Photosynthetic System Based on a Polyoxometalate-Based Dehydrated Metal-Organic Framework for Nitrogen Fixation.

In nature, biological nitrogen fixation is accomplished through the π-back-bonding mechanism of nitrogenase, which poses significant challenges for mimic artificial systems, thanks to the activation barrier associated with the N≡N bond. Consequently, this motivates us to develop efficient and reusable photocatalysts for artificial nitrogen fixation under mild conditions. We employ a charge-assisted self-assembly process toward encapsulating one polyoxometalate (POM) within a dehydrated Zr-based metal-organic framework (d-UiO-66) exhibiting nitrogen photofixation activities, thereby constructing an enzyme-mimicking photocatalyst. The dehydration of d-UiO-66 is favorable for facilitating nitrogen chemisorption and activation via the unpaired d-orbital electron at the [Zr6O6] cluster. The incorporation of POM guests enhanced the charge separation in the composites, thereby facilitating the transfer of photoexcited electrons into the π* antibonding orbital of chemisorbed N2 for efficient nitrogen fixation. Simultaneously, the catalytic efficiency of SiW9Fe3@d-UiO-66 is enhanced by 9.0 times compared to that of d-UiO-66. Moreover, SiW9Fe3@d-UiO-66 exhibits an apparent quantum efficiency (AQE) of 0.254% at 550 nm. The tactics of "working-in-tandem" achieved by POMs and d-UiO-66 are extremely vital for enhancing artificial ammonia synthesis. This study presents a paradigm for the development of an efficient artificial catalyst for nitrogen photofixation, aiming to mimic the process of biological nitrogen fixation.

High-Throughput-Methyl-Reading (HTMR) assay: a solution based on nucleotide methyl-binding proteins enables large-scale screening for DNA/RNA methyltransferases and demethylases.

Epigenetic therapy has significant potential for cancer treatment. However, few small potent molecules have been identified against DNA or RNA modification regulatory proteins. Current approaches for activity detection of DNA/RNA methyltransferases and demethylases are time-consuming and labor-intensive, making it difficult to subject them to high-throughput screening. Here, we developed a fluorescence polarization-based 'High-Throughput Methyl Reading' (HTMR) assay to implement large-scale compound screening for DNA/RNA methyltransferases and demethylases-DNMTs, TETs, ALKBH5 and METTL3/METTL14. This assay is simple to perform in a mix-and-read manner by adding the methyl-binding proteins MBD1 or YTHDF1. The proteins can be used to distinguish FAM-labelled substrates or product oligonucleotides with different methylation statuses catalyzed by enzymes. Therefore, the extent of the enzymatic reactions can be coupled with the variation of FP binding signals. Furthermore, this assay can be effectively used to conduct a cofactor competition study. Based on the assay, we identified two natural products as candidate compounds for DNMT1 and ALKBH5. In summary, this study outlines a powerful homogeneous approach for high-throughput screening and evaluating enzymatic activity for DNA/RNA methyltransferases and demethylases that is cheap, easy, quick, and highly sensitive.

Peripheral atherosclerosis in acute coronary syndrome patients with plaque rupture vs plaque erosion: A prospective coronary optical coherence tomography and peripheral ultrasound study.

BACKGROUND: Plaque rupture (PR) and plaque erosion (PE) are 2 distinct, different, and most common culprit lesion morphologies responsible for acute coronary syndrome (ACS). However, the prevalence, distribution, and characteristics of peripheral atherosclerosis in ACS patients with PR vs PE has never been studied. The aim of this study was to assess peripheral atherosclerosis burden and vulnerability evaluated by vascular ultrasound in ACS patients with coronary PR vs PE identified by optical coherence tomography (OCT). METHODS: Between October 2018 and December 2019, 297 ACS patients who underwent preintervention OCT examination of the culprit coronary artery were enrolled. Peripheral ultrasound examinations of carotid, femoral, and popliteal arteries were performed before discharge. RESULTS: Overall, 265 of 297 (89.2%) patients had at least one atherosclerotic plaque in a peripheral arterial bed. Compared with coronary PE, patients with coronary PR had a higher prevalence of peripheral atherosclerotic plaques (93.4% vs 79.1%, P < .001), regardless of location: carotid, femoral, or popliteal arteries. The number of peripheral plaques per patient was significantly larger in the coronary PR group than coronary PE (4 [2-7] vs 2 [1-5], P < .001). Additionally, there was a greater prevalence of peripheral vulnerable characteristics including plaque surface irregularity, heterogeneous plaque, and calcification in patients with coronary PR vs PE. CONCLUSIONS: Peripheral atherosclerosis exists commonly in patients presenting with ACS. Patients with coronary PR had greater peripheral atherosclerosis burden and more peripheral vulnerability compared to those with coronary PE, suggesting that comprehensive evaluation of peripheral atherosclerosis and multidisciplinary cooperative management maybe necessary, especially in patients with PR. TRIAL REGISTRATION: clinicaltrials.gov (NCT03971864).

Optical Coherence Tomography Assessment of Coronary Lesions Associated With Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Microvascular reperfusion following percutaneous coronary intervention (PCI) is associated with the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We investigated how plaque characteristics detected by optical coherence tomography (OCT) in STEMI patients affect the status of the microcirculation during PCI.Methods and Results: This retrospective, single-center study was a post hoc analysis basedon the multicenter SALVAGE randomized control trial (NCT03581513) that enrolled 629 STEMI patients, and finally we enrolled 235 patients who underwent PCI and pre-intervention OCT. Microvascular perfusion was evaluated using the Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion frame count (TMPFC). Patients were divided into 3 groups based on the change in TMPFC from before to after PCI: improving TMPFC (n=11; 4.7%), stable TMPFC (n=182; 77.4%), and worsening TMPFC group (n=42; 17.9%). The proportion of patients with a microcirculation dysfunction before reperfusion was 11.9%, which increased significantly by (P=0.079) 8.5% to 20.4% after reperfusion. Compared with plaque characteristics in the stable and worsening TMPFC groups, the improving TMPFC group had fewer thrombi (90.7% and 90.5% vs. 89.4%, respectively; P=0.018), a lower proportion of plaque rupture (66.5% and 66.3% vs. 54.5%, respectively; P=0.029), and a lower proportion of lipid-rich plaques (89.6% and 88.1% vs. 63.6%, respectively; P=0.036). CONCLUSIONS: PCI may not always achieve complete myocardial reperfusion. Thrombi, plaque rupture, and lipid-rich plaques detected by OCT can indicate microcirculation dysfunction during the reperfusion period.

Ratiometric Sensing of Intracellular pH Based on Dual Emissive Carbon Dots.

Accurate monitoring of intracellular pH in living cells is critical for developing a better understanding of cellular activities. In the current study, label-free carbon dots (p-CDs), which were fabricated using a straightforward one-pot solvothermal treatment of p-phenylenediamine and urea, were employed to create a new ratiometric pH nanosensor. Under single-wavelength excitation (λex = 500 nm), the p-CDs gave dual emission bands at 525 and 623 nm. The fluorescent intensity ratio (I525/I623) was linearly related to pH over the range 4.0 to 8.8 in buffer solutions, indicating that the ratiometric fluorescence nanoprobe may be useful for pH sensing. In pH measurements, the p-CDs also demonstrated outstanding selectivity, reversibility, and photostability. Owing to the advantages outlined above, the nanoprobe was used to monitor the pH of HeLa cells effectively. The label-free CD-based ratiometric nanoprobe features comparatively easy manufacturing and longer excitation and emission wavelengths than the majority of previously reported CD-based ratiometric pH sensors, which is ultimately beneficial for applications in biological imaging.

Rapid detection of pathogens of peritoneal dialysis-related peritonitis, especially in patients who have taken antibiotics, using metagenomic next-generation sequencing: a pilot study.

INTRODUCTION: Peritoneal dialysis (PD)-related peritonitis is a serious complication of PD. Improving the diagnostic rate of peritonitis pathogens may substantially benefit peritonitis patients. METHODS: The study was conducted in the People's Liberation Army (PLA) General Hospital from 1 June 2021 to 31 May 2022. Information about peritonitis, culture and metagenomic next-generation sequencing (mNGS) results and so on were collected. Patients were divided into antibiotic-use and antibiotic-free groups. The culture and mNGS results were compared using the paired χ2 test. RESULTS: Data from 26 patients with peritonitis were collected. 50% of the patients had used antibiotics before samples were obtained (antibiotic-use group). The positivity rate using culture was 92.3% (12 cases) in the antibiotic-free group and 38.5% (5 cases) in the antibiotic-use group (p = 0.011). However, the positivity rate using mNGS was 92.3% (12 cases) regardless of whether antibiotics were used (p = 1.000). After revising the mNGS results, the positivity rate was 84.6% (11 cases) in both groups (p = 1.000). A significant difference between culture and mNGS results of all groups was observed (p = 0.039). The difference no matter between culture and mNGS (p = 0.016) or between culture and modified mNGS (p = 0.031) of the antibiotic-use group was observed. CONCLUSION: For patients with PD-related peritonitis who previously received antibiotics, mNGS is suggested. For other patients, mNGS testing can be performed, but the results should be interpreted with caution. Much more research should be done to identify a powerful and ideal tool to detect pathogens underlying PD-related peritonitis.

SOX2 maintains the stemness of retinoblastoma stem-like cells through Hippo/YAP signaling pathway.

PURPOSE: To explore the mechanisms underlying stemness maintenance of retinoblastoma (RB) stem cells (RSCs). METHODS: The retinoblastoma stem-like cells (RSLCs) were isolated by single cell cloning in combination of examination of sphere-forming capacities. The stemness of the cells were characterized by the sphere-forming capacity and the expression levels of RSCs markers. Gene manipulation was performed by lentivirus system. Transcriptional regulation was identified by qRT-PCR, luciferase reporter, nuclear run-on and DNA pull-down assay. Spearman analysis was employed for correlation analysis of genes in tumor tissues of RB patients. RESULTS: The isolated RSLCs exhibited enhanced sphere-forming capacity and constantly higher levels of CD44, ABCG2, SOX2 and PAX6, but not CD133. SOX2 positively regulated the stemness of RSLCs. SOX2 directly binds to the promoters of WWTR1 and YAP and transcriptionally activates WWTR1 and YAP. Knockdown of WWTR1 or YAP partially abolished the effect of SOX2 on the stemness of RSLCs. CONCLUSIONS: SOX2, as a key deriver, maintains RB stemness by activating Hippo/YAP signaling. Inhibition of Hippo/YAP signaling would be an effective strategy for human RB caused by SOX2 upregulation.

Construction of an immune-related prognostic model by exploring the tumor microenvironment of clear cell renal cell carcinoma.

OBJECTIVE: In this study, bioinformatics methods were performed to screen the candidate prognosis-related genes of clear cell renal cell carcinoma (ccRCC) by analyzing the tumor microenvironment (TME). METHODS: Gene expression and clinical data of ccRCC patients were accessed from TCGA, and R package ESTIMATE was applied to calculate immune, stromal, and ESTIMATE scores of the patients. Survival analysis was conducted per median of these three scores. Based on the scoring results, differentially expressed genes (DEGs) were screened. Regression algorithms were utilized to screen prognostic genes and establish a risk model. Finally, pathway activity differences were analyzed through GSEA. RESULTS: Patients with the unfavorable prognosis had high immune scores. 619 DEGs (499 up-regulated and 120 down-regulated) were screened based on the differences in gene expression of the patients with high and low immune scores. These genes mainly participated in immune-related signaling pathways. A prognostic risk model for ccRCC patients was constructed and 7 immune-related signature genes (RORB, TNFSF14, UCN2, USP2, TOX3, KLRC2, SLAMF9) were obtained through regression analysis. The constructed prognostic risk model could be used for determining prognoses of patients with ccRCC. CONCLUSION: We unraveled the association between TME and prognosis of ccRCC patients and established a prognostic risk model based on the differentially expressed genes. These results contributed to understanding of TME that affected patients' prognosis and progression of ccRCC and conduced to finding potential biomarkers of ccRCC.

Impact of nodular calcification in patients with acute coronary syndrome (ACS) treated with primary percutaneous coronary intervention (PCI).

BACKGROUND: Calcified plaque is thought to adversely impact outcomes after percutaneous coronary intervention (PCI). This study sought to evaluate the impact of nodular calcification in patients with acute coronary syndrome treated with primary percutaneous coronary intervention. METHODS: Using optical coherence tomography (OCT), 500 culprit plaques with calcification were analyzed from 495 acute coronary syndrome (ACS) patients on whom PCI was performed. Based on morphology, we classified calcification into two subtypes: nodular calcification and non-nodular calcification. Nodular calcification was defined as protruding mass with an irregular surface, high backscattering, and signal attenuation while non-nodular calcification was defined as an area with low backscattering heterogeneous region with a well-delineated border without protrusion into the lumen on OCT. RESULTS: Calcified culprit plaques were divided into nodular calcification group (n = 238) and non-nodular calcification group (n = 262). Patients with nodular calcification were older (p < 0.001) and had lower left ventricular ejection fraction (p = 0.006) compared to patients with non-nodular calcification. Minimum stent area (5.0 (3.9, 6.3) mm2 vs. 5.4 (4.2, 6.7) mm2, p = 0.011) and stent expansion (70 (62.7, 81.8) % vs. 75 (65.2, 86.6) %, p = 0.004) were significantly smaller in the nodular calcification group than in the non-nodular calcification group. Stent under-expansion was most frequent (p = 0.003) in the nodular calcification group. CONCLUSION: This study demonstrate that the presence of nodular calcification is associated with a smaller minimum stent area and a higher incidence of stent under-expansion. Lesions with nodular calcification may be at risk of stent under-expansion.

Nano-gold-enhanced LAMP method for qualitative visual detection of Salmonella in milk.

Since Salmonella can cause foodborne disease and public health safety issues and requires a robust, rapid, on-site detection method, a novel visual qualitative method with nano-gold-enhanced loop-mediated isothermal amplification (LAMP) reaction was established for detecting Salmonella in an integrated tube. During the experiment, nano-gold were used to enhance LAMP amplification, improving amplification efficiency and shortening the reaction time to within 30 min. Visual qualitative detection is achieved via negative staining, involving the addition of CuSO4 to the final products of the LAMP reaction. Ring-like white accumulation occurs in the absence of Salmonella targets but not when they are present. After completing the LAMP reaction, the integration tube was shaken gently for 1 min to observe the liquid phase system changes, realizing the closed tube detection of Salmonella. The process resolved the challenge presented by cross-contamination, false positives, and nonspecific amplification during the LAMP reaction. This method was used to detect Salmonella in milk, further highlighting its prospects in the field of rapid food safety detection.

Development of Environmentally Friendly Wool Shrink-Proof Finishing Technology Based on L-Cysteine/Protease Treatment Solution System.

The particular scale structure and mechanical properties of wool fiber make its associated fabrics prone to felting, seriously affecting the service life of wool products. Although the existing Chlorine-Hercosett treatment has a remarkable effect, it can lead to environmental pollution. Therefore, it is of great significance to develop an environmentally friendly and effective shrink-proof finishing technology. For this study, L-cysteine was mixed with protease to form a treatment solution system for shrink-proof finishing of wool fibers. The reduction performance of L-cysteine and its effect on wool were compared with those of other reagents, demonstrating that L-cysteine has an obvious reduction and destruction effect on the wool scale layer. Based on this, L-cysteine and protease 16L were mixed in a certain proportion to prepare an L-cysteine/protease treatment solution system (L/PTSS). The shrink-proof finishing of a wool top was carried out by the continuous multiple-padding method, and the processing parameters were optimized using the response surface method. The results indicated that when the concentrations of L-cysteine and protease 16L were 9 g/L and 1 g/L, respectively, the wool was padded five times at 50 °C, and each immersion time was 30 s, the felt ball density of the treated wool reduced from 135.86 kg/m3 to 48.65 kg/m3. The structure and properties of the treated wool were also characterized using SEM, TG, and tensile strength tests, which indicated that the fiber scale structure was stripped evenly. Meanwhile, the treated fibers still retained adequate thermal and mechanical properties, indicating suitable application value. XPS, FT-IR, Raman, UV absorbance, and other test results revealed the reaction mechanism of L/PTSS with the wool fibers. After L-cysteine rapidly reduced the disulfide bonds in wool, protease can hydrolyze peptide chains more effectively, causing the scale layer to gradually peel off. Compared with the chlorination method and other protease shrink-proof technologies, L/PTSS can achieve the finishing effect on wool rapidly and effectively, without causing excessive pollution to the environment. The conclusions of this study provide a foundation for the development and industrial application of biological enzyme shrink-proof finishing technology.

Intestinal vitamin D receptor signaling ameliorates dextran sulfate sodium-induced colitis by suppressing necroptosis of intestinal epithelial cells.

Vitamin D status is closely related to inflammatory bowel disease (IBD), but the mechanism has not been fully elucidated. This study explored the effect of intestinal vitamin D signaling on necroptosis and the underlying mechanism in colitis. Serum 25(OH)D levels and the expression of necroptotic proteins were examined in patients with IBD. Colitis was induced in an intestinal-specific hVDR transgenic model, and the gross manifestation, histological integrity, and intestinal barrier function were tested. The findings were further confirmed in vitro. Immunoprecipitation and colocalization were performed to investigate the association between the vitamin D receptor and necroptotic proteins. We found that serum 25(OH)D decreased in patients with IBD, while the expression of necroptotic proteins increased. The intestinal hVDR transgenic model could largely ameliorate the structural destruction, restore barrier dysfunction, and suppress necroptosis caused by DSS. This was probably achieved by binding to RIPK1/3 necrosomes, as we observed decreased RIPK1/3 necrosome formation and increased VDR expression in the cytosol. This study demonstrated an inhibitory effect of the intestinal vitamin D signaling pathway on necroptosis in DSS-induced colitis. The vitamin D receptor shifts from the nucleus to the cytosol to impede the formation of RIPK1/3. Our findings may offer some theoretical basis for a novel treatment of IBD in clinical practice.

Discovery of a novel 53BP1 inhibitor through AlphaScreen-based high-throughput screening.

Tumor suppressor p53-binding protein 1 (53BP1), a tantem tudor domain (TTD) protein, takes part in DNA Damage Repair (DDR) pathways through the specific recognition of lysine methylation on histones. The dysregulation of 53BP1 is closely related to the development of many diseases including cancer. Moreover, recent studies found that deficiency of 53BP1 could increase the efficiency of precise CRISPR/Cas9 genome editing. Thus, discovery of inhibitor is beneficial to the study of biological functions of 53BP1 and the application of CRISPR/Cas9 genome editing. UNC2170 and its derivatives have been reported as 53BP1 targeted small molecular inhibitors with modest activities. Hence, to discover better 53BP1 inhibitors, we conducted an AlphaScreen assay based high-throughput screening (HTS) and identified a novel and effective 53BP1-TTD inhibitor DP308 which disrupts the binding between 53BP1 and H4K20me2 peptide with an IC50 value of 1.69 ± 0.73 µM. Both Microscale Themophoresis (MST) and Surface Plasmon Resonance (SPR) assays confirmed the direct binding between DP308 and 53BP1-TTD protein with binding affinity (Kd) of about 2.7 µM. Molecular docking studies further suggested that DP308 possibly occupies the H4K20me2 binding pocket of the 53BP1-TTD aromatic cage. These results demonstrated that DP308 is a promising small molecule inhibitor for further optimization towards a more potent chemical probe of 53BP1. Additionally, it could be a potential valuable tool for applying to gene editing therapy by increasing the efficiency of CRISPR/Cas9 genome editing.

Prediction model for the risk of osteoporosis incorporating factors of disease history and living habits in physical examination of population in Chongqing, Southwest China: based on artificial neural network.

BACKGROUND: Osteoporosis is a gradually recognized health problem with risks related to disease history and living habits. This study aims to establish the optimal prediction model by comparing the performance of four prediction models that incorporated disease history and living habits in predicting the risk of Osteoporosis in Chongqing adults. METHODS: We conduct a cross-sectional survey with convenience sampling in this study. We use a questionnaire From January 2019 to December 2019 to collect data on disease history and adults' living habits who got dual-energy X-ray absorptiometry. We established the prediction models of osteoporosis in three steps. Firstly, we performed feature selection to identify risk factors related to osteoporosis. Secondly, the qualified participants were randomly divided into a training set and a test set in the ratio of 7:3. Then the prediction models of osteoporosis were established based on Artificial Neural Network (ANN), Deep Belief Network (DBN), Support Vector Machine (SVM) and combinatorial heuristic method (Genetic Algorithm - Decision Tree (GA-DT)). Finally, we compared the prediction models' performance through accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) to select the optimal prediction model. RESULTS: The univariate logistic model found that taking calcium tablet (odds ratio [OR] = 0.431), SBP (OR = 1.010), fracture (OR = 1.796), coronary heart disease (OR = 4.299), drinking alcohol (OR = 1.835), physical exercise (OR = 0.747) and other factors were related to the risk of osteoporosis. The AUCs of the training set and test set of the prediction models based on ANN, DBN, SVM and GA-DT were 0.901, 0.762; 0.622, 0.618; 0.698, 0.627; 0.744, 0.724, respectively. After evaluating four prediction models' performance, we selected a three-layer back propagation neural network (BPNN) with 18, 4, and 1 neuron in the input layer, hidden and output layers respectively, as the optimal prediction model. When the probability was greater than 0.330, osteoporosis would occur. CONCLUSIONS: Compared with DBN, SVM and GA-DT, the established ANN model had the best prediction ability and can be used to predict the risk of osteoporosis in physical examination of the Chongqing population. The model needs to be further improved through large sample research.

LINC00662 contributes to the progression and the radioresistance of cervical cancer by regulating miR-497-5p and CDC25A.

It is reported that long intergenic non-coding RNA 00662 (LINC00662) plays an oncogenic role in tumours. However, the mechanism of LINC00662 in regulating the progression and radiosensitivity of cervical cancer (CC) is not clear. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) was adopted to detect LINC00662 and miR-497-5p expressions in CC tissues and cells. The expression of cell division cycle 25 A (CDC25A) in CC cells was examined by Western blot. CC cell proliferation was determined by cell counting kit-8 (CCK-8) and BrdU assays. The survival rate of CC cells was evaluated by colony formation assay under different doses of X-ray irradiation. CC cell migration and invasion were probed by Transwell assay. Besides, the interactions between miR-497-5p and LINC00662, and miR-497-5p and the 3'UTR of CDC25A were verified by dual-luciferase reporter assay, RIP assay, and RNA pull-down experiments. We demonstrated that, LINC00662 expression was remarkably raised in CC tissues and cell lines. LINC00662 overexpression promoted proliferation, migration, invasion and radioresistance of CC cells, and LINC00662 knockdown inhibited the above malignant phenotypes of CC cells. In terms of mechanism, LINC00662 facilitated CC progression and radioresistance by adsorbing miR-497-5p and indirectly up-regulating CDC25A expression. In a word, the LINC00662/miR-497-5p/CDC25A axis boosts proliferation and metastasis of CC cells and enhances the radioresistance of cancer cells. SIGNIFICANCE OF THE STUDY: CC poses a threat to the health of women all over the world. In this study, we demonstrated for the first time that LINC00662 expression was remarkably raised in CC tissues and cells. Cellular experiments confirmed that LINC00662 facilitated cell proliferation, migration, invasion and radiation resistance through the miR-497-5p/CDC25A axis, which might be a promising target for CC treatments.

Percutaneous insertion of peritoneal dialysis catheter is a safe and effective technique irrespective of BMI.

BACKGROUND: A large body mass index (BMI) has been considered as a relative contraindication for percutaneous catheter insertion, although this technique has many advantages. Up to now, there are few studies on peritoneal catheter placement and obesity. The aim of this study was to determine whether patients with large BMI can also choose the percutaneous technique for peritoneal dialysis catheter insertion. METHODS: One hundred eighty seven consecutive patients underwent peritoneal catheter insertions in the Chinese PLA General Hospital between January 1, 2015 and December 31, 2016, with 178 eligible cases being included in the analysis. Two groups were created based on the catheter insertion techniques, the percutaneous group (group P) and the surgical group (group S). Subgroups were created according to BMI > 28 or ≤ 28. The outcomes included catheter related complications and catheter survival. RESULTS: Total infectious complication rates were significantly lower in group P than in group S. There were no significant differences in peritonitis rate between group P and group S (1.20% vs. 3.16% with P = 0.71 in early stage, and 4.82% vs. 11.58% with P = 0.11 in late stage). All other measured complications were similar between the two groups. Though the one-year infection-free catheter survival in group P was 7.5% higher than group S, the difference was not significant. The one-year dysfunction-free catheter survival, one-year dysfunction-and-infection-free catheter survival, and overall catheter survival were similar between the two groups. Subgroup analyses showed a superior one-year infection-free catheter survival of percutaneous technique in patients with BMI > 28, which was confirmed by Kaplan-Meier analysis. CONCLUSIONS: Despite the challenges that may be encountered with patients who have a large BMI, the percutaneous technique seems to be a safe and effective approach to placing a peritoneal dialysis catheter.

Atheroprotective effects of methotrexate via the inhibition of YAP/TAZ under disturbed flow.

BACKGROUND: Atherosclerosis preferentially develops in regions of disturbed flow (DF). Emerging evidence indicates that yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway, sense different blood flow patterns and regulate atherosclerotic lesions. We previously found that methotrexate (MTX) reduces in-stent neoatherosclerosis, decreases the plaque burden, and has an effect on local fluid shear stress. Here, we investigated the atheroprotective effect of MTX under DF and the mechanisms underlying these properties. METHODS: Human umbilical vein endothelial cells (HUVECs) were subjected to biomechanical stretch using a parallel-plate flow system and treated with or without MTX at therapeutically relevant concentrations. Additionally, an extravascular device was used to induce DF in the left common carotid artery of C57BL/6 mice, followed by treatment with MTX or 0.9% saline. The artery was then assessed histopathologically after 4 weeks on a Western diet. RESULTS: We observed that MTX significantly inhibited DF-induced endothelial YAP/TAZ activation. Furthermore, it markedly decreased pro-inflammatory factor secretion and monocyte adhesion in HUVECs but had no effect on apoptosis. Mechanistically, AMPKa1 depletion attenuated these effects of MTX. Accordingly, MTX decreased DF-induced plaque formation, which was accompanied by YAP/TAZ downregulation in vivo. CONCLUSIONS: Taken together, we conclude that MTX exerts protective effects via the AMP-dependent kinase (AMPK)-YAP/TAZ pathway. These results provide a basis for the prevention and treatment of atherosclerosis via the inhibition of YAP/TAZ.

First case of AML with rare chromosome translocations: a case report of twins.

BACKGROUND: Leukemia is different from solid tumor by harboring genetic rearrangements that predict prognosis and guide treatment strategy. PML-RARA, RUNX1-RUNX1T1, and KMT2A-rearrangement are common genetic rearrangements that drive the development of acute myeloid leukemia (AML). By contrast, rare genetic rearrangements may also contribute to leukemogenesis but are less summarized. CASE PRESENTATION: Here we reported rare fusion genes ZNF717-ZNF37A, ZNF273-DGKA, and ZDHHC2-TTTY15 in a 47-year-old AML-M4 patient with FLT3 internal tandem duplication (ITD) discovered by whole genome sequencing (WGS) using the patient's healthy sibling as a sequencing control. CONCLUSION: This is, to our knowledge, the first case of AML with fusion gene ZNF717-ZNF37A, ZNF273-DGKA, and ZDHHC2-TTTY15.

Overexpression of modified human TRß1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.

Association studies suggest that TRß1 functions as a tumor suppressor. Thyroid hormone receptors (TRs) mediate transcriptional responses through a highly conserved DNA-binding domain (DBD). We previously constructed an artificially modified human TRß1 (m-TRß1) via the introduction of a 108-bp exon sequence into the corresponding position of the wild-type human TRß1 (TRß1) DBD. Studies confirmed that m-TRß1 was functional and could inhibit the proliferation of breast cancer MDA-MB-468 cells in vitro. To understand the role of m-TRß1 in liver tumor development, we adopted a gain-of-function approach by stably expressing TRß (m-TRß1 and TRß1) genes in a human hepatocarcinoma cell line, SK-hep1 (without endogenous TRß), and then evaluated the effects of the expressed TRß on cancer cell proliferation, migration, and tumor growth in cell-based studies and xenograft models. In the presence of 3,5,3-L-triiodothyronine (T3), the expression of TRß in SK-hep1 cells inhibited cancer cell proliferation and impeded tumor cell migration through the up-regulation of 4-1BB, Caspase-3, and Bak gene expression; down-regulation of Bcl-2 gene expression; and activation of the Caspase-3 protein. TRß expression in SK-hep1 led to less tumor growth in xenograft models. Additionally, the anti-tumor effect of m-TRß1 was stronger than that of TRß1. These data indicate that m-TRß1 can act as a tumor suppressor in hepatocarcinoma and its role was significantly better than that of TRß1.

[Correlation of dietary patterns and cognitive function among preschool children in Ma'anshan City in 2014-2015].

OBJECTIVE: To classify the dietary patterns in preschoolers and explore the correlation between dietary patterns and executive functions. METHODS: Between April 2014 and June 2015, 12363 preschoolers were selected from 91 kindergartens of Ma 'anshan City. The classification of dietary patterns and executive functions by Brief-P were evaluated. Unconditional binary logistics regression model was used to analyze the effects of different dietary patterns and executive functions in preschool chidlren. RESULTS: The higher the parents' education level, the lower the executive functions scores, the difference was statistically significant in preschoolers( P < 0. 05). The less intake of "processed model", "drinks model"and "snacks model", the more "vegetarian model"and "health model"intake, executive functions score was lower, and the difference was statistically significant( P < 0. 05). Logistic regression analysis showed that dietary patterns of"processed model"( OR = 1. 44, 95% CI 1. 20-1. 72), "drinks model"( OR = 1. 22, 95% CI 1. 03-1. 46) and "snacks model"( OR = 1. 28, 95% CI 1. 08-1. 52) were risk factors of cognitive functions, and the dietary patterns of "vegetarian model"( OR = 0. 80, 95% CI 0. 67-0. 95) and "health model "( OR = 0. 84, 95% CI 0. 71-0. 98) were protective factors. CONCLUSION: The present study suggests that cognitive functions might be closely related with dietary pattern. The more "vegetarian model"and "health model"intake, the better cognitive functions developed in preschool children.