Phylogenomics and the rise of the angiosperms.

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.

The origin and speciation of orchids.

Orchids constitute one of the most spectacular radiations of flowering plants. However, their origin, spread across the globe, and hotspots of speciation remain uncertain due to the lack of an up-to-date phylogeographic analysis. We present a new Orchidaceae phylogeny based on combined high-throughput and Sanger sequencing data, covering all five subfamilies, 17/22 tribes, 40/49 subtribes, 285/736 genera, and c. 7% (1921) of the 29 524 accepted species, and use it to infer geographic range evolution, diversity, and speciation patterns by adding curated geographical distributions from the World Checklist of Vascular Plants. The orchids' most recent common ancestor is inferred to have lived in Late Cretaceous Laurasia. The modern range of Apostasioideae, which comprises two genera with 16 species from India to northern Australia, is interpreted as relictual, similar to that of numerous other groups that went extinct at higher latitudes following the global climate cooling during the Oligocene. Despite their ancient origin, modern orchid species diversity mainly originated over the last 5 Ma, with the highest speciation rates in Panama and Costa Rica. These results alter our understanding of the geographic origin of orchids, previously proposed as Australian, and pinpoint Central America as a region of recent, explosive speciation.

Sex difference in nocturnal blood pressure dipping in adolescents with varying degrees of adiposity.

BACKGROUND: For adolescents, abnormal dipping patterns in blood pressure (BP) are associated with early-onset organ damage and a higher risk of cardiovascular disorders in adulthood. Obesity is one of the most common reasons for abnormal BP dipping in young people. However, it is unknown whether the severity of obesity is associated with BP dipping status and whether this association is sex-dependent. METHODS: 499 participants between 12 and 17 years old with overweight or obesity underwent ambulatory blood pressure monitoring (ABPM) between April 2018 and January 2019 in Beijing and Baoding. Participants were grouped by body mass index (BMI) into overweight (BMI 85th-95th percentile), obese (BMI ≥ 95th percentile) and severely obese (BMI ≥ 120% of 95th percentile or ≥ 35 kg/m2) groups. Non-dipping was defined as a < 10% reduction in BP from day to night. The interaction effect between sex and obesity degree was also analyzed. RESULTS: 326 boys and 173 girls were included, of whom 130 were overweight, 189 were obese, and 180 were severely obese. Girls with severe obesity had a higher prevalence of non-dipping, but boys showed no significant differences in BP dipping status between obesity categories. In addition, as obesity severity went up, a more evident increase in night-time SBP was observed in girls than in boys. CONCLUSIONS: Severely obese is associated with a higher prevalence of non-BP dipping patterns in girls than in boys, which suggests that the relationship between the severity of obesity and BP dipping status might be sex-specific.

Development of machine learning models to predict perioperative blood transfusion in hip surgery.

BACKGROUND: Allogeneic Blood transfusion is common in hip surgery but is associated with increased morbidity. Accurate prediction of transfusion risk is necessary for minimizing blood product waste and preoperative decision-making. The study aimed to develop machine learning models for predicting perioperative blood transfusion in hip surgery and identify significant risk factors. METHODS: Data of patients undergoing hip surgery between January 2013 and October 2021 in the Peking Union Medical College Hospital were collected to train and test predictive models. The primary outcome was perioperative red blood cell (RBC) transfusion within 72 h of surgery. Fourteen machine learning algorithms were established to predict blood transfusion risk incorporating patient demographic characteristics, preoperative laboratory tests, and surgical information. Discrimination, calibration, and decision curve analysis were used to evaluate machine learning models. SHapley Additive exPlanations (SHAP) was performed to interpret models. RESULTS: In this study, 2431 hip surgeries were included. The Ridge Classifier performed the best with an AUC = 0.85 (95% CI, 0.81 to 0.88) and a Brier score = 0.21. Patient-related risk factors included lower preoperative hemoglobin, American Society of Anesthesiologists (ASA) Physical Status > 2, anemia, lower preoperative fibrinogen, and lower preoperative albumin. Surgery-related risk factors included longer operation time, total hip arthroplasty, and autotransfusion. CONCLUSIONS: The machine learning model developed in this study achieved high predictive performance using available variables for perioperative blood transfusion in hip surgery. The predictors identified could be helpful for risk stratification, preoperative optimization, and outcomes improvement.

Design, synthesis and neuraminidase inhibitory activity of 4-methyl-5-(3-phenylacryloyl) thiazoles.

A series of 4-methyl-5-(3-phenylacryloyl)thiazoles based on chalcones were designed, synthesized and evaluated for their influenza neuraminidase (NA) inhibitory activity in vitro. A preliminary structure-activity relationship (SAR) analysis showed that thiazoles bearing amide had greater potency. It also showed that mono-hydroxyl group at 4-position on phenyl ring was more effective than other electron-releasing groups or electron-withdraw groups. Compounds A2 and A26 were more potent against NA with IC50 values of 8.2 ± 0.5 µg/mL and 6.2 ± 1.4 µg/mL, respectively. Molecular docking study demonstrated that thiazoles skeleton was benefit for the NA inhibitory activity.

Histopathological evidence of intrahepatic cholangiocarcinoma occurring in ductal plate malformation: A clinicopathologic study of 5 cases.

Ductal plate malformations (DPM) arise from abnormal remodeling of the embryologic ductal plate of the liver. Malignant transformation of DPMs to intrahepatic cholangiocarcinoma (iCCA) has been reported in very rare instances but is viewed with some skepticism. We report the clinicopathological findings in five cases of iCCA, occurring in liver with DPM-like features. All tumors were less than 5 cm, often presented as stage T1a tumors. Histologically, a typical tumor showed a vague multinodular architecture with larger, irregular, tortuous glandular structures with microcystic dilation, intraluminal fibroepithelial projection, and bridge/island formation. The tumor cells were relatively small, bland, and without obvious pleomorphism. Interestingly, DPM presented as a histopathological transition sequence of definitively benign to biliary intraepithelial neoplasia (bilIN), then finally to iCCA. A complete pushing border, with entrapped portal tracts at the edge of the main tumor, suggested a replacing growth pattern. There was gradually increased expression of Ki-67 and p53 in these transition phases from benign to bilIN then to iCCA with DPM-like features. The neoplastic epithelium exhibited immunoreactivity in EpCAM, MUC1, NCAM, and CK19. KRAS mutation was found in 2 of the 5 iCCA cases with DPM-like features. Multifocal DPMs or VMCs with bilIN were dispersed in the non-tumor liver parenchyma in 3 of the 5 cases. The neoplasm was interpreted as iCCA arising in DPM, which may have originated from small bile duct or hepatic precursor cells. More studies are needed to verify this scarce entity and its premalignant properties.

Ascorbate Oxidase Mimetic Activity of Copper(II) Oxide Nanoparticles.

Although oxidase mimetic nanozymes have been widely investigated, specific biological molecules have rarely been explored as substrates, particularly in the case of ascorbate oxidase (AAO) mimetic nanozymes. Herein, we demonstrate for the first time that copper(II) oxide nanoparticles (CuO NPs) catalyze the oxidation of ascorbic acid (AA) by dissolved O2 (as a green oxidant) to form dehydroascorbic acid (DHAA), thus functioning as a new kind of AAO mimic. Under neutral conditions, the Michaelis-Menten constant of CuO NPs (0.1302 mm) is similar to that of AAO (0.0840 mm). Furthermore, the robustness of CuO NPs is greater than that of AAO, thus making them suitable for applications under various conditions. As a demonstration, a fluorescence AA sensor based on the AAO mimetic activity of CuO NPs was developed. To obtain a fluorescent product, o-phenylenediamine (OPDA) was used to react with the DHAA produced by the oxidation of AA catalyzed by CuO NPs. The developed sensor was cost-effective and easy to fabricate and exhibited high selectivity/sensitivity with a wide linear range (1.25×10-6 to 1.125×10-4 m) and a low detection limit (3.2×10-8 m). The results are expected to aid in expanding the applicability of oxidase mimetic nanozymes in a variety of fields such as biology, medicine, and detection science.

Molecular phylogenetics and floral evolution of the Cirrhopetalum alliance (Bulbophyllum, Orchidaceae): Evolutionary transitions and phylogenetic signal variation.

The Cirrhopetalum alliance is a loosely circumscribed species-rich group within the mega-diverse genus Bulbophyllum (Orchidaceae). The monophyletic status of the alliance has been challenged by previous studies, although established sectional classifications have yet to be tested in a phylogenetic context. We used maximum likelihood and Bayesian analyses of DNA sequence data (cpDNA: matK and psbA-trnH; nrDNA: ITS and Xdh; 3509 aligned characters; 117 taxa), including all sections putatively associated with the Cirrhopetalum alliance, to reconstruct the phylogeny. We mapped 11 selected categorical floral characters onto the phylogeny to identify synapomorphies and assess potential evolutionary transitions across major clades. Our results unequivocally support the recognition of an amended Cirrhopetalum alliance as a well-supported monophyletic group characterized by clear synapomorphies, following the inclusion of sect. Desmosanthes and the exclusion of five putative Cirrhopetalum-allied sections. Most sections within the Cirrhopetalum alliance are demonstrated to be polyphyletic or paraphyletic, necessitating a new sectional classification. The inclusion of sect. Desmosanthes revolutionizes our understanding of the alliance, with significant evolutionary transitions in floral characters detected. We further investigated six continuously variable characters of the sepals and labellum, and detect phylogenetic conservatism in labellum width and the evolutionary lability of lateral sepal length, which can partly be explained by the different functional roles they play in pollination and pollinator trapping.

An animal model of transfusion-related acute lung injury and the role of soluble CD40 ligand.

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is a life-threatening complication of transfusion and is one of leading causes of transfusion-associated fatalities. However, the pathogenesis of TRALI is still unclear. Soluble CD40 ligand (sCD40L) is a proinflammatory cytokine that accumulates during blood component storage and is involved in transfusion reactions. The objective of this study was to establish a clinically relevant TRALI animal model and to evaluate the role of sCD40L in TRALI. MATERIALS AND METHODS: Rats' red-blood-cell (RBC) suspensions were prepared, and the quality of RBC was evaluated. A trauma-haemorrhage-transfusion strategy was applied to build the animal model. Lung oedema was evaluated by histopathology examination, total bronchoalveolar lavage fluid (BALF) protein concentration, Evans blue dye (EBD) leakage and inflammatory cytokines. The sCD40L concentrations were measured. RESULTS: Storage lesions of RBCs gradually increased over time. Obvious histological evidence of lung injury of rats transfused with a 35-day RBC was observed. The total BALF protein concentration, EBD leakage, inflammatory cytokines concentration were increased significantly in the Day 35 group. The sCD40L concentration increased significantly in the storage RBC suspension over time but was slightly elevated in rat plasma. CONCLUSIONS: These findings indicated successful establishment of a TRALI animal model with trauma-haemorrhage-transfusion, in which sCD40L may play a minor role in the development of TRALI.

Bioassay of ferulic acid derivatives as influenza neuraminidase inhibitors.

Four series of ferulic acid derivatives were designed, synthesized, and evaluated for their neuraminidase (NA) inhibitory activities against influenza virus H1N1 in vitro. The pharmacological results showed that the majority of the target compounds exhibited moderate influenza NA inhibitory activity, which was also better than that of ferulic acid. The two most potent compounds were 1m and 4a with IC50 values of 12.77 ± 0.47 and 12.96 ± 1.34 µg/ml, respectively. On the basis of the biological results, a preliminary structure-activity relationship (SAR) was derived and discussed. Besides, molecular docking was performed to study the possible interactions of compounds 1p, 2d, 3b, and 4a with the active site of NA. It was found that the 4-OH-3-OMe group and the amide group (CON) of ferulic acid amide derivatives were two key pharmacophores for NA inhibitory activity. It is meaningful to further modify the natural product ferulic acid to improve its influenza NA inhibitory activity.

[Advances in the Pathogenesis,Prevention,and Treatment of Transfusion-related Acute Lung Injury].

Transfusion-related acute lung injury(TRALI)is a severe pulmonary complication of transfusion and has been one of the leading causes of transfusion-associated deaths.However,the pathogenesis of TRALI is still unclear,and treatment and prevention of this condition also face huge challenges.Many recent studies have explored the roles of various effector cells and effector molecules in TRALI and possible related mechanisms based on various hypotheses,in order to find the key factors that induce TRALI and the potential prevention measures.This article reviews the pathogenesis,prevention,and treatment of TRALI.

Design, synthesis and biological evaluation of honokiol derivatives as influenza neuraminidase inhibitors.

Honokiol, a natural polyphenol, which was reported to have satisfactory influenza neuraminidase (NA) inhibitory activity, was structurally modified. Twenty-three compounds were synthesized and the ortho-effects in the epoxidation and hydrolyzation reactions were studied. The derivatives were evaluated for NA inhibitory activity and the benzoylhydrazone derivatives showed much better anti-NA activity than honokiol. Structure-activity relationship analysis suggested that the polyphenols exhibited better anti-NA activity than monophenols and biphenols. Furthermore, probable binding mode of drug with target revealed that the most active compound had much stronger interactions with the active site of NA than honokiol suggesting the potent anti-influenza virus activity.

[Establishment of An Animal Model of Transfusion-related Acute Lung Injury and the Role of Soluble CD40 Ligand in the Development of Transfusion-related Acute Lung Injury].

Objective To establish an animal model of transfusion-related acute lung injury (TRALI) and investigate the role of soluble CD40 ligand (sCD40L) in the development of TRALI. Methods The TRALI animal model established by trauma-hemorrhage-transfusion. Lung edema was evaluated by histopathological examination and the protein and Evans blue dye accumulation in bronchoalveolar lavage fluid. The concentration of sCD40L in storage packed red blood cell (PRBC) and rat's plasma was measured by enzyme-linked immunosorbent assay (ELISA). Results There were obvious epithelial hyperplasia and inflammatory cell infiltration in the lung tissue of 7 d-PRBC-treated group. The accumulation of protein in bronchoalveolar lavage fluid of 7 d-PRBC-treated group [(13.17±5.76)mg] was significantly higher than that in normal controls [(1.21±0.66)mg] and normal saline (NS)-treated group [(4.94±2.15) mg] (F=17.605,P<0.001). The leakage amount of Evans blue dye in 7 d-PRBC-treated group [(0.0109±0.0067)%/min] was significantly higher than that in NS-treated group [(0.0026±0.0006) %/min] (t=2.998,P=0.03). The concentration of sCD40L of the 7 d PRBC [(451.58±73.28) pg/ml] was significantly higher than 0 d PRBC [(277.94±98.18)pg/ml] (t=2.834,P=0.03). The concentration of sCD40L in the plasma of 7 d-PRBC-treated group [(878.21±125.30)pg/ml] was significantly higher than those in normal controls [(289.78±62.60)pg/ml] and NS-treated group [(418.07±47.68)pg/ml] (F=78.715,P<0.001). Conclusion The TRALI animal model was successfully established with trauma-hemorrhage-transfusion. The concentration of sCD40L in plasma of rats with massive transfusion is remarkably increased,suggesting sCD40L may play a role in the development of TRALI.

Identification of Key Gene Modules in Human Osteosarcoma by Co-Expression Analysis Weighted Gene Co-Expression Network Analysis (WGCNA).

Osteosarcoma is the eighth-most common form of childhood cancer, comprising about 20% of all primary bone cancers. To date, systemic co-expression analysis for this cancer is still insufficient to explain the pathogenesis of poorly understood OC. The objective of this study was to construct a gene co-expression network to predict clusters of candidate genes involved in the pathogenesis of osteosarcoma. First, we contributed co-expression modules via weighted gene co-expression network analysis (WGCNA) and investigated the functional enrichment analysis of co-expression genes in terms of GO and KEGG. In result, seven co-expression modules were identified, containing 2,228 differentially expressed genes identified from the 22 human osteosarcoma samples. Subsequently, correlation study showed that the hub-genes between pair-wise modules displayed significant differences. Lastly, functional enrichment analysis of the co-expression modules showed that the module 5 enriched in progresses of immune response, antigen processing, and presentation. In conclusion, we identified essential genes in module 5 which were associated to human osteosarcoma. The key genes in our findings might provide the framework of co-expression gene modules of human osteosarcoma. Further, the functional analysis of these associated genes provides references to understand the mechanism of Osteosarcoma. J. Cell. Biochem. 118: 3953-3959, 2017. © 2017 Wiley Periodicals, Inc.

Preponderance of clonality triggers loss of sex in Bulbophyllum bicolor, an obligately outcrossing epiphytic orchid.

Vegetative propagation (clonal growth) conveys several evolutionary advantages that positively affect life history fitness and is a widespread phenomenon among angiosperms that also reproduce sexually. However, a bias towards clonality can interfere with sexual reproduction and lead to sexual extinction, although a dearth of effective genetic tools and mathematical models for clonal plants has hampered assessment of these impacts. Using the endangered tropical epiphytic or lithophytic orchid Bulbophyllum bicolor as a model, we integrated an examination of breeding system with 12 microsatellite loci and models valid for clonal species to test for the "loss of sex" and infer likely consequences for long-term reproductive dynamics. Bagging experiments and field observations revealed B. bicolor to be self-incompatible and pollinator-dependent, with an absence of fruit-set over 4 years. Challenging the assumptions that clonal populations can be as genotypically diverse as sexually reproducing ones and that clonality does not greatly influence genetic structure, just 22 multilocus genotypes were confirmed among all 15 extant natural populations, 12 of the populations were found to be monoclonal, and all three multiclonal ones exhibited a distinct phalanx clonal architecture. Our results suggest that all B. bicolor populations depend overwhelmingly on clonal growth for persistence, with a concomitant loss of sex due to an absence of pollinators and a lack of mating opportunities at virtually all sites, both of which are further entrenched by habitat fragmentation. Such cryptic life history impacts, potentially contributing to extinction debt, could be widespread among similarly fragmented, outcrossing tropical epiphytes, demanding urgent conservation attention.

Potential prognostic long non-coding RNA identification and their validation in predicting survival of patients with multiple myeloma.

Multiple myeloma, a typical hematological malignancy, is characterized by malignant proliferation of plasma cells. This study was to identify differently expressed long non-coding RNAs to predict the survival of patients with multiple myeloma efficiently. Gene expressing profiles of diagnosed patients with multiple myeloma, GSE24080 (559 samples) and GSE57317 (55 samples), were downloaded from Gene Expression Omnibus database. After processing, survival-related long non-coding RNAs were identified by Cox regression analysis. The prognosis of multiple myeloma patients with differently expressed long non-coding RNAs was predicted by Kaplan-Meier analysis. Meanwhile, stratified analysis was performed based on the concentrations of serum beta 2-microglobulin (S-beta 2m), albumin, and lactate dehydrogenase of multiple myeloma patients. Gene set enrichment analysis was performed to further explore the functions of identified long non-coding RNAs. A total of 176 long non-coding RNAs significantly related to the survival of multiple myeloma patients (p < 0.05) were identified. In dataset GSE24080 and GSE57317, there were 558 and 55 patients being clustered into two groups with significant differences, respectively. Stratified analysis indicated that prediction of the prognoses with these long non-coding RNAs was independent from other clinical phenotype of multiple myeloma. Gene set enrichment analysis-identified pathways of cell cycle, focal adhesion, and G2-M checkpoint were associated with these long non-coding RNAs. A total of 176 long non-coding RNAs, especially RP1-286D6.1, AC008875.2, MTMR9L, AC069360.2, and AL512791.1, were potential biomarkers to evaluate the prognosis of multiple myeloma patients. These long non-coding RNAs participated indispensably in many pathways associated to the development of multiple myeloma; however, the molecular mechanisms need to be further studied.

A new ten-gene risk fraction model serving as prognostic indicator for clinical outcome of multiple myeloma.

Multiple myeloma (MM) is a kind of aggressive tumor prevalent with high heterogeneity. Abnormal expression of certain genes may lead to the occurrence and development of MM. Nowadays, it is not commonly seen in clinical research to predict the prognostic circumstances of patients with MM by multiple gene expression profiling method. Identification of potential genes in prognostic process could be beneficial for clinical management of MM. Therefore, we aimed to build a risk fraction model to screen out the prognostic indicator for clinical outcome of MM. Microarray data were downloaded from the Genome Expression Omnibus (GEO) datasets with accession numbers GSE24080 and GSE57317. A total of 279 samples were selected out randomly. Besides, a risk formula was constructed and verified in the dataset. Time-dependent receiver operating characteristic (ROC) curve was applied in evaluating the accurate prognostic conditions of patients. Finally, a ten genes model in the training dataset was found to be closely related to the survival condition of MM patients. Patients with MM were divided into two groups, high-risk and low-risk, by the expression of these ten genes, and significant statistical difference was found between the two groups. Furthermore, the result of multivariate cox regression and stratified analysis indicated that this model was independent of other clinical phenotypes. ROC curves also showed its feasibility to predict the survival status of MM patients. Our results demonstrated that the fraction risk model constructed by the selected ten genes could be used to predict survival status of multiple myeloma patients, which could also help in improvement of prognostic and therapeutic tool of MM.

MicroRNA-219-5p Inhibits Morphine-Induced Apoptosis by Targeting Key Cell Cycle Regulator WEE1.

BACKGROUND To identify the effects of microRNA (miR)-219-5p on morphine-induced apoptosis by targeting WEE1. MATERIAL AND METHODS Forty Balb/C mice (Toll-like receptor 9, TLR9 knockout) were randomly allocated to the experimental and control groups (20 in each group). The baseline miR-219-5p expression was detected using quantitative real-time PCR (qRT-PCR). After morphine was injected at 6 h on the 2nd and 6th days, experimental and control groups received miR-219-5p mimics or miRNA-negative control (NC), respectively, compound injection. Tissues and cells were later obtained from subjects in each group separately after mice were killed. TUNEL assay was used to investigate apoptosis in both groups. RAW264.7 cells were treated with miR-219-5p mimics and controls, respectively. After 24 h, 10 µM of morphine was added at 24 h. Cell apoptosis was assessed by flow cytometer. The WEE1 and Phospho-cdc2 (Tyr15) expressions were examined by Western blotting. RESULTS MiR-219-5p expression in the experimental group was significantly lower than that in the control group (P<0.05). Mice injected with miR-219-5p mimic experienced an evident increase in apoptosis rate compared with the control group (P<0.05). The miR-219-5p NC group and the morphine group both presented an elevated apoptosis rate compared with the blank control group (both, P<0.05). The apoptosis rate in the miR-219-5p mimic group was 10.06%, remarkably lower than in the miR-219-5p NC group and blank control group (both P<0.05). WEE1 and Tyr15 protein expressions in the miR-219-5p NC group and morphine group were obviously stronger than those in the blank control group (all P<0.05). In the miR-219-5p mimic group, WEE1 and Tyr15 protein expressions were significantly lower compared with those in the miR-219-5p NC group and morphine group (all P<0.05). CONCLUSIONS Morphine significantly downregulated the expression of miRNA-219-5p, which targets WEE1 to suppress Tyr15 expressions and activate Cdc2, thus inhibiting the morphine-induced macrophage apoptosis.

Outcomes of Interferon/Ribavirin Therapy in Patients with HCV Defined by Expression of Plasma Soluble Human Leukocyte Antigen-G but Not IL-37.

BACKGROUND Chronic hepatitis C virus (HCV) infection leads to life-threatening complications worldwide. Immunomodulation signals the response to virus clearance. The immune-suppressive molecule human leukocyte antigen-G (HLA-G) has been shown to function in inhibiting both innate and adaptive immune responses. The objective of this study was to investigate the expression of HLA-G and IL-37 in sustained virological response (SVR) and non-SVR HCV-positive patients before and after complete treatment with a combination of pegylated interferon (IFN) and ribavirin (RBV). MATERIAL AND METHODS Our study included 132 chronic hepatitis C patents who received combined therapy with IFN-a and RBV. Both SVR and non-SVR patients were included. The end-of-treatment response was defined as undetectable HCV RNA at week 48. Patients with end-of-treatment response were detected by HCV RNA at 24 weeks after therapy. The expression levels of HLA-G and IL-37 at the end and 24 weeks after treatment were detected by ELISA. RESULTS Plasma HLA-G and IL-37 were significantly increased in HCV-infected patients compared with healthy individuals before treatment. Furthermore, HLA-G in SVR patients was noticeably decreased after treatment, while HLA-G in non-SVR patients had no changes after treatment. Additionally, both in SVR and non-SVR patients, the expression of IL-37 was remarkably reduced compared with baseline after treatment. CONCLUSIONS These findings suggest that elevation of HLA-G and IL-37 in HCV may play an important role in response to combined therapy with IFN-a and RBV. Monitoring the expression of HLA-G during therapy could contribute to adjusting the treatment program of HCV-infected patients.

One-Pot Three-Component Synthesis of Novel Diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(arylamino)methyl)phosphonate as Potential Anticancer Agents.

With the aim of discovering new anticancer agents, we have designed and synthesized novel α-aminophosphonate derivatives containing a 2-oxoquinoline structure using a convenient one-pot three-component method. The newly synthesized compounds were evaluated for antitumor activities against the A549 (human lung adenocarcinoma cell), HeLa (human cervical carcinoma cell), MCF-7 (human breast cancer cell), and U2OS (human osteosarcoma cell) cancer cell lines in vitro, employing a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The results of pharmacological screening indicated that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most compounds showed more potent inhibitory activities comparable to 5-fluorouracil (5-FU) which was used as a positive control. The mechanism of representative compound 4u (diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(phenyl-amino)methyl)phosphonate) indicated that the compound mainly arrested HeLa cells in S and G2 stages and was accompanied by apoptosis in HeLa cells. This action was confirmed by acridine orange/ethidium bromide staining, Hoechst 33342 staining, and flow cytometry.