Galectin-7 Induction by EHMT2 Inhibition Enhances Immunity in Microsatellite Stability Colorectal Cancer.

BACKGROUND & AIMS: Although immunotherapy shows substantial advancement in colorectal cancer (CRC) with microsatellite instability high, it has limited efficacy for CRC with microsatellite stability (MSS). Identifying combinations that reverse immune suppression and prime MSS tumors for current immunotherapy approaches remains an urgent need. METHODS: An in vitro CRISPR screen was performed using coculture models of primary tumor cells and autologous immune cells from MSS CRC patients to identify epigenetic targets that could enhance immunotherapy efficacy in MSS tumors. RESULTS: We revealed EHMT2, a histone methyltransferase, as a potential target for MSS CRC. EHMT2 inhibition transformed the immunosuppressive microenvironment of MSS tumors into an immunomodulatory one by altering cytokine expression, leading to T-cell-mediated cytotoxicity activation and improved responsiveness to anti-PD1 treatment. We observed galectin-7 up-regulation upon EHMT2 inhibition, which converted a "cold" MSS tumor environment into a T-cell-inflamed one. Mechanistically, CHD4 repressed galectin-7 expression by recruiting EHMT2 to form a cotranscriptional silencing complex. Galectin-7 administration enhanced anti-PD1 efficacy in MSS CRC, serving as a potent adjunct cytokine therapy. CONCLUSIONS: Our findings suggest that targeting the EHMT2/galectin-7 axis could provide a novel combination strategy for immunotherapy in MSS CRC.

A safe and simple exposure and Pringle maneuver in laparoscopic anatomical liver resection of segment 7.

BACKGROUND: Laparoscopic access to liver segment 7 (S7) is difficult for deep surgical situations and bleeding control. Herein, our proposed laparoscopic technique for S7 lesions using a self-designed tube method is introduced. METHODS: Clinical data of patients who underwent laparoscopic anatomical liver resection of S7 (LALR-S7) with the help of our self-designed tube to improve the exposure of S7 and bleeding control in the Second Affiliated Hospital, Third Military Medical University (Army Medical University) from April 2019 to December 2021 were retrospectively analyzed to evaluate feasibility and safety. RESULTS: Nineteen patients were retrospectively reviewed. The mean age was 51.3 ± 10.3 years; mean operation time, 194.5 ± 22.7 min; median blood loss, 160.0 ml (150.0-205.0 ml); and median length of hospital stay, 8.0 days (7.0-9.0 days). There was no case conversion to open surgery. Postoperative pathology revealed all cases of hepatocellular carcinoma (HCC). Free surgical margins were achieved in all patients. No major postoperative complications were observed. Patients with postoperative complications recovered after conservative treatment. During outpatient follow-up examination, no other abnormality was presented. All patients survived without tumor recurrence. CONCLUSIONS: The preliminary clinical effect of our method was safe, reproducible and effective for LALR-S7. Further research is needed due to some limitations of this study.

Laparoscopic surgical management of hepatocellular carcinoma patients with diaphragmatic involvement.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy of the digestive system with high morbidity and high mortality worldwide. Currently, surgical resection is considered the most effective treatment for HCC. Laparoscopic surgery is a major trend in contemporary minimally invasive surgery. However, is laparoscopic resection suitable for HCC patients with diaphragmatic involvement? If so, then what is the preferred resection method, and how safe and effective is this treatment? Are there any factors that require special attention? METHODS: Clinical data of 17 patients who underwent laparoscopic surgery in the Second Affiliated Hospital, Third Military Medical University (Army Medical University) from January 2018 to February 2021 were retrospectively analyzed. RESULTS: The mean age was 48.9 ± 14.0 years; mean operation time, 186.00 ± 18.3 min; median blood loss, 170.0 ml (140.8-207.5 ml); and median length of hospital stay, 8.0 days (7.0-9.5 days). There was no case of open conversion. Pathologic findings revealed all cases of HCC. Intraoperative frozen pathology and postoperative pathology showed free surgical margins. Six patients had pathologically confirmed diaphragmatic invasion (DI), and eleven was confirmed as having diaphragmatic fibrous adhesion (DFA) only. Post-operative complications included liver section effusion, pleural effusion, pneumonia and bile leak. All the complications responded well to conservative treatment. No other abnormality was noted during outpatient follow-up examination. Sixteen patients survived tumor-free; one patient with HCC developed intrahepatic metastasis 1 year after surgery, and this patient survived with tumor after treatment. CONCLUSIONS: Our experience initially provides valuable support for the laparoscopic surgical treatment of HCC patients with diaphragmatic involvement.

Bronchiectasis in Low-Dose CT Screening for Lung Cancer.

Background Bronchiectasis is associated with loss of lung function, substantial use of health care resources, and increased morbidity and mortality in people with cardiopulmonary diseases. Purpose To assess the frequency and severity of bronchiectasis and related clinical findings of participants in a low-dose CT (LDCT) screening program. Materials and Methods The Early Lung and Cardiac Action Program (ELCAP) bronchiectasis score (range, 0-42; higher values indicate more severe bronchiectasis) was developed to facilitate bronchiectasis assessment. This quantitative scoring system screened participants based on accumulated knowledge and improved CT imaging capabilities. Secondary review of LDCT studies from smokers aged 40-90 years was performed when they were initially enrolled in the prospective Mount Sinai ELCAP screening study between 2010 and 2019. Medical records were reviewed to identify associated respiratory symptoms and acute respiratory events during the 2 years after LDCT. Logistic regression analysis was performed to examine factors associated with bronchiectasis. Results LDCT studies of 2191 screening participants (mean age, 65 years ± 9; 1140 [52%] women) were obtained, and bronchiectasis was identified in 504 (23%) participants. Median ELCAP bronchiectasis score was 12 (interquartile range, 9-16). Bronchiectasis was most common in the lower lobes for all participants, and lower lobe prevalence was greater with higher ELCAP score (eg, 91% prevalence with an ELCAP score of 16-42). In the fourth quartile, however, midlung involvement was higher compared with lower lung involvement (128 of 131 participants [98%] vs 122 of 131 participants [93%]). Bronchiectasis was more frequent with greater age (odds ratio [OR] = 2.0 per decade; 95% CI: 1.7, 2.4); being a former smoker (OR = 1.33; 95% CI: 1.01, 1.73); and having self-reported chronic obstructive pulmonary disease (OR = 1.38; 95% CI: 1.02, 1.88), an elevated hemidiaphragm (OR = 4; 95% CI: 2, 11), or consolidation (OR = 5; 95% CI: 3, 11). It was less frequent in overweight (OR = 0.7; 95% CI: 0.5, 0.9) or obese (OR = 0.6; 95% CI: 0.4, 0.8) participants. Two years after baseline LDCT, respiratory symptoms, acute respiratory events, and respiratory events that required hospitalization were more frequent with increasing severity of the ELCAP bronchiectasis score (P < .005 for all trends). Conclusion Prevalence of bronchiectasis in smokers undergoing low-dose CT screening was high, and respiratory symptoms and acute events were more frequent with increasing severity of the Early Lung and Cardiac Action Program Bronchiectasis score. © RSNA, 2022 See also the editorial by Verschakelen in this issue.

Optimal time point of response assessment for predicting survival is associated with tumor burden in hepatocellular carcinoma receiving repeated transarterial chemoembolization.

OBJECTIVES: Objective response rate (ORR) under mRECIST criteria after transarterial chemoembolization (TACE) is a well-perceived surrogate endpoint of overall survival (OS). However, its optimal time point remains controversial and may be influenced by tumor burden. We aim to investigate the surrogacy of initial/best ORR in relation to tumor burden. METHODS: A total of 1549 eligible treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh score ≤ 7, and performance status score ≤ 1 undergoing TACE between January 2010 and May 2016 from 17 academic hospitals were retrospectively analyzed. Based on "six-and-twelve" criteria, tumor burden was graded as low, intermediate, and high if the sum of the maximum tumor diameter and tumor number was ≤ 6, > 6 but ≤ 12, and > 12, respectively. RESULTS: Both initial and best ORRs interacted with tumor burden. Initial and best ORRs could equivalently predict and correlate with OS in low (adjusted HR, 2.55 and 2.95, respectively, both p < 0.001; R = 0.84, p = 0.035, and R = 0.97, p = 0.002, respectively) and intermediate strata (adjusted HR, 1.81 and 2.22, respectively, both p < 0.001; R = 0.74, p = 0.023, and R = 0.9, p = 0.002, respectively). For high strata, only best ORR exhibited qualified surrogacy (adjusted HR, 2.61, p < 0.001; R = 0.70, p = 0.035), whereas initial ORR was not significant (adjusted HR, 1.08, p = 0.357; R = 0.22, p = 0.54). CONCLUSIONS: ORR as surrogacy of OS is associated with tumor burden. For patients with low/intermediate tumor burden, initial ORR should be preferred in its early availability upon similar sensitivity, whereas for patients with high tumor burden, best ORR has optimal sensitivity. Timing of OR assessment should be tailored according to tumor burden. KEY POINTS: • This is the first study utilizing individual patient data to comprehensively analyze the surrogacy of ORR with a long follow-up period. • Optimal timing of ORR assessment for predicting survival should be tailored according to tumor burden. • For patients with low and intermediate tumor burden, initial ORR is optimal for its timeliness upon similar sensitivity with best ORR. For patients with high tumor burden, best ORR has optimal sensitivity.

Laparoscopic liver resection of segment 8 via a hepatic parenchymal transection-first approach guided by the middle hepatic vein.

BACKGROUND: Pure laparoscopic liver resection (LLR) of segment 8 (S8) is still rarely performed due to the lack of an appropriate surgical approach. This article discusses the technical tips and operation methods for LLR of S8 via a hepatic parenchymal transection-first approach. METHODS: Clinical data of 22 patients who underwent LLR of S8 via a hepatic parenchymal transection-first approach guided by the middle hepatic vein (MHV) in the Second Affiliated Hospital, Third Military Medical University (Army Medical University) from May 2017 to February 2020 were retrospectively analyzed. RESULTS: The mean age was 51.1 ± 11.6 years; mean operation time, 186.6 ± 18.4 min; median blood loss, 170.0 ml (143.8-205.0 ml); and median length of hospital stay, 8.0 days (7.0-9.0 days). There was no case of open conversion. Pathologic findings revealed all cases of hepatocellular carcinoma (HCC). Pathology showed free surgical margins. Post-operative complications included liver section effusion, pleural effusion, pneumonia, intra-abdomen bleeding and bile leak. All the complications responded well to conservative treatment. No other abnormality was noted during outpatient follow-up examination. All patients survived tumor-free. CONCLUSIONS: LLR of S8 is still quite challenging at present, and it is our goal to design a reasonable procedure with accurate efficacy and high safety. We use hepatic parenchymal transection-first approach guided by the MHV for LLR of S8. This technique overcomes the problem of high technical risk, greatly reduces the surgical difficulty and achieves technological breakthroughs, but there are still many problems worth further exploration.

Nanocomposites of immobilized nano-zirconia on low-cost activated carbon derived from hazelnut shell for enhanced removal of 3-Nitro-4-Hydroxy-Phenylarsonic acid from water.

3-Nitro-4-hydroxy-phenylarsonic acid (NHPA) as a veterinary drug can degraded into highly toxic inorganic arsenic and will be harmful to environment and food safety. Nanocomposites for the uptake of NHPA were obtained by efficiently immobilizing the nano-sized zirconium oxide onto hazelnut shell-based activated carbon using pyrolysis method. We found that the pyrolysis temperature played a crucial role in the adsorptive performances of the nanocomposites. The prepared nanocomposite at pyrolysis temperature of 600 °C with a mass ratio of ZrOCl2/activated carbon of 1:3 exhibited a fast adsorption equilibrium for NHPA within 5 min, excellent adsorption capacity of 825.7 mg g-1 and the higher adsorption capacity with the increase in temperature from 20 to 45 °C across a pH range of 4-6. 90% of the NHPA uptake was sustained in the NaNO3 solution of 0.7 mol L-1. The adsorption data were well simulated by the Langmuir and pseudo-second order equations. Thermodynamic parameters suggested that the uptake of the NHPA occurred spontaneously (ΔG0<0) with an endothermic characteristic (ΔH0>0). A synergetic effect of electrostatic attraction, As-O-Zr surface coordination and π-π interaction is the main adsorption mechanism of the nanocomposites for the removal of the NHPA.

Characterization of Newly Detected Costal Pleura-attached Noncalcified Nodules at Annual Low-Dose CT Screenings.

Background Solid costal pleura-attached noncalcified nodules (CP-NCNs) less than 10.0 mm with lentiform, oval, or semicircular (LOS) or triangular shapes and smooth margins on baseline low-dose CT scans from the Mount Sinai Early Lung and Cardiac Action Program (MS-ELCAP) were reviewed, and it was determined that they can be followed up at the first annual screening rather than having a shorter-term work-up. Purpose To determine whether the same criteria could be used for solid CP-NCNs newly identified at annual screening examinations. Materials and Methods With use of the same MS-ELCAP database, all new solid CP-NCNs measuring 30.0 mm or less were identified at 4425 annual screening examinations between 2010 and 2019. In addition, to ensure that no malignant CP-NCNs met the criteria, all solid malignant CP-NCNs of 30.0 mm or less in the International Early Lung Cancer Action Program, or I-ELCAP, database of 111 102 annual screening examinations from the 76 participating institutions between 1992 and 2019 were identified; Mount Sinai is one of these institutions. All identified solid CP-NCNs were reviewed-with the radiologists blinded to diagnosis-for shape (triangular, LOS, polygonal, round, or irregular), margin (smooth or nonsmooth), pleural attachment (broad or narrow), and the presence of emphysema and/or fibrosis within 10.0 mm of each CP-NCN. Intra- and interreader readings were performed, and agreements were determined by using the B-statistic. Results Of the 76 new solid CP-NCNs, 21 were lung cancers. Benign CP-NCNs were smaller than malignant ones (median diameter, 4.2 mm vs 11 mm; P < .001), had a different shape distributions, more frequently had smooth margins (67% vs 14%; P < .001), and less frequently had emphysema (38% vs 81%; P = .003) or fibrosis (3.6% vs 19%; P = .045) within a 10.0 mm radius. All 22 solid CP-NCNs less than 10.0 mm in average diameter with triangular or LOS shapes and smooth margins were benign, and none of the 21 solid malignant CP-NCNs had these characteristics. Intra- and interobserver agreement for triangular or LOS-shaped CP-NCNs with smooth margins was almost perfect (0.77 and 0.69, respectively). Conclusion The same follow-up recommendation developed for baseline costal pleura-attached noncalcified nodules (CP-NCNs) can be used for CP-NCNs newly identified at annual screening rounds. © RSNA, 2021.

Upregulation of Tubulointerstitial nephritis antigen like 1 promotes gastric cancer growth and metastasis by regulating multiple matrix metallopeptidase expression.

BACKGROUND AND AIM: Tubulointerstitial nephritis antigen-like 1 (TINAGL1), as a novel matricellular protein, has been demonstrated to participate in cancer progression, whereas the potential function of TINAGL1 in gastric cancer (GC) remains unknown. METHODS: The expression pattern of TINAGL1 in GC was examined by immunohistochemistry, ELISA, real-time polymerase chain reaction, and Western blot. Correlation between TINAGL1 and matrix metalloproteinases (MMPs) was analyzed by the GEPIA website and Kaplan-Meier plots database. The lentivirus-based TINAGL1 knockdown, CCK-8, and transwell assays were used to test the function of TINAGL1 in vitro. The role of TINAGL1 was confirmed by subcutaneous xenograft, abdominal dissemination, and lung metastasis model. Microarray experiments, ELISA, real-time polymerase chain reaction, and Western blot were used to identify molecular mechanism. RESULTS: TINAGL1 was increased in GC tumor tissues and associated with poor patient survival. Moreover, TINAGL1 significantly promoted GC cell proliferation and migration in vitro as well as facilitated GC tumor growth and metastasis in vivo. TINAGL1 expression in GC cells was accompanied with increasing MMPs including MMP2, MMP9, MMP11, MMP14, and MMP16. GEPIA database revealed that these MMPs were correlated with TINAGL1 in GC tumors and that the most highly expressed MMP was MMP2. Mechanically, TINAGL1 regulated MMP2 through the JNK signaling pathway activation. CONCLUSIONS: Our data highlight that TINAGL1 promotes GC growth and metastasis and regulates MMP2 expression, indicating that TINAGL1 may serve as a therapeutic target for GC.

Liver Parenchyma Transection-First Approach for Laparoscopic Left Hemihepatectomy: A Propensity Score Matching Analysis.

BACKGROUND: Laparoscopic major liver resection, such as laparoscopic left hemihepatectomy (LLH), is still perceived as a complicated procedure due to technical difficulties and slow learning curve. The study introduced an optimized procedure using the liver parenchyma transection-first approach and investigated its advantages on surgical outcomes by comparison with the conventional hilar dissection approach for LLH. METHODS: Between January 2015 and May 2019, 96 patients who underwent laparoscopic left hemihepatectomy for hepatocellular carcinoma (HCC) were enrolled in the study. Among these, 41 patients underwent the liver parenchyma transection-first approach (LP-first group) and the other 55 underwent the conventional hilar dissection approach (conventional group). A 1:1 propensity score matching (PSM) was performed to compare the perioperative and long-term oncological outcomes of the two groups. RESULTS: After 1:1 PSM, 37 patients in each group were selected for further analysis. The LP-first group was associated with shorter median operative time (210 vs 235 min, P = 0.035) and less blood loss (200 vs 300 mL, P = 0.410). In addition, no statistical differences were found in overall complications between the two groups (8.1% vs 24.3%, P = 0.058). There were no significant differences between the two groups in terms of 1-year and 3-year disease-free survival (DFS, P = 0.608) and overall survival (OS, P = 0.414). CONCLUSION: The prior liver parenchyma approach for LLH is safe and reproducible in selected patients, which showed improved perioperative outcomes and comparable long-term oncological outcomes compared with the conventional approach.

Management of Nodules Attached to the Costal Pleura at Low-Dose CT Screening for Lung Cancer.

Background Pulmonary nodule features have been used to differentiate benign from malignant nodules. Purpose To determine the frequency of solid noncalcified nodules attached to the costal pleura (CP-NCNs) at baseline low-dose CT and to identify key features of benignity. Materials and Methods A retrospective review was performed of baseline low-dose CT scans obtained in 8730 participants in the Mount Sinai Early Lung and Cardiac Action Program screening cohort between 1992 and 2019. Participants with one or more solid CP-NCNs between 3.0 mm and 30.0 mm in average diameter were included. For each CP-NCN, the size, location, shape (lentiform, oval, or semicircular [LOS]; triangular; polygonal; round; or irregular), margin (smooth or nonsmooth), and attachment to the costal pleura (broad or narrow) were documented. The manifestation of emphysema and fibrosis within a 10-mm radius of the CP-NCN was determined. Multivariable logistic regression analysis, with synthetic minority oversampling techniques, was used. Results The 569 eligible participants (average age, 62 years ± 9 [standard deviation]; 343 women) had 943 solid CP-NCNs, of which 934 (99.0%) were benign and nine (1.0%) were malignant. Multivariable analysis showed that five shapes could be consolidated into three (LOS and/or triangular, round and/or polygonal, and irregular shape); pleural attachment was not a significant independent predictor (odds ratio, 1.24; P = .70); and interaction terms of size with shape (odds ratio, 0.73; P = .005) and margin were significant (odds ratio, 0.80; P = .001). All 603 CP-NCNs less than 10.0 mm with LOS or triangular shapes and smooth margins were benign. Conclusion All baseline noncalcified solid nodules attached to the costal pleura less than 10.0 mm in average diameter with lentiform, oval, semicircular, or triangular shapes and smooth margins were benign; thus, for these nodules, an annual repeat scan in 1 year, rather than a more immediate work-up, is recommended. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Godoy in this issue.

In situ sampling of tetracycline antibiotics in culture wastewater using diffusive gradients in thin films equipped with graphene nanoplatelets.

A device of graphene nanoplatelet-based diffusion gradients in thin-films (G-DGT) was developed for in situ sampling of tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC) in aquatic environment. The accumulation of antibiotics in a synthetic solution by the proposed G-DGT was consistent with the theoretical curves predicted by the DGT equation. The values of the detection and quantification limits of G-DGT using high-performance liquid chromatography over the deployment time of 7 days were at the level of µg L-1 for the three antibiotics. The performance of the proposed G-DGT was unaffected by pH (3-9) and ionic strength (0.001-0.7 mol L-1 NaNO3). Fulvic acid did not significantly interfere with the performance of the proposed G-DGT device when the mass ratios between the three antibiotics and fulvic acid were within the range of 1:10-1:100. Humic acid had a significant effect on the performance of the proposed G-DGT for the sampling of the three antibiotics due to strong complexation and coprecipitation between the antibiotics and humic acid. The proposed G-DGT was used for the in situ sampling in spiked freshwaters and livestock culture wastewater and exhibited good precision and accuracy without notable interference from the matrices.

Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: A multicentre observational study.

BACKGROUND & AIMS: Previous prognostic scores for transarterial chemoembolization (TACE) were mainly derived from real-world settings, which are beyond guideline recommendations. A robust model for outcome prediction and risk stratification of recommended TACE candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS: Between January 2010 and May 2016, 1,604 treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh A5-B7 and performance status 0 undergoing TACE were included from 24 tertiary centres. Patients were randomly divided into training (n = 807) and validation (n = 797) cohorts. A prognostic model was developed and subsequently validated. Predictive performance and discrimination were further evaluated and compared with other prognostic models. RESULTS: The final presentation of the model was "linear predictor = largest tumour diameter (cm) + tumour number", which consistently outperformed other currently available models in both training and validation datasets as well as in different subgroups. The thirtieth percentile and the third quartile of the linear predictor, namely 6 and 12, were further selected as cut-off values, leading to the "six-and-twelve" score which could divide patients into 3 strata with the sum of tumour size and number ≤6, >6 but ≤12, and >12 presenting significantly different median survival of 49.1 (95% CI 43.7-59.4) months, 32.0 (95% CI 29.9-37.5) months, and 15.8 (95% CI 14.1-17.7) months, respectively. CONCLUSIONS: The six-and-twelve score may prove an easy-to-use tool to stratify recommended TACE candidates (Barcelona Clinic Liver Cancer stage-A/B) and predict individual survival with favourable performance and discrimination. Moreover, the score could stratify these patients in clinical practice as well as help design clinical trials with comparable criteria involving these patients. Further external validation of the score is required. LAY SUMMARY: There is currently no prognostic model specifically developed for recommended or ideal transarterial chemoembolization (TACE) candidates with hepatocellular carcinoma, despite these patients being frequently identified as the best target population in pivotal randomized controlled trials. The six-and-twelve score provides patient survival prediction, especially in ideal candidates of TACE, outperforming other currently available models in both training and validation sets, as well as different subgroups. With cut-off values of 6 and 12, the score can stratify ideal TACE candidates into 3 strata with significantly different outcomes and may shed light on risk stratification of these patients in clinical practice as well as in clinical trials.

Carbon nanodot aqueous binding phase-based diffusive gradients in thin films device for measurement of dissolved copper and lead species in the aquatic environment.

A reliable method for the determination of dissolved Cu2+ and Pb2+ species in water via a diffusive gradient in thin films (DGT) device using water-soluble carbon nanodots (CD) as the binding agent was developed (CD-DGT). The uptake of dissolved Cu2+ and Pb2+ species by CD-DGT increased linearly with a deployment time of over 120 h, while the uptake of Ca2+, Mg2+, Cd2+, Zn2+, Ni2+, and Co2+ by CD-DGT has no significant linear accumulation during the same deployment time. The concentrations of the dissolved Cu2+ and Pb2+ species measured using CD-DGT are in good agreement with the element concentrations spiked directly in a tested synthesis solution. The performance of CD-DGT for the determination of dissolved Cu2+ and Pb2+ species is found to be independent of ionic strength in the range of 0.001-0.05 mol L-1 and in the pH range from 5 to 8. The presence of fulvic acid and tannic acid has no significant influence on the uptake of dissolved Cu2+ and Pb2+ species by CD-DGT under the tested conditions. In different water samples, good agreement was observed between the dissolved Cu2+ and Pb2+ concentrations measured by CD-DGT, and diffusive equilibration in the thin film devices was found. Based on the results obtained, CD-DGT enables the selective and quantitative determination of dissolved Cu2+ and Pb2+ species in water.

Tg737 acts as a key driver of invasion and migration in liver cancer stem cells and correlates with poor prognosis in patients with hepatocellular carcinoma.

We previously demonstrated that the Tg737 gene plays a critical role in the carcinogenesis of hepatocellular carcinoma (HCC). However, few systematic investigations have focused on the biological function of Tg737 in the invasion and migration of liver cancer stem cells (LCSCs) and on its clinical significance. In this study, Tg737 overexpression was achieved via gene transfection in MHCC97-H side population (SP) cells, which are considered a model for LCSCs in scientific studies. Tg737 overexpression significantly inhibited the invasion and migration of SP cells in an extracellular signal-regulated kinase1/2 (ERK1/2)/matrix metalloproteinase-2 (MMP-2)-dependent manner. Furthermore, Tg737 expression was frequently decreased in HCC tissues relative to that in adjacent noncancerous liver tissues. This decreased expression was significantly associated with tumor differentiation, the American Joint Committee on Cancer (AJCC) stage, metastasis, tumor size, vascular invasion, alpha-fetoprotein (AFP) levels, and tumor number. Moreover, multivariate Cox regression analyses demonstrated that Tg737 expression was an independent factor for predicting the overall survival of HCC patients. Notably, Kaplan-Meier analysis further showed that overall survival was significantly worse among patients with low Tg737 expression. Collectively, our findings demonstrated that Tg737 is a poor prognostic marker in patients with HCC, which may be due to its ability to promote LCSCs invasion and migration. These results provide a basis for investigating of Tg737 as a novel prognostic biomarker and therapeutic target.

Cadmium remobilization from shoot to grain is related to pH of vascular bundle in rice.

The remobilization of cadmium (Cd) from shoots to grain is the key process to determine the Cd accumulation in grain. The apoplastic pH of plants is an important factor and signal in influencing on plant responding to environmental variation and inorganic elements uptake. It is proposed that pH of rice plants responds and influences on Cd remobilization from shoots to grain when rice is exposed to Cd stress. The results of hydroponic experiment showed that: pH of the rice leaf vascular bundles among 3 cultivars was almost increased, pH value of 1 cultivar was slightly increasing when rice plants were treated with Cd. The decrease degree of H+ concentration in leaf vascular bundles was different among cultivars. The cultivar with higher decreasing in H+ concentration, showed higher Cd transfer efficiency from shoots to grain. The H+ concentration of leaf vascular bundles under normal condition was negatively correlated to cadmium accumulation in leaf. Moreover, pH change was related to Cd accumulation in shots and remobilization from shoots to grain. Uncovering the role of pH response is a key component for the understanding Cd uptake and remobilization mechanism for rice production.

COMMD7 functions as molecular target in pancreatic ductal adenocarcinoma.

Our previous studies provided evidence that COMMD7 was associated with tumor progression in human solid cancer. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in pancreatic ductal adenocarcinoma (PDAC). We found that high COMMD7 expression was specifically detected in PDAC tissues and PDAC cell lines. In addition, COMMD7 overexpression positively correlated with histological differentiation and tumor node metastasis (TNM) stage. Patients with high COMMD7 expression had significantly poorer overall survival, and high COMMD7 expression was an independent predictor of poor prognosis. To further explore the regulatory mechanism of COMMD7, we used stable short hairpin RNA (shRNA)-mediated knockdown and divided the work into in vitro and in vivo experiments. In vitro, the anti-proliferation effects of COMMD7 inhibition were observed under long-time stress conditions, which correlated with cyclin D1 and Bcl-2 downregulation and Bax upregulation. We found that under short-time stress conditions, decreased COMMD7 expression also inhibited PDAC cell invasion in vitro which decreased the secretion of matrix metalloproteinase 2 (MMP-2). Moreover, extracellular signal-regulated kinase1/2 (ERK1/2) was identified as a direct target of COMMD7. The inhibition of ERK1/2 activity under short- or long-time stress conditions using specific inhibitors in COMMD7 inhibition cells all exhibited a strong tumorigenic role. In vivo, COMMD7 was sufficient to impair tumor growth. Our results suggest that COMMD7 plays an important role in the late progression of PDAC and is a potential novel target. © 2016 Wiley Periodicals, Inc.

[Sesamin Preconditioning Attenuates Myocardial Ischemia Reperfusion Injury in Rats Through Activation of Akt/eNOS Signaling Pathway].

Objective: To investigate the protective effect of sesamin on myocardial ischemia reperfusion injury in rats, and to study the possible mechanism. Methods: 50 SD rats were randomly divided into control group, sham operated group, model group, high-dose sesamin group( 160 mg / kg) and low-dose sesamin group( 80 mg / kg),with 10 rats in each group. Rats in sesamin groups were administered intragastrically with sesamin for 7 d. Then all rats except those in sham operated group were subjected to myocardial ischemia-myocardial ischemia reperfusion injury model by coronary artery ligation for 40 min and subsequent reperfusion for 120 min. Serum cardiac troponin Ⅰ( c TnⅠ) and lactate dehydrogenase( LDH),levels of total antioxidant capacity( TAOC) and nitric oxide( NO) in serum and myocardial tissues,Caspase-3 activity in myocardial tissues were detected by colorimetric assay. Cardiomyocyte apoptosis was evaluated by TUNEL assay. Phosphorylation level of endothelial nitric oxide synthase( eNOS) and Protein kinase B( Akt), protein expression of superoxide dismutase( SOD) in cardiac tissue were determined by Western blot. Results: Pretreatment with sesamin significantly ameliorated myocardial injury in rats which induced myocardial ischemia and reperfusion injury by reduced levels of serum c TnⅠand LDH( P <0. 05 or P < 0. 01). Supplementation with sesamin resulted in a significant increasing of total antioxidant capacity and NO level in serum and myocardial tissues and cardiomyocyte apoptosis( P < 0. 05 or P < 0. 01),and remarkable decrease the Caspase-3 activity in myocardial tissues and cardiomyocyte apoptosis( P < 0. 05 or P < 0. 01). Sesamin significantly up-regulated the protein expression of SOD in cardiac tissues, and the levels of phosphorylated eNOS and Akt increased notably( P < 0. 05 or P < 0. 01). Conclusion: Pretreatment with sesamin effectively ameliorated myocardial ischemia reperfusion injury in rats, and the mechanism might be related to enhancing its antioxidant capacity and the activation of Akt / eNOS signaling pathway and subsequent increase of NO synthesis and suppression of cardiac myocyte apoptosis.

[The effect of Salvianolic Acid B on the Apoptosis of HUVECs Induced by Intermittent High Glucose].

Objective: To investigate the effect of Salvianolic acid B (Sal B) on the apoptosis of human umbilical vein endothelial cells (HUVECs) induced by intermittent high glucose and to explore the possible mechanisms. Methods: HUVECs were preincubated with Sal B for 24 h, followed by incubation with intermittent high glucose (IHG, 5.5 mmol/L 12 h, 33.3 mmol/L 12 h) for 72 h. The viability of the HUVECs was determined by MTT assay, and the cells apoptosis was measured flow cytometry, respectively. The levels of nitric oxide (NO), total antioxidant capacity (T-AOC), malondialdehyde (MDA), and Caspase-3 activity were determined by colorimetric method. Intracellular ROS was evaluated by fluorescent microscopy. The protein levels of NOX4, p-eNOS, BAX, and BCL-2 were determined by Western-blot. Results: Pretreatment with Sal B significantly ameliorated IHG-induced cells injury as was manifested by increased cell viability, up-regulated eNOS activation, and promoted the release of NO in HUVECs (P < 0.05 or P < 0.01). Sal B evidently suppressed IHG-induced cell apoptosis, down-regulated the expression of BAX protein and up-regulated the expression of BCL-2 protein. The activity of Capase-3 was also significantly reduced. Pre-incubation with Sal B led to a significant enhancement of antioxidant capacity and a reduction of NOX4 protein expression, accompanied by a remarkable decrease of intracellular ROS and MDA content (P < 0.05 or P < 0.01). Conclusion: Sal B is capable of suppressing IHG-induced injury and apoptosis in HUVECs, which might be attributed to the attenuation of oxidative stress, regulation of BCL-2/BAX protein expression, and subsequent suppression of Caspase-3 activity.

[Effects of crocetin on VCAM-1 expression in human umbilical vein endothelial cells and monocyte-endothelial cell adhesion].

Crocetin, a naturally occurring carotenoid, possesses antioxidant and antiatherosclerotic properties, of which the underlying mechanism remains unclear. In the present study, we examined the effects of crocetin (0.1, 1, 10 µmol·L(-1)) on angiotensin II (Ang II, 0.1 µmol·L(-1)) induced expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and monocyte-endothelial cell adhesion. The effects of crocetin on the activation of nuclear factor kappa B (NF-κB) and intracellular reactive oxygen species (ROS) were also observed. The results demonstrated that crocetin notably suppressed Ang II induced NF-κB activation (P<0.01) and VCAM-1 expression (P<0.05, P<0.01) in HUVECs, accompanied by a markedly reduced monocyte-endothelial cell adhesion (P<0.05, P<0.01). In addition, preincubation with crocetin resulted in a significant enhancement of cellular antioxidant capacity (P<0.05, P<0.01), while Ang II induced intracellular ROS decreased markedly (P<0.05, P<0.01). These results indicated that crocetin was capable of suppressing Ang II induced VCAM-1 expression and monocyte-endothelial cell adhesion by suppression of NF-κB activation, which might be derived from the enhancement of antioxidant capacity and subsequent reduction of intracellular ROS.