Hyaluronic acid-CD44 interactions promote BMP4/7-dependent Id1/3 expression in melanoma cells

Abstract BMP4/7-dependent expression of inhibitor of differentiation/DNA binding (Id) proteins 1 and 3 has been implicated in tumor progression and poor prognosis of malignant melanoma patients. Hyaluronic acid (HA), a pericellular matrix component, supports BMP7 signalling in murine chondrocytes through its receptor CD44. However, its role in regulating BMP signalling in melanoma is not clear. In this study we found that depletion of endogenously-produced HA by hyaluronidase treatment or by inhibition of HA synthesis by 4-methylumbelliferone (4-MU) resulted in reduced BMP4/7-dependent Id1/3 protein expression in mouse melanoma B16-F10 and Ret cells. Conversely, exogenous HA treatment increased BMP4/7-dependent Id1/3 protein expression. Knockdown of CD44 reduced BMP4/7-dependent Id1/3 protein expression, and attenuated the ability of exogenous HA to stimulate Id1 and Id3 expression in response to BMP. Co-IP experiments demonstrated that CD44 can physically associate with the BMP type II receptor (BMPR) ACVR2B. Importantly, we found that coordinate expression of Id1 or Id3 with HA synthases HAS2, HAS3, and CD44 is associated with reduced overall survival of cutaneous melanoma patients. Our results suggest that HA-CD44 interactions with BMPR promote BMP4/7-dependent Id1/3 protein expression in melanoma, contributing to reduced survival in melanoma patients

The Impact of Climate Change on Rainfall Frequency in Taiwan

The purpose of this research is to assess climate change impacts on rainfall frequency in Taiwan. The changes in future precipitation were projected statistically from general circulation model (GCM) outputs. Based on five downscaled GCM outputs [China’s FGOALS-g1.0, Japan’s CGCM2.3.2, the USA’s CM2.0, Canada’s CGCM3(T47), and France’s CM3] under the SRES A1B scenario, the frequency of the maximum consecutive dry days and maximum 1-, 2-, and 3-day rainfall during 2080 - 2099 are evaluated and compared with those in the period of 1980 - 1999. The results show that by the end of the 21st century, the risk of droughts and floods over Taiwan has a tendency to increase. The distribution of water resources in Taiwan will be more uneven, with a noticeable change in the ratio of wet and dry seasons. Due to these climate change impacts, future water conservation work will be a major challenge for governments

Tunable interfacial chemisorption with atomic-level precision in a graphene WSe2 heterostructure

It has long been an ultimate goal to introduce chemical doping at the atomic level to precisely tune properties of materials. Two-dimensional materials have natural advantage because of its highly-exposed surface atoms, however, it is still a grand challenge to achieve this goal experimentally. Here, we demonstrate the ability to introduce chemical doping in graphene with atomic-level precision by controlling chemical adsorption of individual Se atoms, which are extracted from the underneath WSe2, at the interface of graphene-WSe2 heterostructures. Our scanning tunneling microscopy (STM) measurements, combined with first-principles calculations, reveal that individual Se atoms can chemisorbed on three possible positions in graphene, which generate distinct pseudospin-mediated atomic-scale vortices in graphene. We demonstrate that the chemisorbed positions of individual Se atoms can be manipulated by STM tip, which enables us to achieve atomic-scale controlling quantum interference of the pseudospin-mediated vortices in graphene. This result offers the promise of controlling properties of materials through chemical doping with atomic-level precision

DFT Studies on Ni-Mediated C–F Cleavage for the Synthesis of Cyclopentadiene Derivatives

Density functional theory calculations have been performed to study the detailed mechanism of Ni-mediated [3+2] cycloaddition of 2-trifluoromethyl-1-alkenes with alkynes via cleavage of two C-F bonds. It was found that the reaction pathway involves oxidative cyclization, the first β-fluorine elimination, and then intramolecular 5-endo insertion of difluoroalkene, followed by the second cleavage of C-F bond, and finally the dissociation of difluorides yields the fluorine-containing product cyclopentadienes in sequence. The overall rate-determining step is the combined processes of the β-fluorine elimination and the 5-endo insertion. Furthermore, we investigated the effect of different ligands and the regioselectivity of asymmetric alkynes. The detailed energy profiles and structures are presented in this study

Effects of vasodilator and esmolol-induced hemodynamic stability on early post-operative cognitive dysfunction in elderly patients: a randomized trial.

Objective: To investigate the effect of continuous intravenous injection of nicardipine and/or nitroglycerin with or without esmolol on the occurrence of early post-operative cognitive dysfunction (POCD) in elderly patients. Methods: Elderly patients (n=340) who underwent radiofrequency ablation for atrial fibrillation were randomized into five groups: A, nicardipine; B nicardipine+esmolol; C, (nitroglycerin) group; D nitroglycerin+esmolol; E (control) groups. The hemodynamic parameters were recorded, and Mini Mental State Examination was used to assess cognitive function. Results: At 30 min and 60 minutes after anesthesia and at the conclusion of surgery, the rate pressure product value was significantly lower in Groups B (10621.1\ub1321.7, 10544.2\ub1321.8, and 10701.3\ub1325.5, respectively) and D (10807.4\ub1351.1, 10784.3\ub1360.3, and 10771.7\ub1345.7, respectively) than in Group E (13217.1\ub1377.6, 13203.5\ub1357.3, and 13119.2\ub1379.5, respectively). The heart rate was significantly higher in Groups A (104.1\ub110.3, 104.9\ub111.1, and 103.9\ub111.8, respectively) and C (103.7\ub111.3, 105.5\ub110.5, and 107.7\ub111.7, respectively) than in Group E (89.3\ub112.0, 88.5\ub111.5, and 85.5\ub111.6, respectively). The incidence of POCD was significantly lower in Groups A and B than in Groups C, D, and E. Univariate regression analysis showed that regimens in Groups A, B, and E and doses of propofol and fentanyl were risk factors for POCD. Multivariate logistic regression analysis revealed significant associations between the incidence of POCD and interventions in Groups A and B. Conclusion: Maintenance of stable intraoperative hemodynamics using nicardipine and nitroglycerin or their combinations with esmolol, especially nicardipine with esmolol, reduced the incidence of POCD in the elderly with potential cardiovascular diseases

A Chinese patent medicine’s long-term efficacy on non-dialysis patients with CKD stages 3–5: a retrospective cohort study

BackgroundChinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3–5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear.MethodsPatients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules.ResultsA total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were −0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were −0.207 (95% CI: −0.346, −0.068, p = 0.004), −0.214 (95% CI: 0.389, −0.039, p = 0.017), −0.324 (95% CI: 0.538, −0.109, p = 0.003), −0.502 (95% CI: 0.761, −0.243, p = 0.000), and −0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489–0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)).ConclusionThe long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%

Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation

Erratum to : Analysis of the mitochondrial maxicircle of Trypanosoma lewisi, a neglected human pathogen

BACKGROUND The haemoflagellate Trypanosoma lewisi is a kinetoplastid parasite which, as it has been recently reported to cause human disease, deserves increased attention. Characteristic features of all kinetoplastid flagellates are a uniquely structured mitochondrial DNA or kinetoplast, comprised of a network of catenated DNA circles, and RNA editing of mitochondrial transcripts. The aim of this study was to describe the kinetoplast DNA of T. lewisi. METHODS/RESULTS In this study, purified kinetoplast DNA from T. lewisi was sequenced using high-throughput sequencing in combination with sequencing of PCR amplicons. This allowed the assembly of the T. lewisi kinetoplast maxicircle DNA, which is a homologue of the mitochondrial genome in other eukaryotes. The assembly of 23,745 bp comprises the non-coding and coding regions. Comparative analysis of the maxicircle sequence of T. lewisi with Trypanosoma cruzi, Trypanosoma rangeli, Trypanosoma brucei and Leishmania tarentolae revealed that it shares 78 %, 77 %, 74 % and 66 % sequence identity with these parasites, respectively. The high GC content in at least 9 maxicircle genes of T. lewisi (ATPase6; NADH dehydrogenase subunits ND3, ND7, ND8 and ND9; G-rich regions GR3 and GR4; cytochrome oxidase subunit COIII and ribosomal protein RPS12) implies that their products may be extensively edited. A detailed analysis of the non-coding region revealed that it contains numerous repeat motifs and palindromes. CONCLUSIONS We have sequenced and comprehensively annotated the kinetoplast maxicircle of T. lewisi. Our analysis reveals that T. lewisi is closely related to T. cruzi and T. brucei, and may share similar RNA editing patterns with them rather than with L. tarentolae. These findings provide novel insight into the biological features of this emerging human pathogen