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Abstract Background Thyroid cancer (TC) is the most common endocrine malignancy; basigin (also known as BSG) plays a crucial role in tumor cell invasion, metastasis, and angiogenesis. This study was designed to identify the change of BSG expression in TC and its possible potential mechanism. Methods The BSG expression levels in TC were demonstrated using data collected from in-house immunohistochemical (IHC), RNA-sequencing (RNA-seq), microarrays, and literatures. Integrated analysis was performed to determined BSG expression levels in TC comprehensively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the integration of BSG co-expressed genes and differentially expressed genes (DEGs) in TC tissues to explore the potential mechanisms of BSG in TC. Results The protein expression level of BSG was significantly higher in TC cases based on the IHC experiments. In addition, the combined SMD for BSG expression was 0.39 (p < 0.0001), the diagnostic odds ratio was 3.69, and the AUC of the sROC curve was 0.6986 using 1182 TC cases and 437 non-cancerous cases from 17 independent datasets. Furthermore, BSG co-expressed genes tended to be enriched in gene terms of the extracellular matrix (ECM), cell adhesion, and cell-cell interactions. The expression levels of nine hub BSG co-expressed genes were markedly upregulated in TC cases. Conclusion BSG expression levels were closely correlated with the progression of TC and may affect the signals of the ECM, cell adhesion, and cell-cell interactions.

Abstract Background The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. Methods Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. Results COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55–1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76–0.83) with sensitivity of 0.77 (95% CI 0.69–0.83) and specificity of 0.70 (95% CI 0.61–0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. Conclusions Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.

BACKGROUND At present, iodine content in edible salt and kelp products is mainly determined as the form of total iodine content, but the speciation analysis of inorganic iodine and organic iodine mainly relies on the hyphenated techniques of large-scale instruments. OBJECTIVES To establish the determination method of iodine content in edible salt and kelp as well as the digestion method for the organic iodine in the closed PTFE bomb. METHODS Rapid determination of inorganic and organic iodine content in edible salt and kelp products by using crystal membrane electrode technique with a solid-state and no internal reference liquid crystal film electrode (Z-Ⅱ iodine probe) developed by silver sulfide iodide method, combined with PTFE bomb microwave digestion technique. RESULTS Table salt contained 20mg/kg of inorganic iodine, and 2mg/kg of organic iodine. The concentration of organic iodine was 2.9×103mg/kg in kelp. The linear correlation of inorganic and organic iodine contents in the range of 10-100mg/kg was good. The standard-addition recoveries were 97.1%-101.0%, and the detection limit was up to 1mg/kg. This method was applied to the determination of iodine content in actual edible salt and kelp on the market, the relative standard deviation of inorganic and organic iodine in the samples was less than 0.92% and 4.20%, respectively. The analytical results were in agreement with those of the national standard method and ultraviolet spectrophotometry method, which indicated that the established method was reliable. CONCLUSIONS The analytical method has the advantages of low reagent consumption, low cost and convenient operation, which can be used for the determination of inorganic and organic iodine contents.

Nickel salts of Keggin-type heteropolyacid on Zr(IV)-based metal-organic frameworks (UiO-66) has been synthesized via ion-exchange followed by a facile one-pot hydrothermal method. The synthesized catalysts underwent FT-IR, N2 adsorption-desorption, powder XRD, SEM and TEM analysis. The NiHSiW/UiO-66 catalyst was used as a new and effective solid acid in the catalytic transfer free fatty acid to biodiesel with an optimum conversion of 86.7%. The excellent activity of the NiHSiW/UiO-66 nanocatalyst was closely related to its high specific surface area, nano-sized catalyst, and the synergistic effects of NiHSiW salts and UiO-66 matrix. Importantly, a relatively stable catalytic performance was achieved for 8 repeated cycles. Finally, kinetics of the esterification reaction have been assumed to be of pseudo first order.

BACKGROUND The eutrophication level in water is related to the phosphorus species in porewater and sediment closely. At present, as the one of the eutrophic elements, the vertical distribution characteristics of phosphorus species, the transfer and transformation behavior among phosphorus species and its influencing factors have made clear research progress. OBJECTIVES In order to further reveal the temporal and spatial characteristics of the transfer and transformation of different forms of phosphorus in porewaters and sediments, and assess the ecological restoration in the area by analyzing the soluble reactive phosphorus (SRP), soluble unreactive phosphorus (SUP) and total dissolved phosphorus (TDP) in porewaters, and by analyzing total inorganic phosphorus (TIP), total phosphorus (TP), residual phosphorus (Res-P), exchangeable phosphorus (Exc-P), Fe-bound phosphorus(Fe-P), Al-bound phosphorus (Al-P) and Ca-bound phosphorus (Ca-P) in sediments in Jianyang section of Tuojiang River. And the results were compared with the records of phosphorus species in the same place ten years ago to discuss the change trend and influencing factors of phosphorus occurrence. METHODS SRP, SUP and TDP in porewaters were determined by phosphomolybdate blue spectrophotometry. TIP, TP, Res-P, Exc-P, Fe-P, Al-P and Ca-P in sediments were extracted by SMT method and the improved sequential extraction method. The concentration of the phosphorus species were determined by phosphomolybdate blue spectrophotometry. RESULTS The content of SRP, SUP and TDP in porewaters ranged from 0.004 to 0.36mg/L, 0.080 to 3.19mg/L and 0.056 to 3.28mg/L, respectively. The content of TP, TIP, Res-P, Exc-P, Al-P and Ca-P in sediment ranged from 1235.40 to 1646.94mg/kg, 860.00 to 1318.59mg/kg, 130.31 to 537.13mg/kg, 1.35 to 14.10mg/kg, 0.007 to 0.12mg/kg and 743.13 to 1109.91mg/kg, respectively. However, Fe-P in the sediment samples were not detected. Compared with the results of phosphorus species in sediment-water system ten years ago, it was found that although the content of SRP, SUP and TDP in porewaters were not significantly changed above -10cm, but they increased below -10cm due to the influence of exogenous phosphorus input, which also led to the increase of TP and TIP in sediments. The weak alkaline environment resulted in the release of Al-P, and the decrease of Exc-P was related to its transformation into stable forms of Ca-P or Res-P. CONCLUSIONS The sediment in Jianyang section of Tuojiang River presents the comprehensive pollution of exogenous input and endogenous release. Generally speaking, because most of the input phosphorus exist in the forms of stable Ca-P and Res-P in sediments finally, the part of phosphorus which can be directly used by organisms in the sediment-water interface has little changed. So the eutrophication degree in this area has not increased with the change of time and space. To maintain the weak alkalinity of the sedimentary environment is conducive to the effective conversion of Al-P and Exc-P to Ca-P, and to inhibit the river eutrophication.

Fluctuation ('noise') in gene expression is critical for mammalian cellular processes. Numerous mechanisms contribute to its origins, yet the mechanisms behind large fluctuations that are induced by single transcriptional activators remain elusive. Here, we probed putative mechanisms by studying the dynamic regulation of transcriptional activator binding, histone regulator inhibitors, chromatin accessibility, and levels of mRNAs and proteins in single cells. Using a light-induced expression system, we showed that the transcriptional activator could form an interplay with dual functional co-activator/histone acetyltransferases CBP/p300. This interplay resulted in substantial heterogeneity in H3K27ac, chromatin accessibility, and transcription. Simultaneous attenuation of CBP/p300 and HDAC4/5 reduced heterogeneity in the expression of endogenous genes, suggesting that this mechanism is universal. We further found that the noise was reduced by pulse-wide modulation of transcriptional activator binding possibly as a result of alternating the epigenetic states. Our findings suggest a mechanism for the modulation of noise in synthetic and endogenous gene expression systems.

Ketoacidosis is one of the common diseases that sometimes result in death. In forensic autopsy cases, the measuring of ketone bodies, especially β-hydroxybutyrate (BHB), is useful in diagnosing postmortem ketoacidosis as a cause of death. However, increased BHB values are not always indicative of ketoacidosis. Other causes of death, such as hypothermia, are known to increase BHB values. In addition, sometimes, we experience cases of increased BHB values that are unlikely to be associated with the pathophysiology or the cause of death resulting in an increase in BHB values. In this study, autopsies were performed to determine the relationship between blood BHB values and the postmortem interval (PMI). The patients were divided into four groups: PMI ≤ 24 h, PMI ≤ 48 h, PMI ≤ 72 h, and PMI > 72 h. The BHB values for each group were then compared. Based on the analysis, patients with a PMI ≤ 72 h and those with a PMI > 72 h had significantly higher BHB values than patients with a PMI ≤ 24 h. In conclusion, there remains a possibility that the BHB values increase after death. Forensic pathologists should consider PMI when diagnosing ketoacidosis as the cause of death.

OBJECTIVE: SUMOylation plays critical roles in a variety of physiological and pathological processes including tumorigenesis. SUMOylation is a reversible process which is mediated by the SENP (Sentrin/SUMO-specific protease) family to remove SUMO from conjugated substrates. SENP5 has been reported to play critical roles in the control of several cancers including breast cancer, osteosarcoma and oral squamous cell carcinoma. In this study, we uncovered a role of SENP5 in promoting tumorigenesis process in hepatocellular carcinoma (HCC) via regulating DNA damage response. MATERIALS AND METHODS: The mRNA and protein levels of SENP5 in 10 pairs of HCC samples were determined by Realtime PCR and Western blot, respectively. SiRNAs were used to silence the expression of SENP5 in HepG2 cells. Male BALB/c nude mice were used to determine the roles of SENP5 on tumorigenesis. In vivo SUMOylation assay was used to detect the SUMOylation of ATRIP. Immunoprecipitation (IP) was used to detect the interaction between SENP5 and ATRIP. RESULTS: We found that SENP5 was over-expressed in HCC samples and required for HCC cells proliferation both in vitro and in vivo. SENP5-depleted HepG2 cells exhibited hypersensitivity to IR and etoposide treatment with defective checkpoint activation including decreased activation of ATR and phosphorylation of ATR targets. At the molecular level, we found that SENP5 interacted with ATRIP and promoted ATRIP deSUMOylation. CONCLUSIONS: Overall, our data suggest that SENP5 is required for HCC cell growth and might be a promising drug target for HCC. [ABSTRACT FROM AUTHOR]

Solid-solution phase K(Mn,Zn)F3 mesoporous microspheres have been successfully prepared via a simple one-pot hydrothermal method by using citrate ions as a chelating agent. Effects of the reaction time on the phase transformation and morphological evolution of the K(Mn,Zn)F3 microspheres have been carefully investigated. The results revealed that the hierarchical mesoporous spherical structures with a solid-solution phase were formed from a core–shell structure with mixed phases via the nanoscale Kirkendall effect. It is noted that Yb3+/Er3+-codoped K(Mn,Zn)F3 microspheres exhibit intense single-band red up-conversion emission with environmental responsivity upon excitation using a 980 nm laser diode, indicating a promising potential biomedical application for drug delivery. [ABSTRACT FROM AUTHOR]

Hong-qing Zhou,1,* Ming-sheng Liu,1,* Ti-bin Deng,1 Ping-bo Xie,1 Wei Wang,1 Tao Shao,1 Yao Wu,1 Peng Zhang2 1Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Qujing City 655000, Yunnan Province, People’s Republic of China; 2Department of Urology, State Key Laboratory of Kidney Diseases, Chinese People’s Liberation Army (PLA) General Hospital/Chinese PLA Medical Academy, Beijing 100853, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming-sheng LiuSecond Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Huayuan Road, Qilin District, Qujing City 655000, Yunnan Province, People’s Republic of ChinaTel +86 874 3326975Fax +86 874 3311977Email 18908741981@189.cnPeng ZhangDepartment of Urology, State Key Laboratory of Kidney Diseases, Chinese People’s Liberation Army (PLA) General Hospital/Chinese PLA Medical Academy, No. 28 Fuxing Road, Haidian District, Beijing City 100853, People’s Republic of ChinaTel +86 10 6693 8008Fax +86 10 6693 8008Email alwaysjumper@126.comBackground: Despite progress achieved in bladder cancer (BC) treatment, the prognosis of patients with advanced BC (ie, metastasized from the bladder to other organs) is poor. Although mortality in cases of low-grade BC is rare, the treatment, such as a radical cystectomy, often has a serious impact on the quality of life. Thus, research is needed to identify more effective treatment strategies and this work is aiming to examine the potential application of combination of radiofrequency ablation (RFA) and SB435142, a inhibitor of transforming growth factor β (TGFβ)/Smad pathway.Methods: BC cells were transplanted into nude mice (thymusdeficiency Bal B/c) to form subcutaneous tumors. The mice with subcutaneous tumors were then treated with RFA and oral administration of SB431542, an inhibitor of TGFβ/Smad signaling pathway. The antitumor effect of RFA was measured by tumor proliferation curves and micro-positron emission computed tomography (micro-PET). The effect of SB431542 on epithelial–mesenchymal transition (EMT) related regulators in subcutaneous tumor tissues formed by BC cells were examined by quantitative real-time polymerase chain reaction (qPCR) experiments.Results: The SB431542 treatment enhanced the antitumor effect of RFA on subcutaneous growth of BCs. SB431542 also decreased EMT-related regulators in subcutaneous tumor tissues formed by BC cells in nude mice.Conclusion: SB431542 enhances the effect of RFA on BC.Keywords: bladder cancer, radiofrequency ablation, SB431542, epithelial–mesenchymal transition

With the rapid development of communication and chip technology, IoT will be an important part of the next generation of information technology, a powerful driving force to promote the intelligent process of our lives. Among the IoT terminal applications, ultra-low-power microcontroller plays an indispensable role. Based on the design goal of ultra-low-power embedded applications, this paper proposes a pipeline structure of a processor based on RISC-V instruction set architecture. Taking into account the compromise between power consumption and performance, the main body uses a two-stage pipeline, and was supplemented by a pipeline structure with variable length of other components. The logic function of the microcontroller is verified in the VCS environment. At the same time, the area ratio report of the microcontroller is obtained by using the SMIC180 process library to complete the simulation in the DC environment. Finally, by running the running subroutine test and comparing it with the ARM Cortex-M microcontroller, the comparison results show that this work can also be applied to the low-power scene of IoT.

Sensitive solar-blind ultraviolet (UV) photodetectors are important to various military and civilian applications, such as flame sensors, missile interception, biological analysis, and UV radiation monitoring below the ozone hole. In this paper, a solar-blind UV photodetector based on a buried-gate graphene field-effect transistor (GFET) decorated with titanium dioxide (TiO2) nanoparticles (NPs) was demonstrated. Under the illumination of a 325-nm laser (spot size ~2 μm) with a total power of 0.35 μW, a photoresponsivity as high as 118.3 A/W was obtained, at the conditions of zero gate bias and a source-drain bias voltage of 0.2 V. This photoresponsivity is over 600 times higher than that of a recently reported solar-blind UV photodetector based on graphene/vertical Ga2O3 nanowire array heterojunction (0.185 A/W). Experiments showed that the photoresponsivity of the TiO2 NPs decorated GFET photodetectors can be further enhanced by increasing the source-drain bias voltage or properly tuning the gate bias voltage. Furthermore, the photoresponse time of the TiO2 NPs decorated GFET photodetectors can also be tuned by the source-drain bias and gate bias. This study paves a simple and feasible way to fabricate highly sensitive, cost-efficient, and integrable solar-blind UV photodetectors.

Exchange records of terrestrial mammals can be combined with available tectonic and climatic documents to evaluate major biological and environmental events. Previous studies identified four carnivoran dispersals between Eurasia and North America in the Neogene, namely, at ~ 20, 13-11, 8-7, and ~ 4Ma. In order to evaluate driving mechanism of these biological events, we collected, compared and analyzed a large number of published records. The results indicate that the carnivoran dispersal from Eurasia to North America at ~ 20Ma was probably caused by intense tectonic movements in Asia. During 13-11 Ma, global cooling possibly drove the mammal exchanges between Eurasia and North America. By comparison, the carnivoran dispersal from Eurasia to North America at 8-7Ma was probably caused by the combination of global cooling and tectonic movements of the Tibetan Plateau. Similar to during 13-11 Ma, the carnivoran exchanges between Eurasia and North America at ~ 4Ma were possibly driven by global cooling. [ABSTRACT FROM AUTHOR]

Guangzhou, one of China's megacities, is beset with frequent occurrence of high-concentration ozone events. In this study, online instruments were used to simultaneously monitor ozone, nitrogen oxides (NOx) and volatile organic compounds (VOCs) at GPACS (the Guangzhou Panyu Atmospheric Composition Station) of the China Meteorological Administration, from June 2011 to May 2012, in order to determine their characteristics, the effect of VOCs on ozone photochemical production and the relationship between VOC=NOx ratio and ozone formation. The results showed that during the observation period, the seasonal variation of ozone concentration was lower in spring and winter compared to summer and autumn, which is opposite that for VOCs and NOx. In terms of VOCs, aromatics had the largest ozone formation potential, among which toluene, xylenes, ethylbenzene, 1,2,4-trimethylbenzene and 1,3,5- trimethylbenzene were the most important species, with a total contribution of about 44%. As the VOC=NOx ratios were very high during high-concentration ozone events that occur all year round, we speculate ozone production was likely to be NOx-limited regime (12:00-16:00 LT) in Guangzhou. Further investigation based on numerical models is needed in the future to obtain more detailed and robust conclusions. [ABSTRACT FROM AUTHOR]

In this study, online monitoring instruments were used to monitor ozone, NOx and VOCs at the Guangzhou Panyu Atmospheric Composition Station (GPACS) of the China Meteorological Administration from June 2011 to May 2012, so as to obtain their characteristic seasonal and diurnal variations, as well as the impacts of NOx and VOCs on local ozone formation and Guangzhou ozone control strategies. The results show that during the observation period the seasonal variation of ozone concentration was lower in the spring and winter and higher in the summer and autumn, which is contrary that of NOx and VOCs. At around 09:00 LT in the summer, autumn and winter, both the ozone concentration and NO2/NO ratio begin to increase, and the NO2/NO ratio reached its maximum after a peak of ozone concentration, but this variation was not particularly evident in the spring. Aromatics and alkenes are the largest components for ozone formation potential, among which aromatic toluene, m-xylene, p-xylene and 1,3,5-trimethylbenzene are the most important components, with a total contribution of about 31.6% to ozone formation potential. Through the analysis on local ozone control by the VOC/NOX ratio, it was found that when the ozone concentration reached a peak in the summer and autumn in which high concentrations of ozone were prone to occur, ozone generation was NOx limited, thus NOx emissions must be controlled to regulate the occurrence of high-concentration ozone events. In the spring and winter, ozone generation was always VOCs controlled. Due to the relatively low ozone concentration, although NOx emissions could be controlled to increase ozone concentration, high-concentration ozone events would not occur. Therefore, for the control of ozone in Guangzhou, in addition to the control of VOCs emissions, more attention must be paid to reducing NOx emissions, so as to achieve the purpose of controlling high-concentration ozone. [ABSTRACT FROM AUTHOR]

Background:Syndecan-1 (Sdc-1) shedding induced by matrix metalloproteinase-7 (MMP-7) and additional proteases has an important role in cancer development. However, the impact of Sdc-1 shedding on chemotherapeutic resistance has not been reported.Methods:We examined Sdc-1 shedding in colorectal cancer by enzyme-linked immunosorbent assay (ELISA), Dot blot, reverse transcription-PCR (RT-PCR), immunohistochemistry and so on, its impact on chemotherapeutic sensitivity by collagen gel droplet embedded culture-drug sensitivity test (CD-DST) and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), and potential mechanisms of action by Dot blot, western blot and immunofluorescence.Results:Sdc-1 shedding was increased in colorectal cancer patients, Sdc-1 serum levels in postoperative patients were lower than in preoperative patients, but still higher than those observed in healthy adults. Patients with high preoperative Sdc-1 serum levels were less responsive to 5-Fluorouracil, Oxaliplatin, Irintecan, Cisplatin or Paclitaxel chemotherapy. Moreover, the disease-free survival of patients with high preoperative Sdc-1 serum levels was significantly poorer. The possible mechanism of chemotherapy resistance in colorectal cancer can be attributed to Sdc-1 shedding, which enhances EGFR phosphorylation and downstream signalling.Conclusions:Shed Sdc-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer, and Sdc-1 serum levels could be a new prognostic marker in colorectal cancer. [ABSTRACT FROM AUTHOR]