Human Equilibrative Nucleoside Transporter 1: Novel Biomarker and Prognostic Indicator for Patients with Gemcitabine-Treated Pancreatic Cancer.

Aim: This article aimed to find appropriate pancreatic cancer (PC) patients to treat with Gemcitabine with better survival outcomes by detecting hENT1 levels. Methods: We collected surgical pathological tissues from PC patients who received radical surgery in our hospital from September 2004 to December 2014. A total of 375 PC tissues and paired adjacent nontumor tissues were employed for the construction of 4 tissue microarrays (TMAs). The quality of the 4 TMAs was examined by HE staining. We performed immunohistochemistry analysis to evaluate hENT1 expression in the TMAs. Moreover, we detected hENT1 expression level and proved the role of hENT1 in cell proliferation, drug resistance, migration and invasion in vivo and vitro. Results: The results indicated that low hENT1 expression indicated a significantly poor outcome in PC patients, including shortened DFS (21.6±2.8 months versus 36.9±4.0 months, p<0.001) and OS (33.6±3.9 versus 39.6±3.9, p=0.004). Meanwhile, patients in stage I/II of TNM stage had a longer OS (40.2±3.4 versus 15.4±1.7, p=0.002) and DFS (31.0±3.1 versus 12.4±1.9, p=0.016) than patients in stage III/IV. Patients in M0 stage had a longer OS (39.7±3.4 versus 16.2±1.9, p=0.026) and DFS(30.7±3.0 versus 11.8±2.2, p=0.031) than patients in M1 stage, and patients with tumors not invading the capsule had a better DFS than those with tumor invasion into the capsule (30.8±3.0 versus 12.6±2.3, p=0.053). Patients with preoperative CA19-9 values ≤467 U/mL have longer DFS than that of patients who had preoperative CA19-9 values >467 U/mL (37.9±4.1 versus 22.9±4.0, p=0.04). In the subgroup analysis, a high hENT1 expression level was related to a longer OS(39.4±4.0 versus 31.5±3.9, p=0.001) and DFS(35.7±4.0 versus 20.6±2.7; p<0.0001) in the Gemcitabine subgroup. Conclusion: PC patients with high hENT1 expression have a better survival outcomes when receiving Gemcitabine. hENT1 expression can be a great prognostic indicator for PC patients to receive Gemcitabine treatment.

Visualizing Phase Evolution of Co2C for Efficient Fischer-Tropsch to Olefins.

Cobalt carbide (Co2C) possesses high catalytic efficiency Fischer-Tropsch synthesis (FTS), while the products selectivity appears sensitive to crystallography geometry. Since the Anderson-Schulz-Flory (ASF) distribution in FTS is broken through fabricating facetted Co2C nanocrystals, yet the underlying mechanism of Co2C crystallization remains unclarified suffering from sophisticated catalyst composition involving promoter agents. Herein, the synthesis of high-purity single-crystal nanoprisms (Co2C-p) for highly efficient FTS is reported to lower olefins. Through comprehensive microstructure analysis, e.g., high-resolution TEM, in situ TEM and electron diffraction, as well as finite element simulation of gas flow field, for the first time the full roadmap of forming catalytic active cobalt carbides is disclosed, starting from reduction of Co3O4 precursor to CoO intermediate, then carburization into Co2C-s and subsequent ripening growth into Co2C-p. This gas-induced engineering of crystal phase provides a new synthesis strategy, with many new possibilities for precise design of metal-based catalyst for diverse catalytic applications.

Impact of Combined Chemotherapy and Targeted Therapy on Pancreatic Neuroendocrine Carcinoma with Liver Metastasis: A Single-Center Modified Nomogram Analysis.

Objective: To establish a modified nomogram model for pancreatic neuroendocrine carcinoma (pNEC) patients with liver metastasis via single-center clinical data, and to provide guidelines for improving the diagnosis and treatment of patients. Methods: A retrospective analysis of clinical data from pNEC patients with liver metastasis at Peking Union Medical College Hospital (January 2000 to November 2023) was conducted. Univariate and multivariate Cox regression analyses were employed to identify prognostic factors for overall survival (OS). Kaplan-Meier curves were generated, and a modified nomogram predictive model was developed to illustrate the prognosis of pNEC patients with liver metastasis. Calibration plots and C-index were used to validate the model's feasibility, accuracy, and reliability. Results: Forty-five participants with the rare cancer type pNEC and liver metastasis were included in the study. Kaplan-Meier curves revealed that primary tumor resection (PTR), chemotherapy or targeted therapy, and tumor size equal to or less than 5cm significantly improved OS compared to those without PTR, chemotherapy or targeted therapy, and tumor size larger than 5cm. Multivariate Cox regression analysis identified PTR, a combination of chemotherapy and targeted therapy, and tumor size as independent prognostic factors for OS. The predictive nomogram model exhibited acceptable performance with a C-index of 0.744 (0.639-0.805) through bootstrapping. Conclusion: Combining chemotherapy with targeted therapy enhances the survival of pNEC patients with liver metastasis. The modified nomogram model and predictive score table offer valuable references and insights for both clinicians and patients.

E3 ubiquitin ligase RBCK1 confers ferroptosis resistance in pancreatic cancer by facilitating MFN2 degradation.

Ferroptosis, a novel form of iron-dependent non-apoptotic cell death, plays an active role in the pathogenesis of diverse diseases, including cancer. However, the mechanism through which ferroptosis is regulated in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here, our study, via combining bioinformatic analysis with experimental validation, showed that ferroptosis is inhibited in PDAC. Genome-wide sequencing further revealed that the ferroptosis activator imidazole ketone erastin (IKE) induced upregulation of the E3 ubiquitin ligase RBCK1 in PDAC cells at the transcriptional or translational level. RBCK1 depletion or knockdown rendered PDAC cells more vulnerable to IKE-induced ferroptotic death in vitro. In a mouse xenograft model, genetic depletion of RBCK1 increased the killing effects of ferroptosis inducer on PDAC cells. Mechanistically, RBCK1 interacts with and polyubiquitylates mitofusin 2 (MFN2), a key regulator of mitochondrial dynamics, to facilitate its proteasomal degradation under ferroptotic stress, leading to decreased mitochondrial reactive oxygen species (ROS) production and lipid peroxidation. These findings not only provide new insights into the defense mechanisms of PDAC cells against ferroptotic death but also indicate that targeting the RBCK1-MFN2 axis may be a promising option for treating patients with PDAC.

The new era of pancreatic cancer treatment: Application of nanotechnology breaking through bottlenecks.

Since the advent of nanomedicine, physicians have harnessed these approaches for the prophylaxis, detection, and therapy of life-threatening diseases, particularly cancer. Nanoparticles have demonstrated notable efficacy in cancer therapy, showcasing the primary application of nanotechnology in targeted drug delivery. Pancreatic cancer stands out as the most lethal solid tumour in humans. The low survival rate is attributed to its highly aggressive nature, intrinsic resistance to chemotherapeutics, and the lack of successful therapies, compounded by delayed diagnosis due to nonspecific symptoms and the absence of rapid diagnostic strategies. Despite these challenges, nanotechnology-based carrier methods have been successfully employed in imaging and therapy approaches. Overcoming drug resistance in pancreatic cancer necessitates a comprehensive understanding of the microenvironment associated with the disease, paving the way for innovative nanocarriers. Hindered chemotherapy infiltration, attributed to inadequate vascularization and a dense tumour stroma, is a major hurdle that nanotechnology addresses. Intelligent delivery techniques, based on the Enhanced Permeability and Retention effect, form the basis of recently developed anticancer nanocarriers. These advancements aim to enhance drug accumulation in tumour locations, offering a potential solution to the treatment-resistant nature of cancer. Addressing the challenges in pancreatic cancer treatment demands innovative therapies, and the emergence of active nanocarriers presents a promising avenue for enhancing outcomes. This review specifically delves into the latest advancements in nanotechnology for the treatment of pancreatic cancer.

Study on the Improvement of Droplet Penetration Effect by Nozzle Tilt Angle under the Influence of Orthogonal Side Wind.

This study investigates the impact of varying side wind velocities and nozzle inclination angles on droplet penetration during plant protection spraying operations, focusing on citrus trees. Experiments were conducted across four wind speed levels (0, 1, 2, 3 m/s) perpendicular to the nozzle direction and seven nozzle inclination levels (0°, 8°, 15°, 23°, 30°, 38°, 45°) to evaluate droplet distribution under different spraying parameters. A baseline condition with 0 m/s wind speed and a 0° nozzle angle served as the control. Utilizing Computational Fluid Dynamics (CFD) and regression analysis techniques in conjunction with field trials, the droplet penetration was analyzed. Results indicate that at constant wind speeds, adjusting the nozzle inclination angle against the direction of the side wind can significantly enhance droplet deposition in the canopy, with a 23° inclination providing the optimal increase in deposition volume, averaging a change of +16.705 µL/cm2. Multivariate nonlinear regression analysis revealed that both wind speed and nozzle inclination angle significantly affect the droplet penetration ratio, demonstrating a correlation between these factors, with wind speed exerting a greater impact than nozzle angle. Increasing the nozzle inclination angle at higher wind speeds improves the penetration ratio, with the optimal parameters being a 23° angle and 3 m/s wind speed, showing a 12.6% improvement over the control. The model fitted for the impact of nozzle angle and wind speed on droplet penetration was validated through field experiments, identifying optimal angles for enhancing penetration at wind speeds of 1, 2, and 3 m/s as 8°, 17°, and 25°, respectively. This research provides insights for improving droplet penetration techniques in plant protection operations.

FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide, primarily due to its rapid progression. The current treatment options for PDAC are limited, and a better understanding of the underlying mechanisms responsible for PDAC progression is required to identify improved therapeutic strategies. Here, we identified FBXO32 as an oncogenic driver in PDAC. FBXO32 was aberrantly upregulated in PDAC, and high FBXO32 expression was significantly associated with an unfavorable prognosis in PDAC patients. FRG1 deficiency promoted FBXO32 upregulation in PDAC. FBXO32 promoted cell migration and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, FBXO32 directly interacted with eEF1A1 and promoted its polyubiquitination at the K273 site, leading to enhanced activity of eEF1A1 and increased protein synthesis in PDAC cells. Moreover, FBXO32-catalyzed eEF1A1 ubiquitination boosted the translation of ITGB5 mRNA and activated FAK signaling, thereby facilitating focal adhesion assembly and driving PDAC progression. Importantly, interfering with the FBXO32-eEF1A1 axis or pharmaceutical inhibition of FAK by defactinib, an FDA-approved FAK inhibitor, substantially inhibited PDAC growth and metastasis driven by aberrantly activated FBXO32-eEF1A1 signaling. Overall, this study uncovers a mechanism by which PDAC cells rely on FBXO32-mediated eEF1A1 activation to drive progression and metastasis. FBXO32 may serve as a promising biomarker for selecting eligible PDAC patients for treatment with defactinib.

Multiomics integration reveals NETosis heterogeneity and TLR2 as a prognostic biomarker in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant neoplasm characterized by a poor prognosis and limited therapeutic strategy. The PDAC tumor microenvironment presents a complex heterogeneity, where neutrophils emerge as the predominant constituents of the innate immune cell population. Leveraging the power of single-cell RNA-seq, spatial RNA-seq, and multi-omics approaches, we included both published datasets and our in-house patient cohorts, elucidating the inherent heterogeneity in the formation of neutrophil extracellular traps (NETs) and revealed the correlation between NETs and immune suppression. Meanwhile, we constructed a multi-omics prognostic model that suggested the patients exhibiting downregulated expression of NETs may have an unfavorable outcome. We also confirmed TLR2 as a potent prognosis factor and patients with low TLR2 expression had more effective T cells and an overall survival extension for 6 months. Targeting TLR2 might be a promising strategy to reverse immunosuppression and control tumor progression for an improved prognosis.

The NF-κB/NUAK2 signaling axis regulates pancreatic cancer progression by targeting SMAD2/3.

Nuclear factor kappa B (NF-κB) plays a pivotal role in the development of pancreatic cancer, and its phosphorylation has previously been linked to the regulation of NUAK2. However, the regulatory connection between NF-κB and NUAK2, as well as NUAK2's role in pancreatic cancer, remains unclear. In this study, we observed that inhibiting NUAK2 impeded the proliferation, migration, and invasion of pancreatic cancer cells while triggering apoptosis. NUAK2 overexpression partially resisted apoptosis and reversed the inhibitory effects of the NF-κB inhibitor. NF-κB transcriptionally regulated NUAK2 transcription by binding to the promoter region of NUAK2. Mechanistically, NUAK2 knockdown remarkably reduced the expression levels of p-SMAD2/3 and SMAD2/3, resulting in decreased nuclear translocation of SMAD4. In SMAD4-negative cells, NUAK2 knockdown impacted FAK signaling by downregulating SMAD2/3. Moreover, NUAK2 knockdown heightened the sensitivity of pancreatic cancer cells to gemcitabine, suggesting that NUAK2 inhibitors could be a promising strategy for pancreatic cancer treatment.

A Ce-CuZn catalyst with abundant Cu/Zn-OV-Ce active sites for CO2 hydrogenation to methanol.

CO2 hydrogenation to chemicals and fuels is a significant approach for achieving carbon neutrality. It is essential to rationally design the chemical structure and catalytic active sites towards the development of efficient catalysts. Here we show a Ce-CuZn catalyst with enriched Cu/Zn-OV-Ce active sites fabricated through the atomic-level substitution of Cu and Zn into Ce-MOF precursor. The Ce-CuZn catalyst exhibits a high methanol selectivity of 71.1% and a space-time yield of methanol up to 400.3 g·kgcat-1·h-1 with excellent stability for 170 h at 260 °C, comparable to that of the state-of-the-art CuZnAl catalysts. Controlled experiments and DFT calculations confirm that the incorporation of Cu and Zn into CeO2 with abundant oxygen vacancies can facilitate H2 dissociation energetically and thus improve CO2 hydrogenation over the Ce-CuZn catalyst via formate intermediates. This work offers an atomic-level design strategy for constructing efficient multi-metal catalysts for methanol synthesis through precise control of active sites.

Ribosome profiling: a powerful tool in oncological research.

Neoplastic cells need to adapt their gene expression pattern to survive in an ever-changing or unfavorable tumor microenvironment. Protein synthesis (or mRNA translation), an essential part of gene expression, is dysregulated in cancer. The emergence of distinct translatomic technologies has revolutionized oncological studies to elucidate translational regulatory mechanisms. Ribosome profiling can provide adequate information on diverse aspects of translation by aiding in quantitatively analyzing the intensity of translating ribosome-protected fragments. Here, we review the primary currently used translatomics techniques and highlight their advantages and disadvantages as tools for translatomics studies. Subsequently, we clarified the areas in which ribosome profiling could be applied to better understand translational control. Finally, we summarized the latest advances in cancer studies using ribosome profiling to highlight the extensive application of this powerful and promising translatomic tool.

Boosting Low-Temperature CO2 Hydrogenation over Ni-based Catalysts by Tuning Strong Metal-Support Interactions.

Rational design of low-cost and efficient transition-metal catalysts for low-temperature CO2 activation is significant and poses great challenges. Herein, a strategy via regulating the local electron density of active sites is developed to boost CO2 methanation that normally requires >350 °C for commercial Ni catalysts. An optimal Ni/ZrO2 catalyst affords an excellent low-temperature performance hitherto, with a CO2 conversion of 84.0 %, CH4 selectivity of 98.6 % even at 230 °C and GHSV of 12,000 mL g-1 h-1 for 106 h, reflecting one of the best CO2 methanation performance to date on Ni-based catalysts. Combined a series of in situ spectroscopic characterization studies reveal that re-constructing monoclinic-ZrO2 supported Ni species with abundant oxygen vacancies can facilitate CO2 activation, owing to the enhanced local electron density of Ni induced by the strong metal-support interactions. These findings might be of great aid for construction of robust catalysts with an enhanced performance for CO2 emission abatement and beyond.

Sustainable production of triazoles from lignin major motifs.

An efficiently catalyzed synthesis of pharmaceutically relevant 1,2,3-trazoles from renewable resources is highly desirable. However, due to incompatible catalysis conditions, this endeavor remained challenging so far. Herein, a practical access protocol to 1,2,3-triazoles, starting from lignin phenolic ß-O-4 with γ-OH group utilizing a vanadium-based catalyst is presented. A broad substrate scope reaching up to 97 % yield of 1,2,3-triazoles are obtained. The reaction pathway includes selective cleavage of double C-O bonds, cycloaddition, and dehydrogenation. Mechanistic studies and density-functional theory (DFT) calculations suggest that the V-based complex acts as a bifunctional catalyst for both selective C-O bonds cleavage and dehydrogenation. This synthetic pathway has been applied for the synthesis of pharmacological and biological active carbohydrate derivatives starting from biomass components as feedstock, enabling a potential sustainable route to triazolyl carbohydrate derivatives, which paves the way for lignin-based heterocyclic aromatics in the pharmaceutical applications.

Clinical study of 3D laparoscopic radical prostatectomy by transperitoneal and extraperitoneal approaches.

OBJECTIVE: Comparison of the clinical effectiveness and safety of three-dimensional transperitoneal laparoscopic radical prostatectomy (3D TLRP) versus 3D extraperitoneal LRP (3D ELRP) for prostate cancer. MATERIALS AND METHODS: To retrospectively analyze the clinical and regular postoperative follow-up data of patients who underwent 3D LRP performed by the same attending surgeon at the Affiliated Hospital of Bengbu Medical College between 2017 and 2022. A total of 82 patients who met the criteria were included. They were divided into 3D TLRP (n = 39) and 3D ELRP groups (n = 43) according to the surgical approach. The preoperative, intraoperative, and postoperative data were compared. RESULTS: There were no statistically significant differences in preoperative characteristics between the two groups. There were also no statistically significant differences between the 3D TLRP and 3D ELRP groups in terms of intraoperative blood transfusion rate (12.82% vs. 2.33%), positive lymph node rate (11.11% vs. 2.38%), positive surgical margin rate (12.82% vs. 6.98%), pathological Gleason score, postoperative clinical stage, perioperative complication rate (10.26% vs. 4.65%), immediate urinary control rate (56.41% vs. 58.14%), 3-month postoperative urinary control rate (76.92% vs. 74.42%), 6-month postoperative urinary control rate (87.18% vs. 83.72%), 6-month postoperative biochemical recurrence rate (7.69% vs. 9.30%), or 6-month postoperative sexual function recovery rate (2.56% vs. 2.33%) (P > 0.05). Compared with the 3D ELRP group, the 3D TLRP group had a longer operative time (232.36 ± 48.52 min vs. 212.07 ± 41.76 min), more estimated blood loss (150.000 [100.0, 200.0] vs. 100.000 [100.0, 125.0]), longer recovery of gastrointestinal function (2.72 ± 0.89 vs. 2.26 ± 0.88), longer duration of drainage tube retention (5.69 ± 1.79 vs. 4.28 ± 2.68), and longer hospitalization time (12.54 ± 4.07 vs. 10.88 ± 2.97), with statistical significance (P < 0.05). CONCLUSION: 3D TLRP and 3D ELRP have similar oncologic and functional outcomes. Clinically, physicians can choose a reasonable procedure according to the patient's specific situation and their own surgical experience.

Regulatory role of RNA modifications in the treatment of pancreatic ductal adenocarcinoma (PDAC).

Pancreatic ductal adenocarcinoma (PDAC) is an extremely life-threatening malignancy with a relatively unfavorable prognosis. The early occurrence of metastasis and local recurrence subsequent to surgery contribute to the poor survival rates of PDAC patients, thereby limiting the effectiveness of surgical intervention. Additionally, the desmoplastic and immune-suppressive tumor microenvironment of PDAC diminishes its responsiveness to conventional treatment modalities such as chemotherapy, radiotherapy, and immunotherapy. Therefore, it is imperative to identify novel therapeutic targets for PDAC treatment. Chemical modifications are prevalent in various types of RNA and exert significant influence on their structure and functions. RNA modifications, exemplified by m6A, m5C, m1A, and Ψ, have been identified as general regulators of cellular functions. The abundance of specific modifications, such as m6A, has been correlated with cell proliferation, invasion, migration, and patient prognosis in PDAC. Pre-clinical data has indicated that manipulating RNA modification regulators could enhance the efficacy of chemotherapy, radiotherapy, and immunotherapy. Therefore, targeting RNA modifications in conjunction with current adjuvant or neoadjuvant therapy holds promise. The objective of this review is to provide a comprehensive overview of RNA modifications in PDAC treatment, encompassing their behaviors, mechanisms, and potential treatment targets. Therefore, it aims to stimulate the development of novel therapeutic approaches and future clinical trials.

Epidemiology of pancreatic cancer: New version, new vision.

Pancreatic cancer (PC) is a devastating malignancy with an extremely high mortality rate and poses significant challenges to healthcare systems worldwide. The prevalence of PC risk factors spiked over the years, leading to a global increase in PC incidence rates. The contribution of different risk factors, however, varied from region to region due to genetic predisposition, environmental, social, and political factors underlying disease prevalence in addition to public health strategies. This comprehensive review aims to provide a thorough analysis of the epidemiology of PC, discussing its incidence, risk factors, screening strategies and socioeconomic burden. We compiled a wide range of seminal studies as well as epidemiological investigations to serve this review as a comprehensive guide for researchers, healthcare professionals, and policymakers keen for a more profound understanding of PC epidemiology. This review highlights the essentiality of persistent research efforts, interdisciplinary collaboration, and public health initiatives to address the expanding burden of this malignancy.

Does Oral Microbiota Have a Close Relationship with Pancreatic Cancer? A Systematic Review and Meta-Analysis.

BACKGROUND: The association between oral microbiota and pancreatic cancer (PC) is increasingly recognized and studied. Yet, contrasting results are seen in current studies. This study aimed to provide systematic review and meta-analysis comparing PC and oral microbiota. METHODS: Studies related to the association between oral microbiota and PC were identified through digital databases including PubMed, Medline, EMBASE, COCHRANE, and SCOPUS without limitations on language or publication period. The last identification date was 10 March 2023. Three case-control studies concerning the issue were included. For the meta-analyses, RevMan software version 5.4 was used. The Newcastle-Ottawa scale was used to evaluate articles and measurement of study differences, and publication bias was shown. RESULTS: Porphyromonas gingivalis in oral bacteria was detected at a comparatively high detection rate in PC patients compared with healthy controls (odds ratio [OR], 1.38; 95 % confidence interval [CI], 1.09-1.74; P = 0.007; I2 = 34 %). The detection rate did not differ significantly between PC patients and healthy control patients for Aggregatibacter actinomycetemcomitans (OR 0.98; 95 % CI 0.75-1.29; P = 0.90; I2 = 76 %); Tannerella forsythiaand (OR 1.12; 95 % CI 0.89-1.42; P = 0.33; I2 = 0 %), or Prevotella intermedia (OR 1.08; 95 % CI 0.84-1.39; P = 0.55; I2 = 0 %). CONCLUSION: Oral microbiota were closely related to PC, whereas P. gingivalis was more commonly found in the PC patients than in the healthy controls. For patients with PC, P. gingivalis may play a role in early diagnosis.

Ni-Based Hydrotalcite (HT)-Derived Cu Catalysts for Catalytic Conversion of Bioethanol to Butanol.

Catalytic conversion of biomass-derived ethanol into n-butanol through Guerbet coupling reaction has become one of the key reactions in biomass valorization, thus attracting significant attention recently. Herein, a series of supported Cu catalysts derived from Ni-based hydrotalcite (HT) were prepared and performed in the continuous catalytic conversion of ethanol into butanol. Among the prepared catalysts, Cu/NiAlOx shows the best performance in terms of butanol selectivity and catalyst stability, with a sustained ethanol conversion of ~35% and butanol selectivity of 25% in a time-on-stream (TOS) of 110 h at 280 °C. While for the Cu/NiFeOx and Cu/NiCoOx, obvious catalyst deactivation and/or low butanol selectivity were obtained. Extensive characterization studies of the fresh and spent catalysts, i.e., X-ray diffraction (XRD), Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Hydrogen temperature-programmed reduction (H2-TPR), reveal that the catalysts' deactivation is mainly caused by the support deconstruction during catalysis, which is highly dependent on the reducibility. Additionally, an appropriate acid-base property is pivotal for enhancing the product selectivity, which is beneficial for the key process of aldol-condensation to produce butanol.

Novel strategies optimize immunotherapy by improving the cytotoxic function of T cells for pancreatic cancer treatment.

Pancreatic cancer (PC) is considered highly malignant due to its unsatisfying prognosis and limited response to therapies. Immunotherapy has therefore been developed to harness the antigen-specific properties and cytotoxicity of the immune system, aiming to induce a robust anti-tumor immune response that specifically demolishes PC cells while minimizing lethality in healthy tissue. The activation and augmentation of cytotoxic T cells play a critical role in the initiation and final success of immunotherapy. PC, however, is often immunotherapy resistant due to its intrinsic immunosuppressive tumor microenvironment that consequently hampers effective T cell priming. Emerging therapeutic approaches are orientated to modulate the tumor microenvironment in PC to enhance immune system involvement and heighten T cell efficacy. These novel strategies have shown promising therapeutic effects in the treatment of PC either as standalone approaches or combinatorial with other therapeutic schemes. The objective of this article is to explore innovative approaches to optimize immunotherapy for PC patients through T cell cytotoxic function augmentation.

Reactant enrichment in hollow void of Pt NPs@MnOx nanoreactors for boosting hydrogenation performance.

In confined mesoscopic spaces, the unraveling of a catalytic mechanism with complex mass transfer and adsorption processes such as reactant enrichment is a great challenge. In this study, a hollow nanoarchitecture of MnOx-encapsulated Pt nanoparticles was designed as a nanoreactor to investigate the reactant enrichment in a mesoscopic hollow void. By employing advanced characterization techniques, we found that the reactant-enrichment behavior is derived from directional diffusion of the reactant driven through the local concentration gradient and this increased the amount of reactant. Combining experimental results with density functional theory calculations, the superior cinnamyl alcohol (COL) selectivity originates from the selective adsorption of cinnamaldehyde (CAL) and the rapid formation and desorption of COL in the MnOx shell. The superb performance of 95% CAL conversion and 95% COL selectivity is obtained at only 0.5 MPa H2 and 40 min. Our findings showcase that a rationally designed nanoreactor could boost catalytic performance in chemoselective hydrogenation, which can be of great aid and potential in various application scenarios.