Site-Selective Deuteration of α-Amino Esters with 2-Hydroxynicotinaldehyde as a Catalyst.

An efficient method has been developed for the synthesis of α-deuterated α-amino esters via hydrogen isotope exchange of α-amino esters in D2O with 2-hydroxynicotinaldehyde as a catalyst under mild conditions. This methodology exhibits a wide range of substrate scopes, remarkable functional group tolerance, and affording the desired products in good yields with excellent deuterium incorporation. Notably, the ortho-hydroxyl group and the pyridine ring of the catalyst play a crucial role in the catalytic activity, which not only stabilizes the carbon-anion intermediates but also enhances the acidity of the amino esters' α-C-H bond.

Efficacy of cytoreductive surgery for metastatic upper tract urothelial carcinoma: a Surveillance, Epidemiology and End Results (SEER) study of 508 patients.

Background: Cisplatin-based combination chemotherapy alone is currently considered the standard of care for patients with metastatic upper tract urothelial carcinoma (mUTUC). However, less research has been done on the efficacy of other combinations. In this study, we explored the role of cytoreductive surgery in patients with mUTUC receiving different types of systemic therapy. Methods: Data from 9,436 anonymized records were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2008-2018. Of these, 508 individuals received systemic therapy subsequent to being diagnosed with mUTUC. These patients had all been treated with systemic therapies such as chemotherapy and/or radiotherapy. Patients were stratified into either a non-surgical or surgical group based on cytoreductive surgery status before systemic therapeutics commenced. Kaplan-Meier curves were used to compare overall survival (OS) and cancer-specific survival (CSS). Cox's proportional hazard models were then used to analyze prognostic factors related to OS and CSS. Results: Of the 508 cases, 36.8% (n=187) had received cytoreductive surgery with systemic treatments. The remaining 63.2% (n=321) received either chemotherapy and/or radiotherapy alone. Kaplan-Meier curves showed that 11.6% had 3-year OS [95% confidential interval (CI): 7.1-17.3] for cytoreductive surgery with systemic treatment and 4.9% (95% CI: 2.7-8.0) for systemic treatment alone (P=0.001). The 3-year CSS was 14.9% for cytoreductive surgery plus systemic treatment (95% CI: 9.4-21.7%) and 6.0% (95% CI: 3.4-9.8%) for systemic treatments alone (P=0.003). Under multivariate regression analysis, primary ureter site OS had a hazard ratio (HR) of 0.74 (95% CI: 0.58-0.95, P=0.02) and a CSS HR of 0.72 (95% CI: 0.56-0.94, P=0.01). The cytoreductive surgery OS HR was 0.79 (95% CI: 0.65-0.95, P=0.02) and the CSS HR was 0.75 (95% CI: 0.61-0.92, P=0.006). Additionally, chemotherapy had an OS HR of 0.46 (95% CI: 0.33-0.0.65, P<0.001) and a CSS HR of 0.44 (95% CI: 0.31-0.63, P<0.001). Bones and liver metastases were also indicative of poorer prognosis. Validation was conducted through subgroup analysis which suggested cytoreductive surgery was effective only for patients who received chemotherapy or combined chemo-radiotherapy but not for radiotherapy alone. Conclusions: Cytoreductive surgery provided significantly increased OS and CSS for mUTUC patients who received chemotherapy or combined chemo-radiotherapy in this study. In addition, the primary tumor and metastatic sites were shown to be related to improved patient survival although this was a small and relatively homogeneous cohort of study, sample therefore, further research is required.

Spatiotemporal distribution of oxidative potential in PM2.5 and its key components across six Chinese cities.

Increasing evidence has supported that oxidative potential (OP) serves as a crucial indicator of health risk of exposure to PM2.5 over mass concentration. However, there is a lack of comparative studies across multiple cities, particularly on a fine temporal scale. In this study, we aim to investigate daily variation of ambient PM2.5 OP through simultaneous samplings in six Chinese cities for one year. Results showed that more than 60 % of the sampling days exhibited non-zero ranking difference between volume-normalized oxidative potential (OPv) and mass concentration among the six cities. Key components contributing to OPv inculde Mn, NO3-, and K+, followed by Ca2+, Al, SO42-, Cl-, Fe, and NH4+. Based on these chemical components, we developed a stepwise multivariable linear regression model (R2: 0.71) for OPv prediction. The performance of the model is comparable to both species- and sources-based ones in the literature. These findings suggest that a relatively lower daily-averaged mass concentration of PM2.5 does not necessarily indicate a lower oxidative risk. Future studies and policy developments on health benefits should also consider OPv rather than mass concentration alone. Priority could be given to sources/species that contribute significantly to oxidative potential of ambient PM2.5. SYNOPSIS: This study highlights inclusion of oxidative potential as a complementary metric for air pollution assessment and control.

Association of health-related quality of life with urinary tract infection among kidney stone formers.

Kidney stones and infections significantly affect patients' health-related quality of life (HRQOL); however, the relationship between urinary tract infections (UTIs) and HRQOL in patients with kidney stones remains unclear. This study aimed to investigate the relationship using the validated Chinese version of the Wisconsin Stone Quality of Life questionnaire (C-WISQOL). We prospectively recruited 307 patients with kidney stones to complete the C-WISQOL before and after stone removal. The participants were diagnosed with UTI based on the presence of pyuria or bacteriuria with or without clinical symptoms. The psychometric properties of the C-WISQOL were statistically analyzed. Multivariate linear regression was used to predict the risk factors for impaired HRQOL in patients with stones and UTIs. The questionnaire is a reliable and robust tool for evaluating HRQOL in Chinese-speaking patients with urolithiasis. The UTI and kidney stone co-occurrence was significantly associated with female sex, diabetes mellitus, more previous stone events, higher antibiotic usage, positive stone- or UTI-related symptoms, and postoperative residual stones. The preoperative C-WISQOL scores and improvement in the HRQOL after stone removal in patients clinically diagnosed with UTI were significantly inferior to those in patients without UTI. The regression analyses showed that worse HRQOL was predicted by more previous stone events and positive stone- or UTI-related symptoms. In contrast, the presence of diabetes mellitus and postoperative residual stone fragments predicted a lower improvement in the HRQOL. These findings underscore UTI's harmful impact on perioperative HRQOL in patients with kidney stones and could help strategies benefit those patients.

Severity of depressive and anxious symptoms and its association with birth outcomes among pregnant women during the COVID-19 pandemic: a prospective case-control study.

AIM: Comparing the anxiety and depression severity and their impact on subsequent birth outcomes in pregnant women before and during Omicron wave in Shanghai in 2022. METHODS: The depression-anxiety symptoms networks were compared between the pregnant women during the outbreak period (outbreak group; n = 783) and a matched control group of pregnant women before the outbreak (pre-outbreak group; n = 783). The impact of baseline mental state on follow-up pregnancy and neonatal outcomes was also explored by logistic regression. FINDINGS: Levels of depression and anxiety between the two groups were not significant different. Network analysis showed that central symptom "trouble relaxing" and bridge symptom "depressed mood" shared by both groups. Different symptom associations in different periods of the pandemic. Total scores and sub-symptom scores of prenatal depressive and anxious severities increased the odds ratios of maternal and neonatal syndromes. The influence of mental state on gestational and neonatal outcomes differed across different pandemic periods. CONCLUSION: The Omicron wave did not have a significant negative impact on the depressive and anxious mood in pregnant women. Targeting central and bridge symptoms intervention may be effective in reducing their adverse effects on co-occurring of anxious and depressive mood and birth outcomes.

Electromagnetic Field-Assisted Frozen Tissue Planarization Enhances MALDI-MSI in Plant Spatial Omics.

Plant samples with irregular morphology are challenging for longitudinal tissue sectioning. This has restricted the ability to gain insight into some plants using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Herein, we develop a novel technique termed electromagnetic field-assisted frozen tissue planarization (EMFAFTP). This technique involves using a pair of adjustable electromagnets on both sides of a plant tissue. Under an optimized electromagnetic field strength, nondestructive planarization and regularization of the frozen tissue is induced, allowing the longitudinal tissue sectioning that favors subsequent molecular profiling by MALDI-MSI. As a proof of concept, flowers, leaves and roots with irregular morphology from six plant species are chosen to evaluate the performance of EMFAFTP for MALDI-MSI of secondary metabolites, amino acids, lipids, and proteins among others in the plant samples. The significantly enhanced MALDI-MSI capabilities of these endogenous molecules demonstrate the robustness of EMFAFTP and suggest it has the potential to become a standard technique for advancing MALDI-MSI into a new era of plant spatial omics.

Palladium-catalyzed amidation of carbazole derivatives via hydroamination of isocyanates.

The first amidation of carbazoles at the N9 position via palladium-catalyzed hydroamination of isocyanates is demonstrated. This simple, general and efficient method could deliver a wide range of carbazole-N-carboxamides in up to 99% yield. The salient features of this transformation include simple conditions with no need for a strong base, high chemo- and regio-selectivities and good functional group tolerance. In particular, this work-up-free and chromatography-free protocol is time-saving, cost-effective and user-friendly.

Optimal Strategies for Autologous Fat Grafting in Breast Augmentation and Reconstruction: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Currently, cell-assisted lipotransfer (CAL) and platelet-rich plasma (PRP) -assisted lipotransfer have been used to overcome the low survival rate of conventional lipotransfer. However, there is still insufficient evidence to determine which technique is the best strategy for autologous fat grafting in breast cosmetic and reconstructive surgery. OBJECTIVE: The present study aimed to compare the efficacy of traditional fat transplantation, CAL, and PRP-assisted lipotransfer. METHODS: A systematic search was conducted in several databases including PUBMED, Web of Science, Cochrane, ClinicalTrials.gov, and EMBASE from January 21, 2024, to identify studies that met the inclusion criteria. Twelve studies were included after a rigorous selection process based on predefined criteria. Statistical analyses were conducted using R Ver. 4.0.5 with the netmeta and dmetar packages, employing a frequentist approach with a random-effects model. A network meta-analysis was performed to compare different fat graft procedures regarding fat survival rate and complication events. The review protocol was prospectively registered in PROSPERO (CRD42024501780). RESULTS: The results indicate that CAL and PRP-assisted lipotransfer are better than traditional fat grafts in terms of fat survival rate. And there is no significant difference in the incidence of postoperative complications between the CAL group, PRP group, and traditional group. CONCLUSION: Based on the results of network meta-analysis, it appears that both CAL and PRP-assisted lipotransfer have a higher fat survival rate for autologous fat grafting in breast augmentation and reconstruction. However, the transplantation strategy still needs to be analyzed based on actual conditions in clinical applications.

Effect of oral health education on improving knowledge, attitude, practice, and oral health status of patients with liver cancer: A quasi-experimental study.

PURPOSE: To evaluate the effectiveness of the PRECEDE-PROCEED model (PPM) in helping patients with liver cancer be aware of their knowledge, skills, and abilities in self-oral health behaviors and improve their oral health status. METHODS: This is a quasi-experimental study of 90 patients with liver cancer assigned to an oral health education or a control group. The intervention group was educated with the PRECEDE-PROCEED model. A brief oral scale and the knowledge, attitude, and practice oral health questionnaire were employed to measure the oral health status and cognitive behavioral ability to seek oral health in patients. RESULTS: Among 102 eligible patients, 90 (88.23%) agreed to participate in the present study and were divided to intervention (n = 45) or control (n = 45) groups. After the intervention and one month after discharge, the oral health scores of patients in the Intervention group were lower than those of the control group (P < 0.05). In addition, after the intervention and one month after discharge, the patients in the test group had higher scores on knowledge, beliefs, and behaviors of oral health than the control group (P < 0.05). One month after discharge, the mean knowledge and skills scores were significantly higher in the intervention group than in the control group. CONCLUSIONS: Our findings suggest that oral health education may be a useful health intervention for patients with liver cancer. It may also improve the knowledge and beliefs of liver cancer patients seeking oral health. Larger long-term investigations are necessary to provide more support for these preliminary conclusions.

Safety and efficacy of PCSK9 inhibitor (evolocumab) in patients with non-ST segment elevation acute coronary syndrome and non-culprit artery critical lesions: a randomised controlled trial protocol (SPECIAL study).

INTRODUCTION: Patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) and concomitant multivessel coronary artery disease (CAD) are considered patients with extremely high-risk atherosclerotic cardiovascular disease (ASCVD), and current guidelines specify a lower low-density lipoprotein cholesterol (LDL-C) target for this population. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to effectively reduce LDL-C levels on a statin background. Additionally, several studies have confirmed the role of PCSK9 inhibitors in plaque regression and reducing residual cardiovascular risk in patients with ACS. However, those studies included coronary lesions with a degree of stenosis <50%. Whether the application of PCSK9 inhibitors in patients with NSTE-ACS with non-culprit artery critical lesions (stenosis degree between 50% and 75%) has a similar effect on plaque regression and improvement of cardiovascular outcomes remains unknown, with a lack of relevant research. This study aims to further investigate the safety and efficacy of evolocumab in patients with NSTE-ACS and concomitant multivessel CAD (non-culprit artery stenosis between 50% and 75%). METHODS AND ANALYSIS: In this single-centre clinical randomised controlled trial, 122 patients with NSTE-ACS and concomitant multivessel CAD (non-culprit artery stenosis between 50% and 75%) will be randomly assigned to either the evolocumab treatment group or the standard treatment group after completing culprit vessel revascularisation. The evolocumab treatment group will receive evolocumab in addition to statin therapy, while the standard treatment group will receive standard statin therapy. At baseline and week 50, patients in the evolocumab treatment group will undergo coronary angiography and OCT imaging to visualise pre-existing non-lesional vessels. The primary end point is the absolute change in average minimum fibrous cap thickness (FCT) from baseline to week 50. Secondary end points include changes in plaque lipid arc, lipid length, macrophage grading, lipid levels and major adverse cardiovascular events during the 1-year follow-up period. ETHICS AND DISSEMINATION: Ethics: this study will adhere to the principles outlined in the Helsinki Declaration and other applicable ethical guidelines. This study protocol has received approval from the Medical Research Ethics Committee of the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital), with approval number 2022-ky214. DISSEMINATION: we plan to disseminate the findings of this study through various channels. This includes publication in peer-reviewed academic journals, presentation at relevant academic conferences and communication to the public, policymakers and healthcare professionals. We will also share updates on the research progress through social media and other online platforms to facilitate the exchange and application of scientific knowledge. Efforts will be made to ensure widespread dissemination of the research results and to have a positive impact on society. TRIAL REGISTRATION NUMBER: ChiCTR2200066675.

Percolation thresholds of disks with random nonoverlapping patches on four regular two-dimensional lattices.

In percolation of patchy disks on lattices, each site is occupied by a disk, and neighboring disks are regarded as connected when their patches contact. Clusters of connected disks become larger as the patchy coverage of each disk χ increases. At the percolation threshold χ_{c}, an incipient cluster begins to span the whole lattice. For systems of disks with n symmetric patches on Archimedean lattices, a recent work [Wang et al., Phys. Rev. E 105, 034118 (2022)2470-004510.1103/PhysRevE.105.034118] found symmetric properties of χ_{c}(n), which are due to the coupling of the patches' symmetry and the lattice geometry. How does χ_{c} behave with increasing n if the patches are randomly distributed on the disks? We consider two typical random distributions of the patches, i.e., the equilibrium distribution and a distribution from random sequential adsorption. Combining Monte Carlo simulations and the critical polynomial method, we numerically determine χ_{c} for 106 models of different n on the square, honeycomb, triangular, and kagome lattices. The rules governing χ_{c}(n) are investigated in detail. They are quite different from those for disks with symmetric patches and could be useful for understanding similar systems.

Collaborative management of environmental pollution and carbon emissions drives local green growth: An analysis based on spatial effects.

Collaborative management of environmental pollution and carbon emissions (CMPC) has been a major policy instrument to promote Sustainable Development Goals (SDG) in recent years. However, the relationship between the benefits and drawbacks of this environmental management practice for green growth in and around a local area remains to be clarified. Using 30 provinces in China during 2001-2019 as the object of analysis, we assessed the efficiency of local CMPC practices using the nonradial directional distance function (NDDF) model, predicted local green growth using the frontier green complexity index (GCI), and empirically examined the spatial effects, locational heterogeneity, and threshold characteristics of the relationship using the spatial Durbin model and the panel threshold model. Our study finds that although efficient CMPC does drive local green growth, the promotion effect is nonlinear with decreasing marginal effect. This effect is particularly obvious in economically developed regions with higher CMPCs, which will absorb resources from neighboring regions and create a "siphoning" effect. It was found that local financial support and foreign direct investment (FDI) can radiate green growth to neighboring regions; therefore, CMPC practice needs to pay more attention to the effect of joint governance, supplemented by financial and foreign investment policy tools, to better promote the green transformation of local economy.

Omni-polarized Faraday isolator based on non-Hermitian Faraday system.

Non-Hermitian systems have recently attracted significant attention in photonics due to the realization that the interplay between gain and loss can lead to entirely new and unexpected features. Here, we propose and demonstrate a non-Hermitian Faraday system capable of non-reciprocal omni-polarizer action at the exceptional point. Notably, both forward and backward propagating light with arbitrary polarization converge to the same polarization state. Leveraging the robustness and non-reciprocity of the non-Hermitian Faraday system, we realize an omni-polarized Faraday isolator that can effectively isolate any polarized light without the need for a polarizer at the incident port of backward propagation. Remarkably, under the given parameter configuration, the isolator achieves a maximum isolation ratio of approximately 100 dB and a minimum isolation ratio of around 45 dB for various polarized light, accompanied by near-zero insertion loss. Furthermore, our research reveals the remarkable tolerance of the non-Hermitian Faraday isolator to nonlinear effects. This unique characteristic allows us to harness nonlinear effects to achieve various optical functions, all while maintaining excellent isolation performance. The proposed non-Hermitian Faraday system paves the way for the realization of magnetically or optically switchable non-reciprocal devices.

Study on the influence of a magnetorheological finishing path on the mid-frequency errors of optical element surfaces.

Magnetorheological finishing (MRF) is a deterministic optical processing technique based on CCOS that achieves high removal efficiency and processing accuracy while reducing subsurface damage. This technique still suffers from multiple iterations of processing due to variations in removal efficiency and the inability to fully correct mid-frequency errors below the cut-off frequency of the removal function. For the above problems, this paper attempted to establish the error model of removal function efficiency change for predicting the change of MRF efficiency. Based on the analysis of the distribution of surface shape residuals under different machining paths, a process combining spiral scanning and raster scanning is proposed, which can realize the correction of surface shape and restrain the deterioration of mid-frequency errors. The experimental results show that when the low-frequency errors of fused silica element surface converge rapidly, by optimizing the machining removal coefficient and using the spiral scanning and raster scanning combined method, the PSD analysis results show that the mid-frequency errors of the combined process is lower than the initial value, which expands the process route for the MRF of high-precision optical elements.

Research on the removal characteristics of surface error with different spatial frequency based on shear thickening polishing method.

X-ray mirrors, which are essential for constructing synchrotron radiation light sources, are highly required for full-range spatial wavelength errors. This paper investigated power-law non-Newtonian fluids and pointed out that both three-body removal and shear removal existed in the shear thickening polishing process. Subsequently, this paper calculates the shear force of the power-law non-Newtonian fluid polishing fluid in polishing the surface with different frequency errors. It establishes an MRR model of shear thickening polishing in the frequency domain by combining it with the Archard equation. Then, this model is also applied to optimize the polishing fluid formulation and processing parameters. Finally, the removal effect of the optimized polishing fluid on the mid-frequency ripple error is experimentally verified. On Ф50 mm monocrystalline silicon, the removal of mid-frequency ripple error with a spatial wavelength of 1 mm was achieved by shear thickening polishing technique while converging the surface roughness to 0.14 nm. Finally, the experimental results were applied to monocrystalline silicon with a length of 500 mm. This work provides a new research idea for the existing shear thickening polishing process. It provides theoretical and technical support for removing the mid- and high-frequency errors in high-precision X-ray mirrors.

Causal associations between platelet count, alcohol consumption, and the risk of liver hepatocellular carcinoma based on a Mendelian randomization study.

Background and aims: Liver hepatocellular carcinoma (LIHC) exhibits a multifactorial etiology, insidious onset, and a significantly low 5-year survival rate. We aimed to evaluate the causal impact of exposure factors (Alzheimer's disease, platelet count, ambidextrousness, cigarettes smoked per day, alcohol consumption, and endocarditis) on the risk of LIHC using a two-sample Mendelian randomization (MR) study. Methods: Independent single nucleotide polymorphisms (SNPs) strongly associated with Alzheimer's disease, platelet count, ambidextrousness, daily cigarette consumption, alcohol intake, and endocarditis were selected as instrumental variables (IVs) from the corresponding genome-wide association studies (GWAS). Genetic summary statistics for LIHC came from a GWAS that included 168 cases and 372,016 controls of European individuals. Multivariable MR analyses were performed to find the causal association between 6 exposure factors and LIHC risk. The inverse-variance weighted (IVW)-MR was employed as the primary analysis, and the MR-Egger regression, LASSO regression, and weighted Median approaches were performed as complementary analyses. Results: Multivariable MR analysis showed causal association between Alzheimer's disease [Odds ratio (OR) = 0.9999, 95% confidence intervals (CI) = 0.9998-0.9999, p = 0.0010], platelet count (OR = 0.9997, 95% CI = 0.9995-0.9999, p = 0.0066), alcohol consumption (OR = 0.9994, 95% CI = 0.9990-0.9999, p = 0.0098) and the LIHC outcome. After IVW-MR, MR-Egger and LASSO tests, the results are still significant. Next, we used different MR Methods to analyze platelet count, alcohol consumption, and Alzheimer's disease separately. Moreover, both funnel plots and MR-Egger intercepts provided compelling evidence to refute the presence of directional pleiotropy in the association between platelet count, alcohol consumption, Alzheimer's disease and the risk of LIHC. The IVW-MR analysis revealed a significant causal association between an elevated platelet count and a reduced risk of LIHC (OR = 0.9996, 95% CI= 0.9995-0.9998, p = 0.0005). Similarly, the analysis of weighted median revealed a negative correlation between platelet count and the risk of LIHC (OR = 0.9995, 95% CI = 0.9993-0.9999; p = 0.0160). Conversely, we observed a positive causal effect of alcohol consumption on the incidence of LIHC (OR = 1.0004, 95% CI = 0.9999-1.0009). However, no significant causal relationship was found between alcohol assumption, Alzheimer's disease, and LIHC susceptibility. Conclusions: A significant causal relationship exists between platelet count, alcohol consumption, Alzheimer's disease, and an increased risk of LIHC. The study presents compelling evidence for a genetically predicted decreased susceptibility to LIHC based on platelet count. The research implies that elevated platelet count may serve as a protective mechanism against LIHC. These findings may inform clinical strategies for LIHC prevention.

Reconstruction of High Entropy Alloys on a Metal-Organic Framework Approaching Active Oxygen Reduction Electrocatalysts.

High-entropy alloys (HEAs) have garnered considerable attention as promising nanocatalysts for effectively utilizing Pt in catalysis toward oxygen reduction reactions due to their unique properties. Nonetheless, there is a relative dearth of attention regarding the structural evolution of HEAs in response to electrochemical conditions. In this work, we propose a thermal reduction method to synthesize high entropy nanoparticles by leveraging the confinement effect and abundant nitrogen-anchored sites provided by pyrolyzed metal-organic frameworks (MOFs). Notably, the prepared catalysts exhibit enhanced activity accompanied by structural reconstruction during electrochemical activation, approaching 1 order of magnitude higher mass activity compared to Pt/C in oxygen reduction. Atomic-scale structural characterization reveals that abundant defects and single atoms are formed during the activation process, contributing to a significant boost in the catalytic performance for oxygen reduction reactions. This study provides deep insights into surface reconstruction engineering during electrochemical operations, with practical implications for fuel cell applications.

Pen2/ErbB4 signaling regulates stemness of pancreatic ductal carcinoma.

Cancer stem cells (CSCs) are critical for progression, invasion, metastasis, and chemotherapy resistance of pancreatic ductal adenocarcinoma (PDAC). Presenilin enhancer 2 (Pen2), a vital component of the gamma-secretase complex, is overexpressed in various cancers and plays a significant role in carcinogenesis. Here, we investigated the association between Pen2 expression and the stem-like properties of PDAC cells. We analyzed Pen2 and its downstream target, Erb-B2 Receptor Tyrosine Kinase 4 (ErbB4), using public databases. The expression of Pen2 in CSC populations, marked by CD133+, CD44+, or epithelial cell adhesion molecule (EpCAM)+, was evaluated. Pen2-positive cells were sorted from Pen2-negative ones in PDAC cells transduced with a vector designed to express green fluorescent protein (GFP) under the Pen2 promoter. Stemness was examined in vitro and in vivo in Pen2-positive versus Pen2-negative cells. Our results showed that Pen2 was significantly upregulated, while ErbB4 was significantly downregulated in PDAC tissues compared to adjacent non-tumorous tissues, with an inverse relationship between Pen2 and Erbb4 levels. PDACs with high Pen2 expression are associated with considerably poorer patient survival. The CSC populations identified by CD133+, CD44+, and EpCAM+ markers displayed significantly higher Pen2 and lower EpCAM levels. Compared to Pen2-negative PDAC cells, Pen2-positive cells formed more tumor spheres, were more invasive and migratory, and showed significantly increased resistance to chemotherapy-induced apoptosis. Altering Pen2 levels reversed these oncogenic effects. In vivo, Pen2-positive cells formed larger tumors in immunodeficient mice. Overall, our findings suggest that Pen2 is highly expressed in CSCs within PDAC cells, being a novel therapeutic target.