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Introduction: This study aimed to compare the long-term effects of neoadjuvant therapy and upfront surgery on overall survival (OS) and progression-free survival (PFS) in patients with resectable pancreatic ductal adenocarcinoma (PDAC)., Methods: We retrospectively analyzed 202 patients, including 167 who had upfront surgery and 35 who received neoadjuvant therapy followed by surgery. Surgical outcomes and survival rates were compared using propensity score matching to minimize selection bias., Results: Neoadjuvant therapy showed significantly longer 75% OS (72.7 months vs. 28.3 months, p = 0.032) and PFS (29.6 months vs. 13.2 months, p < 0.001) compared to upfront surgery. Additionally, neoadjuvant therapy demonstrated significant improvements in surgical outcomes, including higher R0 resection rates (74.3% vs. 49.5%, p = 0.034), reduced tumor size (22.0 mm vs. 28.0 mm, p = 0.001), and decreased lymphovascular invasion (20.0% vs. 52.4%, p = 0.001)., Conclusion: Our study demonstrates the potential benefits of neoadjuvant therapy for resectable PDAC. The improved survival rates, delayed disease progression, and enhanced surgical outcomes underscore the potential of neoadjuvant therapy in addressing this aggressive disease. Despite limitations such as the retrospective design and small sample size, these findings support the effectiveness of neoadjuvant therapy in improving treatment outcomes for PDAC patients in real-world settings. Further prospective studies are required to validate these results., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

To identify risk factors and biomarker for early recurrence in patients diagnosed with pancreatic cancer who undergo curative resection. Early recurrence after curative resection of pancreatic cancer is an obstacle to long-term survival. We retrospectively reviewed 162 patients diagnosed with pancreatic cancer who underwent curative resection. Early recurrence was defined as recurrence within 12 months of surgery. We selected S100A2 as a biomarker and investigated its expression using immunohistochemistry. Of the total, 79.6% (n = 129) of patients received adjuvant chemotherapy after surgery and 117 (72.2%) experienced recurrence, of which 73 (45.1%) experience early recurrence. In multivariate analysis, age < 60 years, presence of lymph node metastasis, and no adjuvant chemotherapy were significantly associated with early recurrence (all P < 0.05). The proportion of patients with high S100A2 expression (H-score > 5) was significantly lower in the early recurrence group (41.5% vs. 63.3%, P = 0.020). The cumulative incidence rate of early recurrence was higher in patients with an S100A2 H-score < 5 (41.5% vs. 63.3%, P = 0.012). The median overall survival of patients with higher S100A2 expression was longer than those with lower S100A2 expression (median 30.1 months vs. 24.2 months, P = 0.003). High-risk factors for early recurrence after surgery for pancreatic cancer include young age, lymph node metastasis, and no adjuvant therapy. Neoadjuvant treatment or intensive adjuvant therapy after surgery may improve the prognosis of patients with high-risk signatures. In patients who receive adjuvant therapy, high S100A2 expression is a good predictor., (© 2024. The Author(s).)

Biochar derived from lignocellulosic biomass has been used as a low-cost adsorbent in wastewater treatment applications. Due to its rich porous structure and good electrical conductivity, biochar can be used as a cost-effective electrode material for capacitive deionization of water. In this work, willow biochar was prepared through carbonization of shrub willow chips, activated with potassium hydroxide, and loaded with manganese dioxide (WBC-K-MnO 2 nanocomposite). The prepared materials were used to electrochemically adsorb Pb 2+ from aqueous solutions. Under the applied potential of 1.0 V, the WBC-K-MnO 2 electrode exhibited a high Pb 2+ specific electrosorption capacity (23.3 mg/g) as compared to raw willow biochar (4.0 mg/g) and activated willow biochar (9.2 mg/g). KOH activation followed by MnO 2 loading on the surface of raw biochar enhanced its BET surface area (178.7 m 2 /g) and mesoporous volume ratio (42.1%). Moreover, the WBC-K-MnO 2 nanocomposite exhibited the highest specific capacitance value of 234.3 F/g at a scan rate of 5 mV/s. The electrosorption isotherms and kinetic data were well explained by the Freundlich and pseudo-second order models, respectively. The WBC-K-MnO 2 electrode demonstrated excellent reusability with a Pb 2+ electrosorption efficiency of 76.3% after 15 cycles. Thus, the WBC-K-MnO 2 nanocomposite can serve as a promising candidate for capacitive deionization of heavy metal contaminated water.

Background: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity., Methods: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples., Results: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep&#95;VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep&#95;VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data., Conclusions: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets., (© 2024. The Author(s).)

Introduction: The incidence of postendoscopic retrograde cholangiopancreatography (ERCP) infections is reported to be up to 18% in patients with biliary obstruction. Antibiotic prophylaxis may reduce the risk of infectious complications after ERCP; however, the clinical value of prophylactic antibiotics in ERCP remains controversial., Methods: We conducted a double-blind, placebo-controlled, randomized trial to investigate whether the use of prophylactic antibiotics would reduce infectious complications after ERCP in patients with biliary obstruction. We randomly assigned patients in a 1:1 ratio to receive either a single dose of 1 g intravenous cefoxitin or normal saline as a placebo 30 minutes before undergoing ERCP. The primary outcome was the incidence of infectious complications after ERCP., Results: We enrolled 378 patients, and 189 patients were assigned to each group. The risk of infectious complications after ERCP was 2.8% (5 of 176 patients) in the antibiotic prophylaxis group and 9.8% (17 of 173 patients) in the placebo group (risk ratio, 0.29; 95% confidence interval [CI], 0.11-0.74, P = 0.0073). The incidence rates of bacteremia were 2.3% (4 of 176 patients) and 6.4% (11 of 173 patients), respectively (risk ratio, 0.36; 95% CI, 0.12-1.04; P = 0.0599). The incidence rate of cholangitis was 1.7% (3 of 176 patients) in the antibiotic prophylaxis group and 6.4% (11 of 173 patients) in the placebo group (risk ratio, 0.27; 95% CI, 0.08-0.87; P = 0.0267)., Discussion: Antibiotic prophylaxis before ERCP in patients with biliary obstruction resulted in a significantly lower risk of infectious complications, especially cholangitis, than placebo ( ClinicalTrials.gov trial number NCT02958059)., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objective: Early chemoresistance and tumor mass progression are associated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Circulating tumor cells (CTCs) have been studied as potential predictors of treatment response and prognosis in PDAC; however, this approach has yet to be applied in clinical practice. The aim of our study was to investigate the phenotypic characteristics of CTCs and determine their predictive value for PDAC progression., Methods: We prospectively enrolled 40 patients who were pathologically diagnosed with PDAC and collected blood samples at diagnosis, 2 months after diagnosis, and during disease progression or recurrence. We used a microfabricated filter-based enrichment system to retrieve and analyze CTCs, which were classified using immunofluorescence staining (CD45, EpCAM, and vimentin)., Results: Our study included 20 women and 20 men (median age, 66 years). Overall, 45% of the patients (18/40) had disseminated disease, and 77.5% (31/40) received chemotherapy. Multivariate analysis revealed that the total CTC count and carbohydrate antigen 19-9 level at 2 months after diagnosis were associated with disease progression ( P <0.05). Linear mixed model analysis revealed that the total CTC count and vimentin-positive CTCs were significantly correlated with treatment response during chemotherapy ( P =0.024 and 0.017, respectively). Kaplan-Meier analysis showed that total CTC positivity at 2 months was significantly associated with poor progression-free survival ( P =0.038)., Conclusion: Our study's findings suggest that CTCs can serve as predictive biomarkers of clinical outcomes in patients with PDAC receiving palliative chemotherapy. In particular, the total CTC count and vimentin-positive CTCs showed changes associated with the chemotherapy response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Jung, Shin, Park, Park, Jung, Leem, Kim, Jo, Chung, Park, Bang, Park and Song.)

As genomic analysis technology has advanced, it has become possible to sub-classify intrahepatic cholangiocarcinoma (ICC) at the histological or molecular level. Here, we verify the recently suggested two subgroups of ICC in the organoids model, compare the characteristics between types. ICC patients are subclassified into small-duct (SD) and large-duct (LD) subtype according to histological characteristics. ICC organoids are established, and unsupervised principal component analysis clustering separates each type of ICC. Differential gene expression reveals enrichment on KRAS, TGFβ and ERBB2 signaling pathways in LD-type compared with SD-type (P < 0.05). Gene set enrichment analysis demonstrates that the cholangiocarcinoma class 2 signature, defined by Andersen et al., is enriched in the LD-type (enrichment Score = 2.19, P < 0.001). A protein-protein interaction network analysis identifies ZNF217 as a significant hub protein (odds ratio = 4.96, P = 0.0105). We perform prospective modeling of histological subtype using patient-derived organoids. Moreover, gene expression profiling of ICC organoids enables identification of type-specific targetable pathways., (© 2023. The Author(s).)

The selective cleavage of C-C/C-O linkages represents a key step toward achieving the chemical conversion of biomass to targeted value-added chemical products under ambient conditions. Using photoelectrosynthetic solar cells is a promising method to address the energy intensive depolymerization of lignin for the production of biofuels and valuable chemicals. This feature article gives an in-depth overview of recent progress using dye-sensitized photoelectrosynthetic solar cells (DSPECs) to initiate the cleavage of C-C/C-O bonds in lignin and related model compounds. This approach takes advantage of N -oxyl mediated catalysis in organic electrolytes and presents a promising direction for the sustainable production of chemicals currently derived from fossil fuels.

The photoelectrochemical production of fuels, exemplified by light-driven water splitting to hydrogen and oxygen, offers a sustainable option to offset dependence on fossil fuels. A low-cost, efficient, and stable photoelectrochemical approach to solar fuels remains elusive but using similar materials and photoelectrodes for chemical production or biomass conversion offers an appealing alternative. This work reports a facile method for fabricating pristine (undoped) BiVO 4 photoanodes to carry out TEMPO-mediated benzyl alcohol oxidation to benzaldehyde in organic media (TEMPO=2,2,6,6-tetramethylpiperidinyl-N-oxyl). The best performing BiVO 4 photoanode studied here gave a faradaic efficiency (FE) of 85±5% for benzaldehyde formation in the presence of TEMPO and pyridine during a 2.5-hour reaction. Compared with direct electrocatalytic conversion under the same conditions, light capture and conversion by the BiVO 4 surface decreased the required applied bias by 46 %. To our knowledge, this is the first report of visible light assisted, TEMPO-mediated benzyl alcohol oxidation using pristine BiVO 4 photoanodes in organic media., (© 2022 Wiley-VCH GmbH.)

Background and Aim: This study investigated the administration of combination therapy, allogeneic natural killer (NK) cells and pembrolizumab in the treatment of advanced biliary tract cancer to determine the safety and tolerability (phase 1) and the efficacy and safety (phase 2a)., Methods: Forty patients (phase 1, n = 6; phase 2a, n = 34) were enrolled between December 2019 and June 2021. The patients received highly activated allogeneic NK cells ("SMT-NK") on weeks 1 and 2 and pembrolizumab on week 1. This 3-week schedule (one cycle) was repeated until confirmed disease progression, intolerable adverse events (AEs), patient withdrawal, or finishing the maximum treatment schedule. The tumor response was evaluated after every three cycles., Results: In phase 1, four patients (66.7%) experienced seven AEs, but no severe AE was observed. In phase 2a, 126 AEs occurred in 29 patients (85.3%). Severe AEs (≥grade 3) were reported in 16 patients (47.1%). The overall response rate (ORR) was 17.4% in the full analysis set and 50.0% in the per-protocol set., Conclusions: SMT-NKs plus pembrolizumab resulted in no severe AEs directly related to the drug combination. The combination therapy also exerted antitumor activity with improved efficacy compared to the recent monotherapy with pembrolizumab in patients with advanced biliary tract cancer.

Background: Tumour-unrelated, virus-specific bystander CD8 + T cells were recently shown to be abundant among tumour-infiltrating lymphocytes (TILs). However, their roles in tumour immunity have not been elucidated yet., Methods: We studied the characteristics of bystander CD8 + TILs from non-small cell lung cancer (NSCLC) tissues (N=66) and their activation by interleukin (IL)-15 to repurpose them for tumour immunotherapy., Results: We show that bystander CD8 + TILs specific to various viruses are present in human NSCLC tissues. We stimulated CD8 + TILs ex vivo using IL-15 without cognate antigens and found that IL-15 treatment upregulated NKG2D expression on CD8 + TILs, resulting in NKG2D-dependent production of interferon (IFN)-γ (p=0.0006). Finally, we tested whether IL-15 treatment can control tumour growth in a murine NSCLC model with or without a history of murine cytomegalovirus (MCMV) infection. IL-15 treatment reduced the number of tumour nodules in the lung only in mice with MCMV infection (p=0.0037). We confirmed that MCMV-specific bystander CD8 + TILs produced interferon (IFN)-γ after IL-15 treatment, and that IL-15 treatment in MCMV-infected mice upregulated tumour necrosis factor-α and IFN-γ responsive genes in tumour microenvironment., Conclusion: Thus, the study demonstrates that bystander CD8 + TILs can be repurposed by IL-15 for tumour immunotherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aims to increase the specific surface area of multi-walled carbon nanotubes (MWCNTs) by forming and subsequently removing various metal oxide nanoparticles on them. We used facile methods, such as forming the particles without using a vacuum or gas and removing these particles through simple acid treatment. The shapes of the composite structures on which the metal oxide particles were formed and the formation of multi-vacancy-defect MWCNTs were confirmed via transmission electron microscopy and scanning electron microscopy. The crystallinity of the formed metal oxide particles was confirmed using X-ray diffraction analysis. Through specific surface area analysis and Raman spectroscopy, the number of defects formed and the degree and tendency of defect-formation in each metal were determined. In all the cases where the metal oxide particles were removed, the specific surface area increased, and the metal inducing the highest specific surface area was determined.

Visible-light-driven organic oxidations carried out under mild conditions offer a sustainable approach to performing chemical transformations important to the chemical industry. This work reports an efficient photocatalytic benzyl alcohol oxidation process using one-dimensional (1D) TiO 2 nanorod (NR)-based photoanodes with surface-adsorbed ruthenium polypyridyl photocatalysts at room temperature. The photocatalyst bis(2,2'-bipyridine)(4,4'-dicarboxy-2,2'-bipyridine)Ru(II) (RuC) was covalently anchored onto TiO 2 nanorod arrays grown on fluorine-doped tin oxide (FTO) electrode surfaces (FTO|t-TiO 2 |RuC, t = the thickness of TiO 2 NR). Under aerobic conditions, the photophysical and photocatalytic properties of FTO|t-TiO 2 |RuC ( t = 1, 2, or 3.5 μm) photoanodes were investigated in a solution containing a hydrogen atom transfer mediator (4-acetamido-2,2,6,6-tetramethylpiperidine-N-oxyl, ACT) as cocatalyst. Dye-sensitized photoelectrochemical cells (DSPECs) using the FTO|t-TiO 2 |RuC ( t = 1, 2, or 3.5 μm) photoanodes and ACT-containing electrolyte were investigated for carrying out photocatalytic oxidation of a lignin model compound containing a benzylic alcohol functional group. The best-performing anode surface, FTO|1-TiO 2 |RuC (shortest NR length), oxidized the 2° alcohol of the lignin model compound to the C α -ketone form with a > 99% yield over a 4 h photocatalytic experiment with a Faradaic efficiency of 88%. The length of TiO 2 NR arrays (TiO 2 NRAs) on the FTO substrate influenced the photocatalytic performance with longer NRAs underperforming compared to the shorter arrays. The influence of the NR length is hypothesized to affect the homogeneity of the RuC coating and accessibility of the ACT mediator to the RuC-coated TiO 2 surface. The efficient photocatalytic alcohol oxidation with visible light at room temperature as demonstrated in this study is important to the development of sustainable approaches for lignin depolymerization and biomass conversion.

The seed-mediated method is a general procedure for the synthesis of gold nanorods (Au NRs), and reducing agents such as ascorbic acid (AA) and hydroquinone (HQ) are widely used for the growth process. Further, they are mild reducing agents; however, when AA is used, controlling the size of Au NRs with a higher aspect ratio (localized surface plasmon resonance (LSPR) peak, λ Lmax  > 900 nm) is challenging because it results in a faster growth rate of Au NRs. In contrast, when HQ is used, Au NRs with a higher aspect ratio can be synthesized as it slows down the growth rate of the Au NRs and greatly enhanced the λ Lmax . However, the increase in λ Lmax is still needs not satisfactory due to the limited enhancement in the aspect ratio of Au NRs due to utilization of single reducing agent. The growth kinetics of the Au NRs can be modulated by controlling the reducing power of the reducing agents. In such scenario, judicious use of two reducing agents such as AA and HQ simultaneously can help us to design Au NRs of higher aspect ratio in a controlled manner due to the optimum growth rate resulting from the combined effect of both the reducing agents. In this study, we investigated the effect of the two reducing agents by controlling the volume ratios. When the growth solution contains both the reducing agents, the growth of Au NRs is first initiated by the fast reduction of Au 3+ to Au + due to stronger reducing power of the AA and when the AA in the growth solution is completely utilized, further growth of the Au NRs continues as a result of the HQ thereby resulting to high aspect ratio Au NRs. Consequently, the LSPR peak (λ Lmax  > 1275 nm) can be tuned by controlling the volume ratios of the reducing agents., (© 2022. The Author(s).)

Integrating multidisciplinary research in plant genetic engineering and renewable deep eutectic solvents (DESs) can facilitate a sustainable and economic biorefinery. Herein, we leveraged a plant genetic engineering approach to specifically incorporate C 6 C 1 monomers into the lignin structure. By expressing the bacterial ubiC gene in sorghum, p-hydroxybenzoic acid (PB)-rich lignin was incorporated into the plant cell wall while this monomer was completely absent in the lignin of the wild-type (WT) biomass. A DES was synthesized with choline chloride (ChCl) and PB and applied to the pretreatment of the PB-rich mutant biomass for a sustainable biorefinery. The release of fermentable sugars was significantly enhanced (∼190 % increase) compared to untreated biomass by the DES pretreatment. In particular, the glucose released from the pretreated mutant biomass was up to 12 % higher than that from the pretreated WT biomass. Lignin was effectively removed from the biomass with the preservation of more than half of the β-Ο-4 linkages without condensed aromatic structures. Hydrogenolysis of the fractionated lignin was conducted to demonstrate the potential of phenolic compound production. In addition, a simple hydrothermal treatment could selectively extract PB from the same engineered lignin, showing a possible circular biorefinery. These results suggest that the combination of PB-based DES and engineered PB-rich biomass is a promising strategy to achieve a sustainable closed-loop biorefinery., (© 2021 Wiley-VCH GmbH.)