Dietary γ-mangostin triggers immunogenic cell death and activates cGAS signaling in acute myeloid leukemia.

Immunogenic cell death (ICD), one of cell-death types through release of damage-associated molecular patterns from dying tumor cells, activates tumor-specific immune response and elicits anti-tumor immunity by traditional radiotherapy and chemotherapy. However, whether natural products could induce ICD in leukemia is not elucidated. Here, we report dietary γ-mangostin eradicates murine primary leukemic cells and prolongs the survival of leukemic mice. As well, it restrains primary leukemic cells and CD34+ leukemic progenitor cells from leukemia patients. Strikingly, γ-mangostin attenuates leukemic cells by inducing ICD as characterized by expression of HSP90B1, ANXA1 and IL1B. Additionally, γ-mangostin accelerates cytoplasmic chromatin fragments generation, promoting DNA damage response, and enhances cGAS activation, leading to up-regulation of chemokines. Meanwhile, it induces HDAC4 degradation and acetylated histone H3 accumulation, which promotes chemokines transcription. Ultimately, CD8+ T cell is activated and recruited by γ-mangostin-induced chemokines in the microenvironment. Our study identifies γ-mangostin triggers ICD and activates cGAS signaling through DNA damage response and epigenetic modification. Therefore, dietary γ-mangostin would act as a potential agent to provoke anti-tumor immunity in the prevention and treatment of leukemia.

Image-Based OA-Style Paper Pop-Up Design via Mixed-Integer Programming.

Origami architecture (OA) is a fascinating papercraft that involves only a piece of paper with cuts and folds. Interesting geometric structures 'pop up' when the paper is opened. However, manually designing such a physically valid 2D paper pop-up plan is challenging since fold lines must jointly satisfy hard spatial constraints. Existing works on automatic OA-style paper pop-up design all focused on how to generate a pop-up structure that approximates a given target 3D model. This article presents the first OA-style paper pop-up design framework that takes 2D images instead of 3D models as input. Our work is inspired by the fact that artists often use 2D profiles to guide the design process, thus benefited from the high availability of 2D image resources. Due to the lack of 3D geometry information, we perform novel theoretic analysis to ensure the foldability and stability of the resultant design. Based on a novel graph representation of the paper pop-up plan, we further propose a practical optimization algorithm via mixed-integer programming that jointly optimizes the topology and geometry of the 2D plan. We also allow the user to interactively explore the design space by specifying constraints on fold lines. Finally, we evaluate our framework on various images with interesting 2D shapes. Experiments and comparisons exhibit both the efficacy and efficiency of our framework.

Adaptive Optimization Algorithm for Resetting Techniques in Obstacle-Ridden Environments.

Redirected Walking (RDW) algorithms aim to impose several types of gains on users immersed in Virtual Reality and distort their walking paths in the real world, thus enabling them to explore a larger space. Since collision with physical boundaries is inevitable, a reset strategy needs to be provided to allow users to reset when they hit the boundary. However, most reset strategies are based on simple heuristics by choosing a seemingly suitable solution, which may not perform well in practice. In this article, we propose a novel optimization-based reset algorithm adaptive to different RDW algorithms. Inspired by the approach of finite element analysis, our algorithm splits the boundary of the physical world by a set of endpoints. Each endpoint is assigned a reset vector to represent the optimized reset direction when hitting the boundary. The reset vectors on the edge will be determined by the interpolation between two neighbouring endpoints. We conduct simulation-based experiments for three RDW algorithms with commonly used reset algorithms to compare with. The results demonstrate that the proposed algorithm significantly reduces the number of resets.

Minimally invasive open reduction of greater tuberosity fractures by a modified suture bridge procedure.

BACKGROUND: Most greater tuberosity fractures can be treated without surgery but some have a poor prognosis. The surgical procedures for avulsion fractures of the humeral greater tuberosity include screw fixation, suture anchor fixation, and plate fixation, all of which have treatment-associated complications. To decrease surgical complications, we used a modified suture bridge procedure under direct vision and a minimally invasive small incision to fix fractures of the greater tuberosity of the humerus. AIM: To investigate the clinical efficacy and outcomes of minimally invasive modified suture bridge open reduction of greater tuberosity evulsion fractures. METHODS: Sixteen patients diagnosed between January 2016 and January 2019 with an avulsion-type greater tuberosity fracture of the proximal humerus and treated by minimally invasive open reduction and modified suture bridges with anchors were studied retrospectively. All were followed up by clinical examination and radiographs at 3 and 6 wk, 3, 6 and 12 mo after surgery, and thereafter every 6 mo. Outcomes were assessed preoperatively and postoperatively by a visual analog scale (VAS), the University of California Los Angeles (UCLA) shoulder score, the American Shoulder and Elbow Surgeon score (ASES), and range of motion (ROM) for shoulders. RESULTS: Seven men and nine women, with an average age of 44.94 years, were evaluated. The time between injury and surgery was 1-2 d, with an average of 1.75 d. The mean operation time was 103.1 ± 7.23 min. All patients achieved bone union within 3 mo after surgery. VAS scores were significantly decreased (P = 0.002), and the mean degrees of forward elevation (P = 0.047), mean degrees of abduction (P = 0.035), ASES score (P = 0.092) were increased at 3 wk. The UCLA score was increased at 6 wk (P = 0.029) after surgery. The average degrees of external rotation and internal rotation both improved at 3 mo after surgery (P = 0.012 and P = 0.007, respectively). No procedure-related deaths or incision-related superficial or deep tissue infections occurred. CONCLUSION: Modified suture bridge was effective for the treatment of greater tuberosity evulsion fractures, was easier to perform, and had fewer implants than other procedures.

Fast 3D Indoor Scene Synthesis by Learning Spatial Relation Priors of Objects.

We present a framework for fast synthesizing indoor scenes, given a room geometry and a list of objects with learnt priors. Unlike existing data-driven solutions, which often learn priors by co-occurrence analysis and statistical model fitting, our method measures the strengths of spatial relations by tests for complete spatial randomness (CSR), and learns discrete priors based on samples with the ability to accurately represent exact layout patterns. With the learnt priors, our method achieves both acceleration and plausibility by partitioning the input objects into disjoint groups, followed by layout optimization using position-based dynamics (PBD) based on the Hausdorff metric. Experiments show that our framework is capable of measuring more reasonable relations among objects and simultaneously generating varied arrangements in seconds compared with the state-of-the-art works.

Pharmacological prevention of renal ischemia-reperfusion injury in a rat model.

INTRODUCTION: Renal ischemia-reperfusion injury (IRI) can lead to significant morbidity and mortality. It remains a leading cause of acute kidney injury and is therefore an important issue in trauma and renal transplant surgery. Various pharmaceutical agents have been used in an attempt to dampen the harmful effects of IRI but few have been shown to be useful clinically. Riluzole, Lidocaine and Lamotrigine have been demonstrated to show anti-ischaemic properties in other organs; however, their use has not been tested in the kidneys. We investigated Riluzole, Lidocaine and Lamotrigine for their preventive effects of renal IRI using a rat model. METHODS: Winstar rats (n = 48) were divided into four groups (n = 12 per group)-three treatment groups and one control group. Riluzole, Lidocaine and Lamotrigine were given prior to renal ischemia only (IO) or IRI. The degree of ischemia was measured by glutathione levels and a TUNEL assay was used to measure DNA fragmentation. RESULTS: Riluzole, Lidocaine and Lamotrigine pre-treatment each resulted in statistically higher glutathione levels compared to controls (P = 0.002; P = 0.007 and P = 0.005, respectively). Riluzole and Lidocaine were also effective at preventing depletion of glutathione following IO (P = 0.007 and P = 0.014 respectively), while Lamotrigine was ineffective in IO (P = 0.71). The degree of DNA fragmentation seen on the TUNEL assay was markedly reduced in all three-drug groups in both IO and IRI. DISCUSSION: Riluzole, Lidocaine and Lamotrigine all have anti-ischaemic effects in the rat kidney and can have potential therapeutic implications.

The Treatment of Subtrochanteric Fracture with Reversed Contralateral Distal Femoral Locking Compression Plate (DF-LCP) Using a Progressive and Intermittent Drilling Procedure in Three Osteopetrosis Patients.

OBJECTIVE: To describe the application of reversed contralateral distal femoral locking compression plate (DF-LCP) inserted through a progressive and intermittent drilling procedure in the treatment of osteopetrotic subtrochanteric fracture (OSF). METHODS: Three patients (one male and two females with an average age of 45.33 ± 11.09 years) with OSF hospitalized between September 2015 and September 2020, were included in this present study. Lateral approach was applied in all patients who accepted open reduction and internal fixation (ORIF) with a reversed contralateral DF-LCP inserted through a progressive and intermittent drilling procedure. The operation time and intraoperative blood loss were recorded to evaluate the efficiency of this surgical method. Physical examination and imaging examination of the fracture site were used to evaluate the fracture union status, the position and stability of the implant, and the alignment of the injured limb at 1, 3, 6, and 12 months after operation, then a subsequent visit was conducted at least once a year. Harris Hip Score (HHS) was used to evaluate the hip joint function at 6 and 12 months after operation. RESULTS: The average operation time was 140 ± 21.60 min (110, 160, and 150 min); The average intraoperative blood loss was about 333.33 ± 23.57 ml (300, 350, and 350 ml). The average follow-up time was 22.33 ± 7.41 months (29, 26, and 12 months). All patients achieved bone union with an average time of 6.67 ± 0.94 months (6, 8, and 6 months). At the time of 6 months after operation, case 1 and 3 were almost pain-free and could walk with full weight bearing while case 2 could walk only with partial weight bearing using a crutch. The HHS scores of cases 1, 2, and 3 were 84/100, 74/100, and 92/100, respectively. At the follow-up at 12 months after operation, the HHS score improved to 91/100, 81/100, and 96/100, respectively. The contralateral incomplete old subtrochanteric fracture was deteriorated in case 1 at 26 months after operation. After 3 months of limited weight bearing using a crutch, bone union was verified in radiograph imaging. Fresh contralateral subtrochanteric fracture occurred in case 2 at 26 months after operation, which was treated using a similar surgical approach, and its clinical outcome is under follow-up. Moreover, no perioperative complications including operation-related death, vascular/nerve injury, deep venous thrombosis, pulmonary embolism, and incision infection, and long-term complications involving malunion, nonunion, implant failure, ankylosis, heterotopic ossification, osteonecrosis, and osteomyelitis were identified. CONCLUSION: The application of reversed contralateral DF-LCP in OSF is practicable and reliable. Progressive and intermittent drilling is a safe and efficient method for implant insertion in this complicated situation.

Efficacy and Safety of Programmed Cell Death 1 Inhibitor Monotherapy Versus Chemotherapy as Second-Line Treatment for Advanced Esophageal Cancer: A Meta-analysis and Systematic Review.

PURPOSE: With programmed cell death 1 (PD-1) inhibitors approved for second-line treatment of advanced esophageal cancer, immunotherapy and chemotherapy have gradually become the main treatments for second-line treatment of patients with advanced esophageal cancer (AEC). This meta-analysis and systematic review were conducted to evaluate the efficacy and safety of PD-1 inhibitors monotherapy versus chemotherapy in second-line treatment of AEC. METHODS: Eligible randomized controlled trials were searched in PubMed, Embase, and the Cochrane Library and abstracts presented at the American Society of Clinical Oncology or European Society of Medical Oncology were reviewed to assess the efficacy and tolerability of PD-1/programmed cell death ligand 1 (PD-L1) inhibitors relative to chemotherapy for AEC from January 2016 to October 2020. Patients diagnosed with AEC and progressing after first-line therapy were included in this study. Hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), risk ratios (RRs) of objective response rate (ORR), and the odds ratios (ORs) of adverse effects (AEs) were calculated. FINDINGS: The study included 4 randomized controlled trials with 1683 patients. The results indicated that PD-1 inhibitors prolonged the OS (HR = 0.79; 95% CI, 0.71-0.88; P < 0.01) and improved the ORR (RR = 3.00; 95% CI, 2.36-3.82; P = 0.01) but did not improve the PFS (HR = 0.96; 95% CI, 0.76-1.20; P = 0.692) compared with chemotherapy in the second-line treatment of AEC. PD-1 inhibitors alone were associated with a lower incidence of all treatment-related AEs (OR = 0.29; 95% CI, 0.09-0.89; P = 0.03) and grade 3 to 5 treatment-related AEs (OR = 0.26; 95% CI, 0.16-0.44; P < 0.01) versus chemotherapy. PD-1 inhibitors prolonged OS mainly in the following patient groups: male, age <65 years, Eastern Cooperative Oncology Group performance status of 1, or PD-L1 tumor proportion score ≥10%. Asian patients had a longer OS than non-Asian patients (P = 0.01). IMPLICATIONS: The available evidence indicates that the efficacy and tolerability of PD-1 inhibitors were better than chemotherapy in the second-line treatment of AEC, and the benefiting population of these patients was limited to males, those <65 years of age, those with a Eastern Cooperative Oncology Group performance status of 1, or those with a PD-L1 tumor proportion score ≥10%. Notably, Asian patients receiving immune monotherapy had longer OS than non-Asian patients.

A naturally occurring FXR agonist, alisol B 23-acetate, protects against renal ischemia-reperfusion injury.

The ligand-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating renal function. Activation of FXR by its specific agonists exerts renoprotective action in animals with acute kidney injury (AKI). In the present study, we aimed to identify naturally occurring agonists of FXR with potential as therapeutic agents in renal ischemia-reperfusion injury. In vitro and in vivo FXR activation was determined by a dual-luciferase assay, docking analysis, site-directed mutagenesis, and whole kidney transcriptome analysis. Wild-type (WT) and FXR knockout (FXR-/-) mice were used to determine the effect of potential FXR agonist on renal ischemia-reperfusion injury (IRI). We found that alisol B 23-acetate (ABA), a major active triterpenoid extracted from Alismatis rhizoma, a well-known traditional Chinese medicine, can activate renal FXR and induce FXR downstream gene expression in mouse kidney. ABA treatment significantly attenuated renal ischemia-reperfusion-induced AKI in WT mice but not in FXR-/- mice. Our results demonstrate that ABA can activate renal FXR to exert renoprotection against ischemia-reperfusion injury-induced AKI. Therefore, ABA may represent a potential therapeutic agent in the treatment of ischemic AKI.NEW & NOTEWORTHY In the present study, we found that alisol B 23-acetate (ABA), an identified natural farnesoid X receptor (FXR) agonist from the well-known traditional Chinese medicine Alismatis rhizoma, protects against ischemic acute kidney injury (AKI) in an FXR-dependent manner, as reflected by improved renal function, reduced renal tubular apoptosis, ameliorated oxidative stress, and suppressed inflammatory factor expression. Therefore, ABA may have great potential as a novel therapeutic agent in the treatment of AKI in the future.

Spatial Information Guided Convolution for Real-Time RGBD Semantic Segmentation.

3D spatial information is known to be beneficial to the semantic segmentation task. Most existing methods take 3D spatial data as an additional input, leading to a two-stream segmentation network that processes RGB and 3D spatial information separately. This solution greatly increases the inference time and severely limits its scope for real-time applications. To solve this problem, we propose Spatial information guided Convolution (S-Conv), which allows efficient RGB feature and 3D spatial information integration. S-Conv is competent to infer the sampling offset of the convolution kernel guided by the 3D spatial information, helping the convolutional layer adjust the receptive field and adapt to geometric transformations. S-Conv also incorporates geometric information into the feature learning process by generating spatially adaptive convolutional weights. The capability of perceiving geometry is largely enhanced without much affecting the amount of parameters and computational cost. Based on S-Conv, we further design a semantic segmentation network, called Spatial information Guided convolutional Network (SGNet), resulting in real-time inference and state-of-the-art performance on NYUDv2 and SUNRGBD datasets.

Comparative efficacy and safety of PD-1/PD-L1 Inhibitors versus platinum-based chemotherapy for the first-line treatment of advanced non-small cell lung cancer: a meta analysis of randomized controlled trials.

OBJECTIVE: The main aim of this study was to systematically evaluate the efficacy and safety of inhibitors of programmed cell death receptor 1 (PD-1) and its ligand, programmed cell death ligand-1 (PD-L1), in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials assessing the efficacy of PD-1/PD-L1 inhibitors relative to platinum-based chemotherapy for advanced NSCLC in PubMed, EMBASE, and Cochrane libraries from 2015 to 2020 were searched, along with review of studies at American Society of Clinical Oncology (ASCO) and European society for Medical Oncology (ESMO). Pooled hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) and odds ratios (OR) for adverse events (AE) were calculated using STATA and Revman software. RESULTS: PD-1/PD-L1 inhibitors alone or combined with chemotherapy significantly improved OS (HR = 0.82, 95% CI:0.74-0.91, P = 0.01 or HR = 0.74, 95% CI:0.67-0.82, P = 0.001). PD-1/PD-L1 inhibitors alone did not benefit PFS (HR = 0.99, 95% CI: 0.89-1.10, P = 0.892), while combination therapy led to prolonged PFS (HR = 0.61, 95% CI: 0.56-0.67, P < 0.001). Subgroup analysis showed that in NSCLC with PD-L1 ≥ 50%, treatment with PD-1/PD-L1 inhibitors alone significantly improved both PFS and OS. In patients subjected to the combined treatment regimen, we observed significant differences in PFS among groups stratified by PD-L1 expression (p < 0.001), immune drug type (p = 0.029), gender (p = 0.014) and liver metastasis (p = 0.035) and OS among groups stratified by immune drug type (p < 0.001), gender (P = 0.001) and smoking status (P = 0.041). Safety analysis showed that combination therapy increased chemotherapy-induced adverse events (AE), while PD-1/PD-L1 inhibitors alone were associated with a lower incidence of any grade of treatment-related AEs (TRAE). A higher incidence of Grade 3-5 TRAEs and hypothyroidism was observed with PD-1 inhibitors than PD-L1 inhibitors. CONCLUSIONS: First-line treatment of advanced NSCLC with immune monotherapy or immunochemotherapy confers a greater survival benefit than chemotherapy alone. Combination of chemotherapy with PD-1/PD-L1 inhibitors leads to an increase in adverse events, and PD-1 inhibitors offer enhanced survival benefits and fewer adverse events than PD-L1 inhibitors. Remarkably, female patients undergoing combination therapy had longer overall survival than male patients.

Treatment of Chronic Anterior Shoulder Dislocation by Coracoid Osteotomy with or without Bristow-Latarjet Procedure.

OBJECTIVE: To investigate the clinical efficacy and outcomes of the coracoid osteotomy with or without Bristow-Latarjet procedures in the treatment of chronic anterior shoulder dislocation (CASD). METHODS: Between January 2013 and January 2019, 20 shoulders of 18 patients who were diagnosed with chronic anterior dislocation and underwent open reduction in our trauma center were retrospectively studied. Open coracoid osteotomy with Bristow-Latarjet procedures were performed on 16 shoulders and open coracoid osteotomy without Bristow-Latarjet procedures were performed on four shoulders. Open coracoid osteotomy with or without Bristow-Latarjet procedures were chosen on the basis of the stability of the shoulder after reduction. Outcomes were assessed preoperatively and postoperatively with the visual analog scale (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, the University of California Los Angeles (UCLA) shoulder rating scale, and the range of motion (ROM) for shoulder activity. RESULTS: There were three males and 15 females with an average age of 60.94 ± 2.69 years. The time between dislocation and treatment ranged from 21 to 240 days with an average of 73.3 ± 14.4 days. All patients were available for a mean follow-up of 15.2 ± 4.3 months. No procedure-related death or incision-related superficial or deep tissue infection was identified in all cases. No iatrogenic neurovascular injuries or fractures were found in this study. At the time of 12 months follow-up, the range of motion and the shoulder functional evaluation (VAS [P < 0.001], ASES [P < 0.001], and UCLA score [P < 0.001]) in patients who underwent Bristow-Latarjet procedures were significantly improved. Subluxation after surgical procedure was found and confirmed in one patient and this patient refused to undergo revision surgery. According to the Samilson and Prieto classification system, 16 shoulders were assessed as grade 0, three shoulders were grade 1, one shoulder was grade 2. CONCLUSIONS: Coracoid osteotomy with or without Bristow-Latarjet procedure yielded an acceptable clinical result in this study. This method has the advantages of enlarging the exposure of surgical field, assisting reduction of shoulder, and convenient conversion to Bristow-Latarjet procedure. It is an efficient and reliable method for treatment of chronic anterior shoulder dislocation. A 69-year-old woman diagnosed with right chronic anterior shoulder dislocation with large Hill-Sachs lesion. The latarjet procedure with remplissage technique was applied for this patient.

Source Tracking and Risk Assessment of Pharmaceutical and Personal Care Products in Surface Waters of Qingdao, China, with Emphasis on Influence of Animal Farming in Rural Areas.

The occurrence and potential sources of pharmaceuticals and personal care products (PPCPs) in surface waters from a large coastal city Qingdao, North China, were investigated. Forty-five compounds were analyzed by high-performance liquid chromatography-tandem mass spectrometry. The results showed that 28 compounds of PPCPs were detected. The most frequently detected compounds were atrazine, clarithromycin, nonylphenol, and bisphenol A with the detection rates > 90%. Paracetamol showed the highest concentration up to 4400 ng/L (mean 152.5 ng/L), followed by ampicillin (max. 2980 ng/L) with the highest mean concentration (229.3 ng/L), iopromide (max. 1744 ng/L, mean 74.5 ng/L), atrazine (max. 1612 ng/L, mean 96.1 ng/L), and bisphenol A (max. 1384 ng/L, mean 78.3 ng/L). The contamination levels and composition profiles of PPCPs along the rivers flowing through rural and urban areas and in seawater showed large spatial variability. Typical source markers and principle component analysis were used to track and differentiate the potential PPCP sources. The emphases of the study were the influence of animal farming in rural areas on PPCP composition profiles and the ecological risk. The results indicated that PPCPs in Qingdao surface water mainly came from three potential sources, i.e., treated wastewater (effluents from WWTPs), untreated wastewater, and nonpoint sources in agricultural areas.

Pharmaceutical and Personal Care Products in Surface Waters from the Inner City of Beijing, China: Influence of Hospitals and Reclaimed Water Irrigation.

Surface waters from five districts in the inner city of Beijing were collected for analysis of 43 target compounds of pharmaceuticals and personal care products (PPCPs) to understand the spatial distribution patterns of different groups of PPCPs in the central urban area of a metropolitan city characterized by many hospitals and public parks. The total concentrations of PPCPs showed large spatial variability, ranging from 71.1 to 2400 ng/L. The x-ray contrast medium iopromide was the compound with the highest concentrations. Pharmaceuticals showed similar spatial distributional patterns with large hospitals. Positive correlations between iopromide and pharmaceuticals were observed. In contrast, in general there is no correlation between iopromide and personal care products. The concentrations of PPCPs in the landscape waters were not high but were characterized by high proportions of acidic, nonsteroidal anti-inflammatory drugs with low or even negative removal efficiencies in the WWTP in Beijing, suggesting that the reclaimed water irrigation can be another source of PPCPs in surface waters in the inner city of Beijing.

Perfluoroalkyl Substances in Water from the Yangtze River and Its Tributaries at the Dividing Point Between the Middle and Lower Reaches.

The Yangtze River drainage basins are China's most important economic development zones and also the locations of several large-scale fluorine chemical industries. In order to reveal the contribution from the tributaries at the dividing point between the middle and lower reaches of the Yangtze River with respect to perfluorinated substances (PFASs), 17 PFAS compounds in surface water, groundwater, and tap water samples were analyzed in the tributary system of the Jiujiang section of the Yangtze River. The total concentrations of PFASs in the surface waters ranged from 7.8 to 586.2 ng/L. High proportion of short-chain compound PFBS in surface waters in Nanchang City, Poyang Lake, and the Yangtze River was observed which is likely of WWTPs' origin.

The Extent of the Impact of a Fluorochemical Industrial Park in Eastern China on Adjacent Rural Areas.

High levels of perfluoroalkyl substances (PFASs) were observed in rural areas near a fluorochemical industrial park (FCIP) in the Yangtze River Delta region. The concentrations of total PFAS (∑PFASs) in soil, surface water, groundwater, and rainwater were in the range of 0.6-64.6 ng/g dry weight, 15.6-480.9, 4.8-614.6, and 13.4-542.2 ng/L, respectively. PFASs in rainwater and groundwater were higher than in surface water. The influence of the FCIP on rural soils extended to a distance of approximately 4 km based on the changes in PFAS compositions. The impact on surface water is mainly through direct river flow connected with contaminated sources, which may extend farther than 7 km in the case of unrestricted flow but much shorter distance for unconnected rivers. The penetration of PFASs in groundwater aquifers can extend as far as ca. 6 km, while direct water flow is the main transport route for PFASs. The influence radius of the FCIP can be as far as 60 km due to atmospheric precipitation.

Perfluoroalkyl acids in surface waters and tapwater in the Qiantang River watershed-Influences from paper, textile, and leather industries.

Perfluoroalkyl acids (PFAAs) are widely used as multi-purpose surfactants or water/oil repellents. In order to understand the contamination level and compositional profiles of PFAAs in aqueous environment in textile, leather, and paper making industrial areas, surface waters and tap waters were collected along the watershed of the Qiantang River where China's largest textile, leather, and paper making industrial bases are located. For comparison, surface water and tapwater samples were also collected in Hangzhou and its adjacent areas. 17 PFAAs were analyzed by solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. The results show that the total concentrations of PFAAs (ΣPFAAs) in the Qiantang River waters ranged from 106.1 to 322.9 ng/L, averaging 164.2 ng/L. The contamination levels have been found to be extremely high, comparable to the levels of the most serious PFAA contamination in surface waters of China. The PFAA composition profiles were characterized by the dominant PFOA (average 58.1% of the total PFAAs), and PFHxA (average 18.8%). The ΣPFAAs in tap water ranged from 9.5 to 174.8 ng/L, showing PFAA compositional pattern similar to the surface waters. Good correlations between PFAA composition profiles in tap waters and the surface waters were observed.

Current Contamination Status of Perfluoroalkyl Substances in Tapwater from 17 Cities in the Eastern China and Their Correlations with Surface Waters.

The contamination status of perfluoroalkyl substances (PFASs) were investigated in 64 tapwater samples collected from 17 cities and 45 surface water samples from adjacent areas in the eastern China. The total PFAS concentrations in tapwater ranged from 1.4 to 175 ng/L; relatively higher PFAS levels were observed in samples collected from the Yangtze River Delta region, which was similar to the geographical distribution pattern of PFAS levels observed in rivers and lakes. The highest total PFASs in tapwater was found in Changshu, where several fluorine-related industries are located, whereas the lowest was observed in Beijing. Significant positive correlations between PFAS compositions in tap water sample and their source waters were noted. Several industries such as paper, textile, and leather industries may contribute to the contamination of PFASs in tapwater.

Phenethyl isothiocyanate suppresses the metastasis of ovarian cancer associated with the inhibition of CRM1-mediated nuclear export and mTOR-STAT3 pathway.

Epithelial ovarian cancer is prone to metastasizing at an early stage, but their mechanisms remain unclear. CRM1 is an important nuclear exportin and inhibitors targeting CRM1 has been explored as an anti-cancer strategy. In previous study, we observed that PEITC could combine with the hydrophobic pocket of CRM1. In this study, we focused on the effects of PEITC on EOC and its mechanisms. Results showed that IC50 values of PEITC on SKOV3 and HO8910 cell line were 42.14 µM and 37.29 µM, respectively. PEITC inhibits the migration and invasion of SKOV3 and HO8910 cells in vitro. Oral administration of 10 µmol PEITC suppressed the metastasis of EOC in a xenograft mouse model in vivo. PEITC treatment decreased the expressions of CRM1 and mTOR (cargo protein of CRM1) in EOC cell lines and in xenograft mouse tissues. Moreover, CRM1-mediated nuclear export was attenuated by PEITC, mTOR accumulated in nucleus, expressions of mTORS2448 and downstream effectors STAT3S727, MMP2 and MMP9 were decreased in a dose- and time-dependent manner. Furthermore, immunohistochemical analysis showed that CRM1 and mTOR were increased in EOC tissues compared with benign ovarian tumors, and related with advanced stage, type II EOC, positive peritoneal cytology and decreased overall survival. In addition, CRM1 was positively correlated with mTOR levels. In conclusion, our data demonstrated that PEITC suppresses the metastasis of EOC through inhibiting CRM1-mediated nuclear export, subsequently suppressing the mTOR-STAT3 pathway. Both CRM1 and mTOR were increased in EOC patients, providing a rationale for further clinical investigation of PEITC in EOC treatment.

Perfluorinated compounds in soil, surface water, and groundwater from rural areas in eastern China.

Little research on perfluorinated compounds (PFCs) has been conducted in rural areas, although rural PFC sources are less complicated than in urban and industrial areas. To determine the levels and geographical distribution of 17 PFC compounds, samples of soil, surface water, and groundwater were collected from eight rural areas in eastern China. The total PFC concentrations (∑PFCs) in soils ranged from 0.34 to 65.8 ng/g ∑PFCs in surface waters ranged from 7.0 to 489 ng/L and ∑PFCs in groundwater ranged from 5.3 to 615 ng/L. Ratios of perfluorononanoic acid/perfluorooctanoic acid (PFNA/PFOA), perfluoro-n-butyric acid/perfluorooctanoic acid (PFBA/PFOA), and perfluoroheptanoic acid/perfluorooctanoic acid (PFHpA/PFOA) in rainwater increased due to the fluorine chemical plants in the surrounding rural and urban areas, suggesting that atmospheric precipitation may carry PFCs and their precursors from the fluorochemical industrial area to the adjacent rural areas.