Synthesis and Evaluation of [18F]AlF-NOTA-c-DVAP: A Novel PET Probe for Imaging GRP78 in Cancer.

GRP78, a member of the HSP70 superfamily, is an endoplasmic reticulum chaperone protein overexpressed in various cancers, making it a promising target for cancer imaging and therapy. Positron emission tomography (PET) imaging offers unique advantages in real time, noninvasive tumor imaging, rendering it a suitable tool for targeting GRP78 in tumor imaging to guide targeted therapy. Several studies have reported successful tumor imaging using PET probes targeting GRP78. However, existing PET probes face challenges such as low tumor uptake, inadequate in vivo distribution, and high abdominal background signal. Therefore, this study introduces a novel peptide PET probe, [18F]AlF-NOTA-c-DVAP, for targeted tumor imaging of GRP78. [18F]AlF-NOTA-c-DVAP was radiolabeled with fluoride-18 using the aluminum-[18F]fluoride ([18F]AlF) method. The study assessed the partition coefficients, stability in vitro, and metabolic stability of [18F]AlF-NOTA-c-DVAP. Micro-PET imaging, pharmacokinetic analysis, and biodistribution studies were carried out in tumor-bearing mice to evaluate the probe's performance. Docking studies and pharmacokinetic analyses of [18F]AlF-NOTA-c-DVAP were also performed. Immunohistochemical and immunofluorescence analyses were conducted to confirm GRP78 expression in tumor tissues. The probe's binding affinity to GRP78 was analyzed by molecular docking simulation. [18F]AlF-NOTA-c-DVAP was radiolabeled in just 25 min with a high yield of 51 ± 16%, a radiochemical purity of 99%, and molar activity within the range of 20-50 GBq/µmol. [18F]AlF-NOTA-c-DVAP demonstrated high stability in vitro and in vivo, with a logD value of -3.41 ± 0.03. Dynamic PET imaging of [18F]AlF-NOTA-c-DVAP in tumors showed rapid uptake and sustained retention, with minimal background uptake. Biodistribution studies revealed rapid blood clearance and excretion through the kidneys following a single-compartment reversible metabolic model. In PET imaging, the T/M ratios for A549 tumors (high GRP78 expression), MDA-MB-231 tumors (medium expression), and HepG2 tumors (low expression) at 60 min postintravenous injection were 10.48 ± 1.39, 6.25 ± 0.47, and 3.15 ± 1.15% ID/g, respectively, indicating a positive correlation with GRP78 expression. This study demonstrates the feasibility of using [18F]AlF-NOTA-c-DVAP as a PET tracer for imaging GRP78 in tumors. The probe shows promising results in terms of stability, specificity, and tumor targeting. Further research may explore the clinical utility and potential therapeutic applications of this PET tracer for cancer diagnosis.

ASH2L upregulation contributes to diabetic endothelial dysfunction in mice through STEAP4-mediated copper uptake.

Endothelial dysfunction is a common complication of diabetes mellitus (DM) and contributes to the high incidence and mortality of cardiovascular and cerebrovascular diseases. Aberrant epigenetic regulation under diabetic conditions, including histone modifications, DNA methylation, and non-coding RNAs (ncRNAs) play key roles in the initiation and progression of diabetic vascular complications. ASH2L, a H3K4me3 regulator, triggers genetic transcription, which is critical for physiological and pathogenic processes. In this study we investigated the role of ASH2L in mediating diabetic endothelial dysfunction. We showed that ASH2L expression was significantly elevated in vascular tissues from diabetic db/db mice and in rat aortic endothelial cells (RAECs) treated with high glucose medium (11 and 22 mM). Knockdown of ASH2L in RAECs markedly inhibited the deteriorating effects of high glucose, characterized by reduced oxidative stress and inflammatory responses. Deletion of endothelial ASH2L in db/db mice by injection of an adeno-associated virus (AAV)-endothelial specific system carrying shRNA against Ash2l (AAV-shAsh2l) restored the impaired endothelium-dependent relaxations, and ameliorated DM-induced vascular dysfunction. We revealed that ASH2L expression activated reductase STEAP4 transcription in vitro and in vivo, which consequently elevated Cu(I) transportation into ECs by the copper transporter CTR1. Excess copper produced by STEAP4-mediated copper uptake triggered oxidative stress and inflammatory responses, resulting in endothelial dysfunction. Our results demonstrate that hyperglycemia triggered ASH2L-STEAP4 axis contributes to diabetic endothelial dysfunction by modulating copper uptake into ECs and highlight the therapeutic potential of blocking the endothelial ASH2L in the pathogenesis of diabetic vascular complications.

Perioperative and Oncological Outcomes of Robotic Versus Open Pancreaticoduodenectomy in Low-Risk Surgical Candidates: A Multicenter Propensity Score-Matched Study.

OBJECTIVES: This study aimed to perform a multicenter comparison between robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD). BACKGROUND: Previous comparisons of RPD versus OPD have only been carried out in small, single-center studies of variable quality. METHODS: Consecutive patients who underwent RPD (n = 1032) or OPD (n = 1154) at 7 centers in China between July 2012 and July 2020 were included. A 1:1 propensity score matching (PSM) was performed. RESULTS: After PSM, 982 patients in each group were enrolled. The RPD group had significantly lower estimated blood loss (EBL) (190.0 vs 260.0 mL; P < 0.001), and a shorter postoperative 1length of hospital stay (LOS) (12.0 (9.0-16.0) days vs 14.5 (11.0-19.0) days; P < 0.001) than the OPD group. There were no significant differences in operative time, major morbidity including clinically relevant postoperative pancreatic fistula (CR-POPF), bile leakage, delayed gastric emptying, postoperative pancreatectomy hemorrhage (PPH), reoperation, readmission or 90-day mortality rates. Multivariable analysis showed R0 resection, CR-POPF, PPH and reoperation to be independent risk factors for 90-day mortality. Subgroup analysis on patients with pancreatic ductal adenocarcinoma (PDAC) (n = 326 in each subgroup) showed RPD had advantages over OPD in EBL and postoperative LOS. There were no significant differences in median disease-free survival (15.2 vs 14.3 months, P = 0.94) or median overall survival (24.2 vs 24.1 months, P = 0.88) between the 2 subgroups. CONCLUSIONS: RPD was comparable to OPD in feasibility and safety. For patients with PDAC, RPD resulted in similar oncologic and survival outcomes as OPD.

Noninvasive imaging of FAP expression using positron emission tomography: A comparative evaluation of a [18F]-labeled glycopeptide-containing FAPI with [18F]FAPI-42.

PURPOSE: Research on fibroblast activating protein (FAP)-targeting inhibitor (FAPI) has become an important focus for cancer imaging and radiotherapy. Quinoline-based tracers [68 Ga]FAPI-04 and [18F]FAPI-42 have been widely used for positron emission tomography (PET) imaging of most tumors. However, there exist some limitations of these tracers with high uptake in biliary duct system and unstable uptake in pancreas, unsuitable for abdominal tumors PET imaging. Here we developed a [18F]-labeled glycopeptide-containing FAPI tracer (named [18F]FAPT) for PET imaging of FAP in cancers. METHODS: [18F]FAPT was synthesized manually and automatically. The competitive binding to FAP, cellular internalization, and efflux characteristics were examined in vitro using A549-FAP cells. Dynamic MicroPET and biodistribution studies of [18F]FAPT were then conducted in A549-FAP and U87MG xenograft tumor mouse models compared with [18F]FAPI-42. Five healthy volunteers and three patients with cancer underwent [18F]FAPT PET/CT. RESULTS: Preclinical and clinical studies showed specific binding of [18F]FAPT to FAP and favorable pharmacokinetic properties with better hydrophilicity, lower uptake in biliary duct system, higher tumor uptake and longer tumor retention compared with [18F]FAPI-42. The biodistribution of [18F]FAPT in healthy volunteers and patients with cancer displayed low uptake in most normal tissues except for pancreas, thyroid and salivary gland, which could contribute to high tumor-to-background ratios in most cancers. CONCLUSION: [18F]FAPT is better PET tracer than [18F]FAPI-42 for imaging of biliary duct system cancer, potentially providing a tool to examine FAP expression in most cancers with high tumor-to-background ratios.

Pharmacokinetic analysis of 6-O-[18F]FEE for PET imaging of EGFR mutation.

6-O-[18F]Fluoroethylerlotinib (6-O-[18F]FEE), with a suitable half-life for commercial distribution, may be a good replacement for [11C]erlotinib to identify epidermal growth factor receptor (EGFR) positive tumors with activating mutations to tyrosine kinase inhibitors therapy. In this study, we explored the fully automated synthesis of 6-O-[18F]FEE and investigated its pharmacokinetics in tumor-bearing mice. 6-O-[18F]FEE with high specific activity (28-100 GBq/µmol) and radiochemistry purity (over 99 %) was obtained by two-step reaction and Radio-HPLC separation in PET-MF-2 V-IT-1 automated synthesizer. PET imaging of 6-O-[18F]FEE in HCC827, A431, and U87 tumor-bearing mice with different EGFR expression and mutation was performed. Uptake and blocking of PET imaging indicated that the probe specifically targeted exon 19 deleted EGFR (the quantitative analysis of tumor-to-mouse ratio for HCC827, HCC827 blocking, U87, A431 was 2.58 ± 0.24, 1.20 ± 0.15, 1.18 ± 0.19, and 1.05 ± 0.13 respectively). Dynamic imaging was used to study the pharmacokinetics of the probe in tumor-bearing mice. Logan plot graphical analysis demonstrated late linearity and a high fitting correlation coefficient (0.998), supporting reversible kinetics. According to the Akaike Information Criterion (AIC) rule, the 2-compartment reversible model was more consistent with the metabolic properties of 6-O-[18F]FEE. The automated radiosynthesis and pharmacokinetic analysis will promote clinically transformation of 6-O-[18F]FEE.

Tuning the persistent luminescence property of a Y3Al2Ga3O12:Ce3+,Yb3+ phosphor by controlling the intrinsic oxygen vacancy concentration.

Oxygen vacancies (VO), acting as electron traps, have a significant impact on the persistent luminescence (PersL) property of persistent phosphors. However, the effect of VO on PersL remains still unclear enough to limit the development of PersL materials. In this study, the VO concentration of the Y2.978Ce0.018Yb0.004Al2Ga3O12 phosphor is accurately controlled by annealing in air and 10%H2/90%Ar atmospheres at various temperatures. The results show as the annealing temperature increases during the air annealing the VO concentration, the PersL durations, and the thermoluminescence (TL) intensity constantly decreases, and the three data coincide well with each other, indicating the PersL property of the Y2.978Ce0.018Yb0.004Al2Ga3O12 is successfully tuned. Besides, the trap structure of the Y2.978Ce0.018Yb0.004Al2Ga3O12 and the charge compensation effect of Yb ions on VO defects are also discussed. By deconvoluting the TL curves, the Yb trap with a depth of 0.58 eV has been distinctly separated from the VO traps with a quasi-continuous and broad distribution of depths ranging from 0.58 to 1.21 eV. Our work demonstrates a better understanding of the relationship between VO and PersL is of great significance to design a high-performance phosphor.

Expression of fibroblast activation protein in lung cancer and its correlation with tumor glucose metabolism and histopathology.

PURPOSE: To explore the expression of fibroblast activation protein (FAP) in lung cancer (LC) and its correlation with tumor glucose metabolism and histopathology. METHODS: From June 2018 to November 2020, 73 patients with newly diagnosed LC were included. Immunohistochemical staining was used to quantify FAP expression in tumors. The histopathological type and tumor grade were determined via histopathological examination. The tumor glucose metabolism parameters and tumor maximal diameter were measured via [18F] F-FDG PET/CT. Univariate and multivariate analysis were performed to study the correlation of FAP expression levels with glucose metabolism variables and tumor histopathology. RESULTS: Positive FAP expression was observed in 97.3% (71/73) LC lesions, which was significantly higher than 87.7% (64/73) of [18F] F-FDG positivity observed on PET/CT (χ2 = 4.818, P = 0.028). In 12 early adenocarcinomas (ADCs), only three lesions (25%) were positive for [18F] F-FDG on PET/CT; however, 10 lesions (83.3%) were positive for FAP. When FAP expression was classified into low level (scores ≤ 3) and high level (scores > 4), high FAP level was found in 80.8% tumors and low FAP level in the other 19.2% tumors. High FAP level was identified in 100.0% of squamous cell carcinomas (SCCs), 85.7% of ADCs, 66.7% (4/6) of large cell neuroendocrine carcinomas (LCNCs), and 40.0% (4/10) of small cell lung cancers (SCLCs) (P < 0.05). In non-mucinous ADC lesions, on univariate analysis, FAP expression level showed a close relationship with tumor metabolism parameters (maximal standard uptake value (SUVmax), mean standard uptake value (SUVmean), and total lesion glycolysis (TLG)), tumor diameter, tumor grade, and lesion attenuation (P < 0.05). CONCLUSION: The present study demonstrates that FAP is widely expressed in LC and shows great variation in different histopathological types. A high positive rate of FAP expression implies that FAP-targeted imaging may be a sensitive modality for diagnosing LC, especially in early ADCs. Further validation with such probes is warranted.

Superiority of [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT to [18F]FDG PET/CT in delineating the primary tumor and peritoneal metastasis in initial gastric cancer.

OBJECTIVE: This study aimed to compare [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT with [18F]FDG PET/CT in the evaluation of initial gastric cancer. METHODS: We retrospectively compared [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT with [18F]FDG PET/CT in patients with initial gastric cancer from September 2020 to March 2021. Lesion detectability and the uptake of lesions quantified by the maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) were compared between the two modalities using the Wilcoxon signed-rank test, Mann-Whitney U test, and McNemar's chi-square test. RESULTS: A total of 61 patients (37 males, aged 23-81 years) were included, of which 22 underwent radical gastrectomy. For primary lesions, higher uptake of [68Ga]Ga-FAPI-04/[18F]FAPI-42 was observed compared to [18F]FDG (median SUVmax, 14.60 vs 4.35, p < 0.001), resulting in higher positive detection using [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT than [18F]FDG PET/CT (95.1% vs 73.8%, p < 0.001), particularly for tumors with signet-ring cell carcinoma (SRCC) (96.4% vs 57.1%, p < 0.001). [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT detected more positive lymph nodes than [18F]FDG PET/CT (637 vs 407). However, both modalities underestimated N staging compared to pathological N staging. [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT showed a higher sensitivity (92.3% vs 53.8%, p = 0.002) and peritoneal cancer index score (18 vs 3, p < 0.001) in peritoneum metastasis and other suspect metastases compared to [18F]FDG PET/CT. CONCLUSION: Our findings indicate that [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT outperformed [18F]FDG PET/CT in the evaluation of primary tumors with SRCC and peritoneum metastasis in initial gastric cancer. However, no clinically useful improvement was seen in N staging. KEY POINTS: • The uptake of [68Ga]Ga-FAPI-04/[18F]FAPI-42 in primary tumor and metastasis was intensely higher than that of [18F]FDG (p < 0.001) in 61 patients with initial gastric cancer. • [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT had a higher sensitivity detection in primary tumors (95.1% vs 73.8%, p < 0.001) and peritoneal metastases (92.3% vs 53.8%, p = 0.002) than [18F]FDG PET/CT. • [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT depicted more positive lymph nodes than [18F]FDG PET/CT (637 vs 407); however, both underestimated N staging compared to pathological N staging.

Physicochemical, Structural and Antioxidant Properties of Collagens from the Swim Bladder of Four Fish Species.

This study aimed to isolate and characterize pepsin-solubilized collagen (PSC) from marine and freshwater fish swim bladders. The physicochemical properties, protein pattern, amino acid composition, structure, thermal denaturation temperature, and antioxidant activity of PSC from four different swim bladder sources were investigated and compared. The results demonstrated that the four types of collagen extracted were all type I collagen. The yield of PSC extracted from grass carp (GCSB-PSC), bighead carp (BCSB-PSC), grouper (GSB-PSC), and monkfish swim bladders (MSB-PSC) were 38.98, 27.97, 18.16, and 10.35%, respectively. Compared to the other three PSCs, BCSB-PSC has the highest thermal denaturation temperature (38.60 °C). Based on FTIR spectroscopy and circular dichroism (CD) analysis, the extracted PSCs retained the triple helix and secondary structure well. Antioxidant studies showed that in the swim bladders of four species the swim bladder PSC could scavenge DPPH and ABTS radicals. Overall, swim bladders from marine and freshwater fish can be utilized as raw materials for collagen extraction, and the extracted collagen has potential commercial applications.

Diagnostic value of an enhanced MRI combined with serum CEA, CA19-9, CA125 and CA72-4 in the liver metastasis of colorectal cancer.

OBJECTIVE: This paper aims to explore the diagnostic value of enhanced magnetic resonance imaging (MRI) combined with a carcinoembryonic antigen (CEA) and carbohydrate antigen in terms of the liver metastasis of colorectal cancer. METHODS: A total of 167 colorectal cancer patients with liver metastasis and 167 colorectal cancer patients without liver metastasis were selected as the subjects. An automatic electrochemiluminescence analyser was then used to detect the tumour markers CEA, CA19-9, CA125 and CA72-4. The consistency between the MRI examination and clinical pathological examination was also analysed, and the sensitivity, specificity and positive and negative predictive values of various combined detection methods were compared. RESULTS: The abnormal rates of CEA, CA19-9, CA125 and CA72-4 in the two groups were statistically significant (P < 0.05), while the results of the enhanced MRI and clinicopathological examination for liver metastasis in patients with colon cancer were largely consistent (Kappa coefficient = 0.788, P < 0.000). However, the two methods were inconsistent. The false positive rate of the enhanced MRI examination was 15.3%, while the false negative rate was 6.0%. The specificity (94.61%), positive predictive value (92.68%) and positive likelihood ratio (12.67%) were the highest for the MRI combined with serial CEA, while the sensitivity (98.80%) and negative predictive value (97.22%) were the highest with the MRI combined with parallel CEA, and this combination returned the lowest negative likelihood ratio (0.03). CONCLUSION: The combination of MRI and CEA excludes non-metastatic patients and identifies colorectal liver metastasis cancer patients. Overall, it has a higher diagnostic value.

Acute Nitrite Exposure Induces Dysfunction and Oxidative Damage in Grass Carp Isolated Hemocytes.

To evaluate the effects of nitrite on the oxidative damage of blood cells of Grass Carp Ctenopharyngodon idella, the isolated hemocytes were exposed to nitrite (0, 1, 10, or 100 mg/L) for up to 24 h. Hemoglobin (Hb) and methemoglobin (MetHb) concentrations, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, mitochondrial membrane potential (∆Ψm), and antioxidant enzyme activity were assayed to assess hematological parameters and the antioxidant defense mechanism. Results showed a remarkable decrease in Hb concentration with increasing nitrite concentration after a 24-h exposure, while the MetHb concentration increased significantly in nitrite exposure groups. The levels of ROS, ∆Ψm, and MDA increased to varying degrees with increases in nitrite exposure concentration and time. The total antioxidant capacity, catalase (CAT) activity, glutathione peroxidase (GPx) activity, and glutathione content showed a trend of rising initially and then decreasing with prolonged exposure time. Superoxide dismutase (SOD) activity was higher in the 1-mg/L nitrite exposure group and lower in the 100-mg/L group than in the control. The relative messenger RNA expression ratios of cat, sod1, and gpx were up-regulated significantly in the 1- and 10-mg/L groups and then declined in the 100-mg/L group. Therefore, it can be concluded that nitrite exposure activates the antioxidant defense mechanism of Grass Carp hemocytes and that the balance of oxidant-antioxidant homeostasis will be undermined by higher nitrite doses or longer exposure periods.

Effect of Oxygen Vacancies on the Persistent Luminescence of Y3Al2Ga3O12:Ce3+,Yb3+ Phosphors.

The effect of oxygen vacancies (VO) and the atmosphere influence on persistent luminescence (PersL) in Y3Al2Ga3O12 (YAGG):Ce3+,Yb3+ are investigated by heating it in CO2, air, and 10% H2/90% Ar atmospheres. The VO-rich YAGG phosphors with outstanding PersL are successfully obtained by the common contribution of the reducing atmosphere and the incorporated Yb3+ ions, and the concentration of oxygen vacancies in the phosphors is characterized by X-ray photoelectron spectroscopy and electron paramagnetic resonance measurements. Compared to the best sample prepared in neutral CO2, the reduced sample shows an increase of 30% in initial intensity and 100% in duration time, while the oxidized sample decreases drastically and shows a faint and undetectable PersL. The enhancement is mainly caused by the abundant formation of VO, which is achieved by the pairing of VO with Yb2+ ions. The newly created VO by the reducing calcination is inferred to be adjacent to the Yb site and forms a compensation-type defect cluster due to the charge compensation effect. These findings reveal that understanding the effect and formation of VO is of great significance to design a high-performance phosphor.

Efficacy and safety of general anesthesia deep brain stimulation for dystonia: an individual patient data meta-analysis of 341 cases.

OBJECTIVE: The efficacy and safety of deep brain stimulation (DBS) under general anesthesia for the treatment of dystonia have not yet been confirmed with high level of evidence. This meta-analysis with pooled individual patient data aims to assess the clinical outcomes and identify the potential prognostic factors of dystonia patients who underwent general anesthesia DBS. METHODS: We searched PubMed, Web of Science, and Embase for articles describing patients with dystonia who underwent asleep DBS and had individual Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores. The relative improvement in BFMDRS scores was considered the primary outcome. Pearson correlation analyses and multivariate linear regression analysis were conducted to explore the prognostic factors. RESULTS: A total of 34 studies involving 341 patients were included. The mean postoperative improvement in BFMDRS-M (BFMDRS movement subscale) and BFMDRS-D (BFMDRS disability subscale) scores were 58.6±36.2% and 48.5±38.7% at the last follow-up visit, respectively, with a mean follow-up time of 22.4±27.6 months. Age at surgery and disease duration showed a negative correlation with the percent improvement of BFMDRS-M (%) at the last visit (r=-0.134, P=0.013; r=-0.165, P=0.006). In the stepwise multivariate regression, only disease duration remained a relevant factor. Additionally, the adverse events were acceptable. CONCLUSION: General anesthesia DBS is a safe, effective, and feasible option for dystonia patients in the long term. Shorter disease duration predicts better clinical outcomes.

Benefits of 18F-FDG PET/CT for the preoperative characterisation or staging of disease in the ampullary and duodenal papillary.

OBJECTIVES: Diagnosing ampullary and duodenal papillary carcinomas (ADPCs) is challenging. In the present study, we investigated the application value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the preoperative evaluation of these tumours. METHODS: 18F-FDG PET/CT images of 58 patients with ADPC and 28 patients with benign disease were retrospectively analysed. Preoperative 18F-FDG PET/CT was compared to contrast-enhanced (CE) CT and magnetic resonance imaging (MRI) in terms of diagnostic efficacy, certainty, staging and impact on treatment decisions. RESULTS: 18F-FDG PET/CT showed a high sensitivity (93.1%) and a medium specificity (78.6%) for diagnosing ADPC. Compared to CE CT/MRI, 18F-FDG PET/CT had a higher diagnostic specificity (78.6 vs. 35.7%, p = 0.001) but a similar sensitivity (93.1 vs. 89.6%, p = 0.508). 18F-FDG PET/CT provided a much higher diagnostic certainty than CE CT/MRI (definite reports, 88.4 vs. 50.0%, χ2 = 29.698, p < 0.001), especially for small tumours ≤ 1.5 cm, and found distant metastases in five patients. The 18F-FDG PET/CT findings affected the treatment plans of 11 patients and improved the confidence in the diagnoses of 28 patients. CONCLUSIONS: The present study demonstrated that 18F-FDG PET/CT can supplement CE CT/MRI to provide a more accurate diagnosis for ADPC, and thus, plays an important role in the decision-making process before complicated pancreaticoduodenectomy procedures. KEY POINTS: • It is a challenge for CT and MRI to diagnose ampullary carcinoma, especially at their early stage. • Our study demonstrated that the benefit of PET/CT was improving the diagnostic confidence for ampullary and duodenal papillary carcinomas. • 18F-FDG PET/CT can change the treatment decision for ampullary and duodenal papillary carcinomas.

Effect of nonionic surfactant Brij 35 on morphology, cloud point, and pigment stability in Monascus extractive fermentation.

BACKGROUND: Nonionic surfactant Brij 35 in submerged fermentation of Monascus can significantly increase Monascus pigment yield. Here, the effects of nonionic surfactant Brij 35 on Monascus pigment secretion in extractive fermentation are discussed in terms of cell morphology, cloud point change, and pigment stability. RESULTS: At Brij 35 concentrations up to 32 g L-1 , the higher concentrations led to the loosening of the network structure on the surface of the fungal wall, enhanced cell wall permeability, and increased abundance of lipid droplets. Alternatively, when the concentration of Brij 35 exceeded 32 g L-1 , a large amount of substances accumulated on the surface of the fungal wall, permeability reduced, and the degree of oil droplet dispersion in cells decreased. Further, during extractive fermentation, Brij 35 induced formation of a grid structure on the fungal wall surface beginning on day 2, increased the number of intracellular lipid droplets, and promoted intracellular pigment secretion into the extracellular environment. When the cloud point temperature in the fermentation system approached that of fermentation, the nonionic surfactant exhibited stronger Monascus pigment extraction capacity, thereby enhancing pigment yield. Hence, Brij 35 can improve pigment stability and effectively reduce damage caused by natural factors, such as light and temperature. CONCLUSION: Brij 35 promotes the secretion of pigment by changing the fungal wall structure and cloud point, as well as by improving pigment stability. © 2020 Society of Chemical Industry.

In-Situ Imaging of Azoreductase Activity in the Acute and Chronic Ulcerative Colitis Mice by a Near-Infrared Fluorescent Probe.

Azoreductase (AzoR) is an essential reductive enzyme which is closely associated with the intestinal disease such as ulcerative colitis (UC). To date, only a few fluorescent probes for detecting AzoR activity in bacteria or cells have been constructed successfully. It is still challenging to design fluorescent probes for in situ monitoring AzoR in vivo. In this paper, a near-infrared (NIR) fluorescent probe (Cy-Azo) based on hemicyanine is designed and synthesized. The emission of the probe is located at 735 nm in the NIR region, which is favorable for its application in vivo. In addition, Cy-Azo shows high sensitivity to AzoR activity with 17-fold fluorescence enhancement and is particularly selective to AzoR over other enzymes, ions, and amino acids. Meanwhile, a possible response mechanism (the azo group in Cy-Azo is reduced by AzoR and cleaved resulting in the production of Cy-NH2) was proposed and verified by HPLC, MS, and theory calculation. In addition, based on low cell cytotoxicity, Cy-Azo is successfully applied in visualizing the activity of AzoR in two cell lines (HCT116 and HepG2 cells) and three types of bacteria (E. coli, S. aureus, and P. aeruginosa). In particular, due to its NIR emission, the probe can monitor AzoR activity in acute and chronic UC mice models. To our knowledge this is the first fluorescent probe for detecting AzoR activity in vivo, which can provide much important information for the diagnosis and treatment of UC.

Effects of nonionic surfactants on pigment excretion and cell morphology in extractive fermentation of Monascus sp. NJ1.

BACKGROUND: Different nonionic surfactants in submerged fermentation of Monascus sp. demonstrate significant differences regarding increasing pigment yield. In this study, 15 surfactants from five series were analyzed to investigate the influence of nonionic surfactants on Monascus pigments, with the aim of simultaneously obtaining a novel nonionic surfactant. RESULTS: Addition of the novel surfactant Brij 35 greatly enhanced pigment excretion and demonstrated good biocompatibility. Extracellular red, orange and yellow pigments increased by 1.47-, 1.71- and 2.07-fold respectively. Production of extracellular pigments was not only related to the hydrophile-lipophile balance value (HLB) but also affected by the cloud point temperature (CP) of the fermentation medium. It was found that nonionic surfactants can improve cell membrane permeability and cell storage capacity by modifying the cell walls of Monascus mycelium and by increasing lipid droplet levels, enhancing pigment excretion. Different nonionic surfactants modify Monascus mycelium to different degrees. CONCLUSION: The novel surfactant Brij 35, which has good capacity for pigment extraction and biocompatibility, was identified in the analysis. The effects of nonionic surfactants on the secretion of pigments are related to not only the modification of the cell wall and internal structure but also the CP and HLB. © 2018 Society of Chemical Industry.

Effect of microRNA-128 on cisplatin resistance of glioma SHG-44 cells by targeting JAG1.

This current study intends to investigate the effect of microRNA-128 (miR-128) on cisplatin (DDP) resistance in glioma SHG-44 cells. SHG-44/DDP cells were transfected with miR-128 antisense oligonucleotide (ASO) and assigned into blank, resistance, NC, anti-miR-128, miR-128 mimic, si-JAG1, and anti-miR-128 + si-JAG1 groups. qRT-PCR and Western blotting were employed for determining expression of miR-128, JAG1, Bax and Bcl-2. MTT assay, Giemsa staining, and flow cytometry were applied to detect DDP resistance, cellular morphology, and cell cycle, respectively. JAG1 is targeted and negatively regulated by miR-128. In in vitro experiments, compared with the blank group, the rest groups exhibited declined miR-28 and Bax expression, lowered cell inhibition rate and apoptosis rate, but elevated JAG1 and Bcl-2 expression with cells arrested in the S phase. Compared with the resistance group, the anti-miR-128 group showed decreasedBax expression along with a lowered cell inhibition rate and apoptosis rate, but increased JAG1 and Bcl-2 expression with reduced cells arrested in the S phase; while the miR-128 mimic group showed an opposite trend; the si-JAG1 group showed decreased Bcl-2 expression and reduced cells in the S phase. In in vivo experiments, compared with the resistance group, the tumor growth rate, tumor volume, and weight as well as JAG1 expression accelerated in the anti-miR-128 group; whereas the miR-128 mimic and si-JAG1 groups exhibited an opposite trend. Our findings demonstrated that miR-128 ASO transfection might down-regulate the expression of miR-128 in SHG-44/DDP and up-regulate the DDP resistance in SHG-44/DDP cells, providing a potential treatment target for glioma.

A Dual-Response Fluorescent Probe for the Detection of Viscosity and H2S and Its Application in Studying Their Cross-Talk Influence in Mitochondria.

Intracellular viscosity is an essential microenvironmental parameter and H2S is a critical gaseous signaling molecule, which are both related to various physiological processes. It is reported that the change of viscosity and an imbalance of H2S production in the mitochondria are both associated with overexpression of amyloid betapeptide (Aß), which is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, to our best knowledge, no fluorescent probe is found for dual detection of mitochondrial viscosity and H2S. Herein, a dual-response fluorescent probe (Mito-VS) is designed and synthesized to monitor the level of viscosity and H2S, respectively. Mito-VS itself is nonfluorescent due to a free intramolecular rotation between dimethylaniline and pyridine. After the increase of viscosity, the rotation is prohibited and an intense red fluorescence is released. Upon the addition of H2S, the probe can react with H2S to form compound 3 and a strong green fluorescence can be observed. Moreover, the probe possesses a good mitochondrion-targeting ability and is applied for imaging the change of viscosity on the red channel and visualizing the variation of exogenous and endogenous H2S concentration on the green channel in mitochondria. Most importantly, the probe is capable of studying the cross-talk influence of viscosity and H2S in mitochondria, which is very beneficial for knowing the pathogenesis of AD.