of the synthesized gold nanoparticles. The FTIR results prove that the biological components present in the Siberian ginseng had reduced the gold ions to synthesis gold nanoparticles. After characterization, the efficacy of SG-GNPS against the melanoma, a deadliest skin carcinoma, was assessed in vitro using B16 murine melanoma cells. The CC50 dose of SG-GNPs against B16 cells were assessed with MTT assay and the anticancer activity was evaluated using Rhodamine 123, H2DCFDA and dual staining techniques. The induction of apoptosis by SG-GNPs against melanoma cells were confirmed with q-PCR analysis. The results of staining techniques prove that SG-GNPs increase the reactive oxygen species and decreased the mitochondrial membrane potential. It is further confirmed by the results of q-PCR analysis which shows increased apoptotic Bid, Bad, Casp3, Casp 9 genes and decreased antiapoptotic Bcl2 gene expression in SG-GNPs treated cells. Our results authentically prove the biosynthesized SG-GNPs induces apoptosis in melanoma cells and it possesses anticancer property.

Zinc oxide nanoparticles synthesized from Allium cepa prevents UVB radiation mediated inflammation in human epidermal keratinocytes (HaCaT cells).

The extensive relevance of nanoparticles arouses the requirement for manufacturing although the predictable technique are frequently perilous and energy saving. In the current study, zinc oxide nanoparticles manufactured from Allium cepa avert UVB radiation interceded irritation in human epidermal keratinocytes (HaCaT cells). In the current study, the zinc oxide nanoparticles (ZnO-NPs) was synthesized from the extract of A. cepa. The optimized ZnO-NPs hence attained and was enumerated and exemplified by UV visible spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscope (SEM) and EDAX impending analysis. In addition, amalgamated ZnO-NPs were experienced for cell viability (MTT), formation of reactive oxygen species (ROS), apoptosis, and antioxidant and lipid peroxidation (TBARS) levels. Also, we explored the effect of A. cepa ZnO-NPs in molecular level by evaluating the inflammatory and apoptotic markers, in which ZnO-NPs reinstated the interleukins 6, 10 and related signaling molecules like iNOS, COX-2 levels. Ultimately, ZnO-NPs induce apoptotic markers (Bax, Bcl-2) and also recommended that ZnO-NPs might aggravate cancer cell apoptosis in HaCaT cells.

Mineral and bone disorder in hemodialysis patients in the Tibetan Plateau: a multicenter cross-sectional study.

Background: Mineral and bone disorder (MBD) in hemodialysis patients is associated with increased morbidity and mortality. Studies on the MBD status of hemodialysis patients at high altitudes are extremely limited. Methods: A total of 146 hemodialysis patients from 5 local hospitals across all districts with hemodialysis centers in the Tibetan Plateau were enrolled in this cross-sectional study. Parameters related to MBD, including serum phosphorus (P), calcium (Ca), and intact parathyroid hormone (iPTH) levels, were measured. The achievement of MBD goals was compared with the achievement in the Dialysis Outcomes and Practice Study (DOPPS) 3, DOPPS 4 and a multicenter study of MBD in China. Factors associated with hyperphosphatemia were examined. Results: Altogether, 146 hemodialysis patients were recruited from the Tibetan Plateau. According to the K/DIGO guidelines, there were low achievement rates for serum Ca (40.4%), P (29.7%), and iPTH (47.1%). As for the (KDOQI) guidelines, the rates of achievement of defined targets were 38.4%, 33.7% and 16.4% for serum Ca, P and iPTH, respectively. The percentages of patients reaching the KDOQI targets for corrected Ca, P, and iPTH were significantly lower for Tibetan patients than the percentages found in DOPPS 3 (38.4% vs. 50.4%, 33.7% vs. 49.8%, and 16.4% vs. 31.4%, respectively, all p < .001) and DOPPS 4 (38.4% vs. 56.0%, 33.7% vs. 54.5%, and 16.4% vs. 35.3%, respectively, all p < .001). The percentage of patients reaching the KDOQI targets for iPTH was significantly lower in Tibet than in the plain areas of China (16.4% vs. 26.5%, p < .001). The proportion of patients with hypocalcemia was higher in Tibet than in the plain areas (44.5% vs. 19.4%, p < .001). The percentage of local patients with optimal P was significantly higher for patients with an activated vitamin D prescription than for patients without an activated vitamin D prescription (45.3% vs. 19.3%, p < .001). Age and the activated vitamin D prescription were independently associated with hyperphosphatemia. Conclusion: The MBD status of hemodialysis patients in Tibet is far from the ideal level. High altitude is one of the possible causes of the differences found, but not the principal one. It is necessary for medical staff in Tibet to improve the detection and treatment of MBD.

Bio-related applications of porous organic frameworks (POFs).

Increasing attention has been given to the field of porous organic frameworks (POFs) due to their unique properties, outstanding performance, and broad applications. Given their extremely high surface area, ordered crystal structure, and ease of tailoring, POFs are promising candidates for gas adsorption and separation, catalysis, supercapacitors, chemosensors, and bio-related applications. Furthermore, their tunable pore size and high agent loading capacity make them promising candidates for drug delivery, whereas their ease of functionalization leads to target specificity and long blood circulation times, which are important properties in bioimaging. For biosensing applications, the pores and channels of POFs can accommodate target molecules and induce specific recognition. POFs can also be applied in phototherapy in combination with photosensitizers. Finally, POF-based artificial shells can encapsulate bioactive molecules and strengthen the resistance of cells to adverse environmental conditions. In this review, we will highlight the research progress of POF-based bio-related applications, including drug delivery, bioimaging, biosensing agents, as well as in phototherapy and artificial shells. Furthermore, the in vitro and in vivo toxicological studies of POFs are discussed as are the prospects and future research directions for POFs in bio-related applications.

Robust hybrid enzyme nanoreactor mediated plasmonic sensing strategy for ultrasensitive screening of anti-diabetic drug.

Enzyme inhibition based drug screening strategy has been widely employed for new drug discovery. But this strategy faces some challenges in practical application especially for the trace active compound screening from natural products such as the stability of enzyme and the sensitivity of screening approach. Inspired by the above, we for the first time demonstrate the self-assembly of α-glucosidase (GAA) and glucose oxidase (GOx) into one multi-enzymes-inorganic nanoreactor with hierarchical structure (flower shape). The hybrid enzyme nanoreactor enjoys the merits including the character of assembly line, the enhanced enzymatic activity and robust stability. The flower shape of enzyme nanoreactor possessed a bigger specific surface area, facilitating the trace GAA inhibitor detection. Based on the above, we proposed an enzyme nanoreactor mediated plasmonic sensing strategy for anti-diabetic drug screening. First, maltose was chosen as the substrate for GAA and the generated glucose were immediately utilized by GOx to generate H2O2, and finally, H2O2 etched the Ag nanoprism to round nanodiscs, resulting in the blue shift of surface plasmon resonance (SPR) absorption band. With the aid of hybrid enzyme nanoreactor guided SPR, the ultrasensitive screening of GAA inhibitor (i.e. anti-diabetic drug) can be realized with the detection limit of 5nM for acarbose. The proposed approach was successfully utilized for GAA inhibitor screening from natural products. We anticipate that the proposed sensing method may provide new insights and inspirations in the enzyme inhibition based drug discovery and clinical diagnosis.

Perillanolides A and B, new monoterpene glycosides from the leaves of Perilla frutescens

Abstract Two new monoterpene glycosides, perillanolides A and B, together with a known compound reported from the genus Perilla for the first time were isolated and characterized from the leaves of Perilla frutescens (L.) Britton, Lamiaceae, a garnish and colorant for foods as well as commonly used for traditional medicine. The structures of the isolated compounds were elucidated on the basis of extensive spectroscopic evidences derived from nuclear magnetic resonance experiments, mass spectrometry and by comparing their physical and spectroscopic data of literature. These compounds, together with the previously isolated secondary metabolites of this species, were investigated for their inhibitory effects on xanthine oxidase in vitro. Of the compounds, luteolin showed the strongest inhibitory activity with an IC50 value of 2.18 µM. Esculetin and scutellarein moderately inhibited the enzyme, while perillanolides A and B, and 4-(3,4-dihydroxybenzoyloxymethyl)phenyl-O-β-D-glucopyranoside exerted weak activities.

Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps.

Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. l-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case-control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11-1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were .002 for all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma [OR (95% CI): 1.73 (1.27-2.36)] and advanced/multiple adenomas [1.62 (1.05-2.50)], whereas among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64 (0.42-0.99)] and advanced/multiple adenomas [0.55 (0.31-1.00)].

Epsilon wave on an electronic loop in a case of arrhythmogenic right ventricular dysplasia with myocarditis: an updated definition of the Epsilon wave.

A young man presented with a history of myocarditis with palpitations and dizziness. He had implantation of a loop recorder that showed repetitive short episodes of VT. In addition, there were fragmented potentials immediately following the large and sharp electrograms (EGMs) before as well as after episodes of VT suggesting an Epsilon wave. This signal can be observed in multiple cardiac conditions including coronary artery disease. It was originally recorded on the epicardium as well as on the endocardium. However, in ARVD it can be defined as an electric signal observed after the end of the QRS complex in the right as opposed to the left precordial leads (difference ≥ 25 ms). It can also be an aid to the diagnosis of patients with ARVD who have other signs or symptoms suggesting ARVD including episodes of myocarditis. This potential consists of a slurring at the end of the QRS complex or an independent potential after the return to the isoelectric line. It can be better observed by increasing amplification of the ECG tracing as well as double speed using the Fontaine lead system. Epsilon wave too small to be recorded on the standard ECG can be extracted by Signal Averaging ECG SAECG).

A Polysaccharide from the Culinary-Medicinal Mushroom Pholiota nameko (Agaricomycetes) Inhibits the NF-κB Pathway in Dendritic Cells Through the TLR2 Receptor.

A polysaccharide purified from Pholiota nameko (PNPS-1) was found to have anticancer and anti-inflammatory activity. This study investigated the effect of PNPS-1 on the nuclear factor (NF)-κB signaling pathway of TLR2 small interfering RNA-silenced murine bone marrow-derived dendritic cells (BMDCs) and relevant mechanisms. The expression of messenger RNA of 4 NF-κB-related genes, including MyD88, IKBKB, RelA(p65), and CCL2, was determined by real-time polymerase chain reaction; the expression of the phenotype molecule intercellular adhesion molecule-1 (ICAM-1) by flow cytometry; the protein expression of IKKß and p65 by Western blot; the production of p65 by enzyme-linked immunosorbent assay; and the expression of p65 by immunocytochemistry. The results showed that TLR2-specific small interfering RNA could effectively inhibit the decrease in the expression of MyD88, IKBKB, CCL2, p65, and ICAM-1 in BMDCs induced by PNPS-1, and thus the transcription inactivation of NF-κB, which obviously suggests that PNPS-1 could downregulate the NF-κB signaling pathway via the TLR2 receptor.