BCAR4 facilitates trastuzumab resistance and EMT in breast cancer via sponging miR-665 and interacting with YAP1.

Breast cancer antiestrogen resistance 4 (BCAR4) has been suggested that can modulate cell behavior, resulting in tumorigenesis and chemoresistance. However, the underlying mechanisms of BCAR4 in trastuzumab resistance (TR) is still elusive. Here, we explored the function and the underlying mechanism of BCAR4 involving in TR. We found that BCAR4 is significantly upregulated in trastuzumab-resistant BC cells. Knockdown of BCAR4 could sensitize the BC cells to trastuzumab and suppress epithelial-mesenchymal transition (EMT). Mechanically, BCAR4 promotes yes-associated protein 1 (YAP1) expression by competitively sponging miR-665, to activated TGF-ß signaling. Reciprocally, YAP1 could occupy the BCAR4 promoter to enhance its transcription, suggesting that there exists a positive feedback regulation between YAP1 and BCAR4. Targeting the BCAR4/miR-665/YAP1 axis may provide a novel insight of therapeutic approaches for TR in BC.

Metabolic adaptation to high-starch diet in largemouth bass (Micropterus salmoides) was associated with the restoration of metabolic functions via inflammation, bile acid synthesis and energy metabolism.

A short-term 2-week (2w) and long-term 8-week (8w) feeding trial was conducted to investigate the effects of low-starch (LS) and high-starch (HS) diets on the growth performance, metabolism and liver health of largemouth bass (Micropterus salmoides). Two isonitrogenous and isolipidic diets containing two levels of starch (LS, 9·06 %; HS, 13·56 %) were fed to largemouth bass. The results indicated that HS diet had no significant effects on specific growth rate during 2w, whereas significantly lowered specific growth rate at 8w. HS diet significantly increased hepatic glycolysis and gluconeogenesis at postprandial 24 h in 2w. The hepatosomatic index, plasma alkaline phosphatase, total bile acid (TBA) levels, and hepatic glycogen, TAG, total cholesterol, TBA, and NEFA contents were significantly increased in the HS group at 2w. Moreover, HS diet up-regulated fatty acid and TAG synthesis-related genes and down-regulated TAG hydrolysis and ß-oxidation-related genes. Therefore, the glucolipid metabolism disorders resulted in metabolic liver disease induced by HS diet at 2w. However, the up-regulation of bile acid synthesis, inflammation and energy metabolism-related genes in 2w indicated that largemouth bass was still in a state of 'self-repair' response. Interestingly, all the metabolic parameters were returned to homoeostasis, with up-regulation of intestinal glucose uptake and transport-related genes, even hepatic histopathological analysis showed no obvious abnormality in the HS group in 8w. In conclusion, HS feed induced short-term acute metabolic disorder, but long-term metabolic adaptation to HS diet was related to repairing metabolism disorders via improving inflammatory responses, bile acid synthesis and energy metabolism. These results strongly indicated that the largemouth bass owned certain adaptability to HS diet.

Pulses outweigh cumulative effects of water diversion from river to lake on lacustrine phytoplankton communities.

Due to the allochthonous input of nutrients and species, the cumulative effects of water diversion on water-receiving lakes deserve attention. Taking the water diversion project from the Yangtze River to Lake Taihu (WDYT) as an example, we explored the temporal effects of WDYT on the phytoplankton community and physicochemical habitat of Lake Taihu in autumn and winter from 2013 to 2018. Although the short-term diversion significantly increased the risk of importing nutrients, the relatively high quality of the diversion water compared with other inflow rivers had improved the water quality of the water-receiving lake region. The seasonal water diversion significantly increased phytoplankton diversity and community network complexity and reshaped the lacustrine community to be diatom-dominated with their relative proportions of 24.1-64.9% during water diversion periods. The contributions of physicochemical habitat changes induced by water diversion to variations in phytoplankton communities were 24.0-28.0%. The differences in phytoplankton diversity, community composition and physicochemical habitat in the water-receiving lake region between the diversion and non-diversion years were more evident than those between the non-diversion years in the same season, when comparing the multivariate dispersion indices among them. However, the lacustrine phytoplankton community during non-diversion periods still has not been essentially altered after several years of diversion, so the pulse effects of short-term water diversion were more obvious than the long-term cumulative impacts. Better control of allochthonous nutrients, appropriate increase in inflow water, adhering to the long-term operation, should be effective to enhance ecological benefits of such water diversion projects.

Synergistic Regulation Effect of Nitrate and Calcium Ions for Highly Luminescent and Robust α-CsPbI3 Perovskite.

The α-CsPbI3 nanocrystals (NCs) easily transform into yellow non-perovskite, accompanying with declining photoelectric properties that restricting their practical applications in diverse fields. Herein, the highly luminescent and robust α-CsPbI3 NCs is achieved through engineering the lattice symmetry of perovskite, enabled by the synergistic effect of NO3- ion passivation and Ca2+ ion doping. The introduced NO3- ions enhance the phase-change energy barrier and the surface steric hindrance, thus promoting the formation of α-CsPbI3 NCs with hyper-symmetric crystal structure, while the Ca2+ ion doping contributes to improving their lattice symmetry by significant regulation of the tolerance factor. As a result, the obtained α-CsPbI3 NCs display an outstanding photoluminescence quantum yield of 96.6%, together with the reduced defect state density and eminent conductivity. Most importantly, the as-engineered α-CsPbI3 NCs exhibit excellent stability under ambient conditions for 9 months and UV illumination for 32 h. It displays brilliant thermal stability, maintaining luminous intensity for 15 min under 140 °C, and performing desired durability and reversibility, evidenced by 160 °C cyclic test and 120 °C reversibility test. Given enhanced robustness, the as-engineered α-CsPbI3 NCs based light-emitting-diode devices are constructed, exhibiting a power efficiency of 105.3 lm W-1 and the excellent working stability for 18 h.

Apelin is associated with clinicopathological parameters and prognosis in breast cancer patients.

PURPOSE: Apelin has been shown to be a novel angiogenic factor in various cancers. However, there is limited information regarding the role of apelin in breast cancer. The aim of the present study is to examine associations between apelin, clinicopathological variables, and clinical outcome in breast cancer patients. METHODS: In this study, we began by investigating the apelin expression in breast cancer with long-term follow-up using immunohistochemistry. We then analyzed the relationship between apelin expression and microvessel density (MVD), lymphatic vessel density (LVD), lymph node status as well as other established clinicopathological parameters. The relationship between apelin expression and prognosis was also studied. In addition, we compared the apelin and its ligant APJ expression between 30 breast cancer samples and normal breast tissues adjacent to the breast tumors using western blot (WB) and RT-PCR. RESULTS: Apelin protein expression was detected in the cytoplasm of the breast carcinoma cells at various intensities. Apelin expression was positive in 59.2% (84/142) of the breast cancer patients and apelin expression was significantly correlated with tumor size (p = 0.030), stage (p = 0.000), histological type (p = 0.009), MVD (p = 0.000), LVD (p = 0.000), and lymph node metastasis (p = 0.041). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that high expression of apelin was associated with both worse disease-free survival (p < 0.001) and overall survival (p < 0.001). Interestingly, a significant difference in apelin and APJ expression by WB as well as RT-PCR was observed between normal breast tissues adjacent to the breast tumors and breast cancer tissues. CONCLUSIONS: Our results showed apelin expression was associated with tumor size, stage, histological type, MVD, LVD, lymph node metastasis and poor prognosis. The presence of apelin may be a new prognostic factor and potential therapeutic target for breast cancer.

Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer.

BACKGROUND: Basic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC). METHODS: We assessed the differences in BATF2 mRNA expression between cancerous and noncancerous tissues in BC using GEPIA and UALCAN data and in BATF2 protein expression pattern using Human Protein Atlas (HPA) data. BATF2 co-expression networks were analyzed in Coexpedia. The association between the differentially expressed BATF2 mRNA and BC prognosis was assessed using UALCAN, OSbrca, and GEPIA databases. In external validations, BATF2 protein expression in BC tissues was quantitated using a tissue microarray and immunohistochemistry (IHC) analysis, and BATF2 mRNA expression in serum and serum-derived exosomes of BC patients using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: No difference in the BATF2 mRNA expression level was found between cancerous and noncancerous tissues in BC based on databases. There were low-to-moderate levels of increases in BATF2 protein expressions in BC cases from the HPA cohort. BATF2 mRNA expression was negatively correlated with androgen receptor (AR) and positively correlated with BRCA2 DNA repair associated (BRCA2), marker of proliferation Ki-67 (Mki67), and tumor protein p53 (TP53) expressions. Generally, BATF2 mRNA exhibited a non-significant association with BC prognosis; yet the subgroup analyses showed that triple-negative breast cancer (TNBC) patients with high BATF2 mRNA expressions had a longer overall survival (OS). Our IHC analysis revealed a positive rate of BATF2 protein expression of 46.90%, mainly located in the nucleus of cancer cells in BC, and the OS of BC patients with high BATF2 protein expressions was prolonged. The positive rates of BATF2 mRNA expressions in the serum and exosomes were 45.00 and 41.67%, respectively. Besides, the AUCs of serum and exosomal BATF2 mRNA for BC diagnosis were 0.8929 and 0.8869, respectively. CONCLUSIONS: BC patients exhibit low-to-moderate expressions in BATF2 mRNA expression levels in cancerous tissues. The high BATF2 protein expression can be a potential indicator of a better BC prognosis. Serum and exosomal BATF2 mRNA levels also serve as promising noninvasive biomarkers for BC diagnosis.

FoxO1 in Micropterus salmoides: Molecular characterization and its roles in glucose metabolism by glucose or insulin-glucose loading.

Forkhead box O1 (FoxO1), a nuclear transcription factor, plays an important role in insulin-mediated glucose metabolism. In this study, FoxO1 gene from largemouth bass (Micropterus salmoides) was cloned and characterized, and its effects on hepatic glucose metabolism regulated by insulin-AKT pathway were investigated in response to glucose or insulin-glucose injection. The full-length cDNA of FoxO1 consisted of 2541 bp and encoded 680 amino acids. Sequence alignments and phylogenetic analysis revealed that FoxO1 exhibited a high degree of conservation among teleost, retaining one forkhead domain, one transactivation domain, and three phosphorylation sites. FoxO1 mRNA was expressed in a wide range of tissues, and high in the brain and liver. Glucose loading resulted in persistent hyperglycemia, and plasma insulin levels remained unchanged except at 1 h. After the insulin-glucose injection, insulin levels were significantly elevated and glucose levels recovered to the basal value after 6 h, which indicated insufficient insulin secretion caused persistent hyperglycemia in this species. Compared with the glucose injection group, transcript levels and enzyme activities of hepatic glycolysis-related genes (GK and PK) were significantly activated, and gluconeogenesis-related genes (PEPCK and G6Pase) were significantly depressed at 3 h after the insulin-glucose injection. Besides, phosphorylation of AKT-FoxO1 pathway was significantly activated. Therefore, insulin improved glucose metabolism by activating the AKT-FoxO1 phosphorylation  to decrease hyperglycemia stress after the meal, which indicated insufficient insulin secretion was the reason for glucose intolerance in largemouth bass. Meanwhile, conserved S267 and S329 phosphorylation sites of FoxO1 were confirmed to be regulated by AKT and mediated the glucose metabolism. In conclusion, activation of insulin-AKT-FoxO1 pathway improved glucose tolerance through mediating glucose metabolism in largemouth bass.

The combination of contrast-enhanced ultrasonography with blue dye for sentinel lymph node detection in clinically negative node breast cancer.

PURPOSE: The aim of this prospective study was to evaluate the value of the combination of contrast-enhanced ultrasonography (CEUS) and blue dye (BD) for SLN detection in patients with clinically negative node breast cancer. METHODS: Patients with clinically negative node breast cancer were randomized into two cohorts for SLN biopsy (SLNB): the combination method cohort using CEUS and BD together, and the single BD method cohort. Standard axillary lymph node dissection was performed if any of the SLNs confirmed positive by pathology. The identification rate, the number of SLNs removed and recurrence-free survival (RFS) rates were evaluated between two cohorts. In addition, we assessed the sensitivity, specificity, accuracy, false-negative rate of CEUS for diagnosis of SLNs based on patterns of CEUS enhancement. RESULTS: 144 consecutive patients with clinically negative node breast cancer were randomized into two cohorts. Each cohort consisted of 72 cases. In the combination method cohort, contrast-enhanced lymphatic vessels were clearly visualized and SLNs were accurately localized in 72 cases. The identification rate and the mean number of SLNs detected by the combination method were 100% (72/72) and 3.26 (1-9), respectively. In contrast, in the single BD method cohort, SLNs in 69 cases were successfully identified. The identification rate and the mean number of SLNs using BD alone were 95.8% (69/72) and 2.21 (1-4), respectively. According to patterns of CEUS enhancement, the sensitivity, specificity, accuracy, and the FNR of CEUS for SLN diagnosis were 69.2%, 96.6%, 91.7%, and 30.8%, respectively. After a median follow-up of 50 months for the combination method cohort and 51 months for the blue dye alone cohort, five patients in the combination method cohort and nine in the blue dye alone cohort had recurrence. RFS rates showed no significant difference (P = 0.26) between two cohorts. CONCLUSION: The combination of CEUS and BD is more effective than BD alone for SLNB in clinically negative node patients with an identification rate as high as 100%. Use of BD and CEUS in combination may provide the possibility of a non-radioactive alternative method for SLNB in centers without access to radioisotope.

Building blocks for bispecific and trispecific antibodies.

Bispecific antibodies (BsAbs), which target two antigens or epitopes, incorporate the specificities and properties of two distinct monoclonal antibodies (mAbs) into a single molecule. As such, BsAbs can elicit synergistic activities and provide the capacity for enhanced therapeutic efficacy and/or safety compared to what can be achieved with conventional monospecific IgGs. There are many building block formats to generate BsAbs and Trispecific antibodies (TsAbs) based on combining the antigen recognition domains of monoclonal antibodies (mAbs). This review describes the many and varied antibody-based building blocks used to achieve multivalency and multispecificity. These diverse building blocks provide opportunities to tailor the design of BsAbs and TsAbs to match the desired applications.

Contrast-enhanced ultrasonography and blue dye methods in detection of sentinel lymph nodes following neoadjuvant chemotherapy in initially node positive breast cancer.

BACKGROUND: Recent studies show that contrast-enhanced ultrasonography (CEUS) using SonoVue has the potential to improve the performance of sentinel lymph node biopsy (SLNB) in patients with early breast cancer. However, the evidence of SLNB using CEUS in patients converting from cN1 to cN0 after neoadjuvant chemotherapy (NAC) is lacking. The aim of this prospective study is to evaluate the feasibility of CEUS using SonoVue for the identification of sentinel lymph node (SLN) and the value of the combination of CEUS and blue dye (BD) for SLNB in patients converting from cN1 to cN0 following NAC. METHODS: Patients with cytology-proven node positive breast cancer at the initial diagnosis (stage T1-T3N1M0) from January 2018 to January 2019, underwent NAC. Patients converting from cN1 to cN0 following NAC were enrolled and randomized into two groups for SLNB: the combination method group using CEUS and BD together, and the single BD method group. Then all patients underwent complete axillary lymph node dissection (ALND) and primary breast surgery. Compared with the final pathological results, the identification rate, sensitivity, specificity, accuracy, false negative rate, negative predictive value, positive predictive value were recorded and compared between two methods. RESULTS: A total of 400 patients with stage T1-T3N1M0 disease underwent NAC between January 2018 to January 2019, among which 134 (33.5%) patients had clinically negative node confirmed by imaging after NAC and randomized into two groups. Each group included 67 cases. In the combination method group, contrast-enhanced lymphatic vessels in 66 cases of 67 were clearly visualized by US soon after the periareolar injection of SonoVue and the SLNs were accurately localized. The identification rate of the combination method was 98.5%%, which was significantly higher than 83.6% (56/67) using the single BD method. The mean numbers of SLNs identified by the combination method was higher than that by the single BD method. Compared with pathological diagnosis, sensitivity, specificity, accuracy, the positive predictive value, the negative predictive value, and the FNR of the combingation method were 84.4%, 100%, 89.4%, 100%, 75%, and 15.6%, respectively. In contrast, sensitivity, specificity, accuracy, the positive predictive value, the negative predictive value, and the FNR using single blue dye were 73.9%, 100%, 89.3%, 100%, 84.6%, and 26.1%, respectively. The FNR using the combination method was significantly lower than that using single BD. CONCLUSION: Identification of SLNs in patients converting from cN1 to cN0 following NAC by CEUS is a technically feasible. The combination of CEUS and BD is more effective than BD alone for SLNB in patients converting from cN1 to cN0 following NAC.

Prospective comparison of indwelling cannulas drain and needle aspiration for symptomatic seroma after mastectomy in breast cancer patients.

AIMS: Postoperative seroma is the most frequent sequelae after mastectomy and axillary surgery with no optimal regimens for seroma resolution recommended in routine clinical. Indwelling cannulas with needle and catheter have been widely used in long-term medication therapies, but evidence of indwelling cannulas in seroma management after mastectomy is lacking. The purpose of this study is to evaluate the feasibility of indwelling cannulas in seroma management after mastectomy. METHODS: Patients who underwent modified radical mastectomy (MRM) and developed symptomatic seroma after removal of the drains between August 2017 and December 2018, were randomized into two groups either indwelling cannulas drain of seroma (Group A) or needle aspiration of seroma (Group B). We prospectively compared the number of visits for seroma, the time from removal of the drain to the final seroma resolution and the cost between the methods. RESULTS: A total of 860 patients underwent MRM between August 2017 and December 2018, among which 86 patients who developed symptomatic seroma after removal of the drains, were randomized into two groups either Group A or Group B. The number of visits for seroma in Group A was 2.35 ± 0.69 times, which was less than those in Group B (4.86 ± 1.06 times). Similarly, the time of drain removal to final seroma resolution in Group A was 4.65 ± 0.78 days, which was shorter than 7.09 ± 1.54 in Group B. In Group A, the total mean cost per patient (25.81 ± 7.71 RMB) was less than the total mean cost per patient (49.30 ± 9.85 RMB) in Group B. Cost savings were noted with using indwelling cannulas in seroma management. CONCLUSION: It is feasible to drain indwelling cannulas drain for postmastectomy seroma, with less visits for patients, rapid seroma resolution and less cost. Indwelling cannulas can be an efficient, cost effective solution to treat symptomatic seroma after breast surgery.

Lacustrine micro-ecosystem responses to the inflow discharge gradient of water diversion from Yangtze River to Lake Taihu.

Water diversion project is always taken as the emergency and effective engineering measure to deal with the cyanobacterial blooms in eutrophic lakes. The inflow discharge and duration are the critical parameters influencing the effects and costs of the water diversion activities. Due to the impacts of meteorological and hydrological factors such as precipitation and wind-wave currents, the environmental influence of water diversion on shallow eutrophic lakes is always unclear. To explore the quantitative relationships among inflow discharges, duration and ecological parameters in water-receiving lakes, the typical water diversion engineering-Water Diversion Project from Yangtze River to Lake Taihu was taken as an example and the mesocosm experiment modeling the micro-ecosystem of the water-receiving Meiliang Bay in Lake Taihu was conducted with five groups of inflow discharges according to the practical discharges of the main river channel-Wangyu River. Each micro-ecosystem had a volume of 15 L and was studied for a period of 30 days (25 days for the water diversion period and 5 days for the stop period). The results showed that the inflow discharges had different extents of impact on the physicochemical and biological characteristics of the micro-ecosystems. The concentrations of total dissolved solids, total nitrogen, nitrate, active silicate and bacterial abundance in the experimental groups (inflow discharges > 100 m3/s) were all decreased compared with the control group, with the lowest values in the period of 10-15 days. During the stop period, the concentrations of sensitive biotic and abiotic parameters were all recovered with different extents and different from the initial state of this experiment, which revealed that the effects of the short-term water diversion on lake ecosystems were resilient and durable. There were quantitative relationships among the inflow discharge, content interpolation and variation in water nutrients, with different relationships in different periods of the water diversion. The influence of water diversion on lake ecosystems was not only related to the direct impacts of allochthonous inputs, but also with the indirect effects of internal habitat variation in lakes.

A novel method to construct a 3D FeWO4 microsphere-array electrode as a non-enzymatic glucose sensor.

As the special sensor for glucose detection, a non-noble-metal nanoarray architecture is extremely attractive due to its easy accessibility to target molecules and more exposed surface area. In this communication, we report the first synthesis of FeWO4 microsphere-array on the three-dimensional (3D) Ni foam (FeWO4 microspheres/NF) as the mimetic electrode for efficient catalytic oxidation of glucose in an alkaline medium. When used as an artificial analog glucose sensor, the result of the present sensing system can also be calculated with a sensitivity of 2810 µA mM cm-2, a linear range from 0.04 mM to 2 mM and a detection limit up to 1.4 µM (S/N = 3). This glucose sensor with satisfactory stability and reproducibility can also be applied to the detection of glucose in human serum. As a promising sensing platform, this proposed 3D FeWO4 microspheres/NF may open a new strategy for pursuing electrochemical detection of biomolecules.

Mn3 O4 Nanocube: An Efficient Electrocatalyst Toward Artificial N2 Fixation to NH3.

Traditionally, ammonia (NH3 ) is synthesized via the Haber-Bosch process, which is not only commanded by harsh conditions but causes serious environmental pollution. Electrochemical reduction is recognized as a mild and environmentally benign alternative approach for NH3 synthesis, but an efficient electrocatalyst is a prerequisite for NH3 production. In this communication, the first experimental demonstration that Mn3 O4 nanocubes can be used as an efficient non-noble-metal electrocatalyst for N2 reduction reaction (NRR) at ambient conditions is reported. In 0.1 m Na2 SO4 aqueous solution, the catalyst delivers excellent NRR activity with an NH3 yield of 11.6 µg h-1 mg-1 cat. and Faradaic efficiency of 3.0% at -0.8 V versus reversible hydrogen electrode. Notably, this catalyst also possesses satisfactory durability during the electrolysis and recycling test.

High-performance electrochemical glucose sensing enabled by Cu(TCNQ) nanorod array.

It is highly attractive to construct stable enzyme-free glucose sensors based on three-dimensional direct electrochemical detection of glucose. In this paper, a copper 7,7,8,8-tetracyanoquinodimethane (Cu(TCNQ)) nanorod array on Cu foam (Cu(TCNQ) NA/CF) is proposed as an efficient catalyst for electrochemical glucose oxidation in alkaline conditions. When Cu(TCNQ) NA/CF was used as the enzyme-free sensory of glucose, the sensor showed a response time within 3 s, a wide linear detection in the range 0.001-10.0 mM, the minimum limit of detection was as low as 10 nM (S/N = 3), and it had a high sensitivity of 26 987 µA mM-1 cm-2. Moreover, this sensor also possesses long-term stability, high selectivity, reproducibility, and actual applications for fresh human serum sample analysis is also successfully accepted.

Highly sensitive detection of hesperidin using AuNPs/rGO modified glassy carbon electrode.

The highly sensitive and selective electrochemical sensor of hesperidin based on gold nanoparticles (AuNPs) and reduced graphene oxide (rGO) modified glassy carbon electrode (GCE) is reported. The AuNPs and rGO were uniformly introduced on the surface of the GCE via electrodeposition without any reducing agents and have been characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDX), X-ray photoelectron spectroscopy (XPS), FT-IR, and electrochemical methods. The AuNPs/rGO not only promoted the accumulation of hesperidin onto the GCE surface for quantitative analysis but also accelerated the electron transfer between hesperidin and the electrode substrates. Under the optimal conditions, hesperidin was determined quantitatively at the AuNPs/rGO/GCE using amperometric i-t curve. The results showed that the current obtained on detection of hesperidin exhibited a linear correlation with its concentration in the range of 5.0 × 10-8 mol L-1-8.0 × 10-6 mol L-1 with a detection limit of 8.2 × 10-9 mol L-1 (S/N = 3). In addition, good specificity, repeatability, reproducibility, and long-term storage stability were achieved for the modified electrode, which could be used for the detection of hesperidin in the traditional Chinese medicine, Pericarpium Citri Reticulatae.

Circulating tumor cells are correlated with disease progression and treatment response in an orthotopic hepatocellular carcinoma model.

Hepatocellular carcinoma (HCC) is a highly malignant tumor characterized by rapid progression, poor prognosis, and frequent hematogenous metastasis. A minimally invasive diagnostic biomarker that can predict disease progression and treatment response would be of extraordinary benefit. Therefore, we have investigated whether the number of circulating tumor cells (CTCs) is correlated with disease progression and treatment response in HCC. Here we report that the number of CTCs, monitored by in vivo flow cytometry (IVFC), is strongly correlated with disease progression and treatment response in a highly metastatic orthotopic nude mouse model of green fluorescent protein (GFP)-labeled HCC. Sorafenib treatment reduces the number of CTCs significantly. The decreased number of CTCs is consistent with low lung metastasis. This study has demonstrated a considerable clinical value of CTCs as a biomarker in predicting disease progression and monitoring therapeutic efficacy in patients with HCC.

Comparative analysis of alkaline phosphatase-encoding genes (phoX) in two contrasting zones of Lake Taihu.

Limnetic habitats that are dominated by either algae or macrophytes represent the 2 dominant ecosystems in shallow lakes. We assessed seasonal variations in the diversity and abundance of alkaline phosphate-encoding genes (phoX) in these 2 zones of Lake Taihu, which is a large, shallow, eutrophic lake in China. There was no significant difference in seasonal mean phoX diversity between the 2 zones, whereas the seasonal mean phoX abundance in the macrophyte-dominated region was higher than that in the algae-dominated region. The bulk of the genotypes in the 2 regions were most similar to the alphaproteobacterial and betaproteobacterial phoX. Genotypes most similar to phoX affiliated with Betaproteobacteria were present with greater diversity in the macrophyte-dominated zone than in the algae-dominated zone. In the algae-dominated zone, the relative proportion of genotypes most similar to cyanobacterial phoX was highest (38.8%) in summer. In addition to the different genotype structures and environmental factors between the 2 stable states, the lower gene abundances and higher alkaline phosphatase activities in Meiliang Bay in summer than those in Xukou Bay reveals different organophosphate-mineralizing modes in these 2 contrasting habitats.

A multi-center study of using carbon nanoparticles to track lymph node metastasis in T1-2 colorectal cancer.

BACKGROUND: How to identify whether T1-2 colorectal cancers have lymph nodes metastases pre-op or intra-op is a crucial problem in clinic. The purpose of this study was to evaluate the feasibility of using carbon nanoparticles to track lymph nodes metastases in T1-2 colorectal cancers. METHODS: A multi-center study was performed between July 2012 and January 2014. Seventy-three patients with T1-2 colorectal cancer identified by pre-op endoscopic ultrasonography (EUS) were recruited. 1 ml carbon nanoparticles suspension was endoscopically injected into the submucosal layer at four points around the site of the primary tumor 1 day before surgery. Laparoscopic radical resection with lymphadenectomy was performed. Sentinel lymph nodes (SLNs) were defined as nodes that were black-dyed by carbon nanoparticles. Pathology confirmed whether lymph nodes have cancer metastases and the SLNs accuracy. RESULTS: SLNs were easily found under laparoscopy. The mean number of SLNs was 3 (range 1-5). All patients had SLNs lying alongside the mesenteric vessel or main arterial vessel. After pathological analysis, 2 patients (9.52%) had lymph node metastasis in 21 patients with EUS T1 cancers, and 10 patients (19.23%) had lymph node metastasis in 52 patients with EUS T2 cancers. In two T1 cases with lymph node metastasis, SLNs were positive with 100% accuracy. In ten T2 cases with lymph node metastasis, SLNs were positive in nine cases. In pathology, carbon nanoparticles were seen in lymphatic vessels, and lymphoid sinus and macrophages in negative SLNs. When SLNs were positive, carbon nanoparticles were seen around cancer cells in lymph nodes. The overall sensitivity, specificity, accuracy of SLNs in T1-2 colorectal cancers were 91.67, 100, 98.63%, respectively. CONCLUSIONS: We demonstrated the feasibility of using carbon nanoparticles to track lymph nodes metastases in T1-2 colorectal cancers. Carbon nanoparticles black-dyed lymph nodes play a role as SLNs in T1-2 colorectal cancers.

Recovery of novel alkaline phosphatase-encoding genes (phoX) from eutrophic Lake Taihu.

To expand current knowledge on the molecular aspects of alkaline phosphatase PhoX in shallow eutrophic freshwaters, we investigated the genetic diversity and abundance of the PhoX-encoding gene (phoX) in 4 ecological regions in Lake Taihu, China, following a gradient in total phosphorus concentrations ranging from hypereutrophic to mesotrophic. Bacterial phoX was heterogeneously distributed with the highest diversity in the eutrophic regions and the highest abundance in the mesotrophic Xukou Bay. The concentrations of total phosphorus and enzymatically hydrolyzable phosphorus determined the distribution of bacterial phoX in Lake Taihu. Most (70.8%) of the phoX-translated proteins had <90% similarity to the PhoX proteins in the GenBank database, suggesting the presence of novel phoX genotypes in Lake Taihu. The low overlap in phoX genotypes (15.8%) between Lake Taihu and some marine ecosystems, and the dominance of the translated proteins most similar to the Alphaproteobacteria-affiliated PhoX, demonstrate the uniqueness of PhoX in eutrophic freshwaters.