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1.
J Cell Biochem ; 121(1): 632-641, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31452251

RESUMO

Large intergenic noncoding RNA regulator of reprogramming (Linc-RoR) was first identified as a regulator to increase the emergence of induced pluripotent stem cells through reprogramming differentiated cells and is abnormal expression in a variety of malignant tumors. However, the function of Linc-RoR in pancreatic cancer progression needs further clarification. The data from this study demonstrated that Linc-RoR knockdown suppressed cell proliferative capacity and colony formation, while Linc-RoR overexpression promoted these behaviors. In particular, Linc-RoR overexpression promoted the level of mesenchymal markers, inhibited the expression of epithelial markers, as well as enhanced pancreatic cancer cells migration and invasion, whereas Linc-RoR knockdown inhibited the expression of mesenchymal markers, promoted the expression of epithelial markers, as well as weakened pancreatic cancer cells migration and invasion. Further study revealed that Linc-RoR knockdown brought about a significant fall in YAP phosphorylation and a rise in total YAP, while Linc-RoR overexpression produced the opposite results. Specifically, Linc-RoR promoted YAP in the cytoplasm into the nucleus. Taken together, we conjectured that Linc-RoR promoted proliferation, migration, and invasion of pancreatic cancer cells by activating the Hippo/YAP pathway. YAP might be an underlying target of Linc-RoR and mediate epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC); thus, Linc-RoR might be a very meaningful biomarker for PC.

2.
Chin J Integr Med ; 25(12): 902-910, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31802424

RESUMO

OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C) in the treatment of aplastic anemia (AA) model mice. METHODS: Totally 70 mice were divided into 7 groups as follows: normal, model, low-, medium-, high-dose PDS-C (20, 40, 80 mg/kg, namely L-, M-, H-PDS-C), cyclosporine (40 mg/kg), and andriol (25 mg/kg) groups, respectively. An immune-mediated AA mouse model was established in BALB/c mice by exposing to 5.0 Gy total body irradiation at 1.0 Gy/min, and injecting with lymphocytes from DBA mice. On day 4 after establishment of AA model, all drugs were intragastrically administered daily for 15 days, respectively, while the mice in the normal and model groups were administered with saline solution. After treatment, the peripheral blood counts, bone marrow pathological examination, colony forming assay of bone marrow culture, T lymphocyte subpopulation analysis, as well as T-bet, GATA-3 and FoxP3 proteins were detected by flow cytometry and Western blot. RESULTS: The peripheral blood of white blood cell (WBC), platelet, neutrophil counts and hemoglobin (Hb) concentration were significantly decreased in the model group compared with the normal group (all P<0.01). In response to 3 dose PDS-C treatment, the WBC, platelet, neutrophil counts were significantly increased at a dose-dependent manner compared with the model group (all P<0.01). The myelosuppression status of AA was significantly reduced in M-, H-PDS-C groups, and hematopoietic cell quantity of bone marrow was more abundant than the model group. The colony numbers of myeloid, erythroid and megakaryocytic progenitor cells in the model group were less than those of the normal mice in bone marrow culture, while, PDS-C therapy enhanced proliferation of hematopoietic progenitor cells by significantly increasing colony numbers (all P<0.01). Furthermore, PDS-C therapy increased peripheral blood CD3+ and CD3+CD4+ cells and reduced CD3+CD8+ cells (P<0.05 or P<0.01). Meanwhile, PDS-C treatment at medium- and high doses groups also increased CD4+CD25+FoxP3+ cells, downregulated T-bet protein expression, and upregulated GATA-3 and FoxP3 protein expressions in spleen cells (P<0.05). CONCLUSION: PDS-C possesses dual activities, promoting proliferation hematopoietic progenitor cells and modulating T lymphocyte immune functions in the treatment of AA model mice.

3.
Opt Express ; 27(22): 32378-32391, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31684452

RESUMO

The fringe skeleton method is the most straightforward analysis method for phase extraction and widely used in dynamic measurement. Binarization is often required in this method. In the traditional binarization methods, filtering is often a necessary step prior to binarization due to the influence of intrinsic speckle noises in ESPI fringe patterns. In this paper, we propose a binarization method based on local entropy and fuzzy c-means (FCM) clustering algorithm. In this method, the pixels in the given ESPI fringe pattern are clustered into white fringes and black fringes according to their local entropy instead of the original intensity information. There is no need to perform the filtering preprocessing, because the intrinsic speckle noises are utilized as essentials. We evaluate the performance of our method by applying it to the computer-simulated and real fringe patterns. Experimental results demonstrate that the proposed method can achieve the desired binarization results, and the binarization results can give desired skeleton results.

4.
Opt Express ; 27(20): 28324-28336, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684586

RESUMO

In the nano-fabrication field, high precision displacement tracing of the fabricating beam is extensively required. Due to the coherence noise and the sensitivity to environmental disturbances, the commonly used measuring methods base on the laser interferometry are unstable. In this paper, a high-precision measuring method for the three-dimensional displacements is developed based on the low coherence interferometry. The interferogram at a particular location is unique and distinctive, which can be applied as a benchmark for the absolute measurement of positions. Consequently, interferograms are continuously acquired during the movement of the nano-stage, then the quantitative relationship between the stage position/tilt and the interferograms is established by analytic calculation. Besides, the influence of random errors can be suppressed by the averaging effect of the least squares fitting, thereby enhancing the precision by more than an order of magnitude compared with traditional methods. The measuring uncertainty is derived and the impacts of the main influencing factors are investigated. Experiments demonstrate that the measuring repeatability can achieve 1.16 nm. As a result, the proposed method can reliably obtain the absolute position and three dimensional trajectory of the nano-stage, and it is of significance to improve the reliability of nano-measurement and fabrication.

5.
Acta Neurol Belg ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31734794

RESUMO

The computed tomography angiography (CTA) Spot Sign is an effective means of predicting hematoma expansion (HE) in the context of spontaneous intracerebral hemorrhage (ICH). We investigated whether continuous CTA source images could differentiate the Spot Sign and blood vessels in the hematoma, and whether it would improve Spot Sign accuracy as an HE predictor. We screened for the presence of CTA Spot Sign in individuals affected by spontaneous ICH within 24 h of symptom development. Based on our findings, we determined the sensitivity, specificity, and positive/negative predictive values of this sign as a predictor of HE both on its own and following the exclusion of blood vessels. In addition, a receiver-operating characteristic approach was used to assess the accuracy of Spot Sign with and without elimination of vascular interference. A total of 265 patients were included in this study. The Spot Sign was observed in 100 patients, including in 29 patients wherein it was confirmed to be blood vessels as determined based upon continuous CTA source images. With respect to predicting HE, Spot Sign sensitivity, specificity, positive predictive values, and negative predictive values were 57%, 71%, 48% and 78%, respectively. Following the exclusion of blood vessels, these values were 57%, 87%, 68% and 81%, respectively. Spot Sign area under the curve after excluding blood vessels was 0.718, which was higher than that of the Spot Sign (0.638). After continuous CTA, source images are used to exclude blood vessels in the hematoma, the Spot Sign is thus more accurate in predicting HE.

7.
Chem Commun (Camb) ; 55(98): 14840-14843, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31768510

RESUMO

XimA is a unique amide synthetase that belongs to the ANL superfamily of adenylating enzymes, but with a special structural fold. In order to improve the enzyme promiscuity, we engineered XimA by site-directed mutagenesis at a specific position based on our theoretical model of XimA. Thus, we were able to produce diverse benzopyran derivatives with up to 15 different l-form and d-form amino acid substitutions, catalyzed by several XimA variants. Molecular docking and molecular dynamics simulations conducted for various XimA systems provide further structural insights into the substitution effects of the phenylalanine-201 as an active site residue on protein dynamics and enzyme catalysis.

9.
Int J Psychophysiol ; 147: 1-8, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31697960

RESUMO

Temporary self-construal (independent vs. interdependent) priming can modulate the neural response to the reward for an individual. Our previous event-related potential (ERP) studies have indicated that people experience the rewards for a friend less strongly than they experience the same amount rewards for themselves. However, an issue remaining unclear is whether the ERP responses to rewards for a friend vary according to the way in which the self is construed. In the present study, we manipulated participants' self-construal (independent vs. interdependent) and found that independent self-construal priming resulted in a greater feedback-related negativity (FRN) in response to outcome feedback for oneself than for a friend during a monetary gambling task. In contrast, interdependent self-construal priming resulted in a comparable FRN in response to outcome feedback for oneself and for a friend. The P3 amplitude was insensitive to the self-construal manipulation. Our findings suggest that interdependent priming may result in comparable motivation elicited by rewards for participants themselves and for their friends. This study provides novel evidence that the neural response to rewards for friend varies according to the way in which the self is construed.

10.
Mar Pollut Bull ; : 110720, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31780092

RESUMO

The Jiangsu coastal environment in China is affected by pollution, and the Cu, Pb, Cd, Zn, Cr, As, and Hg concentrations in the surface sediment of Dafeng Port during 2011-2017 were analyzed to determine their contamination and ecological risks. The multi-year average of Zn, Cr, Pb, Cu, As, Cd, and Hg concentrations were 50.10, 40.32, 12.41, 11.76, 8.67, 0.08, and 0.04 mg/kg, respectively, which were generally higher than their background values, except for those of Cu and Cr. The spatial distribution of heavy metals were similar, and the highest concentrations were measured near Dafeng Port and coastal river inlets. The geoaccumulation index generally indicated moderate-low ecological risk, except for Cd. Multivariate statistical analyses showed that Pb, Zn, Cr, As, Hg, Cd, and petroleum were strongly influenced by anthropogenic activities, whereas Cu derived from both natural and anthropogenic sources. This study provides important information for the management of heavy metal contamination.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31781763

RESUMO

CONTEXT: ß cell dedifferentiation was recently proposed as a mechanism of ß cell dysfunction, but whether it can be a trigger of ß cell failure preceding hyperglycemia in human is uncertain. Pancreatic cancer can cause new-onset diabetes, yet the underlying mechanism is unknown. OBJECTIVE: To investigate whether ß cell dedifferentiation is present in non-diabetic pancreatic ductal adenocarcinoma (PDAC) patients, we examined pancreatic islets from 15 non-diabetic patients with benign tumor (Control) and 15 non-diabetic PDAC patients. DESIGN: We calculated the number of hormone-negative endocrine cells and evaluated important markers of ß cell dedifferentiation and function in the paraneoplastic islets. We assessed tumor-related inflammatory changes under pancreatic cancer microenvironment, and their influence on ß cell identity. RESULTS: We found nearly 10% of non-hormone expressing endocrine cells in non-diabetic PDAC subjects. PDAC islets were dysfunctional, evidenced by low expression of GLUT2 and UCN3, and concomitant upregulation of ALDH1A3 expression and proinsulin accumulation. Pancreatic cancer caused paraneoplastic inflammation with enhanced tissue fibrosis, monocytes/macrophages infiltration and elevated inflammatory cytokines. Moreover, we detected ß cell dedifferentiation and defects in GSIS in islets exposed to PANC-1-conditioned medium. In a larger cohort, we showed high prevalence of new-onset diabetes in PDAC subjects, and FBG was found to be an additional useful parameter for early diagnosis of PDAC. CONCLUSIONS: Our data provide a rationale for ß cell dedifferentiation in the pathogenesis of pancreatic cancer associated diabetes. We propose that ß cell dedifferentiation can be a trigger for ß cell failure in human, before hyperglycemia occurs.

12.
Pediatr Blood Cancer ; : e28108, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31782614

RESUMO

BACKGROUND: Neuroblastoma (NB) is a deadly solid tumor of children. Krüppel-like factor 9 (KLF9) has prodifferentiation and tumor suppression functions in several types of cancers. Here, we aimed to investigate the effects of KLF9 on NB differentiation and growth and to elucidate the underlying mechanism. PROCEDURE: Sixty-five NB paraffin samples were assessed for expression levels of KLF9 and sonic hedgehog (SHH) signaling pathway proteins by immunohistochemistry. The associations between expression of KLF9 and the SHH pathway components and patients' clinicopathologic characteristics were estimated. The impacts of KLF9 on cell differentiation, proliferation, and invasion were investigated in two NB cell lines (SH-SY5Y and IMR32). Additionally, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to elucidate the mechanism by which KLF9 regulates SHH signaling. RESULTS: Differentiating NB specimens showed significantly higher KLF9 expression levels than undifferentiated/poorly differentiated ones. Moreover, increased KLF9 expression was associated with favorable prognoses in patients with NB. A negative correlation was found between KLF9 and SHH signaling expression levels in NB specimens. In vitro assays revealed that KLF9 promoted the differentiation of NB cells and inhibited their proliferation and invasion via suppression of the SHH pathway. Furthermore, KLF9 binding sites in the SHH promoter were identified by ChIP and luciferase reporter assays. CONCLUSIONS: KLF9 exerts prodifferentiation and growth-inhibition effects on NB via suppression of the SHH pathway, suggesting a potential role of KLF9 in NB therapy.

13.
Hum Pathol ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31698008

RESUMO

The etiology and incidence of cirrhosis in adults has been well studied, however there is scant data in younger patients. The aim of this study was to determine causes of cirrhosis in patients ≤40years old. In this multi-institutional retrospective study, pathology databases were searched for patients ≤40-year-old with a diagnosis of cirrhosis from 1995 to 2018. Clinical charts and pathology reports were reviewed to identify etiologies of cirrhosis in each case. The patients were divided into 4 age groups (<1, 1-<5, 5-<18, and 18-40years old) for further analysis. We identified 594 patients (264 female, 330 male). Among <18-year-old patients, congenital cholestatic diseases and developmental disorders were the most common causes of cirrhosis (50.2%, 172/342). Metabolic and genetic diseases were also seen more commonly in this age group (16.6%, 57/342). In contrast, viral hepatitides were the most common cause of cirrhosis in 18-40-year-old patients (39.6%, 100/252) followed by autoimmune and fatty liver disease (22.2%, 56/252 and 15.07%, 38/252, respectively). Cryptogenic cirrhosis (overall 7.2%, 42/594) was seen in 3% (4/133), 1.4% (1/69), 10.7% (15/140) and 8.7% (22/252) of patients aged <1, 1-<5, 5-<18, and 18-40years, respectively. Developmental and metabolic disorders are the most common causes of cirrhosis in children (<18), while viral hepatitides are leading causes in adolescents and young adults (18-40) similar to adults. The incidence of cryptogenic cirrhosis also varies depending on the age, being lowest in 1-<5 year and highest in 5-<18 year age group children.

14.
J Pak Med Assoc ; 69(11): 1610-1616, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31740865

RESUMO

OBJECTIVE: To investigate the prevalence of coronary artery disease and characteristics of coronary artery in patients with obstructive sleep apnoea. METHODS: The prospective study was conducted at the Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China, from January, 2012, to June, 2015, and comprised consecutive patients with diagnosed obstructive sleep apnoea. High-resolution 320-slice coronary computed tomography was performed in all the patients. Data was evaluated for the presence of coronary lumen narrowing. Demographic, clinical, laboratory, and echocardiographic characteristics were carefully recorded. Logistic regression was used for multivariate analysis of independent risk factors. SPSS 16 was used for data analysis. RESULTS: Of the 277 patients, 186(67.14%) were males. The overallmean age was 55.1±14.3 years. Coronary artery disease was found in 41(14.8%) patients. Prospective Cardiovascular Münster score, uric acid, triglyceride, C-reactive protein, apnoea hypopnoea index, Epworth sleepiness scale values were significantly higher in patients with the disease (p<0.05 each). Higher Prospective Cardiovascular Münster score, C-reactive protein, apnoea hyponoea index levels had a significant ability to reflect the occurrence of coronary artery disease (p<0.05 each). CONCLUSIONS: Coronary heart disease occurrence in obstructive sleep apnoea patients was found to be strongly related to Prospective Cardiovascular Münster score, apnoea hyponoea index and Creactive protein level.

15.
J Nucl Cardiol ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31741330

RESUMO

BACKGROUND: The aim of the study was to investigate the relationship between post-myocardial infarction (MI) inflammation and left ventricular (LV) remodeling in a swine model by 18F-fluorodeoxyglucose (FDG) imaging. METHODS: MI was induced in swine by balloon occlusion of the left anterior descending coronary artery. A series of FDG positron emission tomography (PET) images were taken within 2 weeks post-MI, employing a comprehensive strategy to suppress the physiological uptake of cardiomyocytes. Echocardiography was applied to evaluate LV volume, global and regional function. CD68+ macrophage and glucose transporters (GLUT-1, -3 and -4) were investigated by immunostaining. RESULTS: The physiological uptake of myocardium was adequately suppressed in 92.3% of PET scans verified by visual analysis, which was further confirmed by the minimal expression of myocardial GLUT-4. Higher FDG uptake was observed in the infarct than in the remote area and persisted within the observational period of 2 weeks. The FDG uptake of infarcted myocardium on day 1 post-MI was correlated with LV global remodeling, and the FDG uptake of infarcted myocardium on days 1 and 8 post-MI had a trend of correlating with regional remodeling of the infarct area. CONCLUSIONS: We here report a feasible swine model for investigating post-MI inflammation. FDG signal in the infarct area of swine persisted for a longer duration than has been reported in small animals. FDG activity in the infarct area could predict LV remodeling.

16.
Biol Lett ; 15(11): 20190447, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31690208

RESUMO

Natural and human disturbances have caused widespread regime shifts in shallow lakes of the lower Yangtze basin (LYB, China) resulting in a severe decline of ecosystem services. Improved understanding of the relationship between environmental forcing and ecosystem response, and the mechanisms behind regime shifts has significant implications for management. However, the patterns of these regime shifts and the underlying internal mechanisms are less known. In this study, two typical lakes (Chaohu and Zhangdu) from the LYB were selected to determine the trajectories of ecological regime shifts, both of which transitioned from vegetation- to plankton-dominated states several decades ago. Ecological trajectories since the 1900s in both lakes were reconstructed using palaeolimnological proxies, mainly diatom assemblages. Although results show that regime shifts occurred in both lakes in the 1970s and the 1950s, respectively, their inherent mechanisms were different. In Lake Zhangdu, altered hydrological conditions pushed the ecosystem across an ecological threshold, providing an example of a driver-mediated regime shift. In Lake Chaohu, ongoing nutrient loading influenced ecosystem processes and drove the lake to an alternative stable state, potentially presenting an example of a critical transition after a loss of resilience. This research indicates that palaeolimnological perspectives can provide insights into regime shift changes, as well as important information regarding which restoration methods should be tailored to individual lakes.

17.
Appl Opt ; 58(27): 7523-7530, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674404

RESUMO

The fringe orientation is an important feature of the electronic speckle interferometry (ESPI) fringe pattern. Accurate and efficient calculation of the fringe orientation is very important for subsequent electronic speckle processing such as skeleton extraction and image filtering. To accurately and efficiently estimate fringe orientation, we propose an effective method based on a convolutional neural network. In the proposed method, the network needs clean-noisy image pairs to train and noisy images with theoretical value to test. The aligned noise-free ESPI fringe pattern orientation fields are fairly good estimations for the corresponding noise ones. After the model training is done, the other multiple ESPI fringe patterns are fed to the trained network simultaneously; the corresponding orientation results can be obtained accurately and efficiently. The advantage of using this method to extract the orientation is that the fringe orientation information can be extracted accurately and efficiently without complicated parameter adjustment. We evaluate the performance of our method via applying our method to the computer-simulated and experimentally acquired ESPI fringe patterns and comparing the results with those of three extensively used methods.

18.
PLoS One ; 14(11): e0225105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31725783

RESUMO

The response to environmental stresses by eukaryotic organisms includes activation of protective biological mechanisms, orchestrated in part by transcriptional regulators. The tri-member Hypoxia Inducible Factor (HIF) family of DNA-binding transcription factors include HIF-2, which is activated under conditions of oxygen or glucose deprivation. Although oxygen-dependent protein degradation is a key mechanism by which HIF-1 and HIF-2 activity is regulated, HIF-2 is also influenced substantially by the coupled action of acetylation and deacetylation. The acetylation/deacetylation process that HIF-2 undergoes employs a specific acetyltransferase and deacetylase. Likewise, the supply of the acetyl donor, acetyl CoA, used for HIF-2 acetylation originates from a specific acetyl CoA generator, acetate-dependent acetyl CoA synthetase 2 (Acss2). Although Acss2 is predominantly cytosolic, a subset of the Acss2 cellular pool is enriched in the nucleus following oxygen or glucose deprivation. Prevention of nuclear localization by a directed mutation in a putative nuclear localization signal in Acss2 abrogates HIF-2 acetylation and blunts HIF-2 dependent signaling as well as flank tumor growth for knockdown/rescue cancer cells expressing ectopic Acss2. In this study, we report generation of a novel mouse strain using CRISPR/Cas9 mutagenesis that express this mutant Acss2 allele in the mouse germline. The homozygous mutant mice have impaired induction of the canonical HIF-2 target gene erythropoietin and blunted recovery from acute anemia. Surprisingly, Acss2 protein levels are dramatically reduced in these mutant mice. Functional studies investigating the basis for this phenotype reveal multiple protein instability domains in the Acss2 carboxy terminus. The findings described herein may be of relevance in the regulation of native Acss2 protein as well as for humans carrying missense mutations in these domains.

19.
Acta Otolaryngol ; : 1-6, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769324

RESUMO

Background: The vestibular function in patients of large vestibular aqueduct syndrome (LVAS) has not been clarified yet.Aims/objectives: To investigate the characteristic of otolithic organ in LVAS patients, we accessed their ocular and cervical vestibular evoked myogenic potentials (oVEMPs and cVEMPs).Material and methods: This study was carried out between 29 bilateral LVAS patients and 35 healthy controls. Parameters of VEMPs were analyzed.Result: In children patients, response rate for oVEMP was 93.47% and 86.95% for cVEMP. No statistical significance was found compared to their controls. In adult patients, response rate for oVEMP was 83.33% and 75% for cVEMP, which were statistically lower than their controls. In comparison to parameters of VEMPs, no statistical significance were found in children group. Amplitude of oVEMP was significantly higher and that of cVEMP was lower in LVAS adults. N1 latencies were significantly longer and P1 latencies were shorter in adult patients than in controls of cVEMP. Thresholds and N1-P1 intervals of VEMP were found no statistical significance in adult group.Conclusions and significance: We discovered a severer otolithic dysfunction in adults than in children patients. We recommend cVEMP a more effective and sensitive method than oVEMP in assessment of LAVS adult patients.

20.
Org Lett ; 21(21): 8577-8581, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31613107

RESUMO

The known benzonaphthyridine alkaloid, albogrisin A (1), and six new compounds, including two pyrazinone stereoisomers, albogrisin B (2)/B' (2'), together with four 4H-pyrroloquinolinones, two diastereoisomers, albogrisin C (3)/C' (3'), and their methyl esters, albogrisin D (4)/D' (4'), were isolated from mangrove-derived Streptomyces albogriseolus MGR072. 2 and 2' are converted into 1 in acidic aqueous solution but into 3/3' and 4/4' in 0.05% trifluoroacetic acid acetonitrile. 4 and 4' are new indoleamine 2,3-dioxygenase 1 inhibitors.

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