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Steroid receptors activate gene transcription through recruitment of a number of coregulators to facilitate histone modification, chromatin remodeling, and general transcription machinery stabilization. Understanding the structures of full-length steroid receptor and coregulatory complexes has been difficult due to their large molecular sizes and dynamic structural conformations. Recent developments in cryo-electron microscopy (cryoEM) technology and proteomics have advanced the structural studies of steroid receptor complexes. Here, we will review the insights we learned from cryoEM studies of the estrogen and androgen receptor transcriptional complexes. Despite similar domain organizations, the two receptors have different coregulator interaction modes. The cryoEM structures now have revealed the fundamental differences between the two receptors and their functional mechanisms.

Purpose: This study intends to explore the role of preoperative main pancreatic duct stent placement in reducing intra-operative main pancreatic duct damaging rate and the incidence of postoperative pancreatic leakage. Methods: A retrospective cohort analysis was performed for all patients with pancreatic head benign tumors who were treated with local excision. The patients were divided into two groups (Standard VS Stent) depending on whether received main pancreatic duct stent placement prior to surgery or not. Results: A total of 33 patients were finally included in the analytical pool. Compared with Standard group, patients in the Stent group had shorter distance between tumor and MPD (p=0.01) and presented with larger tumors (ppp (p>0.05). Conclusion: MPD stent placement prior to surgery can facilitate the surgery, minimize MPD injury and decreasing occurrence of postoperative fistula.

Human Nogo-66 receptor 1 (NgR1) is a receptor for mammalian orthoreoviruses (reoviruses), but the mechanism of virus-receptor engagement is unknown. NgR1 binds a variety of structurally dissimilar ligands in the adult central nervous system (CNS) to inhibit axon outgrowth. Disruption of ligand binding to NgR1 and subsequent signaling can improve neuron regrowth, making NgR1 an important therapeutic target for diverse conditions such as spinal crush injuries and Alzheimer disease. To elucidate how NgR1 mediates cell binding and entry of reovirus, we defined the affinity of interaction between virus and receptor, determined the structure of the virus-receptor complex, and identified residues in the receptor required for virus binding and infection. These studies revealed that NgR1 sequences in a central concave region of the molecule establish a bridge between two copies of the viral capsid protein, σ3. This unusual binding interface produces high-avidity interactions between virus and receptor and likely primes early entry steps. NgR1 sequences engaged by reovirus also are required for NgR1 binding to ligands expressed by neurons and oligodendrocytes. These studies redefine models of reovirus cell-attachment and highlight the evolution of viruses to engage multiple receptors using distinct capsid components.

Single-stranded RNA bacteriophages (ssRNA phages) infect Gram-negative bacteria via a single maturation protein (Mat), which attaches to a retractile pilus of the host. Here we present structures of the ssRNA phage MS2 in complex with the Escherichia coli F-pilus, showing a network of hydrophobic and electrostatic interactions at the Mat-pilus interface. Moreover, binding of the pilus induces slight orientational variations of the Mat relative to the rest of the phage capsid, priming the Mat-connected genomic RNA (gRNA) for its release from the virions. The exposed tip of the attached Mat points opposite to the direction of the pilus retraction, which may facilitate the translocation of the gRNA from the capsid into the host cytosol. In addition, our structures determine the orientation of the assembled F-pilin subunits relative to the cell envelope, providing insights into the F-like type IV secretion systems., Single-stranded RNA bacteriophages use a single maturation protein (Mat) to attach to a retractile pilus of the bacterial host. Here, the authors report the structures of the MS2 phage bound to the host receptor F-pili and define the orientations of Mat relative to the cell and emanating F-pili, providing new insights into the F-like type IV secretion systems.

Background & AimsHuman intestinal epithelial organoids (enteroids and colonoids) are tissue cultures used for understanding the physiology of the intestinal epithelium. Here, we explored the effect on the transcriptome of common variations in culture methods, including extracellular matrix substrate, format, tissue segment, differentiation status, and patient heterogeneity.MethodsRNA-sequencing datasets from 251 experiments performed on 35 human enteroid and colonoid lines from 28 patients were aggregated from several groups in the Texas Medical Center. DESeq2 and Gene Set Enrichment Analysis (GSEA) was used to identify differentially expressed genes and enriched of pathways.ResultsPERMANOVA, Pearson correlations, and dendrogram analysis of all data indicated three tiers of influence of culture methods on transcriptomic variation: substrate (collagen vs. Matrigel) and format (3D, transwell, and monolayer) had the largest effect (7,271-1,305 differentially expressed genes-DEGs); segment of origin (duodenum, jejunum, ileum, colon) and differentiation status had a moderate effect (5,977-420 DEGs), and patient heterogeneity and specific experimental manipulations (e.g., pathogen infection) had the smallest effect. GSEA identified hundreds of pathways that varied between culture methods, such as IL1 cytokine signaling enriched in transwell vs. monolayer cultures, and cholesterol biosynthesis genes enriched in Matrigel vs. collagen cultures.ConclusionsSurprisingly large differences in organoid transcriptome were driven by variations in culture methods such as format and substrate, whereas experimental manipulations such as infection had modest effects. These results show that common variations in culture conditions can have large effects on intestinal organoids and should be accounted for when designing experiments and comparing results between laboratories. Our data constitute the largest RNA-seq dataset interrogating human intestinal organoids.

The ultrahigh altitude, complex environment and other problems of Qinghai converter station bring great challenges to the equipment selection and the external insulation design in the construction of UHV converter station project. The external insulation design of UHV DC transmission mainly depends on the contamination performance of insulators under working voltage, and the contamination performance includes the natural contamination accumulation performance of insulators and the flash-over performance of contaminated insulators. First, the accurate prediction of pollution level of the area where the converter station site is located is the primary premise of the external insulation design of the converter station. This paper investigates the meteorological and industrial pollution sources and the situations about operation of power transmission and transformation equipment in Hainan Tibetan Autonomous Prefecture, Qinghai Province, especially in the proposed ±800 kV Qinghai converter station site and its surrounding areas, and predicts the contamination accumulation level of AC insulators in the site and its surrounding areas. On this basis, the pollution level of DC field equipment of converter station is further predicted according to the prediction of DC/AC pollution accumulation ratio. Then, aiming at the problem of difficult selection of large-diameter bushing equipment in Qinghai station, a typical bushing is selected to carry out the experimental study on flash-over performance, and the rule of flash-over characteristics of bushing is obtained. Finally, in consideration of the altitude correction of the converter station, this paper puts forward suggestions on the configuration of external insulation of the bushing of Qinghai converter station, which provides a basis for the external insulation design in the construction of Qinghai converter station project.

Virtual pets are an alternative to real pets, providing a substitute for people with allergies or preparing people for adopting a real pet. Recent advancements in mixed reality pave the way for virtual pets to provide a more natural and seamless experience for users. However, one key challenge is embedding environmental awareness into the virtual pet (e.g., identifying the food bowl’s location) so that they can behave naturally in the real world. We propose a novel approach to synthesize virtual pet behaviors by considering scene semantics, enabling a virtual pet to behave naturally in mixed reality. Given a scene captured from the real world, our approach synthesizes a sequence of pet behaviors (e.g., resting after eating). Then, we assign each behavior in the sequence to a location in the real scene. We conducted user studies to evaluate our approach, which showed the efficacy of our approach in synthesizing natural virtual pet behaviors.

Rotavirus, a global causative agent of life-threatening gastroenteritis, is a double-stranded RNA (dsRNA) virus in the family Reoviridae. A common feature in this family of viruses, containing multiple dsRNA segments, is their ability to transcribe the genomic segments within the capsid interior and extrude the capped mRNA. In rotavirus the 5’ capping of the RNA Is carried out by the structural protein VP3. Here, using a combination of cryo-EM and X-ray crystallography, we describe how rotavirus VP3 with multiple domains integrates as many as five enzymatic activities for the RNA capping activity.

Purpose. Nonsurgical therapies, including biotherapy, chemotherapy, and liver-directed therapy, provided a limit survival benefit for PNET patients with hepatic metastases. With the development of liver resection technique, there was a controversy on whether to perform a liver resection for these patients. Methods. A computerized search was made of the Medline/PubMed, EMbase, Cochrane Library, and SinoMed (CBM) before March 2018. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and nonliver resection treatments based on the evaluation of morbidity, 30-day mortality, symptom relief rate, and 1-, 3-, and 5-year survival. Two investigators reviewed all included articles and extracted the data of them. The meta-analysis was performed via Review Manager 5.3 software. Results. A total of 13 cohort studies with 1524 patients were included in this meta-analysis. Compared with the nonliver resection group, liver resection group had a longer 1-, 3-, and 5-year survival time and a higher symptom relief with an acceptable mortality and morbidity. Conclusions. Liver resection is a safe treatment and could significantly prolong the long-term prognosis for highly selected patients with resectable liver metastases from PNET. Further randomized, controlled trials are needed.

The authors investigated the effect of the insulator hydrophilic fraction on the pollution flashover performance by the up-and-down method. The hydrophobicity of parts subjected to a high electric field intensity such as two ends of an insulator, may be weakened by corona discharge. In this study, they simulated the behaviour of composite insulator surfaces at six hydrophilic fractions. Furthermore, arc discharge was recorded using a high-speed camera and the probability of arc discharge was analysed. They found that as the hydrophilic fraction was increased, the 50% probable flashover voltage first decreased and then increased. The wetting process and discharge type could be classified into two types and the flashover process could be divided into two stages by a clear hydrophilic fraction boundary through leakage current characteristic, discharge probability, and arc shape analysis. The results indicated that uneven hydrophobicity loss might lead to further flashover voltage reduction, up to 26.5% lower, than that with uniform hydrophilicity. This should be considered in transmission line design and maintenance of composite insulators.

Zhongyi Guo,1 Feng Wang,2 Yang Di,1 Lie Yao,1 Xinzhe Yu,1 Deliang Fu,3 Ji Li,3 Chen Jin1 1Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, China; 2School of Pharmacy & Key Laboratory of Smart Drug Delivery, Fudan University, Shanghai, China; 3Pancreatic Disease Institute, Huashan Hospital, Fudan University, Shanghai, China Purpose: Gemcitabine is currently the standard first-line chemotherapeutic drug for treating pancreatic cancer. However, many factors can contribute to gemcitabine resistance. One of the most important reasons is the low hENT1 expression. In this study, we tested the antitumor effect of gemcitabine-loaded human serum albumin nanoparticle (GEM-HSA-NP) on gemcitabine-resistant pancreatic cancer induced by low hENT1 expression. Materials and methods: S-(4-nitrobenzyl)-6-thioinosine was utilized to inhibit the activity of hENT1 and simulate low hENT1 expression. Growth inhibition assays and cell cycle and apoptosis analyses were performed on human pancreatic cancer cell lines such as BxPC-3 and SW1990. The in vivo antitumor effect was studied by using patient-derived xenograft (PDX) models. The in vivo toxicity assessment was performed on healthy Kunming mice. Results: In in vitro studies, GEM-HSA-NP showed its ability to inhibit cell proliferation, arrest cell cycle and induce apoptosis when tumor cells were resistant to gemcitabine. In in vivo studies, GEM-HSA-NP was more effective than gemcitabine on inhibiting tumor growth whether the expression levels of hENT1 were high or low in PDX models. The in vivo toxicity assessment showed that the biotoxicity of GEM-HSA-NP did not increase compared with gemcitabine. Conclusion: GEM-HSA-NP can overcome gemcitabine resistance induced by low hENT1 expression, which suggests its potential role for the clinical application. Keywords: pancreatic cancer, gemcitabine resistance, albumin nanoparticles, low hENT1 expression, PDX model

Xinzhe Yu,1 Wenwen Zhu,2 Yang Di,1 Jichun Gu,1 Zhongyi Guo,1 Hengchao Li,1 Deliang Fu,1 Chen Jin1 1Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, 2Institute of Functional Nano & Soft Materials, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu, China Abstract: Lymphatic metastasis is the major metastatic pattern of pancreatic cancer and considered as an independent risk factor of survival. However, there is still no effective way for the diagnosis and treatment for lymphatic metastases of pancreatic cancer. In this study, using albumin as a carrier of gemcitabine (Gem), further modified by pyropheophorbide-a, we have designed and synthesized a nanoparticle (NP) compound named “pheophorbide-a (P@)-Gem-human serum albumin (HSA)-NPs”. By utilization of its tracer ability of lymphatic metastases, which is triggered by near-infrared irradiation and its visible dying ability, the compound is used for drug delivery tracking, meanwhile as a treating drug, as well as the combined effect of photodynamic therapy and chemotherapy. By the nude mice model of lymphatic metastases of pancreatic cancer (BxPC-3-LN7), we aim to explore the feasibility, effectiveness, and biological safety of diagnosis and treatment for the lymphatic metastases of pancreatic cancer by P@-Gem-HSA-NP, thereby, providing new methods and strategies for the study of nanodrug carrier and research on lymphatic metastases of pancreatic cancer. Keywords: theranostic nanoparticles, chemotherapy, photodynamic therapy, pancreatic cancer, lymphatic metastases, near infrared irradiation

The Escherichia coli uracil:proton symporter UraA is a prototypical member of the nucleobase/ascorbate transporter (NAT) or nucleobase/cation symporter 2 (NCS2) family, which corresponds to the human solute carrier family SLC23. UraA consists of 14 transmembrane segments (TMs) that are organized into two distinct domains, the core domain and the gate domain, a structural fold that is also shared by the SLC4 and SLC26 transporters. Here we present the crystal structure of UraA bound to uracil in an occluded state at 2.5 Å resolution. Structural comparison with the previously reported inward-open UraA reveals pronounced relative motions between the core domain and the gate domain as well as intra-domain rearrangement of the gate domain. The occluded UraA forms a dimer in the structure wherein the gate domains are sandwiched by two core domains. In vitro and in vivo biochemical characterizations show that UraA is at equilibrium between dimer and monomer in all tested detergent micelles, while dimer formation is necessary for the transport activity. Structural comparison between the dimeric UraA and the recently reported inward-facing dimeric UapA provides important insight into the transport mechanism of SLC23 transporters.

Background Previous researches in pancreatic cancer demonstrated a negative correlation between secreted protein acidic and rich in cysteine (SPARC) expression in primary tumor and survival, but not for SPARC expression in lymph node. In the present study, we aimed to evaluate the SPARC expression in various types of tissues and its impact on patients' prognosis. Methods The expression of SPARC was examined by immunohistochemistry in resected pancreatic cancer specimens. Kaplan-Meier analyses and Cox proportional hazards regression were applied to assess the mortality risk. Results A total of 222 tissue samples from 73 patients were collected to evaluate the SPARC expression, which included 73 paired primary tumor and adjacent normal tissues, 38 paired metastatic and normal lymph nodes. The proportion of positive SPARC expression in metastatic lymph node was high (32/38), whereas in normal lymph node it was negative (0/38). Positive SPARC expression in primary tumor cells was associated with a significantly decreased overall survival ( P =0.007) and disease-free survival ( P =0.003), whereas in other types of tissues it did not show a predictive role for prognosis. Univariate and multivariate analyses both confirmed this significance. Conclusion SPARC can serve a dual function role as both predictor for prognosis and potentially biomarker for lymph node metastasis in resected pancreatic cancer patients.

Rotavirus capping enzyme VP3 is a stable tetramer with unique RNA binding, RTPase, and RNA helicase activities., In many viruses, including rotavirus (RV), the major pathogen of infantile gastroenteritis, capping of viral messenger RNAs is a pivotal step for efficient translation of the viral genome. In RV, VP3 caps the nascent transcripts synthesized from the genomic dsRNA segments by the RV polymerase VP1 within the particle core. Here, from cryo–electron microscopy, x-ray crystallography, and biochemical analyses, we show that VP3 forms a stable tetrameric assembly with each subunit having a modular domain organization, which uniquely integrates five distinct enzymatic steps required for capping the transcripts. In addition to the previously known guanylyl- and methyltransferase activities, we show that VP3 exhibits hitherto unsuspected RNA triphosphatase activity necessary for initiating transcript capping and RNA helicase activity likely required for separating the RNA duplex formed transiently during endogenous transcription. From our studies, we propose a new mechanism for how VP3 inside the virion core caps the nascent transcripts exiting from the polymerase.

Steroid hormone receptors activate gene transcription by binding specific DNA sequences and recruiting coactivators to initiate transcription of their target genes. For most nuclear hormone receptors (NRs), the ligand-dependent activation function domain-2 (AF-2), residing in the C-terminal ligand binding domain (LBD), is a primary contributor to the NR transcriptional activity. In contrast to other steroid receptors such as estrogen receptor-α (ERα), the transcriptional activation function of androgen receptor (AR) is thought to be largely dependent on its ligand-independent activation function domain-1 (AF-1) located in its N-terminal domain (NTD). It remains unclear why AR utilizes a different activation function domain from other steroid receptors despite the fact that NRs share similar domain organizations and have a highly conserved DNA binding domain (DBD) and LBD. Here we present cryo-electron microscopic structures of DNA-bound full-length AR and its functional complex structure with its key coactivators, steroid receptor coactivator-3 (SRC-3) and the histone acetyltransferase p300. The structures reveal that androgen-bound full-length AR dimerization follows a unique head-to-head and tail-to-tail manner with all of the domains involved. The DBD and LBD are located at the center of the dimer interface. The NTDs wrap around the LBDs through their unique intra- and inter-molecular N- and C-terminal interactions and connect to each other. We observe that unlike ERα, AR binds a single SRC-3 molecule along with a single p300 molecule. The AR NTD appears to be the primary site for recruitment of both coactivators. The N-terminal region of SRC-3, rather than its receptor interaction domain, is important for this interaction. The structures presented here highlight the importance of the AR NTD for its transcriptional functions and provide a structural basis for understanding the assembly of the AR:coactivator complex and its domain contributions to transcriptional regulation.

Background Solid pseudopapillary tumor of the pancreas (SPTP) is considered to have a low Ki-67 proliferation index, which may explain the generally good clinical outcome. The aim of our study was to evaluate whether Ki-67 has prognostic value in SPTP. Methods A case series study of patients with SPTP treated in our institution from June 2002 to April 2014 was conducted. Prognostic factors for clinical outcomes were analyzed by the use of clinical decision and survival analysis. In addition, we performed a systematic review and pooled analysis to evaluate our results. Results The institutional data included 71 patients (13 male and 58 female) ranging in age from 12 to 64 years (median, 31 years). Three patients developed local recurrence and/or liver metastasis after initial surgery. The 5-year recurrence-free survival rate was 93.6%. One patient died of disease, with the 5-year disease-specific survival rate of 98.5%. Ki-67 index ≥4% was found significantly associated with the survival of SPTP. Twenty-six studies comprising 163 patients were included in the pooled analysis based on our inclusion criteria. A total of 15 cases showed a Ki-67 index ≥4%. Kaplan-Meier survival analysis confirmed that Ki-67 index ≥4% was significantly associated with poorer recurrence-free survival and disease-specific survival (both P Conclusion This study highlighted a potential role of Ki-67 in predicting adverse outcome of patients with SPTP and should be considered as part of routine histological reporting of SPTP.

For most cancer patients, the presence of metastatic lymph nodes usually indicates regional recurrence and poor prognosis. Therefore, lymph node mapping is a requisite for disease staging, prognosis prediction and decision making in the treatment of cancer. Deuteporfin, a second-generation photosensitizer, has a maximum excitation wavelength that can reach the near infrared (NIR) region (650-700 nm). We aimed to take advantage of these aspects of deuteporfin and use it as a fluorescent probe for metastatic lymph node mapping in vivo using NIR fluorescent imaging. In our study, we further investigated whether a photosensitizer could be used as a tracer for metastatic lymph node mapping of pancreatic cancer based on previous reports. Compared to normal tissues, tumor tissues including primary tumors and metastatic lymph nodes had a higher uptake ability of deuteporfin (P

L1 cell adhesion molecule (L1CAM) is the prototype member of the L1-family of closely related neural adhesion molecules. L1CAM is differentially expressed in the normal nervous system as well as pathological tissues and displays a wide range of biological activities. In human malignancies, L1CAM plays a vital role in tumor growth, invasion and metastasis. Recently, increasing evidence has suggested that L1CAM exerts a variety of functions at different steps of tumor progression through a series of signaling pathways. In addition, L1CAM has been identified as a promising target for cancer therapy by using synthetic and natural inhibitors. In this review, we provide an up-to-date overview of the role of L1CAM involved in cancers and the rationale for L1CAM as a novel molecular target for cancer therapy.

Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the levels of trace heavy metals in human urine and sweat, to compare the performance of ICP-MS using three sample processing methods, namely direct dilution, wet digestion, and microwave digestion. The results showed that the wet digestion ICP-MS method has the highest accuracy (relative standard deviation ≤10%) and is more useful for measuring the levels of trace heavy metals in urine and sweat. Hence, we used this method to compare the levels of the five trace heavy metals, namely chromium, copper, zinc, cadmium, and lead, in the urine and sweat of adults after strenuous exercise. The results showed that the levels of these five trace heavy metals in sweat were significantly higher than those in urine after strenuous exercise (The differences between the measurements in urine and those in sweat were significant P ≤ 0.01). The results suggested that exercise-induced sweating can effectively remove the harmful heavy metals from the human body.

Steroid receptors activate gene transcription by recruiting coactivators to initiate transcription of their target genes. For most nuclear receptors, the ligand-dependent activation function domain-2 (AF-2) is a primary contributor to the nuclear receptor (NR) transcriptional activity. In contrast to other steroid receptors, such as ERα, the activation function of androgen receptor (AR) is largely dependent on its ligand-independent AF-1 located in its N-terminal domain (NTD). It remains unclear why AR utilizes a different AF domain from other receptors despite that NRs share similar domain organizations. Here, we present cryoelectron microscopy (cryo-EM) structures of DNA-bound full-length AR and its complex structure with key coactivators, SRC-3 and p300. AR dimerization follows a unique head-to-head and tail-to-tail manner. Unlike ERα, AR directly contacts a single SRC-3 and p300. The AR NTD is the primary site for coactivator recruitment. The structures provide a basis for understanding assembly of the AR:coactivator complex and its domain contributions for coactivator assembly and transcriptional regulation.

Currently, the use of photosensitizers as tracer agents to detect lymphatic metastases is a developing area of study in the field of pancreatic cancer treatment. In the present study, deuteporfin, a novel photosensitizer, was used as a tracer agent to detect lymphatic metastases in a pancreatic cancer xenograft model. The biodistribution and pharmacokinetics of deuteporfin, following intravenous administration and injection of deuteporfin into the left rear footpad, were investigated in Sprague-Dawley rats. The increased difference in deuteporfin concentration between the cancerous and normal tissues was directly observed through the application of a Wood's lamp. In addition, the highly lymphatic BxPC-3-LN5 human metastatic pancreatic cancer cell line was generated from BxPC-3 cells using a continuous screening and seeding method in vivo. A xenograft model of the BxPC-3-LN5 human pancreatic cancer cell line transplanted into the left rear footpad of nude mice, was established. The effects of deuteporfin as a tracer agent in the detection of lymphatic metastases were then characterized in the pancreatic cancer xenograft model. Following intravenous administration, deuteporfin was rapidly enriched in the pancreas and popliteal fossa lymph nodes compared with that of the left rear footpad administration group. In addition, deuteporfin appeared to be selectively enriched in the cancerous pancreatic lymph nodes of the pancreatic cancer xenograft model. These results indicated that deuteporfin may be developed as a novel photosensitizer tracer agent for the detection of lymphatic metastases in pancreatic cancer. The advantages of deuteporfin are that it has a selective tumor-targeting effect due to high tissue uptake, and that it may be administered intravenously and is therefore suitable for surgery.

Bacteria use vitamin C (L-ascorbic acid) as a carbon source under anaerobic conditions. The phosphoenolpyruvate-dependent phosphotransferase system (PTS), comprising a transporter (UlaA), a IIB-like enzyme (UlaB) and a IIA-like enzyme (UlaC), is required for the anaerobic uptake of vitamin C and its phosphorylation to L-ascorbate 6-phosphate. Here, we present the crystal structures of vitamin C-bound UlaA from Escherichia coli in two conformations at 1.65-Å and 2.35-Å resolution. UlaA forms a homodimer and exhibits a new fold. Each UlaA protomer consists of 11 transmembrane segments arranged into a 'V-motif' domain and a 'core' domain. The V motifs form the interface between the two protomers, and the core-domain residues coordinate vitamin C. The alternating access of the substrate from the opposite side of the cell membrane may be achieved through rigid-body rotation of the core relative to the V motif.

Objective The objectives of this systematic review and meta-analysis were to examine morbidity, mortality, and long-term survival after surgical resection of hepatic metastases from pancreatic ductal adenocarcinoma (PDAC) patients. Background Patients with hepatic metastases from pancreatic ductal adenocarcinoma are facing a dilemma of whether to make hepatic resection. Methods A systematic literature research was undertaken through computerized databases as well as manually research from unpublished data. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and non-surgical treatments based on the evaluation of morbidity, 30-day mortality, and 1-, 3-, or 5-year survival. Results 11 cohort studies with 1147 patients were identified in the pool. Compared with the non-surgical approach, hepatic resection can be performed in a safe and feasible manner for all pancreatic cancer patients with liver metastases ( p = 0.13 for overall morbidity; p = 0.63 for mortality). For surgical group, the median 1-year, 3-year, and 5-year survival were 40.9%, 13.3%, 2.9%, respectively, with a median survival of 9.9 months. Surgical resection of hepatic metastases was associated with a significantly improved overall 1-year and 3-year survival ( p Conclusions Hepatic resection is a safe procedure; furthermore, it is worth doing such an extended surgery for PDAC patients due to additional survival benefit in the medium-term (less than 3 years). However, further randomized, controlled trials are urgently needed.

From field experience and laboratory experiments, it was indicated that the flashover performance of contaminated insulators was significantly influenced by the insulator geometry. In the paper, insulators with three different profiles including seven types of deep under-ribs disc insulator, three types of two-shed disc insulator and three types of three-shed disc insulator were tested in an artificial climate chamber to investigate the influences of insulator profile parameters on the flashover performance of large tonnage disc insulators. The artificial contamination test results indicated that 50% flashover voltage stress (E50%) decreased with the increasing insulator diameter and creepage distance. The influence of salt deposit density (SDD) was also investigated, and it was found that E50% of alternating-shed insulator decreased more rapidly than that of deep under-ribs insulator with the increase of SDD. An empirical expression was proposed, by employing the least-square method, to describe the relationships between E50% and insulator configuration parameters as well as SDD. Through analyzing the generalized fitting coefficients (r) of the equation and the standard error of estimate (s), it can be concluded that the calculated results are in good agreement with the experimental data. Moreover, special attentions were also paid to the influence of the under-ribs and the ratio of shed overhang distance to the shed spacing on flashover performance respectively. This work can enrich the investigation of insulators parameters and may provide useful reference for performance evaluation and selection of insulators in EHV and UHV transmission lines.

A double-arc model, which considers the differences between characteristics of AC partial arcs on top and bottom surfaces, was proposed for predicting the flashover voltage of polluted insulators in this paper. The arc constants parameters, the arc reignition criteria, as well as the radii of arc columns in the proposed model were determined by measuring partial arcs on the top and bottom wet-polluted surfaces of a triangular glass plate separately. A “II” type glass model was made to investigate the partial arc propagation process by using an ultra-high speed camera. It has been found that the arc length increased linearly with leakage current amplitude, the ratio of arc length increments on top and bottom surface was related to salt deposit density (SDD) rather than leakage current. Based on above-mentioned researching results, the double arc calculation model was established, and the calculated results were in good agreement with the experimental results.

Pancreaticoduodenectomy combined with portal-superior mesenteric vein synchronous resection for cancer remains a hot debate topic. The present study used meta-analytical technique to provide update information and an evidence-based evaluation on both the perioperative benefit and long-term survival.A meta-analysis was performed to evaluate studies comparing venous resection (VR) versus without venous resection (WVR) groups. 22 retrospective studies including 2890 patients were eligible for an analysis of perioperative morbidity, mortality, and long-term survival. Furthermore, subgroup analysis was made according to histopathology and resection margin status respectively for the purpose of survival assessment.There was no difference in perioperative morbidity, mortality and 1-year, 3-year survival between two groups, but showed differences in median tumor size (P0.001), R0 resection rate (P0.001), lymph node metastasis (P = 0.03), pancreatic fistula (P = 0.01), and 5-year survival (P = 0.03). In subgroup analysis, patients in venous resection group received R0 resection had a significantly better survival comparing with who received R1 resection both at 2-year (P0.001) and 5-year (P = 0.00002). In histopathology subgroup, patients in venous resection groups who had true tumor infiltration had a significantly bad survival comparing with whom only with inflammation pathology.Pancreaticoduodenectomy combined with venous resection can achieve equal perioperative morbidity and mortality as standard resection. However, in order to obtain an optimal survival outcome, surgeons should make an R0 resection as far as possible, especially in cases need synchronous venous resection.

In high altitude area, because of low air pressure, pollution flashover characteristic is different from that in the plain area. Based on up-and-down method, DC pollution flashover tests of long insulator string are carried out in the artificial climate chamber (diameter 22m, height 34m) of Pollution and Environment Lab at China Electric Power Research Institute (CEPRI). During the tests in climate chamber, various air pressures are simulated to achieve conditions at various altitude (0m, 3000m, 5000m above sea level). Insulator string is arranged vertically. Leakage currents before the maximum current occurring in each individual test are analyzed statistically. Current amplitudes and lasting times at various air pressures are obtained. Meanwhile, typical leakage current curves at various conditions are compared. Results show that air pressure significantly affects the leakage current lasting times and amplitudes, which reflects the flashover discharge mechanism at high altitude indirectly. Furthermore, from comparison of typical leakage current curves at various altitudes on various stages in pollution test, effect of altitudes on insulator string leakage currents is obtained, revealing discharge processes distinction at high altitude.

The emerging albumin nanoparticle brings new hope for the delivery of antitumor drugs. However, a lack of robust tumor targeting greatly limits its application. In this paper, cyclic arginine-glycine-aspartic-conjugated, gemcitabine-loaded human serum albumin nanoparticles (cRGD-Gem-HSA-NPs) were successfully prepared, characterized, and tested in vitro in the BxPC-3 cell line. Initially, 4-N-myristoyl-gemcitabine (Gem-C14) was formed by conjugating myristoyl to the 4-amino group of gemcitabine. Then, cRGD-HSA was synthesized using sulfosuccinimidyl-(4-N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC) cross-linkers. Finally, cRGD-Gem-HSA-NPs were formulated based on the nanoparticle albumin-bound (nab) technology. The resulting NPs were characterized for particle size, zeta potential, morphology, encapsulation efficiency, and drug loading efficiency. In vitro cellular uptake and inhibition studies were conducted to compare Gem-HSA-NPs and cRGD-Gem-HSA-NPs in a human pancreatic cancer cell line (BxPC-3). The cRGD-Gem-HSA-NPs exhibited an average particle size of 160 ± 23 nm. The encapsulation rate and drug loading rate were approximately 83 ± 5.6% and 11 ± 4.2%, respectively. In vitro, the cRGD-anchored NPs exhibited a significantly greater affinity for the BxPC-3 cells compared to non-targeted NPs and free drug. The cRGD-Gem-HSA-NPs also showed the strongest inhibitory effect in the BxPC-3 cells among all the analyzed groups. The improved efficacy of cRGD-Gem-HSA-NPs in the BxPC-3 cell line warrants further in vivo investigations.

No ideal serum biomarker currently exists for the early diagnosis of colorectal cancer (CRC). Magnetic bead-based fractionation coupled with MALDI-TOF MS was used to screen serum samples from CRC patients, healthy controls, and other cancer patients. A diagnostic model with five proteomic features (m/z 1778.97, 1866.16, 1934.65, 2022.46, and 4588.53) was generated using Fisher algorithm with best performance. The Fisher-based model could discriminate CRC patients from the controls with 100% (46/46) sensitivity and 100% (35/35) specificity in the training set, 95.6% (43/45) sensitivity and 83.3% (35/42) specificity in the test set. We further validated the model with 94.4% (254/269) sensitivity and 75.5% (83/110) specificity in the external independent group. In other cancers group, the Fisher-based model classified 25 of 46 samples (54.3%) as positive and the other 21 as negative. With FT-ICR-MS, the proteomic features of m/z 1778.97, 1866.16, 1934.65, and 2022.46, of which intensities decreased significantly in CRC, were identified as fragments of complement C3f. Therefore, the Fisher-based model containing five proteomic features was able to effectively differentiate CRC patients from healthy controls and other cancers with a high sensitivity and specificity, and may be CRC-specific. Serum complement C3f, which was significantly decreased in CRC group, may be relevant to the incidence of CRC. J. Cell. Biochem. 114: 448–455, 2013. © 2012 Wiley Periodicals, Inc.

Over the past three decades, tremendous progress has been made in cancer prevention and treatment. Despite these advances, a substantial number of cancer cases experience early recurrence and metastases. Thus, the better management of cancer, especially developing more effective drugs for combating cancer cells, is an arduous task. Albumin-based nanoparticles are emerging as a promising approach to replace the traditional way of carrying therapeutic drugs to a tumor site. In this review, we describe the basic knowledge on albumin-based nanoparticles, recent progress of using albumin-based nanoparticles in the diagnosis and treatment of cancer, and the application of nanoparticle albumin bound (Nab) paclitaxel for the treatment of lung, breast and pancreatic cancer. Last but not least, we try to discuss future goals and perspectives in the field of drug delivery research, thereby facilitating the antitumor activity.