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The long-term seasonal pollution characteristics, environmental effects, and sources of atmospheric volatile organic compounds （VOCs） were investigated based on the one-year （06/2021-05/2022） online observation data of VOCs in the central urban area of Chongqing. The results showed that during the observation period, the mean value of φ （VOCs） was 31.5×10 -9 , of which alkane accounted for the highest proportion （39.6%）, followed by oxygenated VOCs （OVOCs） （15.6%）, halogenated hydrocarbons （13.9%）, aromatic hydrocarbons （11.6%）, olefin （10.5%）, and alkyne （8.3%）. In terms of time, the volume fraction changed to winter （35.7×10 -9 ） > autumn （32.5×10 -9 ） > summer （31.3×10 -9 ） > spring （27.6×10 -9 ）. In summer, the highest contribution of aromatic hydrocarbons to ozone generation was observed in 1,2,4-tritylene, toluene, and m / p -xylene species with higher ozone generation potential （OFP）. In winter, the contribution of aromatic hydrocarbons to the formation potential of secondary organic aerosols （SOA） was as high as 96%, and toluene and m / p -xylene were the main contributing species to the formation potential of SOA. The main sources of VOCs in summer were motor vehicle emissions （30.9%）, industrial emissions （21.2%）, and solvent use sources （18.6%）, and the main sources in winter were motor vehicle exhaust （35.8%）, combustion sources （30.9%）, and industrial sources （20.6%）. The contribution of combustion sources to VOCs in winter （30.9%） was significantly higher than that in summer （17.4%）.

Theanode enables raised microbial fuel cells (MFCs) performance via in-situ growth electroactive material. However, the role of fabricated microstructures in electroactive bacteria loading and extracellular electron transfer (EET) has been paid less attention. Here, MoS2 nanosheets are custom grown on carbon cloth to construct anode models with diverse surface microstructures. Surprisingly, the 3D-MoS2/NS-CC anode only 0.85 d enables the MFC to be started and achieves a maximum power density of 3.85 W/m 2 , which is significantly faster and higher than that of 2D-MoS2/NS-CC (3.6 d, 2.75 W/m 2 ) and CC (4.46 d, 1.98 W/m 2 ). As for the mechanism of 3D-MoS2/NSCCboosting MFC performance, this is attributed to the 3D-open-microarray preventing electroactive bacteria from shedding and facilitating to the establishment of excellent EET channels through the formed hybrid cell-electrode systems and Geobacter enrichment of up to 86.1 %. This research provides promising guidance for integrating nanomaterials and architecture to construct high-performance anodes in MFCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Early detection of cancer remains an unmet need in clinical practice, and high diagnostic sensitivity and specificity biomarkers are urgently required. Here, we attempted to identify secreted proteins encoded by super-enhancer (SE)-driven genes as diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC)., Methods: We conducted an integrative analysis of multiple data sets including ChIP-seq data, secretome data, CCLE data and GEO data to screen secreted proteins encoded by SE-driven genes. Using ELISA, we further identified up-regulated secreted proteins through a small size of clinical samples and verified in a multi-centre validation stage (345 in test cohort and 231 in validation cohort). Receiver operating characteristic curves were used to calculate diagnostic accuracy. Artificial intelligence (AI) method named gradient boosting machine (GBM) were applied for model construction to enhance diagnostic accuracy., Results: Serum EFNA1 and MMP13 were identified, and showed significantly higher levels in ESCC patients compared to normal controls. An integrated Five-Biomarker Panel (iFBPanel) established by combining EFNA1, MMP13, carcino-embryonic antigen, Cyfra21-1 and squmaous cell carcinoma antigen had AUCs of 0.881 and 0.880 for ESCC in test and validation cohorts, respectively. Importantly, the iFBPanel also exhibited good performance in detecting early-stage ESCC patients (0.872 and 0.864). Furthermore, the iFBPanel was further empowered by AI technology which showed excellent diagnostic performance in early-stage ESCC (0.927 and 0.907)., Conclusions: Our study suggested that serum EFNA1 and MMP13 could potentially assist ESCC detection, and provided an easy-to-use detection model that might help the diagnosis of early-stage ESCC., Competing Interests: Conflict of interest The author has no potential conflicts of interest to disclose., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland., (© 2024 The Pathological Society of Great Britain and Ireland.)

Objective: Ribonuclease P RNA component H1 (RPPH1) is a long non-coding RNA (lncRNA) associated with cancer progression. Higher RPPH1 expression in breast and cervical cancer samples than that in normal tissues were observed through the lncRNASNP2 database; therefore, silencing RPPH1 expression might be a potential strategy for cancer treatments, even though RPPH1 is also an RNA subunit of ribonuclease P involved in processing transfer RNA (tRNA) precursors and the effect of RPPH1 knockdown is not yet fully understood., Methods: Differentially expressed genes (DEGs) were identified through RNA sequencing in each shRNA-transfected RPPH1 knockdown MDA-MB-231, RPPH1 knockdown HeLa cell, and respective control cells, then the gene ontology enrichment analysis was performed by IPA and MetaCore database according to these DEGs, with further in vitro experiments validating the effect of RPPH1 silencing in MDA-MB-231 and HeLa cells., Results: Hundreds of down-regulated DEGs were identified in RPPH1 knockdown MDA-MB-231 and HeLa cells while bioinformatics analysis revealed that these genes were involved in pathways related to immune response and cancerogenesis. Compared to mock- and vector-transfected cells, the production of mature tRNAs, cell proliferation and migration capacity were inhibited in RPPH1-silenced HeLa and MDA-MB-231 cells. Additionally, RPPH1 knockdown promoted G1 cell cycle arrest mainly through the down-regulation of cyclin D1, although glycolytic pathways were only affected in RPPH1 knockdown HeLa cells but not MDA-MB-231 cells., Conclusion: This study demonstrated that knockdown RPPH1 affected tRNA production, cell proliferation and metabolism. Our findings might provide insight into the role of RPPH1 in tumor development., Competing Interests: None., (AJTR Copyright © 2023.)

The detection of hydrogen sulfide (H 2 S), the third gas signaling molecule, is a promising strategy for identifying the occurrence of certain diseases. However, the conventional single- or dual-signal detection can introduce false-positive or false-negative results, which ultimately decreases the diagnostic accuracy. To address this limitation, we developed a luminescent, photothermal, and electrochemical triple-signal detection platform by optically trapping the synthetic highly doped upconversion coupled SiO 2 microbeads coated with metal-organic frameworks H-UCNP-SiO 2 @HKUST-1 (H-USH) to detect the concentration of H 2 S. The H-USH was first synthesized and proved to have stable structure and excellent luminescent, photothermal, and electrochemical properties. Under 980 nm optical trapping and 808 nm irradiation, H-USH showed great detection linearity, a low limit of detection, and high specificity for H 2 S quantification via triple-signal detection. Moreover, H-USH was captured by optical tweezers to realize quantitative detection of H 2 S content in serum of acute pancreatitis and spontaneously hypertensive rats. Finally, by analyzing the receiver operating characteristic (ROC) curve, we concluded that triple-signal detection of H 2 S was more accurate than single- or dual-signal detection, which overcame the problem of false-negative/positive results in the detection of H 2 S in actual serum samples.

Cell-cell junctions comprise various structures, including adherens junctions, tight junctions, desmosomes, and gap junctions. They link cells to each other in tissues and regulate tissue homeostasis in critical cellular processes. Recent advances in cell-cell junction research have led to critical discoveries. Cell-cell adhesion components are important for the invasion and metastasis of tumour cells, which are not only related to cell-cell adhesion changes, but they are also involved in critical molecular signal pathways. They are of great significance, especially given that relevant molecular mechanisms are being discovered, there are an increasing number of emerging biomarkers, targeted therapies are becoming a future therapeutic concern, and there is an increased number of therapeutic agents undergoing clinical trials. Oesophageal squamous cell carcinoma (ESCC), the most common histological subtype of oesophageal cancer, is one of the most common cancers to affect epithelial tissue. ESCC progression is accompanied by the abnormal expression or localisation of components at cell-cell junctions. This review will discuss the recent scientific developments related to the molecules at cell-cell junctions and their role in ESCC to offer valuable insights for readers, provide a global view of the relationships between position, construction, and function, and give a reference for future mechanistic studies, diagnoses, and therapeutic developments.

In order to further improve the accuracy of fine particulate matter (PM 2.5 ) source apportionment results, a hybrid source apportionment approach (CTM-RM) combining the capabilities of a receptor model (RM) and chemical transport model (CTM) was developed. The CTM-RM method was evaluated and applied according to a typical PM 2.5 pollution process from January 21 to 27, 2019 in Chongqing. The average value of square prediction error based on CTM-RM was 84.58% lower than that of CAMx/PSAT during the campaign. Compared with that of CAMx/PSAT, the fractional error of PM 2.5 and its chemical component concentrations decreased by 15.69%-92.86%. Furthermore, the temporal and spatial variations in PM 2.5 source impacts could be obtained using the CTM-RM method in Chongqing. The average adjustment factor ( R ) values were 1.39±0.38 (agriculture sources), 1.54±0.48 (industrial sources), 1.01±0.13 (power sources), 1.02±0.58 (residential sources), 0.86±0.59 (transportation sources), and 0.58±0.67 (other sources) in the main urban areas of Chongqing. Additionally, the cumulative distribution functions of R were found to be distinct among the six sources. The residential and industrial sources were the main sources of PM 2.5 , with contributions of 46.23% and 28.23%, respectively. In contrast to that of the other sources, the transportation source impacts of PM 2.5 (8.62%) increased significantly from the clear period to pollution period ( P <0.001), indicating that the increase in PM 2.5 concentrations was mainly driven by vehicular emissions during the pollution period in the main urban areas of Chongqing. The fitting functions between the initial simulated concentrations and R values of each source in the main urban areas of Chongqing could be used to evaluate PM 2.5 concentrations at 47 air quality monitoring stations in Chongqing, and the correlation between the refined simulated concentrations and measured concentration of PM 2.5 was significant ( r =0.82, P <0.001). Compared with that during the clear period, the increases in the percentages of industrial source impacts of PM 2.5 in Northeast Chongqing and residential source impacts of PM 2.5 in Southeast Chongqing were 17.20% and 9.15% higher, respectively, than that in other areas during the pollution period. By contrast, the increasing percentage of transportation source impacts of PM 2.5 in the main urban areas of Chongqing (66.39%) and Western Chongqing (84.16%) from the clear period to the pollution period were higher than that in other areas. The results of CTM-RM on January 26 indicated that the residential source impacts in Northeast Chongqing (64.56%) were higher than those in other areas, and the industry source impacts of PM 2.5 were primarily observed in the main urban areas of Chongqing and Western Chongqing, with contributions of 25.26% and 21.20%, respectively.

Although great headway has been made in DNAzyme-based detection of Pb 2+ , its adaptability, sensitivity, and accessibility in complex media still need to be improved. For this, we introduce new ways to surmount these hurdles. First, a spherical nucleic acid (SNA) fluorescence probe (Au nanoparticles-DNAzyme probe) is utilized to specifically identify Pb 2+ and its suitability for precise detection of Pb 2+ in complex samples due to its excellent nuclease resistance. Second, the sensitivity of Pb 2+ detection is greatly enhanced via the use of a clustered regularly interspaced short palindromic repeats-Cas12a with target recognition accuracy to amplify the fluorescent signal upon the trans cleavage of the SNA (signal probe), and the limit of detection reaches as low as 86 fM. Third, we boost the fluorescence on photonic crystal chips with a bionic periodic arrangement by employing a straightforward detection device (smartphone and portable UV lamp) to achieve on-site detection of Pb 2+ with the limit of detection as low as 24 pM. Based on the abovementioned efforts, the modified Pb 2+ fluorescence sensor has the advantages of higher sensitivity, better specificity, accessibility, less sample consumption, and so forth. Moreover, it can be applied to accurately detect Pb 2+ in complex biological or environmental samples, which is of great promise for widespread applications.

Background: Exploration of serum biomarkers for early detection of upper gastrointestinal cancer is required. Here, we aimed to evaluate the diagnostic potential of serum desmoglein-2 (DSG2) in patients with esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EJA)., Methods: Serum DSG2 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 459 participants including 151 patients with ESCC, 96 with EJA, and 212 healthy controls. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy., Results: Levels of serum DSG2 were significantly higher in patients with ESCC and EJA than those in healthy controls (P<0.001). Detection of serum DSG2 demonstrated an area under the ROC curve (AUC) value of 0.724, sensitivity of 38.1%, and specificity of 84.8% for the diagnosis of ESCC in the training cohort, and AUC 0.736, sensitivity 58.2%, and specificity 84.7% in the validation cohort. For diagnosis of EJA, measurement of DSG2 provided a sensitivity of 29.2%, a specificity of 90.2%, and AUC of 0.698. Similar results were observed for the diagnosis of early-stage ESCC (AUC 0.715 and 0.722, sensitivity 36.3 and 50%, and specificity 84.8 and 84.7%, for training and validation cohorts, respectively) and early-stage EJA (AUC 0.704, sensitivity 44.4%, and specificity 86.9%). Analysis of clinical data indicated that DSG2 levels were significantly associated with patient age and histological grade in ESCC (P<0.05)., Conclusion: Serum DSG2 may be a diagnostic biomarker for ESCC and EJA., (© 2022 The Author(s).)

Background: Castration-resistant prostate cancer (CRPC) with sustained androgen receptor (AR) signaling remains a critical clinical challenge, despite androgen depletion therapy. The Jumonji C-containing histone lysine demethylase family 4 (KDM4) members, KDM4A‒KDM4C, serve as critical coactivators of AR to promote tumor growth in prostate cancer and are candidate therapeutic targets to overcome AR mutations/alterations-mediated resistance in CRPC., Methods: In this study, using a structure-based approach, we identified a natural product, myricetin, able to block the demethylation of histone 3 lysine 9 trimethylation by KDM4 members and evaluated its effects on CRPC. A structure-based screening was employed to search for a natural product that inhibited KDM4B. Inhibition kinetics of myricetin was determined. The cytotoxic effect of myricetin on various prostate cancer cells was evaluated. The combined effect of myricetin with enzalutamide, a second-generation AR inhibitor toward C4-2B, a CRPC cell line, was assessed. To improve bioavailability, myricetin encapsulated by poly lactic-co-glycolic acid (PLGA), the US food and drug administration (FDA)-approved material as drug carriers, was synthesized and its antitumor activity alone or with enzalutamide was evaluated using in vivo C4-2B xenografts., Results: Myricetin was identified as a potent α-ketoglutarate-type inhibitor that blocks the demethylation activity by KDM4s and significantly reduced the proliferation of both androgen-dependent (LNCaP) and androgen-independent CRPC (CWR22Rv1 and C4-2B). A synergistic cytotoxic effect toward C4-2B was detected for the combination of myricetin and enzalutamide. PLGA-myricetin, enzalutamide, and the combined treatment showed significantly greater antitumor activity than that of the control group in the C4-2B xenograft model. Tumor growth was significantly lower for the combination treatment than for enzalutamide or myricetin treatment alone., Conclusions: These results suggest that myricetin is a pan-KDM4 inhibitor and exhibited potent cell cytotoxicity toward CRPC cells. Importantly, the combination of PLGA-encapsulated myricetin with enzalutamide is potentially effective for CRPC., (© 2022. The Author(s).)

Based on the basic information of the Second National Pollution Source Census and the VOCs source profiles of industrial industries, we established the speciated emission inventory of major industrial sources in Chongqing in 2017, estimated their ozone formation potential (OFP), and identified the key control species of industrial VOCs and their sources. The results showed that the total VOCs emission from industrial sources and their OFPs were 144.12 kt and 477.34 kt, respectively. Automobile manufacturing, equipment manufacturing, plastic manufacturing, and chemical raw materials and chemical products were all industries that contributed significantly to VOCs emissions and OFP, with VOCs emissions of 37.18, 33.09, 19.47, and 18.14 kt and OFP of 191.43, 153.69, 27.21, and 57.51 kt, respectively. Aromatics were the components with the largest contribution to VOCs emissions and OFP, accounting for 62.55% of the total VOCs emissions and 82.15% of the total OFP, mainly from metal surface coating and petrochemical industries. The major reactive species of industrial source VOCs were m/p -xylene, toluene, ethylbenzene, o -xylene, and propylene, with OFP of 130.47, 103.37, 46.37, 42.83, and 28.26 kt, respectively, cumulatively accounting for 71.11% of the total OFP. In terms of spatial distribution, the emission intensity of VOCs and O 3 pollution degree in all districts and counties of Chongqing were relatively consistent; the high value points of VOCs emissions and OFP were mainly distributed in the main urban area and the western area, and the sources of VOCs emission in the main urban area and western area were mainly in metal surface coating and the petrochemical industry, respectively.

Esophageal squamous cell carcinoma (ESCC) is a common malignant gastrointestinal tumor threatening global human health. For patients diagnosed with ESCC, determining the prognosis is a huge challenge. Due to their important role in tumor progression, long non-coding RNAs (lncRNAs) may be putative molecular candidates in the survival prediction of ESCC patients. Here, we obtained three datasets of ESCC lncRNA expression profiles (GSE53624, GSE53622, and GSE53625) from the Gene Expression Omnibus (GEO) database. The method of statistics and machine learning including survival analysis and LASSO regression analysis were applied. We identified a six-lncRNA signature composed of AL445524.1, AC109439.2, LINC01273, AC015922.3, LINC00547, and PSPC1-AS2. Kaplan-Meier and Cox analyses were conducted, and the prognostic ability and predictive independence of the lncRNA signature were found in three ESCC datasets. In the entire set, time-dependent ROC curve analysis showed that the prediction accuracy of the lncRNA signature was remarkably greater than that of TNM stage. ROC and stratified analysis indicated that the combination of six-lncRNA signature with the TNM stage has the highest accuracy in subgrouping ESCC patients. Furthermore, experiments subsequently confirmed that one of the lncRNAs LINC01273 may play an oncogenic role in ESCC. This study suggested the six-lncRNA signature could be a valuable survival predictor for patients with ESCC and have potential to be an auxiliary biomarker of TNM stage to subdivide ESCC patients more accurately, which has important clinical significance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Li, Zhu, Zou, Fang, Cui and Xie.)

Objective: Integrins have been shown to play an important role in the tumorigenesis of many cancers. In this work, we aimed to explore the expression and clinical value of Integrin α5β1 in esophageal squamous cell carcinoma (ESCC), and the effect of integrin β1 on the development and chemo-resistance of ESCC cells. Methods: The expression profiling of integrins was analyzed in the mRNA expression dataset of ESCC. The expression of Integrin α5β1 in 278 cases of ESCC tissues and 62 cases of paracancerous tissues was detected by immunohistochemistry (IHC). The association between the expression of Integrin α5β1 and the survival of ESCC patients was analyzed by Kaplan-Meier analysis. The effect of Integrin β1 on the proliferation, migration, and invasion of ESCC cells was examined by MTS, Transwell migration, and Transwell invasion assay. The effect of Integrin β1 and L1 cell adhesion molecule (L1CAM) on cisplatin resistance was detected by MTS and the signal pathways involved were analyzed by Western blotting. Results: Integrin β1 and Integrin α5 were significantly up-regulated in ESCC. High expression of Integrin β1 was also related to worse overall survival of ESCC patients and patients with low levels of both Integrin β1 and Integrin α5 showed the shortest survival. Results of IHC revealed that Integrin α5β1 was up-regulated in ESCC and its high expression was associated with poor prognosis and could serve as an independent prognostic factor. siRNA-mediated Integrin β1 silencing or antibody blocking restrained the proliferation, migration, and invasion of ESCC cells. Simultaneous knockdown of Integrin β1 and L1CAM reduced the cisplatin resistance of ESCC cells. Further studies showed that knockdown of Integrin β1 and L1CAM suppressed the activity of Akt signaling with or without cisplatin treatment. Moreover, dual high expression of Integrin β1 and L1CAM was related to worse overall survival of ESCC patients treated with preoperative chemotherapy. Conclusion: Integrin α5β1 was up-regulated in ESCC and could be used as a new prognostic indicator for ESCC patients. In addition, Integrin β1 was involved in the proliferation, invasion, and chemo-resistance of ESCC cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Benefiting from the outstanding signal amplification effect and the admirable construction flexibility, the currently proposed DNA motors (particularly DNA walkers) based biosensing concepts have provided a forceful fluorescence imaging tool for intracellular detection. Even so, this promising sensing means is not only subject to poor controllability and prone to produce false signals but also requires exogenous powering forces owing to the common employment of DNAzyme. In response to these challenges, we are herein motivated to present some meaningful solving strategies. For one thing, the surfaces of gold nanoparticles are conducted with a photo-gated walking behavior by introducing a photocleave mode, under which the light-switchable DNA walkers are capable of being selectively activated via an external ultraviolet source to faultlessly prevent the sensing frame from being pre-initiated during cellular uptake and intracellular delivery. For another, the intracellular biothiols are consumed by MnO 2 nanosheets to effectively avoid the competitions to Au-S bonds to eliminate potential false outputs and also self-supply sufficient cofactors (Mn 2+ ) to actualize a self-powered operation pattern as well as facilitate the endocytosis process. Following these breakthroughs, a favorable analysis performance towards a model tumor biomarker (survivin mRNA) is endowed with the newly raised biosensor, whose sensitivity is low to pM level with a sound specificity for identifying single base mismatching. Moreover, the significantly improved autonomous three-dimensional DNA walkers can be used to determine and dynamically trace the targets in live cancer cells with an exceptional precise and efficient manner, commendably impelling the sensing ability of DNA motors in biological specimens., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Despite that the currently discovered CRISPR-Cas12a system is beneficial for improving the detection accuracy and design flexibility of luminescent biosensors, there are still challenges to extend target species and strengthen adaptability in complicated biological media. To conquer these obstacles, we present here some useful strategies. For the former, the limitation to nucleic acids assay is broken through by introducing a simple functional DNA regulation pathway to activate the unique trans-cleavage effect of this CRISPR system, under which the expected biosensors are capable of effectively transducing a protein (employing dual aptamers) and a metal ion (employing DNAzyme). For the latter, a time-gated luminescence resonance energy transfer imaging manner using a long-persistent nanophosphor as the energy donor is performed to completely eliminate the background interference and a nature-inspired biomimetic periodic chip constructed by photonic crystals is further combined to enhance the persistent luminescence. In line with the above efforts, the improved CRISPR-Cas12a luminescent biosensor not only exhibits a sound analysis performance toward the model targets (carcinoembryonic antigen and Na + ) but also owns a strong anti-interference feature to actualize accurate sensing in human plasma samples, offering a new and applicative analytical tool for laboratory medicine.

Alzheimer's disease (AD), known as a progressive neurodegenerative disorder, has had a terrible impact on the health of aged people. Due to its severity, early diagnosis of AD is significant to retard the progress and provide timely treatment. Here, we report a fluorescence ratio detection of AD biomarker amyloid β oligomers (AβOs) by combining highly doped upconversion nanoparticles-SiO 2 @metal-organic framework/black hole quencher (H-USM/BHQ-1) microspheres with optical tweezer (OT) microscopic imaging. Optical trapping a single microsphere not only avoids the interference of fluid viscosity but also provides a high power density laser source to efficiently stimulate upconversion luminescence (UCL) of highly doped upconversion nanoparticles (H-UCNPs). Under this condition, H-UCNPs show stronger UCL and greater power-dependent properties compared to low-doped ones. Moreover, the closely packed quenching molecules BHQ-1 on a metal-organic framework (ZIF-8) exhibit excellent quenching efficiency for upconversion 525 and 540 nm emission. Also, the luminescent resonance energy transfer efficiency reaches 89.58%. When different concentrations of AβOs are present, the UCL 540 recovers due to the decomposition of ZIF-8 and the release of BHQ-1. Using 540 and 654 nm emission ratio of highly doped UCNPs as reporters, the limit of detection reaches 28.4 pM for the quantitative determination of AβOs. Besides, this strategy is able to selectively quantify the AβO concentration. Therefore, we demonstrated the combination of optical trapping and highly doped UCNPs which is applied for the detection of AβOs with high sensitivity and specificity.

In late August 2020, a period of O 3 pollution occurred in the main urban area of Chongqing and lasted for approximately 2 weeks (till early September). Ambient air samples, collected using Summa Canisters and DNPH sampling columns at three observation sites in the main urban area, were used to study the composition, photochemical reaction activity, and source apportionment of volatile organic compounds (VOCs) during the period of O 3 pollution. The results showed that the mean volume fraction of TVOCs in the main urban area of Chongqing during the observation period was 45.08×10 -9 , and the components were ranked by volume fraction in the following order:OVOCs, alkanes, halohydrocarbons, alkenes, aromatics, and alkynes. Formaldehyde, ethylene, and acetone made up the higher volume fraction of VOCs, together accounting for more than 30% of TVOCs. OVOCs and alkenes contributed more to · OH loss rate ( L i ·OH ) and ozone formation potential (OFP) and were the key VOCs components for ozone generation. The main active species in the OVOCs component were formaldehyde, acetaldehyde, and acrolein; the main active species in the alkene component were isoprene, ethylene, and n -butene. The ratio of xylene to ethylbenzene in VOCs was low, and they showed a significant correlation, indicating that the VOCs air mass in the main urban area was highly aging and affected by long-distance transmission from other areas. The source apportionment results of the PMF model showed five main sources of VOCs, namely secondary generation (27.67%), vehicle exhaust (26.56%), industrial emission (17.86%), plant (14.51%), and fossil fuel combustion (13.4%).

Owing to their favorable design flexibility and eminent signal amplification ability, DNA nanomachine-supported biosensors have provided an attractive avenue for intracellular fluorescence imaging, especially for DNA walkers. However, this promising option not only suffers from poor controllability but also needs to be supplied with additional driving forces on account of the frequent employment of metal ion-dependent DNAzymes. Aiming at overcoming these obstacles, we introduce some fruitful solutions. On one hand, innovative light-activated walking behavior induced by a photocleavage mode is established on the surfaces of gold nanoparticles, and such a photoselective sensing system can be perfectly prevented from pre-activating during the intracellular delivery process and made to achieve target identification only under irradiation using a moderate ultraviolet light source. On the other hand, this light-switchable sensing frame is encapsulated within a dissociable metal-organic framework (ZIF-8) to facilitate endocytosis and ensure sufficient internal cofactors (Zn 2+ ) to realize a self-driven pattern in the acidic environment of the cell lysosome. Based on the abovementioned efforts, the newly constructed autonomous three-dimensional DNA walkers present satisfactory sensitivity (a limit of detection of down to 19.4 pM) and specificity (even distinguishing single-base changes) toward a model biomarker (microRNA-21). More importantly, the sensing method allows determination of the variations in targets in living cancer cells with exceptional precision and efficiency, offering a powerful assay platform for intracellular imaging.

Background: Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. The present study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor., Methods: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann-Whitney's U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups., Results: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P<0.0001). The sensitivity, specificity and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P>0.05)., Conclusion: The present study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor., (© 2021 The Author(s).)

Desmosomes are intercellular adhesion complexes involved in various aspects of epithelial pathophysiology, including tissue homeostasis, morphogenesis, and disease development. Recent studies have reported that the abnormal expression of various desmosomal components correlates with tumor progression and poor survival. In addition, desmosomes have been shown to act as a signaling platform to regulate the proliferation, invasion, migration, morphogenesis, and apoptosis of cancer cells. The occurrence and progression of head and neck cancer (HNC) is accompanied by abnormal expression of desmosomal components and loss of desmosome structure. However, the role of desmosomal components in the progression of HNC remains controversial. This review aims to provide an overview of recent developments showing the paradoxical roles of desmosomal components in tumor suppression and promotion. It offers valuable insights for HNC diagnosis and therapeutics development.

Background: Low serum L1 cell adhesion molecule (L1CAM) has been found in several malignant tumors. Here, we aimed to evaluate the diagnostic potential for serum L1CAM in patients with gastric cancers (GC) and esophagogastric junction adenocarcinoma (EJA). Methods: Enzyme-linked immunosorbent assay (ELISA) was carried out to detect L1CAM level in sera of 148 GC patients, 59 EJA patients and 148 healthy controls. Receiver operating characteristics (ROC) was employed to evaluate diagnostic accuracy. Results: The concentrations of serum L1CAM were significantly lower in GC and EJA than those in healthy controls (P<0.001). Detection of L1CAM provided a sensitivity of 83.1%, a specificity of 62.2%, and an area under the curve (AUC) of 0.769 (95% CI: 0.715-0.823) in diagnosing GC, and a sensitivity of 66.1%, a specificity of 62.2%, and an AUC of 0.672 (95% CI: 0.590-0.755) in diagnosing EJA. Similar results were observed in the diagnosis of early-stage GC (0.681 (95%CI: 0.596-0.766)) and early-stage EJA (0.674 (95%CI: 0.528-0.820)). Analysis of clinical data showed that the levels of L1CAM were significantly associated with lymph node metastasis in GC (P<0.05). Conclusions: Our study showed that serum L1CAM might be a diagnostic biomarker for GC and EJA., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The time from injury to surgery (TIS) is critical in the functional recovery of individuals with traumatic acute subdural hematoma (TASDH). However, only few studies have confirmed such notion., Methods: The data of TASDH patients who were surgically treated in Chia-Yi Christian Hospital between January 2008 and December 2015 were collected. The significance of variables, including age, sex, traumatic mechanism, coma scale, midline shift on brain computed tomography (CT) scan, and TIS, in functional recovery was assessed using the student's t-test, Mann-Whitney U test, chi-square test, univariate and multivariate models, and receiver operating characteristic (ROC) curve., Results: A total of 37 patients achieved functional recovery (outcome scale score of 4 or 5) and 33 patients had poor recovery (outcome scale score of 1-3) after at least 1 year of follow-up. No significant difference was observed in terms of age, sex, coma scale score, traumatic mechanism, or midline shift on brain CT scan between the functional and poor recovery groups. TIS was found to be significantly shorter in the functional recovery group than in the poor recovery group (145.5 ± 27.0 vs. 181.9 ± 54.5 min, P-value = 0.002). TIS was a significant factor for functional outcomes in the univariate and multivariate regression models. The analysis of TIS with the ROC curve between these two groups showed that the threshold time for functional recovery in comatose patients and those with TASDH who were surgically treated was 2 h and 57.5 min., Conclusions: TIS is an important factor l for the functional recovery of comatose TASDH patients who underwent surgery.

Objective: Colorectal cancer is one of the most important malignant cancer in the world with high incidence and mortality. Some studies have found that the expression of low serum L1 cell adhesion molecule is associated with poor prognosis in some malignancies. It is suggested that L1 cell adhesion molecule is a candidate serum marker for certain tumors. However, the relationship between serum L1 cell adhesion molecule and colorectal cancer, especially about the diagnostic value, is rarely reported. Therefore, this study aimed to evaluate the diagnostic potential of serum L1 cell adhesion molecule in patients with colorectal cancer., Methods: Enzyme-linked immunosorbent assay was carried out to detect L1 cell adhesion molecule level in sera of 229 patients with colorectal cancer and 145 normal controls. Receiver operating characteristic curves were employed to calculate the accuracy of diagnosis., Results: The levels of serum L1 cell adhesion molecule in the colorectal cancer group were significantly lower than that in normal controls ( P < .05). In the normal group, the area under the receiver operating characteristic curve (area under the curve) of all colorectal cancer was 0.781 (95% confidence interval: 0.734-0.828) and early-stage colorectal cancer was 0.764 (95% confidence interval: 0.705-0.823). With optimized cutoff of 17.760 ng/mL, L1 cell adhesion molecule showed certain diagnostic value with specificity of 90.3% and sensitivities of 43.2% and 36.2% in colorectal cancer and early-stage colorectal cancer, respectively. Clinical data analysis showed that the levels of L1 cell adhesion molecule were significantly correlated with gender ( P < .05) and early and late stages ( P < .05). Furthermore, when compared with carcinoembryonic antigen, serum L1 cell adhesion molecule had significantly improved diagnostic accuracy for both colorectal cancer and early-stage colorectal cancer., Conclusions: Our study demonstrated that serum L1 cell adhesion molecule might be served as a potential biomarker for the diagnosis of colorectal cancer.

Magnetite core/zirconia shell nanocomposite (abbreviated as Fe 3 O 4 @ZrO 2 hereafter) was obtained using one-step co-precipitation method and its performance for removal of fluoride ion from water was studied. The results showed that the Langmuir maximum adsorption capacity of fluoride ion by Fe 3 O 4 @ZrO 2 was 35.46 mg·g -1 , which was far higher than those of magnetite, activated alumina and activated carbon. Studies of adsorption kinetics indicated that the adsorption of fluoride ion by Fe 3 O 4 @ZrO 2 was fast and could be well described by the pseudo-second-order model. The adsorption process of fluoride ion was an endothermic reaction. The adsorption of fluoride ion by Fe 3 O 4 @ZrO 2 decreased with increasing pH. Chloride, nitrate and sulfate anions, which commonly coexist in drinking water, had little effect on F - adsorption, although the coexistence of HCO 3 - and CO 3 2- reduced the adsorption significantly by increasing the pH of the solution system. The fluoride adsorbed by Fe 3 O 4 @ZrO 2 could be successfully desorbed with 1 mol·L -1 NaOH solution as desorption agent. The desorption rate reached 99.5%-99.6%. The F - -desorbed Fe 3 O 4 @ZrO 2 could be reused for the removal of F - after regeneration via restoring the protonation status of surface hydroxyl groups on hydrous zirconia. The removal efficiency of fluoride by Fe 3 O 4 @ZrO 2 from actual well water was lower than that from pure water, but concentration limit for fluoride in drinking water could still be attained by increasing the dosage to a sufficiently high level. Fe 3 O 4 @ZrO 2 is a promising material for fluoride removal due to its good performance, simple preparation method and easy separation from water by providing an external magnetic field.

Objective: L1 cell adhesion molecule (L1CAM) has been found to be dysregulated in several types of human cancers. Here, we aimed to determine the level of soluble L1CAM in serum of patients with esophageal squamous cell carcinoma (ESCC)., Methods: Serum levels of L1CAM were determined by an enzyme-linked immunosorbent assay (ELISA) in 191 patients with ESCC and 94 normal controls. Receiver operating characteristics (ROC) was employed to calculate diagnostic accuracy. Cumulative survival time was calculated by the Kaplan-Meier method and analyzed by the logrank test., Results: Levels of L1CAM were significantly lower in all ESCC patients than in normal controls (P < 0.001). Detection of serum L1CAM provided a sensitivity of 28.3%, a specificity of 90.4% and an area under the curve (AUC) of 0.644 (95% CI: 0.579-0.710) in diagnosing ESCC. Similar results were observed in the diagnosis of early-stage ESCC (26.2% sensitivity, 90.4% specificity, and an AUC of 0.629). Moreover, decreased level of L1CAM was correlated with depth of tumor invasion (P < 0.05). Kaplan-Meier analysis showed that lower serum L1CAM level was significantly related to shorter overall survival time (P = 0.036) and disease-free survival time (P = 0.021) of ESCC patients., Conclusions: Our study demonstrated that serum L1CAM might serve as a potential biomarker for the diagnosis and prognosis of ESCC., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background & Aims: Long non-coding RNAs (lncRNAs) are expressed in tissue-specific pattern, but it is not clear how these are regulated. We aimed to identify squamous cell carcinoma (SCC)-specific lncRNAs and investigate mechanisms that control their expression and function., Methods: We studied expression patterns and functions of 4 SCC-specific lncRNAs. We obtained 113 esophageal SCC (ESCC) and matched non-tumor esophageal tissues from a hospital in Shantou City, China, and performed quantitative reverse transcription polymerase chain reaction assays to measure expression levels of LINC01503. We collected clinical data from patients and compared expression levels with survival times. LINC01503 was knocked down using small interfering RNAs and oligonucleotides in TE7, TE5, and KYSE510 cell lines and overexpressed in KYSE30 cells. Cells were analyzed by chromatin immunoprecipitation sequencing, luciferase reporter assays, colony formation, migration and invasion, and mass spectrometry analyses. Cells were injected into nude mice and growth of xenograft tumors was measured. LINC01503 interaction with proteins was studied using fluorescence in situ hybridization, RNA pulldown, and RNA immunoprecipitation analyses., Results: We identified a lncRNA, LINC01503, which is regulated by a super enhancer and is expressed at significantly higher levels in esophageal and head and neck SCCs than in non-tumor tissues. High levels in SCCs correlated with shorter survival times of patients. The transcription factor TP63 bound to the super enhancer at the LINC01503 locus and activated its transcription. Expression of LINC01503 in ESCC cell lines increased their proliferation, colony formation, migration, and invasion. Knockdown of LINC01503 in SCC cells reduced their proliferation, colony formation, migration, and invasion, and the growth of xenograft tumors in nude mice. Expression of LINC01503 in ESCC cell lines reduced ERK2 dephosphorylation by DUSP6, leading to activation of ERK signaling via MAPK. LINC01503 disrupted the interaction between EBP1 and the p85 subunit of PI3K, increasing AKT signaling., Conclusions: We identified an lncRNA, LINC01503, which is increased in SCC cells compared with non-tumor cells. Increased expression of LINC01503 promotes ESCC cell proliferation, migration, invasion, and growth of xenograft tumors. It might be developed as a biomarker of aggressive SCCs in patients., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Upper tract urothelial cancer (UTUC) arises from the urothelial lining of the urinary tract. UTUC spreads in several different ways including direct invasion, lymphatic spread, and hematogeneous metastases. Regional lymph nodes are commonly the initial site of metastasis, followed by the liver, lung, and bone. Brain metastasis is uncommon in patients with urothelial carcinoma. Here, we report an uncommon case of kidney urothelial carcinoma with brain metastasis in a 55-year-old woman presenting with dysarthria with right side limb weakness. The patient recovered well after resection of the brain lesion without any sequelae after 1 year of follow-up., Competing Interests: There are no conflicts of interest.

L1 cell adhesion molecule (L1CAM) is highly expressed in various types of human cancers, displaying yet unknown molecular mechanisms underlying their oncogenic potential. Here, we found that L1CAM expression was significantly increased in esophageal squamous cell carcinoma (ESCC; n = 157) lesions compared with non-cancerous tissues. High tumorous L1CAM expression significantly correlated with reduced overall survival. Experimentally, L1CAM knockdown led to decreased cell growth, migration, and invasiveness in vitro, whereas overexpression of L1CAM showed the opposite effect. In nude mice, L1CAM depletion attenuated tumorigenesis and ability to penetrate the tissues surrounding ESCC cells. Gene set enrichment analysis (GSEA) and SubpathwayMiner analysis on gene expression profiles (microarray data on ESCC tissues, GSE53625; cDNA microarray data on L1CAM-knockdown ESCC cell line, GSE86268) suggested that L1CAM-co-expression genes were related to cell motility, cell proliferation, and regulation of actin cytoskeleton, validating the above experimental findings. Further mechanistical analysis showed that L1CAM upregulated the expression of the cytoskeletal protein ezrin via activating integrin β1/MAPK/ERK/AP1 signaling and thus led to the malignant phenotypes of ESCC cells. Together, our findings suggest that L1CAM may be employed as a valuable prognosis marker and a therapeutic target for ESCC patients and that L1CAM promotes ESCC tumorigenicity by upregulating ezrin expression., Key Messages: L1CAM promotes growth and invasiveness of ESCC cells in vitro and in vivo. L1CAM upregulates the expression of ezrin by integrin α5β1/MAPK/ERK/AP1 pathway. Ezrin is a key downstream effector in the L1CAM-promoted malignant phenotypes. High expression levels of both L1CAM and ezrin significantly correlated with reduced overall survival. Nuclear L1CAM is an independent prognosis marker for esophageal squamous cell carcinoma.

A novel magnetic core/shell structured nano-particle Fe₃O₄@ SiO₂phosphor-removal ahsorbent functionalized with hydrous aluminum oxides (Fe₃O₄@ SiO₂@ Al₂O₃· nH₂O) was synthesized. Fe₃O₄@ SiO₂@ Al₂O₃· nH₂O was characterized by XRD, TEM, VSM and BET nitrogen adsorption experiment. The XRD and TEM results demonstrated the presence of the core/shell structure, with saturated magnetization and specific surface area of 56.00 emu · g⁻¹ and 47.27 m² · g⁻¹, respectively. In batch phosphor adsorption experiment, the Langmuir adsorption maximum capacity was 12.90 mg · g⁻¹ and nearly 96% phosphor could be rapidly removed within a contact time of 40 mm. Adsorption of phosphor on Fe₃O₄@ SiO₂@ Al₂O₃ · nH₂O was highly dependent on pH condition, and the favored pH range was 5-9 in which the phosphor removal rate was above 90%. In the treatment of sewage water, the recommended dosage was 1.25 kg · t⁻¹. In 5 cycles of adsorption-regeneration-desorption experiment, over 90% of the adsorbed phosphor could be desorbed with 1 mol · L⁻¹ NaOH, and Fe₃O₄@ SiO₂@ Al₂O₃· nH₂O could be reused after regeneration by pH adjustment with slightly decreased phosphor removal rate with increasing recycling number, which proved the recyclability of Fe₃O₄@ SiO₂@ Al₂O₃· nH₂O and thereby its potential in recycling of phosphor resources.

Lipocalin 2 (LCN2) is a poor prognostic factor in esophageal squamous cell carcinoma (ESCC), however its functional roles and molecular mechanisms of action remain to be clarified. Here, we described the functions and signaling pathways for LCN2 in ESCC. Overexpression of LCN2 in ESCC cells accelerated cell migration and invasion in vitro, and promoted lung metastasis in vivo. Blocking LCN2 expression inhibited its pro-oncogenic effect. Either overexpression of LCN2 or treatment with recombinant human LCN2 protein enhanced the activation of MEK/ERK pathway, which in turn increases endogenous LCN2 to increase MMP-9 activity. The decreased p-cofilin and increased p-ERM induced by pERK1/2 cause the cytoskeleton F-actin rearrangement and alter the behavior of ESCC cells mediated by LCN2. As a consequence, activation of MMP-9 and the rearrangement of F-actin throw light on the mechanisms for LCN2 in ESCC. These results imply that LCN2 promotes the migration and invasion of ESCC cells through a novel positive feedback loop., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Desmocollin‑2 (DSC2), a transmembrane glycoprotein belonging to the desmosomal cadherin family, has been found to be differentially expressed in several types of cancer and to be involved in tumor progression. The tumor metastasis suppressing property of DSC2 in esophageal squamous cell carcinoma (ESCC) has been described, however, its contribution to cell cohesion in ESCC remains to be elucidated. In the present study, using RNA interference (RNAi), the expression of DSC2 was silenced in SHEEC and KYSE510 cells. Hanging drop and fragmentation assays were performed to investigate the role of DSC2 in cell‑cell adhesion. Western blot analysis and confocal microscopy were used to analyze the expression and localization of cell adhesion molecules and cytoskeletal arrangement. The results demonstrated that DSC2 knock down by RNAi caused defects in cell‑cell adhesion and a concomitant reduction in desmosomal protein expression and adherens junction molecule distribution. A decrease in the expression of DSC2 caused an increase in free γ‑catenin levels, thus promoting its recruitment to the adherens junction complex. In addition, the RNAi‑mediated inhibition of DSC2 led to keratin intermediate filament retraction and filamentous‑actin cytoskeleton rearrangement. Taken together, these data support our previous findings and the proposal that DSC2 may be involved in the regulation of the invasive behavior of cells by a mechanism that controls cell‑cell attachment and cytoskeleton rearrangement.

Lysyl oxidase-like 2 (LOXL2) participates in every stage of cancer progression and promotes invasion and metastasis. In this study, we identified a novel alternative splicing isoform of LOXL2, namely LOXL2 Δe13, which lacked exon 13. Deletion of exon 13 caused an open reading frame shift and produced a truncated protein. LOXL2 Δe13 was expressed ubiquitously in cell lines and tissues and was mainly localized to the cytoplasm. Although it showed impaired deamination enzymatic activity compared with full-length LOXL2, LOXL2 Δe13 promoted the cell mobility and invasion of esophageal squamous cell carcinoma (ESCC) cells to greater degrees. In further research on the mechanisms, gene expression profiling and signaling pathway analysis revealed that LOXL2 Δe13 induced the expression of MAPK8 without affecting the FAK, AKT, and ERK signaling pathways. RNAi-mediated knockdown of MAPK8 could block the cell migration promoted by LOXL2De13, but it had little effect on that of full-length LOXL2. Our data suggest that LOXL2 Δe13 modulates the effects of cancer cell migration and invasion through a different mechanism from that of full-length LOXL2 and that it may play a very important role in tumor carcinogenesis and progression.

Mammalian flavin-containing monooxygenase (FMO) is active towards many drugs with a heteroatom having the properties of a soft nucleophile. Thiocarbamides and thiones are S-oxygenated to the sulfenic acid which can either react with glutathione and initiate a redox-cycle or be oxygenated a second time to the unstable sulfinic acid. In this study, we utilized LC-MS/MS to demonstrate that the oxygenation by hFMO of the thioureas under test terminated at the sulfenic acid. With thiones, hFMO catalyzed the second reaction and the sulfinic acid rapidly lost sulfite to form the corresponding imidazole. Thioureas are often pulmonary toxicants in mammals and, as previously reported by our laboratory, are excellent substrates for hFMO2. This isoform is expressed at high levels in the lung of most mammals, including non-human primates. Genotyping to date indicates that individuals of African (up to 49%) or Hispanic (2-7%) ancestry have at least one allele for functional hFMO2 in lung, but not Caucasians nor Asians. In this study the major metabolite formed by hFMO2 with thioureas from Allergan, Inc. was the sulfenic acid that reacted with glutathione. The majority of thiones were poor substrates for hFMO3, the major form in adult human liver. However, hFMO1, the major isoform expressed in infant and neonatal liver and adult kidney and intestine, readily S-oxygenated thiones under test, with Kms ranging from 7 to 160 μM and turnover numbers of 30-40 min(-1). The product formed was identified by LC-MS/MS as the imidazole. The activities of the mouse and human FMO1 and FMO3 orthologs were in good agreement with the exception of some thiones for which activity was much greater with hFMO1 than mFMO1., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Desmoglein 3 (DSG3), a transmembrane cadherin of the desmosomal cell-cell adhesion structure, plays vital roles in the maintenance of normal epithelial tissue architecture. Reports implicating a role for DSG3 expression in cancer are few and contradictory. In this study, immunohistochemical staining was employed to investigate DSG3 expression and subcellular localization in esophageal squamous cell carcinoma (ESCC), and to correlate changes with clinical characteristics. Results indicate that in normal squamous cell epithelia, strong DSG3 immunoreactivity was observed in the Stratum spinosum, and localization occurred only at the cell membrane. In ESCC, DSG3 immunoreactivity displayed an abnormal cytoplasmic localization that was correlated with cell differentiation (P=0.018). Most strikingly, in 74.1% of the tumors, DSG3 expression was up-regulated and correlated with regional lymph node metastasis (P=0.036). Moreover, in patients without lymph node metastasis, cytoplasmic localization of DSG3 correlated with poor prognosis (P=0.044). These results suggest that DSG3 is involved in the development of ESCC and imply that DSG3 overexpression is likely to be an essential contributor to the aggressive features of esophageal cancer., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Aim: To evaluate the significance of γ-catenin in clinical pathology, cellular function and signaling mechanism in esophageal squamous cell carcinoma (ESCC)., Methods: The mRNA expression of γ-catenin was detected by real-time quantitative reverse transcription-polymerase chain reaction in 95 tissue specimens and evaluated for association with the clinicopathologic characteristics and survival time of patients with ESCC. siRNAs against human γ-catenin were used to inhibit γ-catenin expression. Hanging drop aggregation assay and dispase-based dissociation assay were performed to detect the effect of γ-catenin on ESCC cell-cell adhesion. Transwell assay was performed to determine cell migration. Luciferase-based transcriptional reporter assay (TOPflash) was used to measure β-catenin-dependent transcription in cells with reduced γ-catenin expression. The expression and subcellular localizations of β-catenin and E-cadherin were examined using Western blot and immunofluorescence analysis., Results: γ-catenin mRNA expression was significantly associated with tumor histological grade (P = 0.017) in ESCC. Kaplan-Meier survival analysis showed that γ-catenin expression levels had an impact on the survival curve, with low γ-catenin indicating worse survival (P = 0.003). The multivariate Cox regression analysis demonstrated that γ-catenin was an independent prognostic factor for survival. Experimentally, silencing γ-catenin caused defects in cell-cell adhesion and a concomitant increase in cell migration in both KYSE150 and TE3 ESCC cells. Analysis of Wnt signaling revealed no activation event associated with γ-catenin expression. Total β-catenin and Triton X-100-insoluble β-catenin were significantly reduced in the γ-catenin-specific siRNA-transfected KYSE150 and TE3 cells, whereas Triton X-100-soluble β-catenin was not altered. Moreover, knocking down γ-catenin expression resulted in a significant decrease of E-cadherin and Triton X-100-insoluble desmocollin-2, along with reduced β-catenin and E-cadherin membrane localization in ESCC cells., Conclusion: γ-catenin is a tumor suppressor in ESCC and may serve as a prognostic marker. Dysregulated expression of γ-catenin may play important roles in ESCC progression.

Focal distribution of microvascular and lymphatic vessels is a critical issue in cancer, and is measured by tissue microarray (TMA) construction from paraffin-embedded surgically obtained tissues, a process that may not accurately reflect true focal distribution. The aim of this study was to assess the concordance of microvascular density (MVD) and lymphatic vessel density (LVD) in TMAs with corresponding whole sections, and to correlate the MVD or LVD with clinicopathological parameters in 124 cases of esophageal squamous cell carcinoma (ESCC). MVD, determined by CD105 immunohistochemistry of whole sections, was strongly associated with lymph node metastasis (p=0.000) and pTNM stage (p=0.001). Kaplan-Meier survival analysis showed that increasing CD105 microvessel count correlated with decreasing survival (p<0.001). The same result was acquired when MVD was calculated from tissue microarrays. Analysis of continuous data showed a highly significant correlation between whole sections and TMA data (Pearson r=0.522, p<0.001). Increasing LVD, as determined by D2-40 immunohistochemistry of whole sections, correlated with decreasing survival, but this relationship was undetectable using TMAs. In conclusion, we demonstrate that for the selected endothelial markers, TMAs can provide a realistic and reliable estimate of the extent of MVD, but not LVD in ESCC samples., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

PM2.5 was sampled from commercial, industrial and residential areas in Chongqing urban city from 2nd May to 10th May 2012 in order to find out characteristics and sources of carbon in PM2.5. Eight kinds of carbons were analyzed by the TOR method. Characteristics of carbon pollution in PM2.5 from three kinds of functional areas and six kinds of sources, including coal-combustion, exhausts (vehicle, boat and construction machine), biomass burning, cooking smoke, were analyzed. Based on carbon source profiles, local indicating components of carbon sources in PM2.5 were obtained used the chemical mass balance (CMB) model. Contribution rate of different sources to PM2.5 carbon were parsed out by factor analysis. The results showed the OC/EC of coal-combustion, vehicle exhausts, boat exhausts, construction machine exhausts, biomass burning and cooking smoke were 6.3, 3.0, 1.9, 1.4, 12.7 and 31.3, respectively. High loads of EC2 and EC3 indicated diesel vehicle exhaust emissions, high loads of OC2, OC3, OC4 and OPC indicated coal-combustion emissions, OC1, OC2, OC3, OC4 and EC1 indicated gasoline vehicle exhaust emissions, OC3 indicated cooking emissions, and OPC indicated biomass burning emissions. OC/PM2.5, EC/PM2.5, secondary organic carbon (SOC)/OC in the commercial area were 17.4%, 6.9% and 40.0%, respectively. OC/PM2.5, EC/PM2.5 and SOC/OC in the industrial area were 15.5%, 6.6% and 37.4%, respectively. OC/PM2.5, EC/PM2.5 and SOC/OC in the residential area were 14.6% 5.6% and 42.8%, respectively. In the industrial area, the main sources of carbon in PM2.5 were coal combustion, gasoline vehicle exhausts and diesel exhaust. In the commercial area, the main sources of carbon were gasoline vehicle exhausts, diesel exhausts and cooking. In the residential area, the main sources of carbon were gasoline vehicle exhausts, cooking smoke and diesel exhausts.

Objective: Desmogleins (DSGs) are major members among the desmosomal cadherins critically involved in cell-cell adhesion and the maintenance of normal tissue architecture in epithelia. Reports exploring links of DSG family member expression with cancers are few and vary. The aim of this study was to investigate the ratio of DSG2 and DSG3 mRNA expression in esophageal squamous cell carcinoma (ESCC) tissue to normal tissue (T/N ratio) and evaluate correlations with clinical parameters., Methods: The mRNA expression of DSGs, as well as γ-catenin and desmoplakin, was detected by real-time quantitative RT-PCR in 85 cases of ESCC tissue specimens., Results: The expression level of DSG3 mRNA was significantly higher than that of DSG2 in ESCC specimens (p = 0.000). DSG3 mRNA expression highly correlated with histological grade (p = 0.009), whereas that of DSG2 did not significantly relate to any clinicopathologic parameter. Kaplan-Meier survival analysis showed that only DSG3 expression had an impact on the survival curve, with negative DSG3 expression indicating worse survival (p = 0.038). Multivariate Cox regression analysis demonstrated DSG3 to be an independent prognostic factor for survival. Furthermore, correlation analysis demonstrated the mRNA level of DSG3 to highly correlate with those of γ-catenin and desmoplakin in ESCC samples (p=0.000), implying that the expression of desmosomal components might be regulated by the same upstream regulatory molecules., Conclusions: Our findings suggest that DSG3 may be involved in the progression of ESCC and serve as a prognostic marker, while expression of DSG2 cannot be used as a predictor of ESCC patient outcome.

In contrast to the well-recognized loss of adherens junctions in cancer progression, the role of desmosomal components in cancer development has not been well explored. We previously demonstrated that desmocollin-2 (DSC2), a desmosomal cadherin protein, is reduced in oesophageal squamous cell carcinoma (ESCC), and is associated with enhanced tumour metastasis and poor prognosis. Here, we report that restoration of DSC2 in ESCC cells impeded cell migration and invasion both in vitro and in vivo, whereas siRNA-mediated suppression of DSC2 expression increased cell motility. In E-cadherin-expressing ESCC cells, DSC2 restoration strengthened E-cadherin-mediated adherens junctions and promoted the localization of β-catenin at these junctions, which indirectly inhibited β-catenin-dependent transcription. These effects of DSC2 were not present in EC109 cells that lacked E-cadherin expression. ESCC patients with tumours that had reduced E-cadherin and negative DSC2 had poorer clinical outcomes than patients with tumours that lacked either E-cadherin or DSC2, implying that the invasive potential of ESCC cells was restricted by both DSC2 and E-cadherin-dependent junctions. Further studies revealed that DSC2 was a downstream target of miR-25. Enhanced miR-25 promoted ESCC cell invasiveness, whereas restoration of DSC2 abolished these effects. Collectively, our work suggests that miR-25-mediated down-regulation of DSC2 promotes ESCC cell aggressiveness through redistributing adherens junctions and activating beta-catenin signalling., (Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Purpose: Symptomatic TN accounts for up to 15% of all TN. Though there are many established "red flag" signs, it is still sometimes difficult to sift symptomatic from classic TN. We herein report two cases of isolated TN with normal neurologic examinations and then tissue proved as epidermoid cyst., Case 1: A 17-year-old girl presented with paroxysmal intense pain mixed dull background pain at right mandibular region for one month. The blink reflex demonstrated brainstem lesion and brain magnetic resonance imaging (MRI) revealed a huge lobulated tumor in right cerebellopontine angle (CPA) with obvious brainstem compression. Her right facial pain was nearly completely disappeared postoperatively., Case 2: The 48-year-old woman had chronic paroxysmal electric-like and burning pain in left V3 region for more than 5 years. Because of refractory pain, brain MRI was arranged and showed a non-enhancing cystic lesion at left CPA. Post operative complications occurred as left multiple lower cranial nerve palsies and Horner syndrome, and truncal ataxia. Her facial pain was completely free after 1 month follow up., Conclusion: In the first patient, teenage onset, abnormal trigeminal reflex, and early developing background pain struck us directly to symptomatic TN. In the second case, we suspected symptomatic TN with uncertainty before image study. TN could be the isolated initial symptom of CPA epidermoid cysts. In consideration about pretty high prevalence of symptomatic TN, physicians should be more alert and straightforward arrange neuroimage when facing TN patients with atypical presentation.

Computer-assisted neuronavigation (an image-guided technique that facilitates brain tumor surgery) reduces the risk of neurological morbidity. Postoperative neurological dysfunction is also minimized by performing intraoperative neurological testing during awake craniotomy with proper surgical resection of a brain tumor. However, when the patient's airway is not secured, an awake craniotomy can be hazardous if emergent intubation is necessary. The present report describes a young man with a brain tumor who underwent neuronavigation-guided wake-up craniotomy and surgical resection of an astrocytoma. The patient was intubated throughout the course of the procedure, during which modified intraoperative neurological tests were performed for cortical mapping. The patient recovered well after the operation and without any neurological deficits., (Copyright © 2013. Published by Elsevier B.V.)

Background Context: Lumbar intradural arachnoid cyst (AC) concomitant with hyperacute spinal subdural hematoma (SSDH) has never been reported in the literature., Purpose: To report a case of lumbar AC superimposed by hyperacute SSDH, which was difficult to diagnose preoperatively using magnetic resonance imaging. Herein, we describe diagrams showing the proposed mechanisms underlying the formation of a symptomatic AC., Study Design/setting: The study was designed to be a case report and literature review., Methods: A 65-year-old man presented with acute onset of low back pain, followed by 5-day history of numbness and weakness in both legs before admission. Magnetic resonance imaging of the lumbosacral spine revealed an intradural extramedullary biconvex lesion at the L3-L4 level; the lesion compressed the cauda equina posteriorly. The lesion mainly appeared as hyperintense on T2-weighted images and hypointense on T1-weighted images. On the basis of these findings, the lesion was preoperatively diagnosed as a symptomatic lumbar subdural AC that compressed the cauda equina., Results: The patient underwent laminectomy from L2 to L4. After a dura incision, a partially organized subdural hematoma was noted. Beneath the subdural hematoma was an AC compressing the underlying nerve roots. The patient's back pain and muscle strength markedly improved after the operation., Conclusions: Preoperative diagnosis of concomitant hyperacute SSDH and AC is difficult. In cases of patients who present with intraspinal AC accompanied by an acute onset of clinical presentation, an associated etiology should be considered until proven otherwise., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The earthworm, which has stasis removal and wound-healing functions, is a widely used Chinese herbal medicine in China. Schwann cell migration is critical for the regeneration of injured nerves. Schwann cells provide an essentially supportive activity for neuron regeneration. However, the molecular migration mechanisms induced by earthworms in Schwann cells remain unclear. Here, we investigate the roles of MAPK (ERK1/2, JNK and p38) pathways for earthworm-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in Schwann cells. Moreover, earthworm induced phosphorylation of ERK1/2 and p38, but not JNK, activate the downstream signaling expression of PAs and MMPs in a time-dependent manner. Earthworm-stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with U0126 and SB203580, resulting in migration and uPA-related signal pathway inhibition. The results were confirmed using small interfering ERK1/2 and p38 RNA. These results demonstrated that earthworms can stimulate Schwann cell migration and up-regulate PAs and MMP2/9 expression mediated through the MAPK pathways, ERK1/2 and p38. Taken together, our data suggests the MAPKs (ERK1/2, p38)-, PAs (uPA, tPA)-, MMP (MMP2, MMP9) signaling pathway of Schwann cells regulated by earthworms might play a major role in Schwann cell migration and nerve regeneration.

Desmocollin 2, a desmosomal component, is a key membrane glycoprotein critically involved in cell-cell adhesion and the maintenance of normal tissue architectures in epithelia. Reports exploring the link of desmocollin expression to cancers are limited. The aim of this study was to investigate the expression of desmocollin 2 in esophageal squamous cell carcinoma and, in particular, to determine the extent to which the patterns of desmocollin 2 expression correlated with the clinical parameters. Desmocollin 2 expression was evaluated in 308 cases of esophageal squamous cell carcinoma using immunohistochemistry. Western blotting and reverse transcriptase polymerase chain reaction were performed to characterize the relative expression levels of desmocollin 2 isoforms. The results indicated that desmocollin 2 expression was reduced significantly in esophageal cancer in both protein and messenger RNA levels and that this reduction was associated with poor survival (P = .011). The expression of desmocollin 2 was prominent in normal esophageal epithelia and highly differentiated esophageal tumors, but was reduced or absent in poorly differentiated tumor specimens. Furthermore, in 74.7% of tumor tissues, desmocollin 2 immunoreactivity displayed an abnormal cytoplasmic localization that was correlated with poor tumor differentiation (P < .001), regional lymph node metastasis (P < .001), pathologic tumor-node-metastasis stages (P < .001), and poor prognosis (P = .048). Multivariate analysis showed that desmocollin 2 expression level was an independent prognostic factor for esophageal squamous cell carcinoma. These data suggest that desmocollin 2 is involved in the transformation and development of esophageal tumors and that desmocollin 2 expression level and intracellular localization may serve as a predictor for patient outcomes., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The aim of the study was to evaluate the proliferative effects of chishao on neuron regeneration. A silicone rubber nerve guide across a 15-mm gap was filled with different concentrations of chishao (0-125 mg/ml) in the dissected sciatic nerve of the right leg in SD rats. The left legs were used as control. After eight weeks, the regenerated nerves showed dose-dependently activated fibroblast growth factor-2 (FGF-2) signaling with increased urokinase plasminogen activator (uPA), decreased plasminogen activator inhibitor-1 (PAI-1) and enhanced proliferative proteins, extracellular signal regulated kinase (ERK)- and c-Jun N-terminal kinase (JNK)-signalings. The results imply that applying an appropriate dose of chishao would be a potential approach for enhancing neuron regeneration.

Spinal osteomyelitis with epidural abscess is a rare disease. Most patients have 1 or more predisposing factors, such as impaired immune system secondary to diabetes mellitus, chemotherapy for cancer, immunological compromised disease, and chronic renal or hepatic impairment. We present a case of a physically steady young man without any predisposing risk factor who suffered from cervical osteomyelitis with epidural abscess after neck blunt injury. This patient recovered well after one-stage anterior surgical debridement with implant instrumentation and proper antibiotics treatment. The initial accurate diagnosis rate of spinal epidural abscess is low, even in patients with predisposing factor(s). We present this case to raise the attention of medical staff to this disease in patients with or without any predisposing factor(s) in order to establish early diagnosis and treatment. Our case report also indicates that with adequate debridement and antibiotic coverage, one-stage surgery is a safe and efficacious method to treat patients with cervical spinal epidural abscess.

This study evaluated the proliferation effects of huangqi on neuron regeneration. We investigated the molecular mechanisms, which include: (1) cyclin D1, A, E-cell cycle factors and MAPK signaling proliferation (2) FGF-2-UPA-MMPs migration signaling. After treatment with various Huanqi concentrations (1.25, 12.5, 125, 250 and 500 microg/ml,), we observed that Huanqi can increase Rsc 96 cell proliferation at 12.5 microg/ml (p < 0.01) concentration determined by the MTT and wound healing tests. Examination by RT-PCR and Western blotting assay showed that Huangqi is able to stimulate the mRNA and protein expressions of cyclin D1, A, E, cell cycle controlling proteins and excite ERK and P38 MAPK signaling pathways to promote cell proliferation. Huangqi stimulates the FGF-2-UPA-MMP 9 migration pathway and enhances RSC 96 Schwann cells migration. Using MAPK chemical inhibitors, U0126, SB203580 and SP600125, the proliferative effects of Huangqi on RSC 96 cells were ERK and P38 signaling-dependent. Based on these results, applying an appropriate dose of Huangqi with biomedical materials would be a potential approach to enhancing neuron regeneration.

Purpose: Neutrophil gelatinase-associated lipocalin receptor (NGALR) mRNA level is reduced in isolated chronic myelogenous leukemia blasts but up-regulated in esophageal squamous cell carcinoma (ESCC). The mechanism of NGALR regulation is unknown. Here, we show the expression pattern of NGALR and examine the aberrant methylation of its gene in ESCC and esophageal carcinoma cell lines., Experimental Design: The expression pattern of NGALR was analyzed by immunohistochemistry in 59 ESCCs and compared with noncancerous tissues. The DNA methylation status was investigated by methylation-specific PCR and by bisulfite genomic sequencing in esophageal carcinoma cell lines and surgically resected samples. Methylated cell lines were treated with a methylation inhibitor to restore NGALR expression., Results: The expression of NGALR in ESCC was significantly higher in tumor cell membrane and cytoplasm than in normal esophageal epithelium (P < 0.01). Methylated alleles were detected in three NGALR-nonexpressing cell lines but were not detected in three NGALR-expressing cell lines. Treatment of methylated cell lines with 5-aza-2'-deoxycytidine, a methylation inhibitor, restored NGALR expression. In surgically resected samples, 31 of 77 (40.3%) primary esophageal carcinomas and 46 of 77 (59.7%) paired normal tissues contained methylated NGALR alleles (P < 0.05)., Conclusions: Our results suggest that NGALR hypomethylation contributes to its expression in esophageal carcinomas and that this overexpression may play a role in the pathogenesis of esophageal carcinomas.