Metal Ion Modulated Electron Transfer in Metalloviologen Compounds: Photochromism and Differentiable Amine Detection.

Different types of electron transfers (ETs) underlie the versatile use of various solid viologen-derived compounds, which is still insufficiently understood and difficult to control. Here, we demonstrate an effective strategy for modulating the key ET process in crystalline metalloviologen compounds (MVCs). By adjusting the coordinated transition metal ions bearing different electronic structures (e.g., d5, d7, d10), three MVCs (i.e., Mn-1, Co-2, and Cd-3) with highly consistent coordination environments have been synthesized successfully. Surprisingly, whether the photochromism (energy-induced ET mechanism) or the specific analyte recognition (molecule-induced ET mechanism), compound Cd-3 exhibits obvious photochromic behavior and differential dimethylamine detection. Combined detailed structural analysis with theoretical calculations, such unique ion-dependent properties, were correlated to the fine modulation of the electron density of the bipyridinium cores by metal ions. Additionally, thanks to the delicate recognition of dimethylamine vapor, a convenient test strip Cd-3-PAN was prepared as a sensitive biogenic amine sensor for evaluating the real-time freshness of seafood.

Piezochromism and Conductivity Modulations under High Pressure by Manipulating the Viologen Radical Concentration.

Manipulating the radical concentration to modulate the properties in solid multifunctional materials is an attractive topic in various frontier fields. Viologens have the unique redox capability to generate radical states through reversible electron transfer (ET) under external stimuli. Herein, taking the viologens as the model, two kinds of crystalline compounds with different molecule-conjugated systems were designed and synthesized. By subjecting the specific model viologens to pressure, the cross-conjugated 2-X all exhibit much higher radical concentrations, along with more sensitive piezochromic behaviors, compared to the linear-conjugated 1-X. Unexpectedly, we find that the electrical resistance (R) of 1-NO3 decreased by three orders of magnitude with the increasing pressure, while that in high-radical-concentration 2-NO3 remained almost unchanged. To date, such unusual invariant conductivity has not been documented in molecular-based materials under high pressure, breaking the conventional wisdom that the generations of radicals are beneficial to improve conductivity. We highlight that adjusting the molecular conjugation modes can be used as an effective way to regulate the radical concentrations and thus modulate properties rationally.

Tunable Chromic Properties of Viologen-Metal Polymers Modulated by Coordination Modes for Inkless Erasable Printing.

Inkless and erasable printing (IEP) based on chromic materials holds great promise to alleviate environmental and sustainable problems. Metal-organic polymers (MOPs) are bright platforms for constructing IEP materials. However, it is still challenging to design target MOPs with excellent specific functions rationally due to the intricate component-structure-property relationships. Herein, an effective strategy was proposed for the rational design IEP-MOP materials. The stimuli-responsive viologen moiety was introduced into the construction of MOPs to give it potential chromic behaviors and two different coordination models (i. e. bilateral coordination model, M1 ; unilateral coordinated model, M2 ) based on the same viologen ligand were designed. Aided by theoretical calculations, model M1 was recommended secondarily as a more suitable system for IEP materials. Along this line, two representative viologen-ZnII MOPs 1 and 2 with models M1 and M2 were synthesized successfully. Experiments exhibit that 1 does have quicker stimuli response, stronger color contrast and longer radical lifetime compared to 2. Significantly, the obtained 1-IEP media brightly inherits the excellent chromic characteristics of 1 and the flexibility of the paper at the same time, which achieves most daily printing requirements, as well as enough resolution and durability to be used in identification by smart device.

Clinical Features and Prognosis of Crohn's Disease with Upper Gastrointestinal Tract Phenotype in Chinese Patients.

BACKGROUND: The epidemiology of upper gastrointestinal (L4) Crohn's disease in China remains poorly characterized. AIMS: We aimed to identify the clinical characteristics of L4 disease and clarify the relationship between disease characteristics at diagnosis and early outcomes. METHODS: We retrospectively enrolled 246 patients diagnosed between 2013 and 2017 and followed up for > 1 year post-diagnosis. Primary outcomes included the 1-year rates of hospitalization and abdominal surgery according to disease location and behavior. RESULTS: Of 80 patients with L4 disease (61, 25, and 18 with esophagogastroduodenal, jejunal, and proximal ileal involvement, respectively), none had granuloma, whereas 66.7%, 50%, 46.9%, 75%, and 70% had disease-specific endoscopic lesions in the esophagus, stomach, duodenum, jejunum, and proximal ileum, respectively. Compared to non-L4 disease, L4 disease was associated with higher rates of abdominal surgery (41.3% vs. 11.4%, P < 0.001) but similar rates of hospitalization within 1 year post-diagnosis. In L4 disease, jejunal and proximal ileal involvement was associated with stricturing behavior (P = 0.034, P < 0.001) and higher abdominal surgery rate (both: P < 0.001). Risk factors for abdominal surgery within 1 year post-diagnosis included age ≥ 40 years (OR 1.920; 95% CI 1.095-3.367), L4 phenotype (OR 6.335; 95% CI 3.862-10.390), stricturing disease (OR 3.162; 95% CI 1.103-9.866), and penetrating disease (OR 11.504; 95% CI 3.409-38.825), whereas the protective factor was female sex (OR 0.214; 95% CI 0.123-0.373). CONCLUSIONS: Early outcomes are worse for L4 than for non-L4 disease. Jejunoileum involvement predicts stricturing disease and early surgery. More aggressive initial therapy is needed to improve L4-disease prognosis.

Slow Magnetic Relaxation in a Series of Mononuclear 8-Coordinate Fe(II) and Co(II) Complexes.

A series of homoleptic mononuclear 8-coordinate FeII and CoII compounds, [FeII(L2)2](ClO4)2 (2), [FeII(L3)2](ClO4)2 (3), [FeII(L4)2](ClO4)2 (4), [CoII(L1)2](ClO4)2 (5), [CoII(L2)2](ClO4)2 (6), [CoII(L3)2](ClO4)2 (7), and [CoII(L4)2](ClO4)2 (8) (L1 and L2 are 2,9-dialkylcarboxylate-1,10-phenanthroline ligands; L3 and L4 are 6,6'-dialkylcarboxylate-2,2'-bipyridine ligands), have been obtained, and their crystal structures have been determined by X-ray crystallography. The metal center in all of these compounds has an oversaturated coordination number of 8, which is completed by two neutral homoleptic tetradentate ligands and is unconventional in 3d-metal compounds. These compounds are further characterized by electronic spectroscopy, cyclic voltammetry (CV), and magnetic measurements. CV measurements of these complexes in MeCN solution exhibit rich redox properties. Magnetic measurements on these compounds demonstrate that the observed single-ion magnetic (SIM) behavior in the previously reported [FeII(L1)2](ClO4)2 (1) is not a contingent case, since all of the 8-coordinate compounds 2-8 exhibit interesting slow magnetic relaxation under applied direct current fields.

[Research on Rapid and Non-Destructive Identification of Aging Wheat Based on ATR-Terahertz Spectroscopy Combined with PLS-DA].

In this research, the terahertz spectra data of the aging wheat processed under manual control environment by ATR accessory were collected. After the data diversity based on the composite score by PCA, the non-destructive identification models of aging wheat were developed by PLS-DA algorithm. The results showed that for the absorption coefficient spectrum, the accuracy of the experimental group, control group of the calibration set and cross validation set were 84.2%, 94.7%, 84.2% and 81.6% respectively, while the accuracy of the experimental group and control group of the external validation set were 73.7% and 100.0% respectively; for the refractive index spectrum, the accuracy of the experimental group, control group of the calibration set and cross validation set were 84.2%, 92.0%, 76.3% and 76.3% respectively, while the accuracy of the experimental group and control group of the external validation set were 84.2% and 89.5% respectively. The research indicates that ATR-THz technology should be of great potentials in the application in the non-destructive identification of aging wheat.

[Reason analysis of inadaptability and its correction research on the authenticity identification model of West Lake Longjing tea based on LVF micro-NIR spectrometer].

In the present paper, the micro-NIR spectrometer with the splitter of linear variable filter was used to develop the recognition models of the West Lake Longjing tea and the ordinary flat tea of the year 2012 and 2013. The NIR spectral data of different years and different storage times were decomposed by PCA algorithm. The PLS-DA models were developed by the representative samples selected by the mathematical characteristics of PCA-scores' distribution in order to analyze the reason for the inadaptability of the models according to mathematical principles and find out the solution for its correction. Being examined by the external validation set, the adaptability of the authenticity identification model was enhanced effectively. The result of this research indicated that, for the West Lake Longjing tea and the ordinary flat tea, the correct recognition rate of the model developed by all different-year samples' NIR spectral data would be enhanced effectively. The model developed by the NIR spectral data of different storage time samples indicated that the physicochemical properties of the ordinary flat tea have changed remarkably after cryopreservation for 3 months, while the physicochemical properties of the West Lake Longjing tea are relatively stable. The model adaptabilities for different years and different storage times were studied according to the mathematical perspective of the principal component characteristics of spectral data. After the authenticity identification model of West Lake Longjing tea was developed, the prediction accuracy was enhanced effectively. This research would provide reference for not only the application of NIR spectroscopy in quality grading and safety of agricultural products, but also the enhancement of the prediction accuracy of the NIR grading models for agricultural products.

Slow magnetic relaxation in 8-coordinate Mn(II) compounds.

The design and synthesis of high-spin Mn(II)-based single-molecule magnets (SMMs) have not been well developed to a great extent, as compared with a large number of SMMs based on the other first row transition metal complexes. In light of our success in designing Fe(II), Co(II) and Fe(III)-based SMMs with a high coordination number of 8, it is of great interest to design Mn(II) analogues with such a strategy. In this contribution, four Mn(II) compounds, [MnII(Ln)2](ClO4)2 (1-4) were obtained from reactions of neutral tetradentate ligands, L1-L4, with hydrated MnII(ClO4)2 (L1 = 2,9-bis(carbomethoxy)-1,10-phenanthroline, L2 = 2,9-bis(carbomethoxy)-2,2'-dipyridine, L3 = N2,N9-dibutyl-1,10-phenanthroline-2,9-dicarboxamide, L4 = 6,6'-bis(2-(tert-butyl)-2H-tetrazol-5-yl)-2,2'-bipyridine). Their crystal structures have been determined by X-ray crystallography and it clearly shows that the Mn(II) centers in these compounds have an oversaturated coordination number of 8. Their magnetic properties have been investigated in detail; to our surprise, all of these Mn(II) compounds show interesting slow magnetic relaxation behaviors under an applied direct current field, although they have very small negative D values.

[Mutation screening of LKB1 gene in familial Peutz-Jeghers syndrome patients].

OBJECTIVE: To screen for potential mutations of LKB1 gene in Chinese familial Peutz-Jeghers syndrome (PJS) patients and analyze their clinical manifestations. METHODS: Eleven PJS families were collected and genomic DNA of peripheral blood was extracted. Typically mucosal pigmentation and hamartomatous polyps were present in all 11 probands. Mutation screening of the probands were carried out by PCR and direct sequencing. Two hundred and fifty healthy adults were enrolled as normal controls, for whom genomic DNA of peripheral blood was also extracted. PCR-denaturing high performance liquid chromatography was carried out to verify the mutation identified in the patients. RESULTS: Nine germline mutations were identified in eight PJS patients, which included 7 point mutations, 1 deletion and 1 insertion. Among these, 4 were considered to be pathogenic, of which 2 were de novel, 4 were considered to be polymorphism, and 1 was uncertain. CONCLUSION: LKB1 gene mutations with pathogenic effect are a common cause of familial PJS in Chinese patients. Most mutations are point mutations.

[Survey of influencing factors on smoking and cessation compliance in patients after coronary artery bypass graft surgery].

OBJECTIVE: To analyze the underlying factors related to smoking and cessation compliance in patients following coronary artery bypass graft surgery (CABG). METHODS: From October, 2008 to January, 2009, a total of 160 CABG patients received questionnaires concerning smoking and smoking cessation compliance in Peking university people's hospital, 153 patients completed the questionnaires and were divided into non-smoking (72 patients) and smoking group (81 patients). RESULTS: Cognition was better in non-smokers than smokers on smoking-related health hazards (100% vs. 91.4%, P = 0.011) and on the relationship between smoking and chronic obstructive pulmonary diseases (80.6% vs. 60.5%, P = 0.007) while cognition was better in smokers than non-smokers on the relationship between smoking and ischemic heart disease (61.7% vs. 40.3%, P = 0.008). Compared with non-smoker, smokers acquired significantly more knowledge on smoking and smoking cessation from friends and colleagues (22.2% vs.8.3%, P = 0.018) and from medical professionals (55.6% vs. 26.4%, P = 0.000). In the smoking group, 68 patients quit smoking (84.0%), while the remaining 13 patients failed to quit smoking (16.0%) post CABG. The smoking cessation patients were superior to the smoker patients on smoking cessation compliance (82.4% vs. 38.5%, P = 0.001) and support from family members (94.1% vs. 61.5%, P = 0.003). The nicotine dependence scores of current smokers significantly declined after CABG (preoperative 3.77 ± 2.31 vs. postoperative 2.46 ± 2.30, P = 0.008). CONCLUSIONS: Cognition on the relationship between smoking and coronary heart disease as well as other diseases should be improved in patients underwent CABG. Medical staff and family members play an equal important role on improving the smoking cessation rate for patients post CABG.

Visible light-induced oxidative N-dealkylation of alkylamines by a luminescent osmium(vi) nitrido complex.

N-Dealkylation of amines by metal oxo intermediates (M[double bond, length as m-dash]O) is related to drug detoxification and DNA repair in biological systems. In this study, we report the first example of N-dealkylation of various alkylamines by a luminescent osmium(vi) nitrido complex induced by visible light.

Slow magnetic relaxation in high-coordinate Co(II) and Fe(II) compounds bearing neutral tetradentate ligands.

The first-row transition metal compounds, [MII(L1)2](ClO4)2 (M = Ni (1); Co (2)), have been prepared by treatment of a neutral tetradentate ligand (L1 = N2,N9-dibutyl-1,10-phenanthroline-2,9-dicarboxamide) with metal perchlorate salts in MeOH. Both compounds have been structurally characterized by X-ray crystallography and it was found that the coordination numbers are 6 and 7, respectively. The reaction of 6,6'-bis(2-tbutyl-tetrazol-5-yl)-2,2'-bipyridine (L2) with hydrated FeII(ClO4)2 afforded a 8-coordinate Fe(II) compound, [FeII(L2)2](ClO4)2 (3); however its reaction with hydrated CoII(ClO4)2 resulted in 6-coordinate [CoII(L2)2](ClO4)2. It is interesting to observe field-induced slow magnetic relaxation in the 7-coordinate Co(II) compound 2 and 8-coordinate Fe(II) compound 3, which further supports the validity of designing high coordination number compounds as single-molecule magnets. Direct current magnetic studies demonstrate that 2 has a very large positive D value (56.2 cm-1) and a small E value (0.66 cm-1), indicating easy plane magnetic anisotropy. Consistent with the larger D value, an effective spin-reversal barrier of Ueff = 100 K (71.4 cm-1) is obtained, which is the highest value reported for 7-coordinate Co(II) complexes with a pentagonal bipyramidal geometry. In contrast, 8-coordinate Fe(II) compound 3 exhibits uniaxial magnetic anisotropy.

Slow magnetic relaxation in structurally similar mononuclear 8-coordinate Fe(II) and Fe(III) compounds.

A pair of structurally-similar and stable 8-coordinate high-spin Fe(ii) and Fe(iii) compounds have been obtained. Both compounds exhibit field-induced slow magnetic relaxation behaviour. The Fe(iii) compound represents the first example of 8-coordinate Fe(iii) single-molecule magnets (SMM).

Heparin as a molecular spacer immobilized on microspheres to improve blood compatibility in hemoperfusion.

Heparin, a highly sulfated linear polysaccharide, with anticoagulation function and blood compatibility is widely used as a biomaterials in medical application, but the most importance of heparin is its structure function as the macromolecular space arm. In this study, heparin as a spacer was covalently immobilized on the chloromethylated polystyrene microspheres (Ps) and then connected with l-phenylalanine forming the Ps-Hep-Phe structure, which was developed for endotoxin adsorption in hemoperfusion. The grafting density of heparin reach the maximum when the initial concentration of heparin solution was 5 mg/mL. The adsorbents with the heparin as a spacer showed the prolonged clotting times, low protein adsorption, and reduced the hemolysis rate, indicating that heparin-modified adsorbents have great blood compatibility. The adsorption capacity of Ps-Hep-Phe for endotoxin was 25.15 EU/g in dynamic adsorption, higher than that of Ps. Therefore, this study imply that heparin would be promising for modification of adsorbents in hemoperfusion.

Polynuclear Cu(i) and Ag(i) phosphine complexes containing multi-dentate polytopic ligands: syntheses, crystal structures and photoluminescence properties.

A series of polynuclear metal complexes, [Cu2(L1)(PPh3)4](ClO4)2 (1), [Cu3(L2)(PPh3)6](ClO4) (2), [Cu3(L3)(PPh3)6] (3), [Ag2(L1)(PPh3)4](BF4)2 (4), [Ag4(L2)2(PPh3)6] (5) and [Ag3(L3)(PPh3)5] (6), have been obtained from the reactions of the highly conjugated bridging ligands 2,3-bis(2-pyridyl)pyrazine (L1), 2,3-bis(2-tetrazoyl)pyrazine (H2L2) and 2,3-bis(2-tetrazoyl)imidazole (H3L3) with [Cu(MeCN)4]ClO4 and AgBF4, respectively. Their crystal structures have been determined by X-ray crystallography and their photophysical properties have been investigated in detail. Complexes 1 and 3 show photoluminescence in CH2Cl2 solution, while all the complexes exhibit obvious luminescence in the solid state; detailed photophysical studies and density functional theory calculations of these complexes have revealed that their lowest energy absorptions and emissions are predominantly derived from either metal-to-ligand charge-transfer (MLCT) or intraligand (IL) excited states.

Shipping emission forecasts and cost-benefit analysis of China ports and key regions' control.

China established Domestic Emission Control Area (DECA) for sulphur since 2015 to constrain the increasing shipping emissions. However, future DECA policy-makings are not supported due to a lack of quantitive evaluations. To investigate the effects of current and possible Chinese DECAs policies, a model is presented for the forecast of shipping emissions and evaluation of potential costs and benefits of an DECA policy package set in 2020. It includes a port-level and regional-level projection accounting for shipping trade volume growth, share of ship types, and fuel consumption. The results show that without control measures, both SO2 and particulate matter (PM) emissions are expected to increase by 15.3-61.2% in Jing-Jin-Ji, the Yangtze River Delta, and the Pearl River Delta from 2013 to 2020. However, most emissions can be reduced annually by the establishment of a DECA that depends on the size of the control area and the fuel sulphur content limit. Costs range from 0.667 to 1.561 billion dollars (control regional shipping emissions) based on current fuel price. A social cost method shows the regional control scenarios benefit-cost ratios vary from 4.3 to 5.1 with large uncertainty. Chemical transportation model combined with health model method is used to get the monetary health benefits and then compared with the results from social cost method. This study suggests that Chinese DECAs will reduce the projected emissions at a favorable benefit-cost ratio, and furthermore proposes policy combinations that provide high cost-effective benefits as a reference for future policy-making.

Effects of ω-3 Fatty Acids on Toll-like Receptor 4 and Nuclear Factor κB p56 in the Pancreas of Rats With Severe Acute Pancreatitis.

OBJECTIVES: The aims of this study were to determine the effects of ω-3 fatty acids (ω-3FAs) on the Toll-like receptor 4 (TLR4)/nuclear factor κB p56 (NF-κBp56) signaling pathway in the pancreas of rats with severe acute pancreatitis (SAP). METHODS: Sixty-four Sprague-Dawley rats were randomly divided into 4 groups: the control, SAP-saline, SAP-soybean oil, and SAP-ω-FA groups. Severe acute pancreatitis was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the pancreas was evaluated by immunohistochemistry and Western blot analysis. The levels of the proinflammatory cytokines interleukin 6 and tumor necrosis factor α in the pancreas were measured by enzyme-linked immunosorbent assays. RESULTS: Toll-like receptor 4, NF-κBp56, and inflammatory cytokine expression in the pancreas was increased significantly in the SAP group compared with that in the control group (P < 0.05), but was significantly decreased in the ω-3FA group compared with that in the soybean oil group at 24 and 48 hours (P < 0.05). CONCLUSIONS: Our results suggest that during the initial stage of SAP ω-3FAs could efficiently lower the inflammatory response by activating the TLR4/NF-κBp56 signaling pathway.

Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis.

AIM: To determine the effects of ω-3 fatty acids (ω-3FA) on the toll-like receptor 4 (TLR4)/nuclear factor κB p56 (NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis (SAP). METHODS: A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS: The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group (P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h (P < 0.05). CONCLUSION: During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.

Combination of transcriptomic and metabolomic analyses reveals a JAZ repressor in the jasmonate signaling pathway of Salvia miltiorrhiza.

Jasmonates (JAs) are plant-specific key signaling molecules that respond to various stimuli and are involved in the synthesis of secondary metabolites. However, little is known about the JA signal pathway, especially in economically significant medicinal plants. To determine the functions of novel genes that participate in the JA-mediated accumulation of secondary metabolites, we examined the metabolomic and transcriptomic signatures from Salvia miltiorrhiza. For the metabolome, 35 representative metabolites showing significant changes in rates of accumulation were extracted and identified. We also screened out 2131 differentially expressed unigenes, of which 30 were involeved in the phenolic secondary metabolic pathway, while 25 were in the JA biosynthesis and signal pathways. Among several MeJA-induced novel genes, SmJAZ8 was selected for detailed functional analysis. Transgenic plants over-expressing SmJAZ8 exhibited a JA-insensitive phenotype, suggesting that the gene is a transcriptional regulator in the JA signal pathway of S. miltiorrhiza. Furthermore, this transgenic tool revealed that JAZ genes have novel function in the constitutive accumulation of secondary metabolites. Based on these findings, we propose that the combined strategy of transcriptomic and metabolomic analyses is valuable for efficient discovery of novel genes in plants.

Amino acid polymorphisms flanking the EPIYA-A motif of Helicobacter pylori†CagA C-terminal region is associated with gastric cancer in east China: experience from a single center.

OBJECTIVE: The study aimed to investigate the relationship between gastroduodenal disease and the diversity of the cagA 3' variable region and the amino acid polymorphisms in the Glu-Pro-Ile-Tyr-Ala (EPIYA) segments of the CagA C-terminal region of Helicobacter pylori (H. pylori). METHODS: Gastric mucosal specimens from 170 patients in our center (Nanjing, Jiangsu Province, China) were collected and the genomic DNA of the H. pylori strains was extracted directly from biopsied specimens. Polymerase chain reaction (PCR) was used to amplify the cagA gene, and diversity in its 3' variable region was assessed by direct sequencing. RESULTS: A total of 154 (90.6%) H. pylori isolates were cagA-positive, but the presence of this gene alone was not associated with the type of gastroduodenal disease. A total of 151 (88.8%) strains had the East Asian type EPIYA-D sequence, most of which were of ABD subtype. Three isolates from patients with chronic gastritis possessed the EPIYA-C segment. The sequences flanking the EPIYA motifs contained polymorphisms at seven residues, among which amino acid positions 878 and 879 had a statistically significant association with gastric cancer (P = 0.021). Amino acid change from glycine to aspartic acid at residue 968 was present only in patients with gastric cancer (4/20) (P < 0.001). CONCLUSIONS: Most H. pylori strains present in our study are of the CagA-ABD subtype. Polymorphisms at amino acids 878 and 879 flanking the EPIYA-A motif are statistically associated with gastric cancer.