Highly sensitive passive sampling of new pollutants in urban reclaimed water using hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membrane.

Urban reclaimed water is important water resource in China, while the residual new pollutants in the water largely challenge their safety for further use. China's action program for the management of new pollutants (also known as emerging contaminants) requires effective method for monitoring diverse new pollutants in water. This work proposed a highly sensitive passive sampling method for monitoring diverse new pollutants in urban reclaimed water. Hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membranes (HECAMs) were dynamically deployed in self-developed continuous flow integrative sampling device (CFISD) for sampling four types of new pollutants with wide polarity ranges (1.11 < log Kow < 9.49) in a reclaimed water network for landscape irrigation in Beijing, China. The estimated equilibrium partition ratios of most chemicals between HECAM and water were over 104, which would provide low detection limits. In the 7-d high-efficiency deployment, thirty new pollutants were detected, which indicated incompletely removal of various new pollutants in wastewater treatment process. The dynamical accumulation data were successfully fitted by first-order kinetic model and different contaminants reached different accumulation phases in the HECAMs during 7 d. Acceptable and steady uptake rate constants and sampling rates were obtained with the use of CFISD in field sampling. The estimated time-weighted average concentrations for contaminants had wide concentration range and were from 0.03 ng L-1 (pendimethalin) to 3,394 ng L-1 (dibutyl phthalate) and this may lead to environmental risk for further use the reclaimed water. Dynamical deployment results also provided sensitive information of concentration fluctuations and twelve pollutants showed concentration fluctuations during the sampling period. In summary, HECAM showed high sensitivities and credible performance of monitoring diverse new pollutants in the urban reclaimed water.

Deep learning-based anatomical position recognition for gastroscopic examination.

BACKGROUND: The gastroscopic examination is a preferred method for the detection of upper gastrointestinal lesions. However, gastroscopic examination has high requirements for doctors, especially for the strict position and quantity of the archived images. These requirements are challenging for the education and training of junior doctors. OBJECTIVE: The purpose of this study is to use deep learning to develop automatic position recognition technology for gastroscopic examination. METHODS: A total of 17182 gastroscopic images in eight anatomical position categories are collected. Convolutional neural network model MogaNet is used to identify all the anatomical positions of the stomach for gastroscopic examination The performance of four models is evaluated by sensitivity, precision, and F1 score. RESULTS: The average sensitivity of the method proposed is 0.963, which is 0.074, 0.066 and 0.065 higher than ResNet, GoogleNet and SqueezeNet, respectively. The average precision of the method proposed is 0.964, which is 0.072, 0.067 and 0.068 higher than ResNet, GoogleNet, and SqueezeNet, respectively. And the average F1-Score of the method proposed is 0.964, which is 0.074, 0.067 and 0.067 higher than ResNet, GoogleNet, and SqueezeNet, respectively. The results of the t-test show that the method proposed is significantly different from other methods (p< 0.05). CONCLUSION: The method proposed exhibits the best performance for anatomical positions recognition. And the method proposed can help junior doctors meet the requirements of completeness of gastroscopic examination and the number and position of archived images quickly.

Strategy for establishing sensitive fluorescent sensor toward p-nitrophenol integrating magnetic molecularly imprinted materials and carbon dots.

In this work, a sensitive fluorescent sensor toward p-nitrophenol (4-NP) integrating magnetic molecularly imprinted materials and carbon dots (CDs) was proposed. Magnetic material and CDs derived from K3 [Fe(CN)6] and glucose were simultaneously obtained through simple one-step hydrothermal process. Introducing of molecularly imprinted materials based magnetic solid phase extraction (MSPE) endowed the constructed fluorescent sensor with higher sensitivity and selectivity. The significant factors affecting the sensitivity of the sensor toward 4-NP were optimized. Good linearity was obtained between fluorescent intensity of CDs and different concentration of 4-NP from 0.08 to 62.5 µg L-1. The sensitivity of constructed sensor was very low with detection limit of 0.02 µg L-1. Reliable applicability was also proved by the well-pleasing recoveries of 94.2-97.8% with different spiked concentrations of 4-NP in real environmental waters.

MicroRNA­153 may act as a potential biomarker and prognostic indicator of patients with gastric cancer.

MicroRNA (miR/miRNA)-153, as a novel tumor-related miRNA, has been found to be aberrantly expressed in different types of cancer; however, to the best of our knowledge, the role of miR-153 in gastric cancer (GC) remains unclear. The present study demonstrated that miR-153 expression was markedly decreased in GC, including GC cell lines and culture medium, GC tissues, and serum samples, based on reverse transcription-quantitative PCR, and this was further confirmed by fluorescence in situ hybridization. Transfection with miR-153 mimics inhibited proliferation and migration, and promoted apoptosis in GC cells. The serum expression levels of miR-153 were decreased in 59 patients with GC compared with those of 9 healthy controls, and more decreased in advanced GC compared with early-stage GC, suggesting that miR-153 was associated with tumor progression. Furthermore, serum miR-153 was expressed at significantly lower levels in patients with GC with larger tumor size (≥4 cm; P=0.013), poor differentiation and signet histology (P=0.013), lymph node metastasis (P=0.025) and advanced tumor stage (TNM stage III and IV; P=0.048) compared with patients with a smaller tumor size (<4 cm), well and moderate differentiation, no lymph node metastasis, and TNM stage I and II, respectively. In conclusion, the present study revealed that low miR-153 expression was associated with poor prognosis in GC and miR-153 may potentially act as a tumor biomarker and therapeutic target in GC.

Evaluation of deep learning methods for early gastric cancer detection using gastroscopic images.

BACKGROUND: A timely diagnosis of early gastric cancer (EGC) can greatly reduce the death rate of patients. However, the manual detection of EGC is a costly and low-accuracy task. The artificial intelligence (AI) method based on deep learning is considered as a potential method to detect EGC. AI methods have outperformed endoscopists in EGC detection, especially with the use of the different region convolutional neural network (RCNN) models recently reported. However, no studies compared the performances of different RCNN series models. OBJECTIVE: This study aimed to compare the performances of different RCNN series models for EGC. METHODS: Three typical RCNN models were used to detect gastric cancer using 3659 gastroscopic images, including 1434 images of EGC: Faster RCNN, Cascade RCNN, and Mask RCNN. RESULTS: The models were evaluated in terms of specificity, accuracy, precision, recall, and AP. Fast RCNN, Cascade RCNN, and Mask RCNN had similar accuracy (0.935, 0.938, and 0.935). The specificity of Cascade RCNN was 0.946, which was slightly higher than 0.908 for Faster RCNN and 0.908 for Mask RCNN. CONCLUSION: Faster RCNN and Mask RCNN place more emphasis on positive detection, and Cascade RCNN places more emphasis on negative detection. These methods based on deep learning were conducive to helping in early cancer diagnosis using endoscopic images.

Passive sampling of diverse pesticides in water by hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membrane: Kinetics, equilibrium partitioning and field application.

Pesticides are useful products for agriculture and human life, but they are often released into surface waters and are hazardous to aquatic ecosystems. Pesticides monitoring in surface waters is challenging due to the great variety, ultratrace levels and nonpoint source pollution of pesticides; however, continuous passive sampling may be conducive to solving these problems. This work evaluated the performance of a newly developed passive sampler (hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membrane, HECAM) for six types of currently used/present pesticides. The uptake kinetics and equilibrium partitioning of nineteen pesticides in different dissolved concentrations were studied by dynamic accumulation and equilibrium partitioning experiments, respectively. In the dynamic accumulation experiments, pesticides gradually accumulated in the HECAM and followed a first-order kinetic model. The same type of pesticides had roughly comparable accumulation concentrations. The estimated uptake rate constants ranged from 1.04 to 13.5 L g-1 d-1, and sampling rates ranged from 0.02 to 0.31 L d-1 for the pesticides in the HECAM (size of 2 cm × 3 cm). Pesticide accumulation concentrations in the HECAM increased linearly with increasing dissolved concentrations, which means that varying concentrations can also be monitored by the HECAM. In the equilibrium partitioning experiments, the pesticide partitioning behavior at varying dissolved concentrations can be described by the Freundlich model. The calculated equilibrium partition coefficients (log KD) for pesticides ranged from 3.32 to 4.54, and different pesticide types showed different changes with log Kow. Comparable results were found when estimating chemical equilibrium partition coefficients by the dynamic accumulation and equilibrium partitioning methods. Field deployment of the HECAM in river waters resulted in the detection of four pesticides, and the measured results were comparable to those of active sampling coupled with liquid-liquid extraction. These results suggest that the HECAM would be a promising strategy for simultaneously monitoring diverse pesticides in waters.

FAM83D promotes the proliferation and migration of hepatocellular carcinoma cells by inhibiting the FBXW7/MCL1 pathway.

Background: Hepatocellular carcinoma (HCC) is one of the most malignant tumors and has a poor 5-year survival rate. Family with sequence similarity 83, member D (FAM83D) is characterized as an oncogenic gene related to cell proliferation in many tumors, but the role and underlying mechanism of FAM83D in the development of HCC are still unclear. Methods: FAM83D expression profiles and clinicopathological data were obtained from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC). Additionally, 2 data sets from the Gene Expression Omnibus (GEO) database were used to further validate the FAM83D profile in HCC. We then downregulated the expression of FAM83D in HCC cells transfected with FAM83D small-interfering ribonucleic acid (siRNA) and upregulating its expression by FAM83D-overexpression transfection for further in vitro studies. Results: TCGA and the GEO databases showed that FAM83D was significantly more upregulated in tumor tissues than non-tumor tissues. The high expression of FAM83D in HCC is associated with poor prognostic clinical factors. The knockdown of FAM83D in SNU449 and HUH7 cells in vitro impaired cell proliferation and migration, and promoted apoptosis, while the overexpression of FAM83D in BEL7402 cells had the opposite effect. Further, combined transfection with FBXW7 siRNA or MCL1-overexpression reversed the role of FAM83D knockdown on cell proliferation, migration, and apoptosis in vitro, while FBXW7 expression was negatively correlated with both the FAM83D and MCL1 levels in TCGA-LIHC patients. Conclusions: FAM83D played a significant role in HCC progression by enhancing cell proliferation and migration and inhibiting apoptosis, which may have been caused by the inhibition of the FBXW7/MCL1 signaling pathway. Thus, FAM83D may be a promising therapeutic target for HCC.

Passive sampling hydrophilic and hydrophobic bisphenol analogues using hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membrane in surface waters.

Bisphenol analogues (BPs) are ubiquitous emerging contaminants in water environments and have wide polarity ranges (1.65 < log Kow < 7.2). Integrated passive sampling strategy rarely contains hydrophilic and hydrophobic organics simultaneously, while the method has good application perspective in monitoring organic contaminants. This work evaluated passive sampling performance for fifteen BPs in a newly developed passive sampler, i.e., hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membrane (HECAM). In the dynamic accumulation experiments, both hydrophilic and hydrophobic BPs (including moderately hydrophilic BPs) well followed first-order kinetic uptake in the HECAMs. The estimated uptake rate constants, elimination rate constants, and equilibrium partition coefficients for BPs ranged from 4.4 L g-1 d-1 to 14.7 L g-1 d-1, 0.22 d-1 to 0.72 d-1, and 3.99 to 4.64, respectively. The kinetic parameters for BPs in HECAM show limited correlations to log Kow values, which the rule differs from traditional passive sampler. In the study of elimination kinetics, three deuterium labeled compounds showed incomplete elimination in HECAM and did not follow first-order isotropic exchange kinetics. Dual sorption mechanisms including both adsorption and partition were found for chemicals in HECAM, which the partitioned part could release to water and the adsorbed part could not easily release to water from HECAM. As a result, performance reference compounds (PRCs) calibration may be inapplicable to HLB sorbent-based passive sampler. The field deployment of HECAM in coastal waters of Guangdong, China resulted in the detection of eleven BPs, which indicated that the waters have been polluted by various BPs. Finally, monitoring strategy of simultaneous passive sampling hydrophobic and hydrophilic organic contaminants in surface waters was recommended.

Exploring the influence of concentration fluctuation and matrix effects on a passive sampler of triolein-embedded cellulose acetate membrane measuring polychlorinated biphenyls in water.

A membrane of triolein-embedded cellulose acetate membrane (TECAM), as an integrative passive sampler, was applied to adsorb 28 polychlorinated biphenyls (PCBs) from pure water and sea water in order to probe into the influence of concentration fluctuation and water matrix. The results demonstrated the temporal variations of PCBs concentrations in TECAM followed the first-order kinetics model. The periodic refreshment of solution and matrix effects of sea water significantly prolonged the time that PCBs reached equilibrium stage. The refreshment facilitated the uptake mass in TECAM. On the contrary, the matrix effects of sea water and dissolved organic matter (DOM) declined the PCBs absorption to TECAM. The average logKP values of PCBs in pure water were about 1.2 log unit higher than those in sea water in the experiments that the solution was not refreshed, while the difference of average logKP values narrowed to 0.3 log unit if the PCBs solutions were periodically refreshed. The correlation between logKP and logKOW values fitted the quadratic curve well, which was similar to semi-permeable membrane device (SPMD). The appropriate sampling times (t94%) ranged from 98.8 to 819 h (mean 500 h) for pure water with refreshment, much longer than those in sea water with refreshment (80.1~410 h, mean 189 h). The t94% values in the solution with high DOM content increased significantly, up to 409 h. Furthermore,  comparing the two experiments that the spiked pure water and sea water solution were refreshed frequently, the estimated sampling rates (Rs) in pure water (0.154~2.06 L/day with a mean value of 0.605 L/day) were slightly lower than those in sea water (0.292~3.84 L/day with a mean value of 1.69 L/day). However, the Rs values in sea water with DOM declined sharply to 0.042 L/day. Therefore, concentration fluctuation, matrix effect, and DOM contents of sea water evidently posed significant influence on dynamic parameters of TECAM absorption, which would be screened and probed detailed in future.

Integrated passive sampling and fugacity model to characterize fate and removal of organophosphate flame retardants in an anaerobic-anoxic-oxic municipal wastewater treatment system.

It is crucial to deeply understand the fate and removal mechanism of various organophosphate flame retardants (PFRs) in specified wastewater treatment processes. However, concentration fluctuation and matrix effect in wastewater challenge quantification of PFR flux for both field observation and model validation. We present measured seasonal distribution profiles of time-weighted average (TWA) concentrations by in situ hydrophobic and polar passive samplers and modeled mass transport and transformation by means of fugacity for 11 PFRs with varied structures in an anaerobic-anoxic-oxic (A-A-O) municipal wastewater treatment system, and provided a systematic approach to characterize fate and removal mechanism of PFRs in major compartments via various treatment processes. We find evidence that PFRs have a unique structural-dependent fate and removal in the A-A-O system. Hydrophilic chlorinated-PFRs present persistent in all major compartments and dominate in effluents with significant variations; alkyl-PFRs are majorly reduced by biodegradation; whereas hydrophobic aryl-PFRs have the highest removal percentage, contributed by both sorption on solids and biotransformation. Sensitive analysis shows the most influential operation parameters on removal efficiency varied among the PFRs with different properties. We also conclude passive sampling can be effectively applied to estimate TWA wastewater concentrations and to validate fugacity model prediction.

Accumulation and passive sampling of bisphenol analogues using triolein-embedded cellulose acetate membrane in waters.

Bisphenol analogues (BPs) are emerging contaminants that have been widely detected in water environments. The presence of substituted hydrophilic and hydrophobic groups in the molecule may lead to unclear performance in passive sampling. This study tested the accumulation capacity and passive sampling of fifteen BPs in a triolein-embedded cellulose acetate membrane (TECAM) passive sampler. In a dynamic accumulation experiment, twelve hydrophobic BPs accumulated in the TECAM with concentrations ranging from 251 ng g-1 to 6283 ng g-1, and three hydrophilic BPs did not accumulate during the 72 h exposure duration. BPs accumulations were determined by the hydrophilic and hydrophobic substituent groups in molecule structures. The estimated passive sampling parameters showed correlations to both the log Kow values and chemical structures, and compared to other contaminants, such as organophosphorus flame retardants. Environmental factors, including flow rate, temperature, salinity, and pH, that affect the accumulation of BPs in the TECAM were tested, and the flow rate was found to be an important factor affecting the uptake rate. The isotropic exchange kinetics for BPs in the TECAM were verified, and the results indicated that BPs can be calibrated with performance reference compounds (PRCs) in field applications. Finally, a field deployment of TECAM in river waters successfully estimated the time-weighted concentrations of two hydrophobic BPs. To address the inherent weaknesses of TECAM in sampling hydrophilic and moderately hydrophobic BPs, future studies should explore alternative passive samplers, such as hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membranes, to sample BPs in surface waters.

Spatial pattern analysis reveals multiple sources of organophosphorus flame retardants in coastal waters.

Organophosphorus flame retardants (PFRs) are a group of emerging contaminants which have been detected in worldwide waters. However, source of various PFRs in the large-scale area like coastal water environment have not been clearly revealed. In this study, fifteen PFRs in coast of Guangdong-Hong Kong-Macao Greater Bay area (GBA), China were investigated, and a method of spatial pattern analysis was firstly used for pollution source identification. Seawater samples from different segments of GBA coast were analyzed and thirteen PFRs were quantified with total concentrations ranging from 32.7 to 1032.7 ng L-1. GBA coasts have been seriously polluted by PFRs. A hierarchical cluster analysis of the PFR concentrations in different GBA sites showed significant spatial distributions for different types of PFRs. A series of correlation analysis between PFRs distributions and spatial pattern of GBA socio-economic indicators were performed, and multiple sources including human settlement, wastewater, manufacture, construction industry, vehicles, and shipping transport were found to be correlated to PFRs pollutions in the coasts. This study indicates that spatial pattern analysis based on statistical analysis would be a promising method of analyzing environmental data and exploring pollution source in large-scale area.

Acute and chronic infection of H. pylori caused the difference in apoptosis of gastric epithelial cells.

Helicobacter pylori (H. pylori) is one of the most important pathogenic bacteria associated with various gastrointestinal diseases. At present, its apoptotic or antiapoptotic mechanism on gastric epithelial cells remains unknown and needs further illustrated. In this study, acute infection model (H. pylori and GES-1 cells were co-cultured for 24 h at a multiplicity of infection MOI of 100:1) and chronic infection model (GES-1 cells were infected repeatedly every 24 h at a multiplicity of infection MOI of 100:1 for approximately 8 weeks) were established, respectively. the chronic H. pylori infected GES-1 cells underwent a typically morphological change and Western Blot results showed that there was slight decrease in expression of E-cadherin, and obvious increase in expression of Vimentin. Apoptosis of these two models were analyzed by flow cytometry compared with the control cells, meanwhile, apoptosis associated markers (Bcl-xL, Bcl-2, Bax, etc) were detected by Western blot, additional in clinical H. pylori-positive gastric cancer tissues. Results showed that compared with the control cells, acute infection of H. pylori significantly accelerated the apoptosis of GES-1, increased the expression of Bax and Cleaved caspase-3, down-regulated expression of Bcl-xL and Bcl-2. Moreover, an opposite result was found in chronic infection of model and clinical gastric cancer tissues, and enhanced expression of NF-κB p65. Taken together, these findings suggest that H. pylori infection plays differential effects on apoptosis of gastric epithelial cells.

Will purposely seeking detect more colorectal polyps than routine performing during colonoscopy?

BACKGROUND & GOALS: We observed that the number of colorectal polyps found intraoperatively was often higher than that encountered preoperatively during elective colonoscopic polypectomy. To evaluate whether more polyps can be detected when they are purposely sought than when they are routinely examined during colonoscopy. MATERIALS AND METHODS: Patients undergoing colonoscopy were randomized into groups A and B. Before colonoscopy was performed, endoscopists were instructed to seek polyps for group A purposely but not for group B. Polypectomy was electively completed. In groups A and B, the cases of elective polypectomy were named groups AR and BR, including groups AR-1 and BR-1, during the first colonoscopy and groups AR-2 and BR-2 during the second colonoscopy for polypectomy, respectively. The following data were calculated: the number of polyps detected (NPD) and the polyp detection rate (PDR) in all cases and the number of polyps missed (NPM) and partial polyp miss rate (PPMR) in the cases of colorectal polyps. RESULTS: A total of 419 cases were included in group A, 421 in group B, 43 in group AR, and 35 in group BR. No significant differences in PDR were found between groups A and B and in PPMR between groups AR-1 and BR-1 (P > .05), although PPMR in group AR-1 was higher than in group AR-2 (P < .05), similar results were found in PPMR between groups BR-1 and BR-2 (P < .05). CONCLUSION: Purposely seeking for colorectal polyps did not result in more polyps detected compared with routine colonoscopy.

Distribution, sources and transport of organophosphorus flame retardants in the water and sediment of Ny-Ålesund, Svalbard, the Arctic.

Organophosphorus flame retardants (PFRs) are contaminants of emerging concern which have been detected globally. However, little information on PFRs in the Arctic freshwater environment is currently available. In this study, both hydrophilic and hydrophobic PFRs in the water and sediment of four areas (town, surroundings, coastal marine water, and glacier melt runoff) near Ny-Ålesund Svalbard were investigated by time-integrated passive sampling (water) and grab sampling (sediment). Seven kinds of PFRs were found in the Arctic waters with individual freely dissolved concentrations from 0.007 ng L-1 to 355 ng L-1, and the concentrations of chlorinated PFRs were 3-4 orders of magnitude higher than those of non-chlorinated PFRs. The distribution of different PFRs in freshwater showed significant spatial differences among the different areas, and the town was found to have most kinds of PFRs and highest PFRs concentrations. The sources and transport of different kinds of PFRs were explored based on a spatial overlay analysis of the contaminant distributions, environmental conditions, and PFR applications. As a result, human settlements, industrial activities, atmospheric deposition, and transportation in Ny-Ålesund were proposed to be related to the pollution of different PFRs at Ny-Ålesund. The PFRs in the inshore marine water were found to be affected by both local ship contamination and ocean current transport. Furthermore, nine PFRs were detected in the sediments of Ny-Ålesund. Accumulation of different PFRs in the Arctic sediment was found to be dominated by their physico-chemical properties (polarity).

Organophosphorus flame retardants and persistent, bioaccumulative, and toxic contaminants in Arctic seawaters: On-board passive sampling coupled with target and non-target analysis.

Organic pollutants in the Arctic seas have been of concern to many researchers; however, the vast dynamic marine water poses challenges to their comprehensive monitoring within appropriate spatial and temporal scales in the Arctic. In this study, on-board passive sampling of organic pollutants using a self-developed device coupled with triolein-embedded cellulose acetate membranes (TECAMs) was performed during an Arctic cruise. The TECAM extracts were used for target analysis of organophosphorus flame retardants (PFRs), and non-target screening of persistent, bioaccumulative, and toxic (PBT) contaminants using two-dimensional gas chromatography with time-of-flight mass spectrometry (GC × GC-TOFMS). Sixteen chemicals were screened out as PBT contaminants from the 1500 features in the non-target analysis and further identified. Consequently, two chlorinated PFRs (tris(chloroisopropyl)phosphate and tris(1,3-dichloroisopropyl)phosphate) and four PBT contaminants (4-tert-butylphenol, 2-isopropylnaphthalene, 1,1,3-trimethyl-3-phenylindane, and 1-phenylnonan-1-one) were accurately quantified, with the temporally and spatially integrated concentrations ranging from 0.83 ng L-1 to 20.82 ng L-1 in the seawaters. Sources and transport of the contaminants were studied, and ocean current transport (West Spitsbergen Current, WSC) and local sources (human settlement, Arctic oil exploitation, and petroleum fuel emissions) were found to contribute to the presence of the different contaminants. Finally, annual transport fluxes of the contaminants from the North Atlantic to the Arctic Ocean by WSC were estimated, and the results indicate that their hazard to the Arctic should be concerned.

Simultaneous passive sampling of hydrophilic and hydrophobic emerging organic contaminants in water.

Passive sampling techniques have been considered robust tools for monitoring freely dissolved concentrations of contaminants in aquatic systems. However, few passive samplers are currently available for the simultaneous sampling of both hydrophilic and hydrophobic chemicals. In this study, we developed a novel passive sampler (a hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membrane (HECAM)) for estimating the time-weighted average (TWA) concentrations of both hydrophilic and hydrophobic organic contaminants in water. In our laboratorial controlled dynamic experiments, the accumulation results of thirty-seven target chemicals (including organophosphorus flame retardants, phenols, estrogens, organophosphorus pesticides, and triazine herbicides) with a wide polarity range (1.44 < log Kow < 9.49) in the HECAM followed first-order kinetics well, and the passive sampling parameters were estimated successfully. The estimated sampling rates for the target chemicals in the HECAM ranged from 0.14 to 6.90 L d-1 in the laboratory experiment, and the log Ksw (equilibrium partition coefficient between the sampler and water) values ranged from 2.75 to 6.00. The HECAM exhibited high sampling rate for moderately hydrophilic and moderately hydrophobic chemicals. The field validation study in an urban river resulted in the detection of four target chemicals (tris(chloroisopropyl)phosphate, tris(1,3-dichloroisopropyl)phosphate, prometryn, and 4-tert-octylphenol) by the HECAM at estimated TWA concentrations of 10.9-179.5 ng L-1, which were in agreement with the measured levels found in traditional grab samples by solid-phase extraction. In summary, both the laboratory tests and field deployment showed practicable results for the HECAM passive sampling, which suggests that it is an efficient approach for simultaneous monitoring of hydrophilic and hydrophobic organic contaminants in water.

Small molecule PROTACs in targeted therapy: An emerging strategy to induce protein degradation.

Inhibitors and nucleic acid based techniques were two main approaches to interfere with protein signaling and respective cascade in the past. Until recently, a new class of small molecules named proteolysis-targeting chimeras (PROTACs) have emerged. Each contains a target warhead, a linker and an E3 ligand. These bifunctional molecules recruit E3 ligases and target specific proteins for degradation via the ubiquitin (Ub) proteasome system (UPS). The degradation provides several advantages over inhibition in potency, selectivity and drug resistance. Thus, a variety of small molecule PROTACs have been discovered so far. In this review, we summarize the biological mechanism, advantages and recent progress of PROTACs, trying to offer an outlook in development of drugs targeting degradation in future.

Expression and Localization of Huntingtin-Associated Protein 1 (HAP1) in the Human Digestive System.

BACKGROUND: Huntingtin-associated protein 1 (HAP1) is a neuronal protein that is predominantly expressed in neurons in the brain. HAP1 is critical for maintenance of neuronal survival as well as regulation of food intake and body weight in animals. In addition to the criticalrole of HAP1 in the central nervous system, HAP1 is also found in endocrine cells, raising an interesting issue of whether HAP1 is expressed in the digestive system. AIMS: To examine the expression and localization of HAP1 in the human gastrointestinal tract and to compare the differences of the HAP1 expression between benign and malignant tissues in the digestive system. METHODS: We used Western blot and immunohistochemistry to examine the expression and distribution of HAP1 in the human gastrointestinal tract tissues. RESULTS: We observed that the presence of HAP1-positive cells in the gastrointestinal tract was not uniform with immunohistochemistry staining. Western blot revealed that only one isoform (75KD) HAP1 was present in the human gastrointestinal system. Interestingly, the expression of HAP1 was higher in the stomach than other regions of the gastrointestinal tract and was at the lowest level in the intestine. We also found that HAP1 was unlikely altered in benign gastric polyps, but was downregulated in pancreatic cancer. CONCLUSIONS: This is the first study showing the differential expression and location of HAP1 in the human digestive system. These findings suggested that HAP1 may have cell-type-dependent function in the gastrointestinal tract and may serve as a diagnostic marker for pancreatic cancer.

CDK8 as a therapeutic target for cancers and recent developments in discovery of CDK8 inhibitors.

Cyclin-dependent kinases 8 (CDK8) regulates transcriptional process via associating with the mediator complex or phosphorylating transcription factors (TF). Overexpression of CDK8 has been observed in various cancers. It mediates aberrant activation of Wnt/ß-catenin signaling pathway, which is initially recognized and best studied in colorectal cancer (CRC). CDK8 acts as an oncogene and represents a potential target for developing novel CDK8 inhibitors in cancer therapeutics. However, other study has revealed its contrary role. The function of CDK8 is context dependent. Even so, a variety of potent and selective CDK8 inhibitors have been discovered after crystal structures were resolved in two states (active or inactive). In this review, we summarize co-crystal structures, biological mechanisms, dysregulation in cancers and recent progress in the field of CDK8 inhibitors, trying to offer an outlook of CDK8 inhibitors in cancer therapy in future.