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Background: Although the molecular features of pancreatic ductal adenocarcinoma (PDAC) have been well described, the impact of detailed gene mutation subtypes on disease progression remained unclear. This study aimed to evaluate the impact of different TP53 mutation subtypes on clinical characteristics and outcomes of patients with PDAC. Methods: We included 639 patients treated with PDAC in Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine between Jan 2019 and Jun 2021. The genomic alterations of PDAC were analyzed, and the association of TP53 mutation subtypes and other core gene pathway alterations with patients' clinical characteristics were evaluated by Chi-squared test, Kaplan-Meier method and Cox regression model. Results: TP53 missense mutation was significantly associated with poor differentiation in KRASmut PDAC (50.7% vs. 36.1%, P = 0.001). In small-sized (≤ 2 cm) KRASmut tumors, significantly higher LNs involvement (54.8% vs. 23.5%, P = 0.010) and distal metastic rate (20.5% vs. 2.9%, P = 0.030) were observed in those with TP53 missense mutation instead of truncating mutation. Compared with TP53 truncating mutation, missense mutation was significantly associated with reduced DFS (6.6 [5.6–7.6] vs. 9.2 [5.2–13.3] months, HR 0.368 [0.200–0.677], P = 0.005) and OS (9.6 [8.0-11.1] vs. 18.3 [6.7–30.0] months, HR 0.457 [0.248–0.842], P = 0.012) in patients who failed to receive chemotherapy, while higher OS (24.2 [20.8–27.7] vs. 23.8 [19.0–28.5] months, HR 1.461 [1.005–2.124], P = 0.047) was observed in TP53missense cases after chemotherapy. Conclusions: TP53 missense mutation was associated with poor tumor differentiation, and revealed gain-of-function properties in small-sized KRAS transformed PDAC. Nonetheless, it was not associated with insensitivity to chemotherapy, highlighting the neoadjuvant therapy before surgery as the potential optimized strategy for the treatment of a subset of patients. [ABSTRACT FROM AUTHOR]

Purpose: Venous resection and reconstruction (VR) is a feasible surgical technique to achieve optimal outcomes in selected patients with pancreatic ductal adenocarcinoma (PDAC) who undergo open pancreaticoduodenectomy (OPD). However, data regarding patient outcomes in patients who undergo VR in robotic-assisted pancreaticoduodenectomy (RPD) are scarce. Methods: All patients with a diagnosis of PDAC who underwent upfront open or robotic pancreatoduodenectomy with VR in a high-volume institution for pancreatic surgery between 2011 and 2019 were retrospectively reviewed. Perioperative and long-term outcomes were compared between the RPD and OPD cohorts. Results: A total of 84 patients were included in the final analysis, 14 patients underwent RPD with VR and 70 who had OPD with VR. Reconstructed venous patency, postoperative 30-day morbidity, and 90-day mortality were comparable; however, lymph node resection rates were lower in the RPC cohort (p = 0.029). No difference was identified in 3-year survival rates between the two groups (34.0% versus 25.7% respectively, p = 0.667). Conclusion: RPD with VR is a feasible approach for patients with PDAC and venous invasion. Further studies are needed to assess long-term outcomes compared to the open approach. [ABSTRACT FROM AUTHOR]

Background: Pancreatoduodenectomy is a complex and challenging procedure that requires meticulous tissue dissection and proficient suturing skills. Minimally invasive surgery with the utilization of robotic platforms has demonstrated advantages in perioperative patient outcomes in retrospective studies. The development of robotic pancreatoduodenectomy (RPD) in specific has progressed significantly, since first reported in 2003, and high-volume centers in pancreatic surgery are reporting large patient series with improved pain management and reduced length of stay. However, prospective studies to assess objectively the feasibility and safety of RPD compared to open pancreatoduodenectomy (OPD) are currently lacking.Methods/design: The PORTAL trial is a multicenter randomized controlled, patient-blinded, parallel-group, phase III non-inferiority trial performed in seven high-volume centers for pancreatic and robotic surgery in China (> 20 RPD and > 100 OPD annually in each participating center). The trial is designed to enroll and randomly assign 244 patients with an indication for elective pancreatoduodenectomy for malignant periampullary and pancreatic lesions, as well as premalignant and symptomatic benign periampullary and pancreatic disease. The primary outcome is time to functional recovery postoperatively, measured in days. Secondary outcomes include postoperative morbidity and mortality, as well as perioperative costs. A sub-cohort of 128 patients with pancreatic adenocarcinoma (PDAC) will also be compared to assess the percentage of patients who undergo postoperative adjuvant chemotherapy within 8 weeks, in each arm. Secondary outcomes in this cohort will include patterns of disease recurrence, recurrence-free survival, and overall survival.Discussion: The PORTAL trial is designed to assess the feasibility and safety of RPD compared to OPD, in terms of functional recovery as described previously. Additionally, this trial will explore whether RPD allows increased access to postoperative adjuvant chemotherapy, in a sub-cohort of patients with PDAC.Trial Registration: ClinicalTrials.gov NCT04400357 . Registered on May 22, 2020. [ABSTRACT FROM AUTHOR]

On‐body propagation channels show significant polarization selectivity that has dominant impacts on the on‐body link quality in wireless body area networks. For on‐body relay channels over long distances across the body, the antenna polarization configurations of the relaying nodes are crucial to determine the relay performance, thereby requiring polarization optimization schemes. In this article, narrow band flat‐fading on‐body channels at 2.484 GHz are measured to analyse their polarization distribution above the skin under static postures. The measured on‐body channels show full‐space polarization convergence and dispersion, which are modelled by an extended 3 by 3 channel polarization matrix, and a statistical channel model is also proposed. Multi‐hop polarized on‐body relay channels are analysed on the relay link capacity, which shows polarization dependency between adjacent hop channels when relaying nodes are mounted by linearly polarized antennas. Both regular and iterative polarization selection algorithms are then designed to optimise the antenna polarization configuration of the nodes. Simulations based on the proposed polarization distribution model show significant link capacity increases for two‐hop and tfhree‐hop on‐body relay channels by the optimization algorithms. The results confirm the necessity of proper polarization selection schemes for on‐body relay channels. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the short-term outcomes of open and robotic-assisted distal pancreatectomy (ODP and RDP) for benign and low-grade malignant tumors. Methods: The patients who underwent RDP and ODP for benign or low-grade malignant pancreatic tumors at our center were included. After PSM at a 1:1 ratio, the perioperative variations in the two cohorts were compared. Results: After 1:1 PSM, 219 cases of RDP and ODP were recorded. The RDP cohort showed advantages in the operative duration [120 (90–150) min vs 175 (130–210) min, P < 0.001], estimated blood loss [50 (30–175) ml vs 200 (100–300) ml, P < 0.001], spleen preservation rate (63.5% vs 26.5%, P < 0.001), infection rate (4.6% vs 12.3%, P = 0.006), and gastrointestinal function recovery [3 (2–4) vs. 3 (3–5), P = 0.019]. There were no significant differences in postoperative pancreatic fistula, postoperative hemorrhage, and delayed gastric emptying. Multivariate analysis showed that RDP (HR 0.24; 95% CI 0.16–0.36, P < 0.001), age (HR 1.02; 95% CI 1.00–1.03, P = 0.033), tumor size (HR 1.28; 95% CI 1.17–1.40, P < 0.001), pathological inflammatory neoplasm type (HR 5.12; 95% CI 2.22–11.81, P < 0.001), and estimated blood loss (HR 1.003; 95% CI 1.001–1.004, P < 0.001) were independent predictors of spleen preservation; RDP (HR 0.27; 95% CI 0.17–0.43, P < 0.001), age (HR 1.02; 95% CI 1.00–1.03, P = 0.022), elevated CA 19–9 level (HR 2.55; 95% CI 1.02–6.39, P = 0.046), tumor size (HR 1.44; 95% CI 1.29–1.61, P < 0.001), pathological inflammatory neoplasm type (HR 4.48; 95% CI 1.69–11.85, P = 0.003), and estimated blood loss (HR 1.003; 95% CI 1.001–1.004, P < 0.001) were independent predictors of spleen preservation with the Kimura technique. Conclusion: RDP has advantages in the operative time, blood loss, spleen preservation, infection rate, and gastrointestinal function recovery over ODP in treating benign and low-grade malignant pancreatic tumors. The robotic-assisted approach was an independent predictor of spleen preservation and use of the Kimura technique. [ABSTRACT FROM AUTHOR]

A sensitive and reliable method was developed for multi-target determination of 13 most widely used organic ultraviolet (UV) absorbents (including UV filters and UV stabilizers) in aquatic organism tissues. The organic UV absorbents were extracted using ultrasonic-assisted extraction, purified via gel permeation chromatography coupled with silica gel column chromatography, and determined by ultra-high performance liquid chromatography–tandem mass spectrometry. Recoveries of the UV absorbents from organism tissues mostly ranged from 70% to 120% from fish filet with satisfactory reproducibility. Method quantification limits were 0.003–1.0 ng g −1 dry weight (dw) except for 2-ethylhexyl 4-methoxycinnamate. This method has been applied to analysis of the UV absorbents in wild and farmed aquatic organisms collected from the Pearl River Estuary, South China. 2-Hydroxy-4-methoxybenzophenone and UV-P were frequently detected in both wild and farmed marine organisms at low ng g −1 dw. 3-(4-Methylbenzylidene)camphor and most of the benzotriazole UV stabilizers were also frequently detected in maricultured fish. Octocrylene and 2-ethylhexyl 4-methoxycinnamate were not detected in any sample. This work lays basis for in-depth study about bioaccumulation and biomagnification of the UV absorbents in marine environment. [ABSTRACT FROM AUTHOR]

RuO2–Au compositenanoparticles (RuO2–Au CNPs) are synthesized viaa simple calcination of RuNPsand AuNPs encapsulated within extra-large mesocages of mesoporoussilica (EP-FDU-12). Both the Ru/Au ratio (0.02:0.2) and the nanostructureof the mesoporous supports are critical for its successful formation.Surface-enhanced Raman scattering (SERS) effects are observed forRuO2composite because of the interaction between RuO2and Au of the RuO2–Au CNPs. The nanocontactmodifies the electronic and chemical properties of Au and RuO2, respectively, which in turn benefits their catalytic performancewith enhanced activities and reduced coking-deposition content ingas-phase cyclohexanol-selective oxidation. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia in the elderly. Ubiquitin proteasome system (UPS) is critical for protein homeostasis, while the functional decline of UPS with age contributes to the pathogenesis of AD. Ubiquitin-conjugating enzyme E2O (UBE2O), an E2-E3 hybrid enzyme, is a major component of UPS. However, its role in AD pathogenesis has not been fully defined. Objective: We aimed to identify the age-associated expression of UBE2O and its role AD pathogenesis. Methods: Western blot analysis were used to assess expression of UBE2O in organs/tissues and cell lines. Immunofluorescence staining was performed to examine the cellular distribution of UBE2O. Neuronal death was determined by the activity of lactate dehydrogenase. Results: UBE2O is highly expressed in the cortex and hippocampus. It is predominantly expressed in neurons but not in glial cells. The peak expression of UBE2O is at postnatal day 17 and 14 in the cortex and hippocampus, respectively. Moreover its expression is gradually reduced with age. Importantly, UBE2O is significantly reduced in both cortex and hippocampus of AD mice. Consistently, overexpression of amyloid-β protein precursor (AβPP) with a pathogenic mutation (AβPPswe) for AD reduces the expression of UBE2O and promotes neuronal death, while increased expression of UBE2O rescues AβPPswe-induced neuronal death. Conclusion: Our study indicates that age-associated reduction of UBE2O may facilitates neuronal death in AD, while increasing UBE2O expression or activity may be a potential approach for AD treatment by inhibiting neuronal death. [ABSTRACT FROM AUTHOR]

Rationale: Ultra-high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC/ESI-MS) has been frequently used for chemical analysis. A redox reaction in the ESI source has been observed during the ionization process. However, it is still unclear whether this redox reaction can take place on UPLC columns. Methods: In this study, the oxidation reactions potentially occurring on UPLC columns were investigated using polyphenols including baicalin, baicalein, propyl gallate (PG), quercetin-3-rhamnoside (QR), rutin, naringin and 2,3,5,4'-tetrahydroxystilbene-2- Ο-β-D-glucoside (THS-G) as model compounds. The on-column oxidation reaction was ascertained by post-column infusion of antioxidants such as ammonium sulfide ((NH4)2S). The oxidized products were reduced to their parent forms in the ESI source. This on-column oxidation reaction was further confirmed by means of post-column infusion of baicalin solution. Results: On-column oxidation reactions were observed and confirmed for baicalin, baicalein, PG, rutin, and QR. The exact reaction site was located at the outlet frits of the UPLC columns. (NH4)2S was proved to be the most suitable reducing agent among the tested antioxidants for eliminating negative effects caused by on-column oxidation reaction. It was subsequently proposed to be an efficient additive to suppress oxidation reactions in the ESI source. Conclusions: Oxidation reactions can take place at the outlet frits of UPLC columns. Ascertaining on-column oxidation reactions and consequently eliminating relevant negative effects are of great interest for determination of oxidation-sensitive compounds such as polyphenols. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Hazardous heavy metals and organic substances removal is of great significance for ensuring the safety of aquatic-ecosystem, yet the highly effective and selective extraction always remains challenging. To address this problem, magnetic hollow microcubes were fabricated through thermal carbonization of Fe 3 O 4 -COOH@ γ-CD-MOFs, and core-shell structured precursors were in-situ greenly constructed on a large scale via microwave-assisted self-assembly strategy. As noted, the development of secondary crystallization was utilized to achieve uniform dispersion of cores within MOFs frameworks and thus improved magnetic and adsorption ability of composites. Acquired magnetic Fe 3 O 4 @HC not only can harvest excellent extraction of heavy metals (Cd, Pb, and Cu of 129.87, 151.05, and 106.98 mg·g−1) but also exhibit highly selective adsorption ability for cationic organics (separation efficiency higher than 95.0 %). Impressively, Fe 3 O 4 @HC achieved outstanding adsorption (60–80 %) of Cd in realistic mussel cooking broth with no obvious loss in amino acid. Characterizations better offer mechanistic insight into the enhanced selectivity of positively charged pollutants can be attributed to synergistic effect of ions exchange and electrostatic interaction of abundant oxygen-containing functional groups. Our study provides a feasible route by rationally developing core-shell structured composites to promote the practical applications of sustainable water treatment and value-added utilization of processing by-products. [Display omitted] • Core-shell Fe 3 O 4 @CD-MOFs is fabricated by microwave-assisted self-assembly strategy. • Structure and dispersion of core-shell component is controlled via secondary crystallization. • Derived hollow Fe 3 O 4 @HC show outstanding affinity to heavy metals and cationic organics. • Magnetic microcubes harvest stable performance toward Cd in practical mussel cooking broth. • Selective exchange and electrostatic interaction led active sites fast adsorb cationic pollutants. [ABSTRACT FROM AUTHOR]

Background: The pre‐adjuvant chemotherapy (PAC) status of postoperative pancreatic ductal adenocarcinoma (PDAC) patients has not been studied and elaborated well previously. Method: The association of PAC variables and prognoses was explored using a multivariable Cox model, restricted cubic spline analysis, and correlation analysis. The main outcomes were overall survival (OS) and progression‐free survival (PFS). The secondary outcome was chemotherapy completeness (CHC). Results: A total of 401 eligible patients were enrolled in sequential surgery and chemotherapy. The chemotherapy regimen, PAC fasting blood glucose (FBG), and elevated fasting blood glucose (eFBG) status were associated with CHC (regimen types: p = 0.005, continuous FBG: p = 0.014, eFBG status: p = 0.012). Early administration of adjuvant chemotherapy (<34 days) was a risk factor for the limited OS and PFS (OS: aHR: 1.61 [1.09–2.38], p = 0.016; PFS: aHR: 1.91 [1.29–2.82], p = 0.001). Patients with higher PAC body mass index (BMI), receiving Gemcap regimen, and with lower PAC tumor marker value were observed with better survival prognoses (PAC BMI: OS: 0.927 [0.875–0.983], p = 0.011; Gemcap: OS: 0.533 [0.312–0.913], p = 0.022; Gemcap: PFS: 0.560 [0.341–0.922], p = 0.023; PAC CA125: OS: 1.004 [1.002–1.006], p < 0.001; PAC CA125: PFS: 1.003 [1.000–1.005], p = 0.031; PAC CEA: OS: 1.050 [1.026–1.074], p < 0.001). The BMI decrease was mainly concentrated in the first 3 months of chemotherapy courses (first 3 months: p < 0.001; latter 3 months: p = 0.097). And CEA, compared to CA125 and CA199, was a better prognostic indicator (CEA: first 3 months: PFS p = 0.011, OS p < 0.001; latter 3 months: PFS p = 0.024, OS p = 0.041). Conclusion: PDAC patients should be treated with adjuvant chemotherapy over 34 postoperative days. PAC sarcopenia was a risk factor for OS, but not PFS and limited CHC. Those with higher PAC FBG levels were more likely to finish chemotherapy. CEA, compared to CA125 and CA199, was a better prognostic indicator. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a lipid-laden CAF subpopulation marked by ABCA8a in Setd2 -deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation toward lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells. [Display omitted] • Enhanced OXPHOS in SETD2 -deficient human and mouse pancreatic tumors • Identification of lipid-laden CAF marked by ABCA8a in Setd2 -deficient pancreatic tumors • ABCA8a facilitates lipid transfer from lipid-laden CAFs to tumor cells for fueling OXPHOS • Tumor SETD2 loss unleashes BMP signaling to promote lipid-laden CAF differentiation Niu et al. identify a lipid-laden CAF subset marked by ABCA8a in Setd2 -deficient pancreatic tumors, which transports lipids and metabolically sustains tumor growth via OXPHOS. Both in vivo and ex vivo experiments reveal that tumor-intrinsic SETD2 loss induces epigenetic reprogramming and unleashes BMP signaling to foster the differentiation of lipid-laden CAFs. [ABSTRACT FROM AUTHOR]

Background: Robotic-assisted minimally invasive surgery is associated with worse oncologic outcomes for some but not other types of cancers. We conducted a propensity score-matched analysis to compare oncologic outcomes of robotic-assisted laparoscopic (RPD) vs. open pancreatoduodenectomy (OPD) for pancreatic ductal adenocarcinoma (PDAC).Methods: Treatment-naïve PDAC patients undergoing either RPD or OPD at our hospital between January 2013 and December 2017 were included. Propensity score matching was conducted at a ratio of 1:2. The primary outcome was disease-free survival (DFS) and overall survival (OS).Results: A total of 672 cases were identified. The propensity score-matched cohort included 105 patients receiving RPD and 210 patients receiving OPD. The 2 groups did not differ in the number of retrieved lymph nodes [11 (7-16) vs. 11 (6-17), P = 0.622] and R0 resection rate (88.6% vs. 89.0%, P = 0.899). There was no statistically significant difference in median DFS (14 [95% CI 11-22] vs. 12 [95% CI 10-14] months (HR 0.94; 95% CI 0.87-1.50; log-rank P = 0.345) and median OS (27 [95% CI 22-35] vs. 20 [95% CI 18-24] months (HR 0.77; 95% CI 0.57-1.04; log-rank P = 0.087) between the two groups. Multivariate COX analysis showed that RPD was not an independent predictor of DFS (HR 0.90; 95% CI 0.68-1.19, P = 0.456) or OS (HR 0.77; 95% CI 0.57-1.05, P = 0.094).Conclusion: Comparable DFS and OS were observed between patients receiving RPD and OPD. This preliminary finding requires further confirmation with prospective randomized controlled trials. [ABSTRACT FROM AUTHOR]

Objective: Our study examined the association between molecular features and clinical results of pancreatic ductal adenocarcinoma (PDAC) patients, aiming to explore the genomic determinants of the recurrence and prognosis of PDAC after surgical removal. Methods: This retrospective study analyzed 181 PDAC patients who received pancreatectomy and adjuvant chemotherapy, with 67 patients in the training set. An internal validation set of 48 patients and an external validation set of 66 patients were used to validate the result. Comprehensive genomic profiling was performed on formalin‐fixed paraffin‐embedded (FFPE) tumor specimens to determine genomic features using the designed cancer‐related gene panel based on next‐generation sequencing (NGS). Results: Significant differences were identified between the late recurrence (LR) group and early recurrence (ER) group in tumor copy number instability (CNI) levels. Next, the utility of low CNI (the middle and lowest tertile) with regard to predicting LR was confirmed in the training, internal, and external validation sets. Further univariate and multivariate analyses revealed that CNI was an independent predictive and prognostic biomarker, and had higher predictive accuracy for LR than CA19‐9 level, pathological stage, tumor size, and age. In addition, CNI combined with lymph node (LN) metastasis status could provide a more accurate model for predicting LR of PDAC. Conclusion: We discovered and validated the association between CNI and clinical outcome in 181 patients with resectable PDAC, demonstrating the utility of lower tumor CNI levels as biomarkers of postoperative LR and favorable prognosis. Moreover, the combination of CNI and LN metastasis status elevated the predictive accuracy and illuminated strategies for patient stratification. [ABSTRACT FROM AUTHOR]

Objective: Middle pancreatectomy (MP) is safe and feasible in patients with benign or low-grade malignant tumors located at the neck or proximal body of the pancreas. As a tissue-sparing operation, MP can preserve normal pancreatic function and reduce the risk of postoperative endocrine and exocrine insufficiency. However, the morbidity, especially the postoperative pancreatic fistula (POPF) rate, remains high. A robot-assisted surgical system may provide patients with less trauma; however, there are few reports on robot-assisted middle pancreatectomy (RMP). We describe the experience of RMP at our center to illustrate the learning curve (LC).Methods: From August 2010 to July 2017, 100 patients underwent RMP in the Pancreatic Disease Center of Shanghai Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine. Patient characteristics, operative outcomes, and oncological outcomes were collected and analyzed. The CUSUM curve was analyzed according to operative time and estimated blood loss (EBL) and was used to describe the LC and identify the flexion points.Results: Among the 100 patients who underwent RMP in our hospital, the mean age was 47.5 ± 14.2 years, and 69 patients were female. From the CUSUM curve, we found two flexion points: cases 12 and 44. After 44 cases, the rate of improvement was much faster. We separated the patients into two groups based on the LC (cases 1-44 and cases 45-100). There were significant improvements in operative time (173.1 ± 44.7 min vs. 137.3 ± 30.1 min, p < 0.001) and EBL (103.4 ± 90.0 ml vs. 69.3 ± 53.9 ml, p = 0.021). The overall POPF rate was 32% (32/100), while the incidence rate of biochemical leakage was 14% (14/100). However, there was no significant difference in the risk of POPF or other complications between the two groups. The postoperative length of stay (LOS) was also not different. The 90-day mortality rate was 1%. From our long-term follow-up, pancreatic function was preserved in most patients, with only three cases of endocrine insufficiency and two cases of exocrine insufficiency.Conclusion: RMP was helpful and a good choice for the selected patients. PF was the main complication and has not been improved until now. There were two flexion points in the LC at cases 12 and 44. More cases are needed to gain more experience. A larger sample size and prospective studies are needed to verify the advantage of RMP. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the outcome of pancreatic metastatic renal cell carcinoma (PmRCC) after treatment and share the relevent results. Methods: In total, 13 patients with PmRCC were diagnosed and treated in our institution from December 2013 to October 2017. We retrospectively reviewed the records and analyzed the patient demographics, perioperative outcomes, and overall survival. Simultaneously, our experience including treatment and misdiagnosis was shared. Results: The median time between nephrectomy and reoperation for pancreatic recurrence was 11 years (range 1–20 years). Four patients had multiple tumors and nine patients had solitary tumor. Five patients accepted distal pancreatectomy, and five patients underwent pancreaticoduodenectomy. One patient underwent total pancreatectomy, one patient underwent duodenum-preserving pancreatic head resection plus distal pancreatectomy, and one patient underwent exploratory laparotomy and gastrointestinal bypass due to widespread metastasis with clear obstructive symptoms. The misdiagnosis rate of preoperative diagnosis at our center was 69.2% (9/13). The median follow-up duration was 26 months (range 7–53 months, until June 2018). By the end of follow-up, 12 patients were alive and one patient died of gastrointestinal bleeding within 1 month after surgery. Conclusions: PmRCCs are uncommon, but pancreatic metastasectomy has a relatively good prognosis and may, therefore, be a good therapeutic choice for patients with PmRCCs. Because PmRCC occurs long after the primary tumor resection, long-term follow-up is necessary. Besides, detailed medical history and specific manifestation in imaging features could contribute to avoiding misdiagnosis. [ABSTRACT FROM AUTHOR]

Abstract: The peptide segment of prostatic acid phosphatase (PAP248–286) aggregates to form SEVI (semen‐derived enhancer of virus infection) amyloid fibrils. These are characteristic seminal amyloids that have the ability to promote the effect of HIV infection. In this paper, we explore the binding of sulfonated compounds with PAP248–286 through an in silico study. Three derivatives of suramin, NF110, NF279, and NF340, are selected. All of these sulfonated molecules bind to PAP248–286 and alter the conformation of the peptide, even though they have various structures, sizes, and configurations. The compounds bind with PAP248–286 through multiple interactions, such as hydrogen‐bonding interactions, hydrophobic interactions, π–π stacking interactions, and electrostatic interactions. However, NF110, which has an X‐shaped configuration, has the highest binding affinity of the three derivatives investigated. We also perform surface plasmon resonance and a Congo red assay to validate the results. The interactions between PAP248–286 and the sulfonated compounds are proposed to depend on the orientations of the sulfonate groups and the specific configurations of the compounds instead of the number of sulfonate groups. NF110 molecules occupy the exposed binding sites of PAP248–286, blocking interactions between the peptides. Therefore, these compounds are important in inhibiting the aggregation of PAP248–286. Herein, we provide useful information to develop new efficient microbicides to antagonize seminal amyloid fibrils and to block HIV transmission. [ABSTRACT FROM AUTHOR]

CCL17 is well known for its ability to engage CCR4 + CD8 + T cells, which have been shown to play a critical role in preventing tumorigenesis. In this study, we attempted to inhibit in vivo pancreatic tumorigenesis by engaging murine CCR4 + CD8 + T cells through a drug-eluting scaffold with a payload of CCL17. The drug-eluting scaffold was fabricated by electrospinning polyglyconate and porcine gelatin. The electrospun scaffold featured randomly distributed non-woven fibers with diameters ranging from 1 μm to 4 μm. The in vitro study confirmed that scaffolding materials were non-cytotoxic to pancreatic cancer cells. The in vivo study showed an increased presence of murine CCR4 + CD8 + T cells into the tumor mass treated with drug-eluting scaffold compared to those with non-eluting scaffold or the control groups. The weights of tumor masses were 132.04 mg ± 12.25 mg in the control group, 158.12 mg ± 18.98 mg in the NES group and 96.22 mg ± 14.56 mg in the DES group, respectively. The volumes of tumor masses were 1035.21 mm 3 ± 128.97 mm 3 in the control group, 978.56 mm 3 ± 110.19 mm 3 in the NES group and 634.35 mm 3 ± 87.12 mm 3 in the DES group, respectively. Further study showed that the increased presence of CCR4 + CD8 + T cells also inhibited the hepatic metastasis of pancreatic cancer cells. Our study shed a new light on the post-operative treatment of pancreatic cancer to prevent the recurrence. [ABSTRACT FROM AUTHOR]

A variety of personal care products have been classified as emerging contaminants (ECs). Occurrence, fate, spatial and vertical profiles of 13 ultraviolet absorbents, triclocarban (TCC) and its dechlorinated products, triclosan (TCS), 2-phenylphenol and parabens were investigated in riverine and estuarine sediment of the Pearl River catchment, China. Bisphenol A (BPA), a widely applied plasticizer, was also investigated. The ECs were widely present in the bed sediment. TCC was the most abundant with a maximum concentration of 332 ng g −1 dry weight. The other prominent ECs included BPA, TCS, octocrylene, and benzotriazole UV stabilizers UV326 and UV328. Treated wastewater effluent was the major source of the ECs in the riverine sediment. TCC, BPA, TCS, methyparaben, UV531, UV326, and UV328 were also detected throughout the estuarine sediment cores, indicating their persistence in the sediment. Temporal trends of the ECs in the sediment cores reflected a combined effect of industrial development, population growth, human life quality improvement, and waste treatment capacity in the Pearl River Delta over the last decades. TCC dechlorination products were frequently detected in the bed sediment with higher levels near treated effluent outlets but only occasionally observed in the sediment cores, suggesting insignificant in-situ TCC dechlorination in the sediment. [ABSTRACT FROM AUTHOR]

Metabolite identification is crucial for revealing metabolic pathways and comprehensive potential toxicities of polycyclic aromatic hydrocarbons (PAHs) in human body. In this work, a quasi-targeted analysis strategy was proposed for metabolite identification of monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) in human urine using liquid chromatography triple quadruple mass spectrometry (LC–QqQ-MS/MS) combined with liquid chromatography high resolution mass spectrometry (LC–HRMS). Potential metabolites of OH-PAHs were preliminarily screened out by LC–QqQ-MS/MS in association with filtering in a self-constructed information list of possible metabolites, followed by further identification and confirmation with LC–HRMS. The developed method can provide more reliable and systematic results compared with traditional untargeted analysis using LC–HRMS. In addition, data processing for LC–HRMS analysis were greatly simplified. This quasi-targeted analysis method was successfully applied to identifying phase I and phase II metabolites of OH-PAHs in human urine. Five metabolites of hydroxynaphthalene, seven of hydroxyfluorene, four of hydroxyphenanthrene, and three of hydroxypyrene were tentatively identified. Metabolic pathways of PAHs in human body were putatively revealed based on the identified metabolites. The experimental results will be valuable for investigating the metabolic processes of PAHs in human body, and the quasi-targeted analysis strategy can be expanded to the metabolite identification and profiling of other compounds in vivo. [ABSTRACT FROM AUTHOR]

Pharmaceutical and personal care products (PPCPs), including antibiotics, azole anti-fungals, non-steroid anti-inflammatory drugs, lipid regulators, parabens, antiseptics, and bisphenol A, were investigated in groundwater and reservoirs in the vicinity of two municipal landfills in the metropolis of Guangzhou, South China. Dehydroerythromycin, sulfamethoxazole, fluconazole, salicylic acid, methylparaben, triclosan, and bisphenol A were the mostly frequently detected PPCPs in the groundwater at low ng L − 1 levels. In the reservoirs, the PPCPs were widely detected at higher frequencies and concentrations, especially sulfamethoxazole, propiconazole, and ibuprofen, with maximal concentrations above 1 μg L − 1 . The PPCPs in the groundwater did not show significant seasonal differences or spatial trends. However, in the reservoirs, higher PPCP concentrations were observed in spring than in other seasons. The anti-bacterials in the groundwater posed medium risks to algae. In the reservoirs, the sulfonamides and macrolides posed low to high risks, while ibuprofen, salicylic acid, and clofibric acid presented low to medium risks to aquatic organisms. Overall, the results showed that the PPCP contaminants and subsequent ecological risks in the groundwater and surface water in the vicinity of the landfills may be of serious concern. More research is needed to better correlate the landfill leachates and PPCP contamination in the nearby aquatic environments. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that long non-coding RNAs (lncRNAs) play important roles in cancer biology and that lncRNA gas5 (growth arrest-specific 5) regulates breast cancer cell growth. However, the role of gas5 in pancreatic cancer progression remains largely unknown. In the current study, we assay the expression level of gas5 in pancreatic cancer tissues and define the role of gas5 in the regulation of pancreatic cancer cell proliferation. We verify that the expression level of gas5 is significantly decreased in pancreatic cancer tissues compared with normal control. Overexpression of gas5 in pancreatic cancer cells inhibits cell proliferation, whereas gas5 inhibition induces a significant decrease in G0/G1 phase and an increase in S phase. We further demonstrate that gas5 negatively regulates CDK6 (cyclin-dependent kinase 6) expression in vitro and in vivo. More importantly, knockdown of CDK6 partially abrogates gas5-siRNA-induced cell proliferation. These data suggest an important role of gas5 in the molecular etiology of pancreatic cancer and implicate the potential application of gas5 in pancreatic cancer therapy. [ABSTRACT FROM AUTHOR]