Towards advanced removal of organics in persulfate solution by heterogeneous iron-based catalyst: A review.

Heterogeneous iron-based catalysts have drawn increasing attention in the advanced oxidation of persulfates due to their abundance in nature, the lack of secondary pollution to the environment, and their low cost over the last a few years. In this paper, the latest progress in the research on the activation of persulfate by heterogeneous iron-based catalysts is reviewed from two aspects, in terms of synthesized catalysts (Fe0, Fe2O3, Fe3O4, FeOOH) and natural iron ore catalysts (pyrite, magnetite, hematite, siderite, goethite, ferrohydrite, ilmenite and lepidocrocite) focusing on efforts made to improve the performance of catalysts. The advantages and disadvantages of the synthesized catalysts and natural iron ore were summarized. Particular interests were paid to the activation mechanisms in the catalyst/PS/pollutant system for removal of organic pollutants. Future research challenges in the context of field application were also discussed.

Profiling of m6A methylation in porcine intramuscular adipocytes and unravelling PHKG1 represses porcine intramuscular lipid deposition in an m6A-dependent manner.

Intramuscular fat (IMF) content is mainly determined by intramuscular preadipocyte adipogenesis. Epigenetic modifications are known to have a regulatory effect on IMF. As N6-methyladenosine (m6A) is the most abundant epigenetic modification in eukaryotic RNAs. In the present study, we used m6A methylation and RNA sequencing (seq) to identify the m6A-modified RNAs associated with the adipogenic differentiation of intramuscular preadipocytes. Among them, the expression and m6A level of phosphorylase kinase subunit G1 (PHKG1) were found to be significantly changed during adipogenesis. Further studies revealed that knockdown of the methylase METTL3 decreased the m6A methylation of PHKG1 and led to a reduction in PHKG1. Moreover, knockdown of PHKG1 promoted adipogenic differentiation by upregulating the expression of adipogenic genes. In addition, we found that the IMF content in the longissimus thoracis (LT) of Bamei (BM) pigs was greater than that in Large White (LW) pigs, whereas the m6A and PHKG1 expression levels were lower in BM pigs. These findings indicate that the m6A level and expression of PHKG1 were significantly correlated with IMF content and meat quality. In conclusion, this study sheds light on the mechanism by which m6A modification regulates IMF deposition.

Chanling Gao suppresses colorectal cancer via PI3K/Akt/mTOR pathway modulation and enhances quality of survival.

The Chinese medicine formula Chanling Gao (CLG) exhibits significant tumor inhibitory effects in colorectal cancer (CRC) nude mice. However, the detailed mechanisms remain elusive. CRC in situ nude mouse models were treated with CLG. Small animal magnetic resonance imaging (MRI) tracked tumor progression, and overall health metrics such as food and water intake, body weight, and survival were monitored. Posttreatment, tissues and blood were analyzed for indicators of tumor inhibition and systemic effects. Changes in vital organs were observed via stereoscope and hematoxylin-eosin staining. Immunohistochemistry quantified HIF-1α and P70S6K1 protein expression in xenografts. Double labeling was used to statistically analyze vascular endothelial growth factor (VEGF) and CD31 neovascularization. Enzyme-linked immunosorbent assay was used to determine the levels of VEGF, MMP-2, MMP-9, IL-6, and IL-10 in serum, tumors, and liver. Western blotting was used to assess the expression of the PI3K/Akt/mTOR signaling pathway-related factors TGF-ß1 and smad4 in liver tissues. CLG inhibited tumor growth, improved overall health metrics, and ameliorated abnormal blood cell counts in CRC nude mice. CLG significantly reduced tumor neovascularization and VEGF expression in tumors and blood. It also suppressed HIF-1α, EGFR, p-PI3K, Akt, p-Akt, and p-mTOR expression in tumors while enhancing PTEN oncogene expression. Systemic improvements were noted, with CLG limiting liver metastasis, reducing pro-inflammatory cytokines IL-6 and IL-10 in liver tissues, decreasing MMP-2 in blood and MMP-2 and MMP-9 in tumors, and inhibiting TGF-ß1 expression in liver tissues. CLG can enhance survival quality and inhibit tumor growth in CRC nude mice, likely through the regulation of the PI3K/Akt/mTOR signaling pathway.

Effect of microserum environment stimulation on extraction and biological function of colorectal cancer stem cells.

BACKGROUND: 3D cancer stem cell (CSC) cultures are widely used as in vitro tumor models. In this study, we determined the effects of enriching HCT116 tumor spheres initially cultured in serum-free medium with different concentrations of serum, focusing on the effect of microserum environment stimulation on extraction and biological function of colorectal cancer stem cells (CCSCs). METHODS: CCSCs were enriched in standard serum-free medium and serum-free medium with different concentrations of serum for 1 week. The expression of CSC-associated markers in CCSCs, and the presence and relative proportion of CSCs (CD133/CD44 cell sorting) were then determined to elucidate the effect of the microserum environment on the preservation of CSC-related features. Further, the tumorigenic capacity of CCSCs was evaluated in an immunodeficiency mouse model. RESULTS: Our data indicated that a significantly greater number of spheres with a greater size range and high viability without drastic alteration in biological and structural features, which maintained self-renewal potential after sequential passages were formed after serum supplementation. Real-time analysis showed that both serum spheres and serum-free spheres displayed similar expression patterns for key stemness genes. Serum spheres showed higher expression of the CSC surface markers CD133 and CD44 than did CSCs spheres cultured in serum-free medium. Adherent cultures in complete medium could adapt to the serum-containing microenvironment faster and showed higher proliferation ability. The addition of serum induced EMT and promoted the migration and invasion of serum globular cells. Compared with serum-free cells and adherent cells, serum spheres showed higher tumor initiation ability. CONCLUSIONS: Microserum environment stimulation could be an effective strategy for reliable enrichment of intact CCSCs, and a more efficient CSC enrichment method.

Nur77 is involved in the regulation of obesity-related lower muscle mass by promoting Pten degradation.

Obesity may impair muscle function and is sometimes associated with lower muscle mass. However, the internal regulatory mechanism is still unclear. Nur77 has been reported to improve obesity phenotype by regulating glucose and lipid metabolism and inhibiting the production of inflammatory factors and reactive oxygen species. Concurrently, Nur77 also plays an important role in muscle differentiation and development. We aimed to investigate the role of Nur77 in obesity-related lower muscle mass. Our in vivo and in vitro experiments illustrated that the reduction of obesity-related Nur77 accelerated the occurrence of lower muscle mass by interfering with the signaling pathways involved in the regulation of myoprotein synthesis and degradation. We further demonstrated that Nur77 activates the PI3K/Akt pathway by promoting Pten degradation, which enhances the phosphorylation of the Akt/mTOR/p70S6K pathway and inhibits the expression of skeletal muscle-specific E3 ligases (MAFbx/MuRF1). Nur77 induces Pten degradation by increasing the transcription of its specific E3 ligase Syvn1. Our study confirms that Nur77 is a key factor in ameliorating obesity-related lower muscle mass, providing a new therapeutic target and theoretical basis for the treatment of obesity-related lower muscle mass.

NLRP3 Susceptible Gene Polymorphisms in Patients with Primary Gouty Arthritis and Hyperuricemia.

Polymorphisms have been identified to predispose to primary gouty arthritis (GA) and hyperuricemia (HUA). Here, we accessed the five polymorphisms of rs10754558, rs35829419, rs3738448, rs3806268, and rs7525979 in NLRP3 on GA and HUA susceptibility. We collected 1198 samples (314 GA, 377 HUA, and 507 controls) for this case-control study. Our data detected that the rs3806268 (GA vs. AA: OR = 0.65, p = 0.012) was significantly associated with the susceptibility to GA. The rs3738448 (TT vs. GG: OR = 2.05, p = 0.024) and rs7525979 (TT vs. CC: OR = 1.96, p = 0.037) were significantly associated with the susceptibility to HUA. The rs3806268 AG genotype presented decreased risk of GA among the hypertension (OR = 0.54, p = 0.0093), smoking (OR = 0.59, p = 0.018), and no obesity (OR = 0.60, p = 0.0097) subjects compared to the GG genotype group. The rs3738448 TT genotype demonstrated increased risk of HUA among the hypertension (OR = 4.10, p = 0.0056) and no drinking population (OR = 3.56, p = 0.016) compared to the GG genotype group. The rs7525979 TT genotype demonstrated increased risk of HUA among the hypertension (OR = 4.01, p = 0.0064) and no drinking population (OR = 3.24, p = 0.034) compared to the CC genotype group. Furthermore, a significant haplotype effect of rs10754558/C-rs35829419/C-rs3738448/G-rs3806268/A-rs7525979/C was found (OR = 1.60, p = 0.0046) compared with GCGAC haplotype. Bioinformatics analyses indicated that rs3738448, rs3806268, and rs7525979 might influence the gene regulation, while the T-allele of rs3738448 increased the stability of NLRP3-mRNA. Collectively, our case-control study confirms NLRP3 polymorphisms might participate in regulating immune and inflammation responses in GA and HUA.

Risk SNP-mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway.

As potential biomarkers and therapeutic targets, long noncoding RNAs (lncRNAs) are involved in the tumorigenesis of various tumors. Genetic variation in long noncoding regions can lead to lncRNA dysfunction and even cancer. Nevertheless, studies on the association between lncRNA-associated single-nucleotide polymorphisms (SNPs) and the risk of head and neck squamous cell carcinoma (HNSCC) remain inadequate. Here, we aimed to explore the association between SNPs in LINC01614 and HNSCC risk, and the potential role of LINC01614 in tumorigenesis. In this study, we found that rs16854802 A > G (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.22-1.77, p < 0.001) and rs3113503 G > C (OR = 1.38, 95% CI: 1.15-1.64, p < 0.001) in LINC01614 increased the risk of HNSCC in the Chinese population. Functional bioinformatic analysis and luciferase reporter assay revealed that rs3113503 G > C variant disrupted the binding of miRNA-616-3p to LINC01614, which resulted in the increased expression of LINC01614. Further analysis of the TCGA database demonstrated that the upregulated LINC01614 in HNSCC cancer tissues was associated with poor prognostic in HNSCC patients. In vitro experiments showed that knockdown of LINC01614 inhibited the proliferation, invasion, and migration ability of HNSCC cells. Mechanistically, allele C of rs3113503 in LINC01614 was more effective than allele G in activating the PI3K/AKT signaling pathway. Moreover, the reduced expression of LINC01614 also inhibited the activation of the PI3K/AKT signaling pathway. In summary, our findings revealed that the risk SNP rs3113503 G > C in LINC01614 altered the binding to miR-616-3p, which led to increased LINC01614 expression and promoted HNSCC progression by activating the PI3K/AKT signaling pathway.

The potential of a natural iron ore residue application in the efficient removal of tetracycline hydrochloride from an aqueous solution: insight into the degradation mechanism.

In the existing research, most of the heterogeneous catalysts applied in the activation of persulfate to degrade organic pollutants were synthesized from chemical reagents in the laboratory. In this paper, we have obtained a spent iron ore (IO) residue directly collecting from the iron ore plants, and efficiently activating peroxydisulfate (PS) to produce reactive free radicals. The experimental results demonstrated that the IO could effectively activate PS to degrade tetracycline hydrochloride (TCH), with TCH removal rate reaching up to 85.6% within 2 h at room temperature. The TCH removal rate was increased with increasing iron ore dosage, while the more acidic pH condition would be favorable to TCH removal process. The material characterization results demonstrated that the dominant components of IO were Fe3O4 and FeOOH. The transformation from Fe(II) to Fe(III) at the surface IO was observed after TCH degradation. What's more, the quenching experiment and EPR detection results confirmed that the sulfate radical (SO4•-) and hydroxyl radicals (•OH) would be acting as the main free radicals for TCH degradation. This study could not only explore a novel way to recycle the discarded iron ore, but also further expand its application in an effective activation of PS in an aqueous solution.

COPS3 AS lncRNA enhances myogenic differentiation and maintains fast-type myotube phenotype.

Long non-coding RNAs (lncRNAs) play essential roles in myogenesis. Here, we identified a novel long non-coding RNA, named COPS3 AS lncRNA (COP9 signalosome complex subunit 3 antisense lncRNA), which was transcribed from the mouse COPS3 gene antisense strand and highly expressed in glycolytic muscle fibers. Functionally, COPS3 AS lncRNA knockdown inhibited myogenic differentiation in myoblasts, whereas its overexpression promoted the process. Moreover, COPS3 AS lncRNA maintained the fast-twitch myotubes phenotype. Mechanistically, although COPS3 AS lncRNA did not form AS lncRNA/mRNA dimer with COPS3 mRNA, it as a competing endogenous RNA (ceRNA) to sponge miR-762, promoted myogenic differentiation and Fast-MyHC expression by modulating miR-762 target gene myogenic differentiation 1 (MyoD1). Taken together, COPS3 AS lncRNA is a key candidate regulator of myogenesis and fast-MyHC myotubes specification by miR-762/MyoD signalling axis.

Nur77 Prevents Osteoporosis by Inhibiting the NF-κB Signalling Pathway and Osteoclast Differentiation.

Inflammation is a major risk factor for osteoporosis, and reducing inflammatory levels is important for the prevention of osteoporosis. Although nuclear receptor 77 (Nur77) protects against inflammation in a variety of diseases, its role in osteoporosis is unknown. Therefore, the main purpose of this study was to investigate the osteoprotective and anti-inflammatory effects of Nur77. The microCT and haematoxylin and eosin staining results indicated that knockout of Nur77 accelerated femoral bone loss in mice. The enzyme-linked immunosorbent assay (ELISA) results showed that knockout of Nur77 increased the serum levels of hsCRP and IL-6. The expression levels of NF-κB, IL-6, TNF-α and osteoclastogenesis factors (TRAP, NFATC1, Car2, Ctsk) in the femurs of Nur77 knockout mice were increased significantly. Furthermore, in vitro, shNur77 promoted the differentiation of RAW264.7 cells into osteoclasts by activating NF-κB, which was confirmed by PDTC treatment. Mechanistically, Nur77 inhibited osteoclast differentiation by inducing IκB-α and suppressing IKK-ß. In RAW264.7 cells, overexpression of Nur77 alleviated inflammation induced by siIκB-α, while siIKK-ß alleviated inflammation induced by shNur77. Consistent with the in vivo studies, we found that compared with control group, older adults with high serum hsCRP levels were more likely to suffer from osteoporosis (OR = 1.76, p < 0.001). Our data suggest that Nur77 suppresses osteoclast differentiation by inhibiting the NF-κB signalling pathway, strongly supporting the notion that Nur77 has the potential to prevent and treat osteoporosis.

Effects of Neoadjuvant Radiotherapy on Postoperative Complications in Rectal Cancer: A Meta-Analysis.

OBJECTIVE: Neoadjuvant radiotherapy (nRT) is an important treatment approach for rectal cancer. The relationship, however, between nRT and postoperative complications is still controversial. Here, we conducted a meta-analysis to evaluate such concerns. METHODS: The electronic literature from 1983 to 2021 was searched in PubMed, Embase, and Web of Science. Postoperative complications after nRT were included in the meta-analysis. The pooled odds ratio (OR) was calculated by the random-effects model. Statistical analysis was conducted by Review Manager 5.3 and STATA 14. RESULTS: A total of 23,723 patients from 49 studies were included in the meta-analysis. The pooled results showed that nRT increased the risk of anastomotic leakage (AL) compared to upfront surgery (OR = 1.23; 95% CI, 1.07-1.41; p=0.004). Subgroup analysis suggested that both long-course (OR = 1.20, 95% CI 1.03-1.40; p=0.02) and short-course radiotherapy (OR = 1.25, 95% CI, 1.02-1.53; p=0.04) increased the incidence of AL. In addition, nRT was the main risk factor for wound infection and pelvic abscess. The pooled data in randomized controlled trials, however, indicated that nRT was not associated with AL (OR = 1.01; 95% CI 0.82-1.26; p=0.91). CONCLUSIONS: nRT may increase the risk of AL, wound infection, and pelvic abscess compared to upfront surgery among patients with rectal cancer.

Chryseobacterium endalhagicum sp. nov., isolated from seed of leguminous plant.

A Gram-stain-negative, yellow-pigmented bacterium, designated as L7T, was isolated from seeds of Alhagi sparsifolia Shap., a leguminous plant that grows in northwest PR China. Strain L7T was found to be non-flagellated, non-spore forming rods which can grow at 10-37 °C, pH 6.0-8.5 and in 0-3 % (v/w) NaCl concentration. The 16S rRNA gene sequence analysis showed that strain L7T belongs to the genus Chryseobacterium with sequence similarities to Chryseobacterium vietnamense GIMN1.005T (98.1%), C. bernardetii NCCTC13530T (98.0%), C. vrystaatense LMG 22846T (97.9%), C. nakagawai NCTC13529T (97.7%), C. shigense DSM 17126T (97.6%) and C. rhizosphaerae RSB3-1T (97.5%). The average nucleotide identity of strain L7T to 31 reference strains were 78.6-85.6 %, lower than the species delineation threshold of 95 %. MK-6 was the only respiratory quinone of L7T and major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 1 ω7c and/or C16 : 1 ω6c, isoC17 : 1 ω9c and/or C16 : 0 10-methyl. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, three unidentified aminophospholipids, two unidentified aminolipids, three unidentified glycolipids and two unidentified lipids. The G+C content of the genome was 38.58 mol%. On the basis of polyphasic taxonomy analyses in this study, strain L7T is considered to represent a novel species in the genus Chryseobacterium, for which the name Chryseobacterium endalhagicum sp. nov. is proposed. The type strain is L7T (=MCCC 1K05687T=JCM 34506T).

Genetic variants of cell cycle pathway genes are associated with head and neck squamous cell carcinoma in the Chinese population.

Genetic alterations in the cell cycle pathway are common in head and neck squamous cell carcinoma (HNSCC). We identified four novel HNSCC susceptibility loci (CDKN1C rs452338, CDK4 rs2072052, E2F2 rs3820028 and E2F2 rs2075993) through a two-stage matched case-control study. There was a combined effect among the four single nucleotide polymorphisms (SNPs), as the number of risk genotypes increased, the risk of HNSCC displayed an increasing trend (Ptrend < 0.001). And there were multiplicative interactions between rs452338 and rs2072052, rs2072052 and rs3820028, rs2072052 and rs2075993. Functional bioinformatics analysis and dual-luciferase reporter assay revealed that E2F2 rs2075993 T>C reduced the stability of E2F2 3'-UTR secondary structure and affected the binding of E2F2 to miR-940, which was up-regulated in HNSCC tumor tissues (P = 2.9e-8) and was correlated with poor overall survival of HNSCC (HR = 1.39, 95% CI = 1.02-1.90). In vitro assays, we discovered that the expression of miR-940 was regulated by METTL3, and miR-940 promoted the proliferation, migration and invasion, and inhibited the senescence and autophagy of tumor cells. In terms of mechanism, compared with rs2075993 allele T, we found that the protective variant rs2075993 allele C interfered with the translational inhibition of E2F2 by miR-940, resulting in increased expression of E2F2 protein, which further reduced the proliferation, migration, invasion, and increased the senescence of tumor cells.

Potential of thrombospondin-1 in treatment of polycystic ovary syndrome rat model: a preliminary study.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease in reproductive women, and the endocrine levels are also affected by diseases. The aim of this study was to determine the effect of thrombospondin-1 (TSP-1) on PCOS rat model. METHODS: We established the PCOS rat model, the serum hormones including TSP-1 expression were determined and morphological characteristics were investigated to evaluate the model. These above endocrine and morphological features were investigated again to evaluate the effect of TSP-1 treatment. RESULTS: In the PCOS model group, the serum hormones change (higher luteinizing hormone, testosterone and estrogen) and decreased TSP-1 expression levels were found compared with the control group. Besides, the morphological characteristics of PCOS were also observed in the model group. After TSP-1 treatment, the higher TSP-1, ANGPT2, PDGFB and PDGFD expression levels, the lower LH and T levels, decreased vessel density as well as VEGFA and ANGPT1 expression levels were found compared with the control group, and the ovary morphological changes were also observed in the TSP-1 experimental group. CONCLUSIONS: TSP-1 delivery system might be an alternative therapy for PCOS treatment.

Occurrence and risk assessment of currently used organophosphate pesticides in overlying water and surface sediments in Guangzhou urban waterways, China.

Organophosphate pesticides (OPPs) are one type of the most massively used pesticides and ubiquitously detected in aquatic environments, which may pose potential risks to the aquatic organisms and human health. In the present study, the spatiotemporal distribution and potential risks of OPPs were investigated in overlying water and surficial sediments from urban waterways of Guangzhou. For all studied sites, in general, four target OPPs (i.e., malathion, chlorpyrifos, terbufos, and diazinon) were present in the overlying water, with malathion and chlorpyrifos as major components. Higher concentrations of the four OPPs were found for the water and sediments collected in the dry season compared to the wet season, possibly because of the dilution effect of heavy rains. The results of Pearson's analyses and principal coordinate analyses (PCoA) suggested similar sources for target OPPs in the water and sediments across the Guangzhou urban waterways. Potential ecological risks of the OPPs to three representative taxons (algae, aquatic invertebrates, and fish) were evaluated via toxic units (TUs) and risk quotients (RQs), while risk assessment on human health was performed using hazard index (HI). Although TU results showed no acute risks to the aquatic organisms in the overlying water and surface sediments, RQ results of the mixture showed high risks to the aquatic invertebrate and fish in all water samples. Individual HI values and cumulative HI values were on the order of 10-6-10-3 for children and adults, suggesting no potential risks to either children or adults through drinking and bathing.

[Effect of Signal Transduction Pathway Gene Mutations on the One- course Induced Remission Rate and Analysis of Clinical Characteristics in Patients with CBF-AML].

OBJECTIVE: To investigate the effect of other gene mutations outside the fusion gene on the first complete remission (CR1) induced by one course of induction chemotherapy in patients with core binding factor-associated acute myeloid leukemia (CBF-AML). METHODS: DNA was extracted from bone marrow or peripheral blood samples of newly diagnosed CBF-AML patients admitted to the Hematology Department of the Second Hospital of Shanxi Medical University from January 2015 to January 2019. Next-generation sequencing was used for detection of 34 kinds of hematologic malignancy-related gene mutations in patients with CBF-AML, the effect of related gene mutations on the first complete remission (CR1) rate in one course of induction chemotherapy was analyzed by combineation with clinical characteristics. RESULTS: 34 kinds of genes in bone marrow or peripheral blood of 43 patients were detected by high throughput sequencing and the gene mutations were detected in 16 out of 34 genes. The mutation rate of KIT gene was the highest (48.8%), followed by NRAS (16.3%), ASXL1 (16.3%), TET2 (11.6%), CSF3R (9.3%), FLT3 (9.3%), KRAS (7.0%). The detection rates of mutations in different functional genes were as follows: genes related with signal transduction pathway (KIT, FLT3, CSF3R, KRAS, NRAS, JAK2, CALR, SH2B3, CBL) had the highest mutation frequency (72.1% (31/43); epigenetic modification gene mutation frequency was 30.2% (13/43), including ASXL1, TET2, BCOR); transcriptional regulation gene mutation frequency was 7.0% (3/43), including ETV6, RUNX1, GATA2). Splicing factor related gene mutation frequency was 2.3% (1/43), including ZRSR2). The CR1 rate was 74.4% after one course of induction chemotherapy. At first diagnosis, patients with low expression of WT1 (the median value of WT1 was 788.9) were more likely to get CR1 (P=0.032) and the RFS of patients who got CR1 after one course of induction chemotherapy was significantly longer than that of patients without CR1 [7.6 (2.2-44.1) versus 5.8 (1-19.4), (P=0.048)]. The rate of CR1 in the signal transduction pathway gene mutation group was significantly lower than that in non-mutation group (64.5% vs 100%) (P=0.045), while the level of serum hydroxybutyrate dehydrogenase (HBDH) was significantly higher than that in non-mutation group [(418 (154-2702) vs 246 (110-1068)] (P=0.032). There was no difference in CD56 expression between the two groups (P=0.053), which was limited to the difference between (≥20%) expression and non-expression. (P=0.048). CONCLUSION: CBF-AML patients with signal transduction pathway gene mutation are often accompanied by high HBDH level and CD56 expression, moreover, the remission rate induced by one course of treatment is low.

Serum adenosine deaminase activity and coronary artery disease: a retrospective case-control study based on 9929 participants.

BACKGROUND: Adenosine deaminase (ADA) regulates purine metabolism through the conversion of adenosine to uric acid (UA). Adenosine and UA are closely associated with cardiovascular events, but the correlation between serum ADA activity and coronary artery disease (CAD) has not been defined. METHODS: We performed a hospital-based retrospective case-control study that included a total of 5212 patients with CAD and 4717 sex- and age-matched controls. The serum activity of ADA was determined by peroxidase assays in an automatic biochemistry analyzer. RESULTS: Serum ADA activity in the CAD group (10.08 ± 3.57 U/l) was significantly lower than that of the control group (11.71 ± 4.20 U/l, p < 0.001). After adjusting for conventional factors, serum ADA activity negatively correlated with the presence of CAD (odds ratio = 0.852, 95% confidence interval: 0.839-0.865, p < 0.001). Among the patients with CAD, serum ADA activity was lowest in patients with myocardial infarction (MI; 9.77 ± 3.80 U/l). Diabetes mellitus and hypertension increased the serum ADA activity in CAD patients. CONCLUSIONS: Serum ADA activity is significantly attenuated in patients with CAD, particularly in MI. We propose a mechanism by which the body maintains adenosine levels to protect the cardiovascular system in the event of CAD.

Clonal Analysis of a Patient with Polycythemia Vera and Coexisting Chronic Lymphocytic Leukaemia.

More than 100 cases harboring both myeloproliferative neoplasms (MPN) and chronic lymphocytic leukaemia (CLL) have been reported, suggesting that the two diseases can coexist in one patient. However, the mechanism by which this phenomenon is caused remains unclear. In this study, one patient with polycythemia vera (PV) and CLL is examined. Identifications of the JAK2V617F and P53H179L/ P53R209fs mutations were obtained via targeted next generation sequencing. Furthermore, B lymphocytes and neutrophils were separated from peripheral blood. This led to the discovery that JAK2V617F occurs in neutrophil's compartment, with P53 mutations emerging in B lymphocytes. These results indicate that PV and CLL are independent clonal diseases in this case, rather than phenotypes derived from one clone.

Two activating mutations of MPL in triple-negative myeloproliferative neoplasms.

MPLW515K or W515L mutation plays an important role in the pathogenesis of myeloproliferative neoplasms (MPNs) through signaling molecules of the cytokine receptor axis. Besides MPLW515K or W515L, more than 30 atypical MPL mutations have been reported in patients who are negative for JAK2V617F, MPLW515K/L, and CALR mutations. Here, we aimed to identify the disease-causing mutations in the triple-negative case of ET. We described two MPL mutations in patients diagnosed with ET by target sequencing the hotspot mutation region of MPL gene. The MPLA497-L498ins4 is an insertion mutation detected recurrently in ET patients, and the MPLW515RQ516E is a novel double-point mutation found in an ET patient. Functional studies of MPLA497-L498ins4 and MPLW515RQ516E revealed that they are gain-of-function mutations. Mutants of MPLA497-L498ins4 and MPLW515RQ516E promoted autonomous proliferation on Ba/F3 cells in the absence of IL-3. Autonomous activation of TPO-R without ligand TPO was observed in MPLA497-L498ins4 and MPLW515RQ516E mutants. Lower percentage of cells in G1 phase and higher percentage of cells in S phase of two atypical MPL mutants were detected after culturing without any cytokines. These two atypical MPL mutations also presented increase in phosphorylation of signaling proteins including JAK2/STAT, PI3K/AKT, and MAPK/RAS. In summary, the MPLA497-L498ins4 and MPLW515RQ516E are gain-of-function mutations which may be novel driving factors participating in the pathogenesis of triple-negative MPN.