Catalytic Asymmetric Cascade Dearomatization of Indoles via a Photoinduced Pd-Catalyzed 1,2-Bisfunctionalization of Butadienes.

Photoinduced Pd-catalyzed bisfunctionalization of butadienes with a readily available organic halide and a nucleophile represents an emerging and attractive method to assemble versatile alkenes bearing various functional groups at the allylic position. However, enantiocontrol and/or diastereocontrol in the C-C or C-X bond-formation step have not been solved due to the open-shell process. Herein, we present a cascade asymmetric dearomatization reaction of indoles via photoexcited Pd-catalyzed 1,2-biscarbonfunctionalization of 1,3-butadienes, wherein asymmetric control on both the nucleophile and electrophile part is achieved for the first time in photoinduced bisfunctionalization of butadienes. This method delivers structurally novel chiral spiroindolenines bearing two contiguous stereogenic centers with high diastereomeric ratios (up to >20:1 dr) and good to excellent enantiomeric ratios (up to 97:3 er). Experimental and computational studies of the mechanism have confirmed a radical pathway involving excited-state palladium catalysis. The alignment and non-covalent interactions between the substrate and the catalyst were found to be essential for stereocontrol.

Long-Term Atmosphere Surveillance (2016-2021) of PM2.5-bound Polycyclic Aromatic Hydrocarbons and Health Risk Assessment in Yangtze River Delta, China.

Long-term atmospheric quality monitoring of fine particulate matter (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) was performed in Wuxi from 2016 to 2021. In total, 504 atmospheric PM2.5 samples were collected, and PM2.5-bound 16 PAHs were detected. The PM2.5 and ∑PAHs level decreased annually from 2016 to 2021, from 64.3 to 34.0 µg/m3 and 5.27 to 4.22 ng/m3, respectively. The benzo[a]pyrene (BaP) levels of 42% of the monitoring days in 2017 exceeded the recommended European Union (EU) health-based standard of 1 ng/m3. Five- and six-ring PAHs were found, including benz[a]anthracene, benzo[k]fluoranthene (Bkf), BaP, and benzo[g,h,i]perylene, which were the dominant components (indicating a prominent petroleum, biomass, and coal combustion contribution) using molecular diagnostic ratios and positive matrix factorization analysis. Moreover, PM2.5 and PAHs were significantly negatively associated with local precipitation over a period of six years. Statistically significant temporal and spatial distribution differences of PM2.5, and ∑PAHs were also found. The toxicity equivalent quotient (TEQ) of total PAHs was 0.70, and the TEQ of BaP (0.178) was the highest, followed by that of Bkf (0.090), dibenz[a,h]anthracene (Dah) (0.048), and indeno[1,2,3-cd]pyrene (0.034). The medians of the incremental lifetime cancer risk for long-term exposure to PAHs were 2.74E-8, 1.98E-8, and 1.71E-7 for children, teenagers, and adults, respectively, indicating that the carcinogenic risk of PAHs pollution in air was acceptable to local residents in this area. Sensitivity analysis revealed that BaP, Bkf, and Dah significantly contributed to carcinogenic toxicity. This research provides comprehensive statistics on the local air persistent organic pollutants profile, helps to identify the principal pollution source and compounds, and contributes to the prevention of regional air pollution. Supplementary Information: The online version contains supplementary material available at 10.1007/s12403-023-00572-x.

Palladium-Catalyzed Chemo- and Regioselective C-H Bond Functionalization of Phenols with 1,3-Dienes.

Chemo- and site-selective functionalization of phenols offers a rapid strategy for the synthesis of phenol derivatives with diverse structures. Herein, we report a Pd-catalyzed regioselective C-H bond allylic alkylation of phenols with 1,3-dienes, which has precision reactivity at the ortho C-H bond of 2-naphthols, 1-naphthols, and electron-rich phenols. The reaction is accelerated by a diphosphine ligand, does not need any other additive, and features broad substrate scope and good chemo- and regioselectivity. In addition, we have also investigated the asymmetric variant, and the product could be achieved in up to 55% ee.

Surveillance of long-term environmental elements and PM2.5 health risk assessment in Yangtze River Delta, China, from 2016 to 2020.

PM2.5 metal pollution significantly harms human health. The air quality in Wuxi is poor, especially in winter, and long-term monitoring of PM2.5 elements comprising has not been performed previously. In the present study, 420 PM2.5 samples were collected from January 2016 to December 2020. Eleven elements, including Al, Mn, Ni, Cr, As, Cd, Sb, Hg, Pb, Se, and Tl, were analyzed by inductively coupled plasma mass spectrometry. The mean PM2.5 level was 56.1 ± 31.0 µg/m3, with a tendency of yearly decreasing and a significant seasonal distribution variation. The concentration of 11 elements in the PM2.5 samples was 0.38 ± 0.33 µg/m3. Al was the highest element with a range of 37.5-2148 ng/m3. Meanwhile, the spatial distribution differences were compared by literatures review. Based on the Crystal Ball model, health risks were assessed dynamically using Monte Carlo uncertainty analysis. After 10,000 simulations, the mean value of the hazard index for nine elements was 0.743, and Mn contributed the most to the hazard index among elements, with a correlation of 0.3464. The average carcinogenic risk was 1.01 × 10-5, which indicated that the non-carcinogenic and carcinogenic risks were within the acceptable range. However, considerable attention should be paid to the potential health risks associated with long-term Al, Mn, and As exposure. This study provides detailed data on local atmospheric pollution characteristics, helps identify potential risk elements, and contributes to the development of effective regional air quality management.

Drinking water elements constituent profiles and health risk assessment in Wuxi, China.

Water elements pollution has attracted public attention globally. Wuxi is located in East China, and its water source, Taihu Lake, has been severely polluted since 2007. Studies of elemental pollution profiles have yet to be conducted in this area. In this study, 56 water samples were collected in 2018, and 33 elements were determined using inductively coupled plasma-mass spectrometry (ICP-MS). The results showed that the levels of 33 elements ranged from 1.35 × 10-3 µg/L(Tl) to 101 mg/L(Ca), with Sr, Al, Fe, B, Ti, Ba, and Zn levels being relatively higher. A comprehensive literature review showed spatial distribution of conspicuous elements in drinking water worldwide. Meanwhile, Monte Carlo simulations were applied to evaluate exposure health risks. The total hazard index(HI) for 14 non-carcinogens and the average incremental lifetime cancer risk (ILCR) of As and Pb exposure through drinking water were found acceptable. Sensitivity analyses suggested that Sb and As in the drinking water represent an increasing risk to human health. The results of this study provide key data on local metal pollution characteristics, help identify potential risk factors, and contribute to the development of effective environmental management policies for Taihu Lake.

Different cytotoxicity of disinfection by-product haloacetamides on two exposure pathway-related cell lines: Human gastric epithelial cell line GES-1 and immortalized human keratinocyte cell line HaCaT.

Humans are exposed to disinfection by-products (DBPs) mainly through drinking water ingestion and dermal contact. As an emerging class of nitrogenous DBPs (N-DBPs), haloacetamides (HAcAms) have been found to have significantly higher cytotoxicity than regulated DBPs. In this study, we investigated the cytotoxicity of HAcAms on two exposure pathway-related cell lines: human gastric epithelial GES-1 cells and immortalized keratinocytes HaCaT. Our results showed that the ranking order of cytotoxicity of 13 HAcAms was different between HaCaT and GES-1 cells. In addition, the 50% inhibitive concentration in HaCaT was 1.01-3.29 times that in GES-1. Further comparison among GES-1, HaCaT and CHO cell lines confirmed that different cell lines exhibited different sensitivity to the same compound. Importantly, HAcAms showed 5.83-7.13 × 104 times higher toxicity than the well-clarified DBP chloroform, clearly demonstrating the increased toxicity of HAcAms. Finally, using a novel high-content screening (HCS) analysis, we found that 39.29% of chlorinated HAcAms, 42.86% of brominated HAcAms and 16.07% of iodinated HAcAms significantly affected at least one of the cell-health parameters, such as nuclear size, membrane permeability, mitochondrial membrane potential, or cytochrome c release, in GES-1 or HaCaT cells. Thus, brominated HAcAms appear to have stronger effects under the sublethal exposure dose, possibly causing cytotoxicity via apoptosis. Together, our study provides new insights to the toxicity of HAcAms and a comprehensive toxicology dataset for health risk assessment.

Metabolomics Reveals Metabolic Changes Caused by Low-Dose 4-Tert-Octylphenol in Mice Liver.

Background: Humans are constantly exposed to low concentrations of 4-tert-octylphenol (OP). However, studies investigating the effects of low-dose OP on the liver are scarce, and the mechanism of these effects has not been thoroughly elucidated to date. Methods: Adult male institute of cancer research (ICR) mice were exposed to low-dose OP (0, 0.01 and 1 µg/kg/day) for 7 consecutive days. Weights of mice were recorded daily during the experiment. Blood serum levels of OP, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined, and haematoxylin-eosin (HE) staining of the liver was performed. We applied an integrated metabolomic and enzyme gene expression analysis to investigate liver metabolic changes, and the gene expression of related metabolic enzymes was determined by real-time PCR and ELISA. Results: OP in blood serum was increased after OP exposure, while body weights of mice were unchanged. Liver weight and its organ coefficient were decreased significantly in the OP (1 µg/kg/day) group, but ALT and AST, as well as the HE staining results, were unchanged after OP treatment. The levels of cytidine, uridine, purine and N-acetylglutamine were increased significantly, and the level of vitamin B6 was decreased significantly in mice treated with OP (1 µg/kg/day). The mRNA and protein levels of Cda and Shmt1 were both increased significantly in OP (1 µg/kg/day)-treated mice. Conclusions: Through metabolomic analysis, our study firstly found that pyrimidine and purine synthesis were promoted and that N-acetylglutamine was upregulated after low-dose OP treatment, indicating that the treatment disturbed nucleic acid and amino acid metabolism in mice liver.

A stent film of paclitaxel presenting extreme accumulation of paclitaxel in tumor tissue and excellent antitumor efficacy after implantation beneath the subcutaneous tumor xenograft in mice.

Anti-tumor drug/stent combinations play a dual role of stent and local chemotherapy to cancer. Herein, a series of paclitaxel (PTX) loaded polylactic acid (PLA) stent films were studied on drug release characteristics and in vivo antitumor effects. The film was implanted beneath and released drug towards the subcutaneous PC-3 tumor xenograft in mice, which consisted of a PTX-loaded layer and a drug-free backing layer. The concentrations of PTX were 103-104 times higher than those in normal 20 tissue or organs in 26 days after implantation of the 50% PTX/20% PEG-loaded film, indicating an extreme accumulation of PTX in tumor tissue. The tumor volumes kept unchanged for the initial 10 days after implantation of the PTX-loaded films and then increased slightly, implying tumor growth was remarkably inhibited. Moreover, the results showed that the drug release can be effectively modulated by addition of PEG in the drug-loaded layer, present an unidirectional way by adding a backing layer, and the drug films could arrest PC-3 prostate cancer cells in G2/M phase and induce apoptosis after 300 days of drug release. With the advantages of prolonged drug release and long-term effectiveness, the films have great potential for anti-tumor treatment by local administration.

Investigation of Migration-Preventing Tracheal Stent with High Dose of 5-Fluorouracil or Paclitaxel for Local Drug Delivery.

Stent migration is one of the common reasons for the failure of tracheal stent. An antitumor drug/tracheal stent combination can promptly relieve dyspnea caused by tracheal stenosis and locally treat malignant occupying lesion or tumor. To prevent stent migration for more effective treatment, we prepared a migration-preventing nitinol tracheal stent (TS) with a high dose of 5-fluorouracil or paclitaxel (5-FU/TS or PTX/TS) by stent surface coating with a bilayered film, which is composed of a drug-loaded layer containing Carbopol 974P as mucoadhesive matrix and a blank Carbopol 974P layer. The resulting stent had a similar mechanical performance with the nitinol tracheal stent itself. The bilayered film containing 30% PTX (PTX30) could keep adhesion to porcine mucosa for 221.7 ± 11.4 min in PBS at a stirring speed of 150 rpm, and the corresponding PTX30/TS was difficult to be moved in the porcine tracheal lumen with a pulling force less than 0.7 N, indicating its good migration-preventing ability. The migration-preventing ability of the 5-FU/TS or PTX/TS was related to the compositions of bilayered films. The 5-FU release from the 5-FU/TS was dominated by a relaxation mechanism, while the PTX release was mainly controlled by a diffusion mechanism. Moreover, the 5-FU permeation from the 5-FU loaded film through the porcine tracheal mucosa was determined by the 5-FU dissolution, and PTX permeation was limited by the trans-mucosa process. After the deployment of PTX30/TS, inflammatory responses were observed in the rabbit tracheas and gradually alleviated during the follow-up period.

A PTX/nitinol stent combination with temperature-responsive phase-change 1-hexadecanol for magnetocaloric drug delivery: Magnetocaloric drug release and esophagus tissue penetration.

An antitumor drug/esophagus stent combination can palliatively relieve malignant esophageal stricture and exert local chemotherapy to cancer. It is vital for effective treatment of cancer to control drug release and facilitate drug penetration into deep tissue after the combination is placed in the malignant strictured esophagus part. In this study, we firstly designed and prepared a novel antitumor drug/esophagus stent combination: a magnetocaloric nitinol stent coated with a bilayered film that consisted of one ethylene-vinyl acetate copolymer (EVA) layer as drug blocking layer and one EVA layer containing 10% paclitaxel (PTX) and 30% temperature sensitive phase-change fatty alcohol (1-tetradecanol, 1-hexadecanol or 1-octadecanol). The drug release and penetration into rabbit esophagus wall from the combination were investigated. It was found that, under an alternating electromagnetic field at a power of 0.1 kW, the combination was heated to 43 °C, the PTX was faster and more released from the combination, as well as the amount of PTX in esophagus tissue or its deep muscle tissue penetrated from the combination was much higher than that without alternating electromagnetic field. The pathological data showed that the combination was biocompatible and safe after placement in rabbit esophagus even under an alternating electromagnetic field. Overall, the PTX could be magnetocalorically released and effectively penetrated into esophagus wall from the PTX/nitinol stent combination.

Effects of the combined administration of entecavir and adefovir dipivoxil to improve hepatic fibrosis in hepatitis B patients with interferon resistance.

BACKGROUND: To observe the effect of the combined administration of entecavir and adefovir dipivoxil to improve hepatic fibrosis in hepatitis B patients with interferon resistance. METHODS: This study comprised 90 hepatitis B patients with hepatic fibrosis and interferon (IFN) resistance who were admitted in the hospital's department of infectious disease for diagnosis and treatment between January 2013 and September 2015. They were randomly divided into two groups in accordance with the random number table: the combination treatment group (N.=45) and the entecavir group (N.=45). They were observed for any variations in the indexes of liver function and fibrosis, as well as the Model for end-stage liver disease (MELD) scores, before and after treatment. RESULTS: After treatment, the levels of the indexes in both groups (the combination treatment group vs. the entecavir group) were as follows: bilirubin (67.5±7.7 vs. 82.4±13.5 µmol/L); International Normalized Ratio (INR) (1.21±0.8 vs. 1.14±0.7); creatinine (147.3±12.4 vs. 287.4±21.6 mg/dL); GGT (67.4±23.2 vs. 88.4±23.7 U/L); and ALT (63.4±40.8 vs. 96.5±23.5 U/L). In comparison of the indexes of hepatic fibrosis between the two groups, we found the following differences: PCIII (67.5±7.7 vs. 82.4±13.5 µg/L); IV-C (61.3±18.7 vs. 74.5±17.9 µg/L); HA (147.3±12.4 vs. 87.4±31.6 µg/L); and LN (88.7±13.2 vs 102.5±23.4 µg/L). The results showed that the differences in comparison of the indexes before and after the treatment were statistically significant (P<0.05). After treatment, the MELD score of patients in the combination treatment group was significantly lower than that in the entecavir group (18.7±3.2 vs. 22.5±3.4), with a statistically significant difference (P<0.05). CONCLUSIONS: In the chronic hepatitis B patients with interferon resistance, the combined administration of entecavir and adefovir dipivoxil can significantly improve liver function, hepatic fibrosis and MELD scores. The results highlight the need to promote the benefits of this drug combination in helping chronic hepatitis B patients with interferon resistance, and to promote its application in clinical practices.

Long non-coding RNA XIST regulates PTEN expression by sponging miR-181a and promotes hepatocellular carcinoma progression.

BACKGROUND: Tumor metastasis often occurs in hepatocellular carcinoma (HCC) and influences the patient's prognosis, and microRNAs are reported to play key roles in tumor metastasis. This study was conducted to explore the effect of microRNAs on HCC metastasis. METHODS: The levels of miR-181a in HCC tissues, adjacent tissues, metastatic HCC tissues, and non-metastatic HCC tissues at different stages were determined by qRT-PCR. Effect of miR-181a on the proliferation, invasion, and metastasis of HCC cells was estimated by cell counting kits-8 (CCK-8), wound-healing, and Transwell assays. Software analysis and luciferase assays were used to explore the target gene of miR-181a. RESULTS: MiR-181a was up-regulated in HCC tissues and its expression level in metastatic HCC tissues was much higher than in non-metastasis samples. PTEN was found to be a target gene of miR-181a. MiR-181a had multiple binding sites with the long non-coding RNA (lncRNA) XIST. The regulation of miR-181a on PTEN was mediated by lncRNA XIST. The proliferation and invasion of cells with siXIST were significantly enhanced compared with those of control cells, while knockdown of miR-181a abolished the enhancing effects. CONCLUSIONS: MiR-181a can promote HCC metastasis by targeting PTEN, which is regulated by lncRNA XIST.

Current pesticide profiles in blood serum of adults in Jiangsu Province of China and a comparison with other countries.

Although various pesticides were used globally, the pesticides profiles in human blood serum remain largely unknown. We determined pesticide exposure profiles using solid-phase extraction and gas chromatography tandem with triple quadrupole mass spectrometry in 200 human blood serum samples from the adult population in Jiangsu Province, China. A systematic and comprehensive literature review was carried out to identify the articles investigating pesticide exposure and compare exposure data. Of the 88 pesticides, 76 were found in the blood serum of the population in Jiangsu Province. To the best of our knowledge, 58 pesticides were reported in human blood serum for the first time, and among these pesticides, parathion-methyl, pyrimethanil, fluacrypyrim, simazine, cloquintocet-mexyl and barban were debatable in more than half of the samples. By statistical comparison of the blood serum levels of pesticides between this study and other countries, we found the levels of several organochlorine pesticides were significantly higher in the female population of Jiangsu Province. Health risks related to the pesticide profiling were then revealed, which identified higher carcinogenic toxicity and teratogenic toxicity risk in the female adults of Jiangsu Province caused by organochlorine pesticide exposure. This study not only provides a high-throughput pesticide screening method for future studies of the exposome, but also presents the first human data on exposure to a number of pesticides. It may provide a knowledge database for the risk assessment and management of the pesticides.

[Effectiveness of acetabular revision using a metal reconstruction cage].

Objective: To explore the clinical outcomes of acetabular revision using a metal reconstruction cage. Methods: Between October 2006 and October 2013, 16 patients (16 hips) underwent acetabular revision with a metal reconstruction cage. There were 4 males and 12 females, with the mean age of 62.7 years (range, 49-78 years). The time from total hip arthroplasty to revision was 3-15 years (mean, 8.2 years). The causes for revision were aseptic acetabular loosening in 15 cases, and femoral periprosthetic fracture (Vancouver type B3) in 1 case. According to the American Academy of Orthopaedic Surgeons (AAOS) classification, there were 12 cases of type III and 4 cases of type IV; according to the Paprosky classification, there were 12 cases of type IIIA and 4 cases of type IIIB. Harris score was used for hip function evaluation, and visual analogue scale (VAS) for pain in the thigh. X-ray films were taken for imaging evaluation. Results: Healing of incision by first intention was obtained in all patients. Deep venous thrombosis occurred in 1 patient, and was cured after anticoagulation therapy. No complications of infection, neurovascular injury, and prosthetic dislocation were found. Sixteen patients were followed up 6.8 years on average (range, 2-9 years). The Harris score was significantly increased from preoperative 42.44±4.66 to 91.88±3.28 at last follow-up ( t=-106.30, P=0.00). Two patients had mild pain in the thigh, but pain disappeared at 1 year after operation. At immediate after operation, the abduction angle was 37-54° (mean, 42.9°). The distance between acetabular rotation centre and teardrop line was (33.67±12.19) mm for preoperative value and was (20.67±9.63) mm for postoperative value, showing significant difference ( t=-9.60, P=0.00). The distance between acetabular rotation centre and lateral teardrop was (34.98±12.30) mm for preoperative value and was (40.04±6.61) mm for postoperative value, showing significant difference ( t=-3.15, P=0.00). X-ray film results showed bony fusion at the osteotomy sites at 4 to 12 months after operation. No continuous radiolucent line, prosthetic dislocation, or osteolysis was found, and bony ingrowth was observed in all patients. No patient received re-revision due to prosthetic loosening. Conclusion: The metal reconstruction cage for acetabular revision can achieve good effectiveness for patients with serious bone defect.

Nitinol stents loaded with a high dose of antitumor 5-fluorouracil or paclitaxel: esophageal tissue responses in a porcine model.

BACKGROUND: A poor prognosis associated with esophageal cancer leads to surgical resection not suitable for most patients. Nitinol stents loaded with 50% 5-fluorouracil (5-FU) or paclitaxel (PTX), functioning both as a stent and local chemotherapy, could provide a new therapy modality for these patients. OBJECTIVE: To investigate esophageal tissue responses to nitinol stents loaded with 50% 5-FU or PTX implanted in the esophagus of healthy pigs. DESIGN: Twenty-three healthy Bama mini-pigs were randomly divided into 4 groups for stent implantation: group A (PTX stent, n = 13), group B (5-FU stent, n = 8), group C (blank film-covered stent, n = 1), and group D (bare stent, n = 1). Tissue responses were observed by endoscopy or pathologic analyses, and 5-FU or PTX concentrations were measured in the esophagus at the stent implantation site at different time points. SETTING: Animal laboratory. INTERVENTIONS: Endoscopic placement of esophagus stent. MAIN OUTCOME MEASUREMENTS: Endoscopic examination, histology, and drug concentration analysis. RESULTS: In general, the esophageal tissue responses varied according to different parts of 5-FU or PTX stent (middle part [drug-containing part] and bare ends [drug-free part]). Severe tissue responses at the bare ends of the stent included inflammation, ulceration, and granulation. However, the tissue responses were greatly reduced in the middle part of the stent. The drug concentrations in the esophagus that had contact with the 5-FU stent or PTX stent were very high, especially for the first period after implantation, which did not cause obvious tissue damage. LIMITATION: Some subjects had incomplete follow-up because of unexpected deaths and stent migration. CONCLUSION: The nitinol stents loaded with 50% 5-FU or PTX did not cause severe esophageal tissue responses, although there was a large concentration of the drug in these tissues.

Paclitaxel or 5-fluorouracil/esophageal stent combinations as a novel approach for the treatment of esophageal cancer.

Currently, esophageal cancer is rarely curable, and herein, a paclitaxel or 5-fluorouracil/esophageal stent combination (PTX or 5-FU/stent) was used to provide a new approach to treat this cancer. The PTX or 5-FU/stent was prepared by covering a nitinol stent with a bilayered polymer film that consisted of a layer of 50% PTX or 5-FU and a layer of drug-free backing. These treatment modalities were evaluated in vivo after implantation into the porcine esophagus. The percentages of the drugs that permeated from the backing layer over a period of 95 days were very small (0.61% for 5-FU), and an overwhelming majority of the PTX and the 5-FU was released from the other side of the film. During the follow-up period (120 days), the drug/stent was always maintained in the porcine esophagus, and did not show any obvious systemic or local toxicities. In contrast, this treatment had an effect on the inhibition of tissue proliferation and ulceration. In addition, the drug concentrations were highest in the esophagus compared with in the heart, liver, spleen, lung, kidney and blood (81500.0 ± 9475.2 ng/g vs. 3.9 ± 0.3 ng/mL of PTX in the plasma at 13 days). The PTX/stent and the 5-FU/stent have a dual function as both a stent and a local drug delivery device, which provides a potential treatment modality with high efficacy and non systematic toxicity for esophageal cancer.

Topology-aware evenly spaced streamline placement.

This paper presents a new streamline placement algorithm that produces evenly spaced long streamlines while preserving topological features of a flow field. Singularities and separatrices are extracted to decompose the flow field into topological regions. In each region, a seeding path is selected from a set of streamlines integrated in the orthogonal flow field. The uniform sample points on this path are then used as seeds to generate streamlines in the original flow field. Additional seeds are placed where a large gap between adjacent streamlines occurs. The number of short streamlines is significantly reduced as evenly spaced long streamlines spawned along the seeding paths can fill the topological regions very well. Several metrics for evaluating streamline placement quality are discussed and applied to our method as well as some other approaches. Compared to previous work in uniform streamline placement, our method is more effective in creating evenly spaced long streamlines and preserving topological features. It has the potential to provide both intuitive perception of important flow characteristics and detail reconstruction across visually pleasing streamlines.