Efficacy of nab­paclitaxel vs. Gemcitabine in combination with S­1 for advanced pancreatic cancer: A multicenter phase II randomized trial.

Patients with advanced pancreatic cancer (PC) need a cost-effective treatment regimen. The present study was designed to compare the efficacy and safety of nab-paclitaxel plus S-1 (AS) and gemcitabine plus S-1 (GS) regimens in patients with chemotherapy-naïve advanced PC. In this open-label, multicenter, randomized study named AvGmPC, eligible patients with chemotherapy-naïve advanced PC were randomly assigned (1:1) to receive AS (125 mg/m2 nab-paclitaxel, days 1 and 8; 80-120 mg S-1, days 1-14) or GS (1,000 mg/m2 gemcitabine, days 1 and 8; 80-120 mg S-1, days 1-14). The treatment was administered every 3 weeks until intolerable toxicity or disease progression occurred. The primary endpoint was progression-free survival (PFS). Between December 2018 and March 2022, 101 of 106 randomized patients were treated and evaluated for analysis (AS, n=49; GS, n=52). As of the data cutoff, the median follow-up time was 11.37 months [95% confidence interval (CI), 9.31-13.24]. The median PFS was 7.16 months (95% CI, 5.19-12.32) for patients treated with AS and 6.41 months (95% CI, 3.72-8.84) for patients treated with GS (HR=0.78; 95% CI, 0.51-1.21; P=0.264). The AS regimen showed a slightly improved overall survival (OS; 13.27 vs. 10.64 months) and a significantly improved ORR (44.90 vs. 15.38%; P=0.001) compared with the GS regimen. In the subgroup analyses, PFS and OS benefits were observed in patients treated with the AS regimen who had KRAS gene mutations and high C-reactive protein (CRP) levels (≥5 mg/l). The most common grade ≥3 adverse events were neutropenia, anemia and alopecia in the two groups. Thrombocytopenia occurred more frequently in the GS group than in the AS group. While the study did not meet the primary endpoint, the response benefit observed for AS may be suggestive of meaningful clinical activity in this population. In particular, promising survival benefits were observed in the subsets of patients with KRAS gene mutations and high CRP levels, which is encouraging and warrants further investigation. This trial was retrospectively registered as ChiCTR1900024588 on July 18, 2019.

BMP6 inhibits gastric cancer growth and predicts good prognosis.

Background: Gastric cancer (GC) is a common tumors in the digestive tract, and effective treatment methods are still lacking. Bone morphogenetic protein 6 (BMP6) is closely related to the occurrence and development of various tumors, but its relevance to GC is still unclear. The aim of the study was to explore the relationship between BMP6 and the occurrence and development of GC. Methods: In this study, we investigated the relationship between BMP6 and the prognosis of GC patients using bioinformatics technology and clinical tissue samples. We also explored the connection between BMP6 and the biological behavior of GC cells through molecular biology experiments and relevant in vivo animal experiments. Finally, we examined the mechanisms by which BMP6 inhibits the onset and progression of GC. Results: Through analysis of The Cancer Genomics Atlas (TCGA) database, we observed that BMP6 is expressed at low levels in GC, and its low expression is associated with a poor prognosis in GC patients. Cell experiments demonstrated that BMP6 expression can influence the proliferation of GC cells both in vitro and in vivo. Furthermore, we discovered that BMP6 is linked to the nuclear factor-κB (NF-κB) pathway, and subsequent experiments confirmed that BMP6 can inhibit the biological activity of GC cells by activating the NF-κB pathway. Conclusions: Our findings suggest that BMP6 is a potential prognostic biomarker in GC and can regulate the biological activity of GC cells through the NF-κB pathway. BMP6 may serve as a promising therapeutic target for GC, and our study introduces novel ideas for the prevention and treatment of this disease.

Abrogation of KLF5 sensitizes BRCA1-proficient pancreatic cancer to PARP inhibition.

Poly ADP-ribose polymerase (PARP) inhibitor monotherapies are selectively effective in patients with pancreatic, breast, prostate, and ovarian cancers with BRCA1 mutations. Cancer patients with more frequent wild-type BRCA show poor responses to PARP inhibitors. Moreover, patients who are initially sensitive to these inhibitors eventually respond poorly to drugs. In the present study, we discover that abrogation of Kruppel-like factor 5 (KLF5) significantly inhibits homologous recombination, which is the main mechanism for DNA double-stranded repair. Furthermore, the downregulation of KLF5 expression promotes the DNA damage induced by olaparib and significantly reduces the IC 50 of the RARP inhibitor in pancreatic cancer cells. Overexpression of BRCA1 reverses the above effects caused by silencing of KLF5. Olaparib combined with a KLF5 inhibitor has an enhanced cytotoxic effect. Mechanistically, we identify BRCA1 as a KLF5 target gene. BRCA1 is positively correlated with KLF5 in PDAC tissue. Our results indicate that inhibition of KLF5 may induce BRCAness in a larger pancreatic cancer subset with proficient BRCA. The combination of KLF5 inhibitors and PARP inhibitors provides a novel treatment strategy to enhance the sensitivity of BRCA1-proficient pancreatic cancer to PARP inhibitors.

Beyond Conventional Carbon Activation: Creating Porosity without Etching Using Cesium Effect.

Facile synthesis of porous carbon with high yield and high specific surface area (SSA) from low-cost molecular precursors offers promising opportunities for their industrial applications. However, conventional activation methods using potassium and sodium hydroxides or carbonates suffer from low yields (<20%) and poor control over porosity and composition especially when high SSAs are targeted (>2000 m2 g-1) because nanopores are typically created by etching. Herein, a non-etching activation strategy is demonstrated using cesium salts of low-cost carboxylic acids as the sole precursor in producing porous carbons with yields of up to 25% and SSAs reaching 3008 m2 g-1. The pore size and oxygen content can be adjusted by tuning the synthesis temperature or changing the molecular precursor. Mechanistic investigation unravels the non-classical role of cesium as an activating agent. The cesium compounds that form in situ, including carbonates, oxides, and metallic cesium, have extremely low work function enabling electron injection into organic/carbonaceous framework, promoting condensation, and intercalation of cesium ions into graphitic stacks forming slit pores. The resulting porous carbons deliver a high capacity of 252 mAh g-1 (567 F g-1) and durability of 100 000 cycles as cathodes of Zn-ion capacitors, showing their potential for electrochemical energy storage.

Progress and Perspectives on the Development of Pouch-Type Lithium Metal Batteries.

Lithium (Li) metal batteries (LMBs) are the "holy grail" in the energy storage field due to their high energy density (theoretically >500 Wh kg-1 ). Recently, tremendous efforts have been made to promote the research & development (R&D) of pouch-type LMBs toward practical application. This article aims to provide a comprehensive and in-depth review of recent progress on pouch-type LMBs from full cell aspect, and to offer insights to guide its future development. It will review pouch-type LMBs using both liquid and solid-state electrolytes, and cover topics related to both Li and cathode (including LiNix Coy Mn1-x-y O2 , S and O2 ) as both electrodes impact the battery performance. The key performance criteria of pouch-type LMBs and their relationship in between are introduced first, then the major challenges facing the development of pouch-type LMBs are discussed in detail, especially those severely aggravated in pouch cells compared with coin cells. Subsequently, the recent progress on mechanistic understandings of the degradation of pouch-type LMBs is summarized, followed with the practical strategies that have been utilized to address these issues and to improve the key performance criteria of pouch-type LMBs. In the end, it provides perspectives on advancing the R&Ds of pouch-type LMBs towards their application in practice.

Additional adjuvant radiotherapy improves survival at 1 year after surgical treatment for pancreatic cancer patients with T4, N2 disease, positive resection margin, and receiving adjuvant chemotherapy.

Background: While adjuvant chemotherapy has been established as standard practice following radical resection of pancreatic ductal adenocarcinoma (PDAC), the role of adjuvant radiation therapy (RT) and which patients may benefit remains unclear. Methods: This retrospective study included PDAC patients who received pancreatic surgery from April 2012 to December 2019 in Zhongshan Hospital Fudan University. Patients with carcinoma in situ, distant metastasis, and without adjuvant chemotherapy were excluded. Cox proportional hazards modeling of survival were constructed to find potential prognostic factors. Propensity score matching (PSM) and exploratory subgroup analyses were used to create a balanced covariate distribution between groups and to investigate therapeutic effect of radiotherapy in certain subgroups. Results: A total of 399 patients were finally included, 93 of them receiving adjuvant chemoradiotherapy (C+R+) and 306 of them receiving chemotherapy only. Patients in C+R+ group were more likely to be male patients with T3-4 disease. Lymph node metastases was the only negative prognostic factor associated with overall survival (OS). Additional adjuvant RT was not associated with an OS benefit both before and after PSM. Surprisingly, a trend towards improved OS with RT among patients with either T4, N2 disease or R1 resection becomes significant in patients alive more than 1 year after surgery. Conclusion: Adjuvant RT was not associated with an OS benefit across all patients, though did show a possible OS benefit for the subgroup with T4N2 disease or R1 resection at 1 year after surgery.

Heterostructured and Mesoporous Nb2O5@TiO2 Core-Shell Spheres as the Negative Electrode in Li-Ion Batteries.

Niobium pentoxides have received considerable attention and are promising anode materials for lithium-ion batteries (LIBs), due to their fast Li storage kinetics and high capacity. However, their cycling stability and rate performance are still limited owing to their intrinsic insulating properties and structural degradation during charging and discharging. Herein, a series of mesoporous Nb2O5@TiO2 core-shell spherical heterostructures have been prepared for the first time by a sol-gel method and investigated as anode materials in LIBs. Mesoporosity can provide numerous open and short pathways for Li+ diffusion; meanwhile, heterostructures can simultaneously enhance the electronic conductivity and thus improve the rate capability. The TiO2 coating layer shows robust crystalline skeletons during repeated lithium insertion and extraction processes, retaining high structural integrity and, thereby, enhancing cycling stability. The electrochemical behavior is strongly dependent on the thickness of the TiO2 layer. After optimization, a mesoporous Nb2O5@TiO2 core-shell structure with a ∼13 nm thick TiO2 layer delivers a high specific capacity of 136 mA h g-1 at 5 A g-1 and exceptional cycling stability (88.3% retention over 1000 cycles at 0.5 A g-1). This work provides a facile strategy to obtain mesoporous Nb2O5@TiO2 core-shell spherical structures and underlines the importance of structural engineering for improving the performance of battery materials.

High Eckardt score and previous treatment were associated with poor postperoral endoscopic myotomy pain control: A retrospective study.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a safe and effective endoscopic treatment for achalasia. However, postoperative pain management for these patients is often neglected by anesthesiologists because of the short operative time, short hospital stay and the minimally invasive nature of the procedure. AIM: To assess the pain and sleep quality of achalasia patients receiving the POEM procedure and investigate factors that affect postoperative pain. METHODS: This observational study included patients with achalasia who underwent POEM at Zhongshan Hospital from December 2017 to March 2018. General anesthesia was performed with endotracheal intubation. The postoperative visual analog scale (VAS), postoperative sleep quality, basic patient information, and surgical parameters were collected. Depending on whether the 12-h post-POEM VAS score was less than 4, patients were divided into two groups, a well-controlled pain group and a poorly controlled pain group. Univariate, multivariate, and stepwise logistic regression analyses were used to investigate risk factors for poor pain control. A prediction model of post-POEM pain risk was established in the form of a nomogram. The calibration curve and receiver operating characteristic curve were used to evaluate the clinical usage of the prediction model. Repeated measures analysis of variance and simple effect analysis were used to verify whether differences in the VAS and sleep scores of the high- and low-risk groups, divided by the model from the raw data, were statistically significant. RESULTS: A total of 45 eligible patients were included. Multivariate logistic regression and further stepwise logistic regression analysis found that the preoperative Eckardt score [odds ratio (OR): 1.82, 95% confidence interval (CI): 1.17-2.84, P < 0.001], previous treatment (OR: 7.59, 95%CI: 1.12-51.23, P = 0.037) and the distance between the end of the muscle incision and the cardia (OR: 1.52, 95%CI: 0.79-293.93, P = 0.072) were risk factors for post-POEM pain. Repeated measures analysis of variance demonstrated that VAS (P = 0.0097) and sleep scores (P = 0.043) were higher in the high-risk group, and the interactions between the two main effects were obvious (VAS score: P = 0.019, sleep score: P = 0.035). Further simple effect analysis found that VAS scores were higher in the high-risk group at 2 h, 6 h and 12 h (P = 0.005, P = 0.019, P < 0.001), and sleep scores were higher in the high-risk group at day 1 (P = 0.006). CONCLUSION: Achalasia patients who underwent POEM experienced serious postoperative pain, which may affect sleep quality. A higher Eckardt score, previous treatment, and a longer distance between the muscle incision ending and the cardia were risk factors for poor post-POEM pain control.

Poly(ionic liquid) Nanovesicle-Templated Carbon Nanocapsules Functionalized with Uniform Iron Nitride Nanoparticles as Catalytic Sulfur Host for Li-S Batteries.

Poly(ionic liquid)s (PIL) are common precursors for heteroatom-doped carbon materials. Despite a relatively higher carbonization yield, the PIL-to-carbon conversion process faces challenges in preserving morphological and structural motifs on the nanoscale. Assisted by a thin polydopamine coating route and ion exchange, imidazolium-based PIL nanovesicles were successfully applied in morphology-maintaining carbonization to prepare carbon composite nanocapsules. Extending this strategy further to their composites, we demonstrate the synthesis of carbon composite nanocapsules functionalized with iron nitride nanoparticles of an ultrafine, uniform size of 3-5 nm (termed "FexN@C"). Due to its unique nanostructure, the sulfur-loaded FexN@C electrode was tested to efficiently mitigate the notorious shuttle effect of lithium polysulfides (LiPSs) in Li-S batteries. The cavity of the carbon nanocapsules was spotted to better the loading content of sulfur. The well-dispersed iron nitride nanoparticles effectively catalyze the conversion of LiPSs to Li2S, owing to their high electronic conductivity and strong binding power to LiPSs. Benefiting from this well-crafted composite nanostructure, the constructed FexN@C/S cathode demonstrated a fairly high discharge capacity of 1085 mAh g-1 at 0.5 C initially, and a remaining value of 930 mAh g-1 after 200 cycles. In addition, it exhibits an excellent rate capability with a high initial discharge capacity of 889.8 mAh g-1 at 2 C. This facile PIL-to-nanocarbon synthetic approach is applicable for the exquisite design of complex hybrid carbon nanostructures with potential use in electrochemical energy storage and conversion.

Prognostic Effect of Age in Resected Pancreatic Cancer Patients: A Propensity Score Matching Analysis.

Background: While the elderly population account for an indispensable proportion in pancreatic ductal adenocarcinoma (PDAC), these patients are underrepresented in clinical trials. Whether surgery offered the same benefit for elderly patients as that for younger cohort and which factors affected long-term outcome of elderly population remained unclear. Aims: This study aims to evaluate long-term prognosis of elderly PDAC patients (≥70 years old) after surgery and to investigate potential prognostic factors. Methods: This retrospective study included PDAC patients receiving radical resection from January 2012 to July 2019 in Zhongshan Hospital Fudan University. Patients were divided into young (<70) and old groups (≥70). Propensity score matching (PSM) was conducted to eliminate the confounding factors. We investigated potential prognostic factors via Cox proportional hazards model and Kaplan-Meier estimator. Nomogram model and forest plot were constructed to illustrate the prognostic value of age. Results: A total of 552 PDAC patients who received radical resection were included in this research. Elderly patients showed poorer nutritional status and were less likely to received adjuvant treatment. After matching, although age [hazard ratio (HR)=1.025, 95%CI 0.997-1.054; p=0.083] was not statistically significant in the multivariate cox regression analysis, further survival analysis showed that patients in the old group had poorer overall survival (OS) when compared with young group (p=0.039). Furthermore, reception of adjuvant chemotherapy (HR=0.411, 95%CI 0.201-0.837; p=0.014) was the only independent prognostic factor among elderly patients and could significantly improve OS. Subgroup analysis indicated that age had better prognostic value in PDAC patients with good preoperative nutritional status and relative low tumor burden. Finally, a prognostic prediction model contained age, reception of adjuvant chemotherapy, American Joint Committee on Cancer (AJCC) 8th T and N stage was constructed and presented in nomogram, whose Harrell's concordance index was 0.7478 (95%CI, 0.6960-0.7996). The calibration curves at 1 and 3 years indicated an optimal conformity between actual and nomogram-predicted survival probability in the PDAC patient who received surgery. Conclusion: The elderly PDAC patients were associated with worse OS survival after radical resection, and the noticeable negative effect of age was observed among PDAC patients with better preoperative nutritional status and less aggressive tumor biology. Adjuvant chemotherapy was essential to improve survival outcome of elderly PDAC patients following radical resection.

Multiplexed nanomaterial-assisted laser desorption/ionization for pan-cancer diagnosis and classification.

As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. By multiplexing mass spectrometry fingerprints from two independent nanostructured matrixes through machine learning for highly sensitive detection and high throughput analysis, we report a laser desorption/ionization (LDI) mass spectrometry-based liquid biopsy for pan-cancer screening and classification. The Multiplexed Nanomaterial-Assisted LDI for Cancer Identification (MNALCI) is applied in 1,183 individuals that include 233 healthy controls and 950 patients with liver, lung, pancreatic, colorectal, gastric, thyroid cancers from two independent cohorts. MNALCI demonstrates 93% sensitivity at 91% specificity for distinguishing cancers from healthy controls in the internal validation cohort, and 84% sensitivity at 84% specificity in the external validation cohort, with up to eight metabolite biomarkers identified. In addition, across those six different cancers, the overall accuracy for identifying the tumor tissue of origin is 92% in the internal validation cohort and 85% in the external validation cohort. The excellent accuracy and minimum sample consumption make the high throughput assay a promising solution for non-invasive cancer diagnosis.

Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints.

Immune checkpoint inhibitors (ICIs), Ipilimumab, Nivolumab, Pembrolizumab and Atezolizumab, have been applied in anti-tumor therapy and demonstrated exciting performance compared to conventional treatments. However, the unsatisfactory response rates, high recurrence and adaptive resistance limit their benefits. Metabolic reprogramming appears to be one of the crucial barriers to immunotherapy. The deprivation of required nutrients and altered metabolites not only promote tumor progression but also confer dysfunction on immune cells in the tumor microenvironment (TME). Glycolysis plays a central role in metabolic reprogramming and immunoregulation in the TME, and many therapies targeting glycolysis have been developed, and their combinations with ICIs are in preclinical and clinical trials. Additional attention has been paid to the role of amino acids, lipids, nucleotides and mitochondrial biogenesis in metabolic reprogramming and clinical anti-tumor therapy. This review attempts to describe reprogramming metabolisms within tumor cells and immune cells, from the aspects of glycolysis, amino acid metabolism, lipid metabolism, nucleotide metabolism and mitochondrial biogenesis and their impact on immunity in the TME, as well as the significance of targeting metabolism in anti-tumor therapy, especially in combination with ICIs. In particular, we highlight the expression mechanism of programmed cell death (ligand) 1 [PD-(L)1] in tumor cells and immune cells under reprogramming metabolism, and discuss in detail the potential of targeting key metabolic pathways to break resistance and improve the efficacy of ICIs based on results from current preclinical and clinical trials. Besides, we draw out biomarkers of potential predictive value in ICIs treatment from a metabolic perspective.

Positive Impact of Intraoperative Epidural Ropivacaine Infusion on Oncologic Outcomes in Pancreatic Cancer Patients Undergoing Pancreatectomy: A Retrospective Cohort Study.

Background: Previous literatures have demonstrated that regional anesthesia such as epidural anesthesia may affect long-term survival of cancer patients. In the present study, we conducted a retrospective cohort study to investigate the survival impact of intraoperatively epidural ropivacaine infusion on pancreatic ductal adenocarcinoma (PDAC) patients. Methods: PDAC patients who underwent pancreatic surgery in Zhongshan Hospital Fudan University from January, 2015 to June, 2018 were included. The surgical procedure was performed under combined endotracheal general anesthesia and thoracic epidural anesthesia, and patient-controlled epidural analgesia (PCEA) with 0.12% ropivacaine was given after surgery for further pain control. Patients were divided into two groups according to their intraoperative epidural ropivacaine concentration: high (0.375%-0.5%) and low (0.15%-0.25%). Survival outcome was compared between groups. Results: A total of 215 patients were enrolled and their baseline characteristics were balanced between groups, except that patients with high concentration ropivacaine received higher total dose opioid and had longer operative time. Resected PDAC patients who were administrated with high concentration ropivacaine through epidural catheter intraoperatively had improved overall survival (median overall survival, mOS, high VS low, 37.6 VS 23.7 months, p=0.04). High epidural ropivacaine concentration was an independent prognostic factor (hazard ratio [HR]=0.65, 95% confidence interval [CI], 0.44-0.94; p=0.03). Subgroups analyses shown that T3M0 PDAC patients with preoperative CA 19-9 higher than 200 U/ml, negative resection margin, and those without tumor deposit and adjuvant radiotherapy could benefit from high concentration of ropivacaine. Conclusion: Intraoperatively epidural infusion with high concentration of ropivacaine was associated with improved OS in PDAC patients undergoing pancreatectomy.

Efficient Sulfur Host Based on Yolk-Shell Iron Oxide/Sulfide-Carbon Nanospindles for Lithium-Sulfur Batteries.

Numerous nanostructured materials have been reported as efficient sulfur hosts to suppress the problematic "shuttling" of lithium polysulfides (LiPSs) in lithium-sulfur (Li-S) batteries. However, direct comparison of these materials in their efficiency of suppressing LiPSs shuttling is challenging, owing to the structural and morphological differences between individual materials. This study introduces a simple route to synthesize a series of sulfur host materials with the same yolk-shell nanospindle morphology but tunable compositions (Fe3 O4 , FeS, or FeS2 ), which allows for a systematic investigation into the specific effect of chemical composition on the electrochemical performances of Li-S batteries. Among them, the S/FeS2 -C electrode exhibits the best performance and delivers an initial capacity of 877.6 mAh g-1 at 0.5 C with a retention ratio of 86.7 % after 350 cycles. This approach can also be extended to the optimization of materials for other functionalities and applications.

Upregulated circRNA hsa_circ_0071036 promotes tumourigenesis of pancreatic cancer by sponging miR-489 and predicts unfavorable characteristics and prognosis.

Circular RNAs (circRNAs), the new stars of endogenous non-coding RNAs, are dysregulated in various tumors including pancreatic cancer. Here, we aimed to investigate the biological functions of hsa_circ_0071036 in the tumourigenesis and progression of pancreatic ductal adenocarcinoma (PDAC) and its clinical implications. The differential expression profile of circRNAs in 4 pairs of PDAC tissues was analyzed by microarray assay. Quantitative real-time PCR and fluorescence in situ hybridization (FISH) were utilized to determine the expression patterns and their clinical significance. Functional experiments in vitro and in vivo were performed to explore whether hsa_circ_0071036 functions as an oncogenic circRNA in PDAC. Mechanistically, RT-qPCR, dual luciferase reporter and RNA pull-down assays were conducted to identify the interaction between hsa_circ_0071036 and miR-489 in PDAC. Hsa_circ_0071036 was remarkably overexpressed in PDAC cell lines and tissue samples, which negatively correlated with miR-489 expression. Aberrant expression of hsa_circ_0071036 correlated with poor clinicopathological characteristics and prognoses of PDAC patients. Knockdown of hsa_circ_0071036 suppressed proliferation and invasion and induced apoptosis in vitro. Moreover, the in vivo xenograft model confirmed that silencing of hsa_circ_0071036 attenuated tumor growth. Mechanistic analyses indicated that hsa_circ_0071036 acted as an efficient miRNA sponge for miR-489 in PDAC. In summary, our study revealed that upregulated hsa_circ_0071036 promotes PDAC pathogenesis and progression by directly sponging miR-489, which implies an important role for this circRNA-miRNA functional network.

Unveiling the Formation of Solid Electrolyte Interphase and its Temperature Dependence in "Water-in-Salt" Supercapacitors.

"Water-in-salt" (WIS) electrolytes have emerged as an excellent superconcentrated ionic medium for high-power energy storage systems such as supercapacitors due to their extended working potential compared to the conventional dilute aqueous electrolyte. In this work, we have investigated the performance of WIS supercapacitors using hollow carbon nanoplates as electrodes and compared it to that based on the conventional "salt-in-water" electrolytes. Moreover, the potentiostatic electrochemical impedance spectroscopy has been employed to provide an insightful look into the charge transport properties, which also, for the first time, reveals the formation of a solid-electrolyte interphase (SEI) and their temperature-dependent impedance for charge transfer and adsorption. Furthermore, the effect of temperature on the electrochemical performance of the WIS supercapacitors in the temperature range from 15 to 60 °C has been studied, which presents a gravimetric capacitance of 128 F g-1 and a volumetric capacitance of 197.12 F cm-3 at 55 °C compared to 87.5 F g-1 and 134.75 F cm-3 at 15 °C. The in-depth understanding about the formation of SEI layer and the electrochemical performance at different temperatures for WIS supercapacitors will assist the efforts toward designing better aqueous electrolytes for supercapacitors.

Prognostic value of preoperative glucose to lymphocyte ratio in patients with resected pancreatic cancer.

BACKGROUND: Inflammatory factors and fasting blood glucose were verified to be associated with the prognosis of pancreatic ductal adenocarcinoma. The goal of this study is to confirm the prognostic role of preoperative blood glucose to lymphocyte ratio for patients with resected pancreatic ductal adenocarcinoma. METHODS: A total of 259 pancreatic ductal adenocarcinoma patients were enrolled and randomly divided into training cohort and validation cohort. The training cohort was used to generate an optimal cutoff value and the validation cohort was used to further validate the model. RESULTS: A total of 259 patients were incorporated in this study and randomly divided into the training cohort (n = 130, 1/2 of 259) and the validation cohort (129, 1/2 of 259). The optimal cutoff value of glucose to lymphocyte ratio was calculated to be 3.47 for overall survival. Cox regression analysis found that preoperative blood glucose to lymphocyte ratio was independent risk factor (p = 0.040) for overall survival. Prognostic values of glucose to lymphocyte ratio on overall survival were observed in younger male patients with pancreatic body and tail cancer, American Joint Committee on Cancer 8th N1 stage, without microvascular and peripancreatic fat invasion, and Carbohydrate antigen 19-9 higher than 200 U/ml. A prognostic prediction model of overall survival was designed and presented in nomogram. CONCLUSION: Preoperative blood glucose to lymphocyte ratio is an independent biomarker to predict the overall survival for pancreatic ductal adenocarcinoma patients who underwent curative resection.

Going even smaller: Engineering sub-5 nm nanoparticles for improved delivery, biocompatibility, and functionality.

The rapid development and advances in nanomaterials and nanotechnology in the past two decades have made profound impact in our approaches to individualized disease diagnosis and treatment. Nanomaterials, mostly in the range of 10-200 nm, developed for biomedical applications provide a wide range of platforms for building and engineering functionalized structures, devices, or systems to fulfill the specific diagnostic and therapeutic needs. Driven by achieving the ultimate goal of clinical translation, sub-5 nm nano-constructs, in particular inorganic nanoparticles such as gold, silver, silica, and iron oxide nanoparticles, have been developed in recent years to improve the biocompatibility, delivery and pharmacokinetics of imaging probes and drug delivery systems, as well as in vivo theranostic applications. The emerging studies have provided new findings that demonstrated the unique size-dependent physical properties, physiological behaviors and biological functions of the nanomaterials in the range of the sub-5 nm scale, including renal clearance, novel imaging contrast, and tissue distribution. This advanced review attempts to introduce the new strategies of rational design for engineering nanoparticles with the core sizes under 5 nm in consideration of the clinical and translational requirements. We will provide readers the update on recent discoveries of chemical, physical, and biological properties of some biocompatible sub-5 nm nanomaterials as well as their demonstrated imaging and theranostic applications, followed by sharing our perspectives on the future development of this class of nanomaterials. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

Preoperative radiotherapy improves overall survival of pT4 pancreatic ductal adenocarcinoma patients after surgical resection.

OBJECTIVE: The aim of delivering radiotherapy for pancreatic ductal adenocarcinoma patients was to sterilize vessel margin, increase R0 resection rate and delay local progression. Whether preoperative radiotherapy could prolong overall survival of surgical candidates remained unknown. METHODS: Pancreatic ductal adenocarcinoma patients receiving radical resection from surveillance, epidemiology and end result database were enrolled. Propensity score matching was conducted to balance difference in baseline characteristics, and survival analyses were performed to compare overall survival between preoperative radiotherapy and upfront resection groups. Cox proportional hazard regression model and subgroup analyses were utilized to identify prognostic factors. RESULTS: A total of 11 665 and 597 pancreatic ductal adenocarcinoma patients receiving upfront resection and preoperative radiotherapy followed by resection from 2004 to 2016 were identified, respectively, while baseline characteristics were distinct between groups. After propensity score matching, preoperative radiotherapy was not associated with better overall survival (upfront resection vs preoperative radiotherapy, 26 vs 27 months). Subgroup analyses showed that preoperative radiotherapy was a protective factor in pT4 (hazard ratio = 0.64, 95% confidence interval: 0.47-0.88) but a negative predictor in pT1 (hazard ratio = 1.79, 95% confidence interval: 1.08-2.97) patient populations. Survival analyses showed that preoperative radiotherapy improved overall survival of patients with pT4 stage (upfront resection vs preoperative radiotherapy, 19 vs 25 months) and involvement of celiac axis, superior mesenteric artery and aorta (upfront resection vs preoperative radiotherapy, 20 vs 27 months), while preoperative radiotherapy was associated with worse overall survival in patients with pT1 tumor (upfront resection vs preoperative radiotherapy, 39 vs 24 months). CONCLUSION: Preoperative radiotherapy could improve survival of resected pancreatic ductal adenocarcinoma patients with pT4 stage or with celiac axis, superior mesenteric artery and aorta invasion.

Probing and Enhancing Ligand-Mediated Active Targeting of Tumors Using Sub-5 nm Ultrafine Iron Oxide Nanoparticles.

Rationale: "Active targeting" based on the ligand-target affinity is a common strategy to precisely deliver nanoparticle (NP) imaging probes or drug carriers to the diseased tissue. However, such ligand-mediated active targeting inevitably takes place with prerequisite "passive targeting", driven by the enhanced permeability and retention (EPR) effect. Thus, the efficiency of active targeting in relation to off-targeted unbound NPs is of great importance in quantitative imaging of tumor biomarkers and delivery. With the notion that easy clearance of off-targeted uIONPs may lead to enhanced active targeting and tumor accumulation, we examined the NP size effect on "active targeting" of the transferrin receptor (TfR) using transferrin (Tf)-conjugated sub-5 nm (3 nm core) ultrafine iron oxide NPs (uIONPs) and larger IONPs (30 nm core). Methods: Green fluorescent dye (FITC)-labeled active targeting uIONPs (FITC-Tf-uIONPs) and red fluorescent dye (TRITC)-labeled passive targeting uIONPs (TRITC-uIONPs) were prepared. FITC-Tf-IONPs and TRITC-IONPs were used as comparison for the NP size effect. Multiphoton imaging, confocal fluorescence imaging, histological staining and computational analysis were applied to track different types of NPs in tumors at 1, 3 and 24 hours after co-injection of equal amounts of paired NPs, e.g., active targeting FITC-Tf-uIONPs and non-targeting TRITC-uIONPs, or FITC-Tf-IONPs and TRITC-IONPs into the same mice bearing 4T1 mouse mammary tumors. Results: Active targeting uIONPs exhibited an almost 6-fold higher level of tumor retention with deeper penetration comparing to non-targeting uIONPs at 24 hours after co-injection. However, accumulation of active targeting IONPs with a 30-nm core is only about 1.15-fold higher than non-targeting IONPs. The enhanced active targeting by uIONPs can be attributed to the size dependent clearance of unbound off-targeted NPs, as majority off-targeted uIONPs were readily cleared from the tumor by intravasation back into tumor blood vessels likely due to high interstitial pressure, even though they are not favorable for macrophage uptake. Conclusion: Ligand-mediated active targeting improves the delivery and accumulation of the sub-5 nm NPs. The improvement on active targeting is size-dependent and facilitated by NPs with sub-5 nm core sizes. Thus, sub-5 nm NPs may serve as favorable platforms for development of NP-based molecular imaging probes and targeted drug carriers.