Orbital-dependent electron correlation in double-layer nickelate La3Ni2O7.

The latest discovery of high temperature superconductivity near 80 K in La3Ni2O7 under high pressure has attracted much attention. Many proposals are put forth to understand the origin of superconductivity. The determination of electronic structures is a prerequisite to establish theories to understand superconductivity in nickelates but is still lacking. Here we report our direct measurement of the electronic structures of La3Ni2O7 by high-resolution angle-resolved photoemission spectroscopy. The Fermi surface and band structures of La3Ni2O7 are observed and compared with the band structure calculations. Strong electron correlations are revealed which are orbital- and momentum-dependent. A flat band is formed from the Ni-3d z 2 orbitals around the zone corner which is ~ 50 meV below the Fermi level and exhibits the strongest electron correlation. In many theoretical proposals, this band is expected to play the dominant role in generating superconductivity in La3Ni2O7. Our observations provide key experimental information to understand the electronic structure and origin of high temperature superconductivity in La3Ni2O7.

Activation of Einstein-Podolsky-Rosen steering sharing with unsharp nonlocal measurements.

Einstein-Podolsky-Rosen (EPR) steering is commonly shared among multiple observers by utilizing unsharp measurements. Nevertheless, their usage is restricted to local measurements and does not encompass all nonlocal measurement-based cases. In this work, a method for finding beneficial local measurement settings has been expanded to include nonlocal measurement cases. This method is applicable for any bipartite state and offers benefits even in scenarios with a high number of measurement settings. Using the Greenberger-Horne-Zeilinger state as an illustration, we show that employing unsharp nonlocal measurements can activate the phenomenon of steering sharing in contrast to using local measurements. Furthermore, our findings demonstrate that nonlocal measurements with unequal strength possess a greater activation capability compared to those with equal strength. Our activation method generates fresh concepts for conservation and recycling quantum resources.

Time-resolved ARPES with probe energy of 6.0/7.2 eV and switchable resolution configuration.

We present a detailed exposition of the design for time- and angle-resolved photoemission spectroscopy using a UV probe laser source that combines the nonlinear effects of ß-BaB2O4 and KBe2BO3F2 optical crystals. The photon energy of the probe laser can be switched between 6.0 and 7.2 eV, with the flexibility to operate each photon energy setting under two distinct resolution configurations. Under the fully optimized energy resolution configuration, we achieve an energy resolution of 8.5 meV at 6.0 eV and 10 meV at 7.2 eV. Alternatively, switching to the other configuration enhances the temporal resolution, yielding a temporal resolution of 72 fs for 6.0 eV and 185 fs for 7.2 eV. We validated the performance and reliability of our system by applying it to measuring two typical materials: the topological insulator MnBi2Te4 and the excitonic insulator candidate Ta2NiSe5.

Associations of serum gamma-linolenic acid levels with erythema severity and anxiety/depression status in patients with rosacea.

BACKGROUND: The development of rosacea is suggested to be closely associated with lipid metabolism, inflammation, and anxiety/depression. Gamma linolenic acid (GLA) is a key factor participating in lipid metabolism, which is also confirmed to regulate the inflammatory response. However, the associations of serum GLA levels with rosacea severity and psychological status still remain unclear. OBJECTIVE AND LIMITATIONS OF THE STUDY: The present study aimed to investigate the associations of gamma linolenic acid (GLA), a key factor participating in lipid metabolism and the inflammatory response, with rosacea severity and psychological status. The present study still had some limitations. First, this study is a cross-sectional study and does not provide longitudinal evidence about the relationship between GLA and rosacea; Second, the cohort in this study is also relatively small, and a larger cohort is needed in further investigation to reveal the potential role of lipid metabolism in the pathogenesis of rosacea. METHODS: A total of 62 rosacea patients were consecutively recruited. Patient's Self-Assessment (PSA) scale and Clinician Erythema Assessment (CEA) as well as 7-item Generalized Anxiety Disorder (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) were conducted to evaluate the degree of erythema severity and anxiety/depression, respectively. Serum GLA levels were determined by gas chromatography mass. RESULTS: Lower levels of serum GLA in rosacea patients were observed (p<0.001), and subgroup analysis revealed that patients with higher-level GLA had lower scores of PSA, CEA, GAD-7 and PHQ-9. Moreover, Spearman correlation analysis uncovered that serum GLA levels were negatively associated with PSA, CEA, GAD-7 as well and PHQ-9 scores, respectively. Linear regression model found that serum GLA levels at baseline were a predictive factor for prognosis of clinical outcomes after 1-month conventional treatment. CONCLUSION: The present study indicates that lower levels of serum GLA in rosacea patients are negatively associated with the degree of erythema and anxiety/depression status.

ß-elemene enhances cisplatin sensitivity of non-small cell lung cancer cells via the miR-17-5p/STAT3 axis.

In China, ß-elemene, a sesquiterpene compound derived from Curcuma wenyujin, is clinically used to treat many human malignancies, including non-small cell lung cancer (NSCLC). Nonetheless, the role of ß-elemene in regulating cisplatin sensitivity of NSCLC cells and the related mechanisms are not clear. This study was conducted to investigate the role of ß-elemene in sensitizing NSCLC cells to cisplatin. In this work, cisplatin-resistant NSCLC cell lines were constructed. CCK-8, colony formation, and flow cytometry assays were executed to examine cell viability, growth, and apoptosis. MiR-17-5p and STAT3 expression levels in cells were detected by qRT-PCR. Western blot was executed to determine the expression levels of STAT3 and apoptosis-related proteins (Bax and Bcl-2) in the cells. Dual-luciferase reporter gene experiments were performed to verify the targeting relationship between miR-17-5p and STAT3. Herein, we report that, ß-elemene inhibits the viability, and induces the apoptosis of cisplatin-resistant NSCLC cells. Additionally, ß-elemene induces the upregulation miR-17-5p and downregulation of STAT3. STAT3 is validated to be a target of miR-17-5p in NSCLC cells. Additionally, the role of ß-elemene to repress the viability of cisplatin-resistant NSCLC cells is partially counteracted by miR-17-5p inhibitor or STAT3 overexpression. In summary, our study suggests that ß-elemene enhances cisplatin sensitivity of NSCLC cells by modulating miR-17-5p/STAT3 axis, and it may be a choice for the complementary treatment of NSCLC patients.

Time-resolved ARPES with tunable 12-21.6 eV XUV at 400 kHz repetition rate.

Time-resolved and angle-resolved photoemission spectroscopy (trARPES) is a powerful method to detect the non-equilibrium electronic structure in solid systems. In this study, we report a trARPES apparatus with tunable photon energy selectively among 12, 16.8, and 21.6 eV at a repetition rate of 400 kHz. The energy and temporal resolutions of the three harmonics are determined as 104/111/157 meV and 276/190/154 fs, respectively. The photon flux on the sample is estimated to be 1010-1011 photons/s by using a photodiode. Finally, the performance of this setup is verified by both equilibrium and non-equilibrium ARPES measurements on topological materials Zr2Te2P and Bi2Se3. Meanwhile, the importance of the tunability of the extreme ultraviolet (XUV) source is highlighted by comparing experimental results measured with the three different photon energies.

Nutritional status associated with clinical outcomes in children with solid tumors: A retrospective cohort study from China.

OBJECTIVE: To investigate the long-term changes in nutritional status in children with solid tumors during treatment and the relationship between nutritional status and clinical outcomes. METHODS: This study was a retrospective medical records review of data from children who were diagnosed with solid tumors and followed up for more than 3 months from January 2016 to December 2021 in China. Patient demographics and clinical information, including nutritional status, parenteral nutrition use, intensive care unit (ICU) transfers, infection during hospitalization, hospitalization frequency, length of stay, hospitalization costs and antibiotic costs, were collected to analyze the nutritional status of children with different types of solid tumors, the dynamic changes in nutritional status during treatment, and the relationship between nutritional status and clinical outcomes. RESULTS: Among the 764 patients (383 males (50.1%); 381 females (49.9%); mean age: 2.58 years), 41.6% of the solid tumors were neuroblastomas, 17.1% were hepatoblastomas, and Wilms tumors as the third most common solid tumors (8.9%). The median follow-up duration was 6 months (range: 3-40 months). At diagnosis, the proportion of children who were undernourished (underweight and wasting) versus overweight or obese were 26.71% versus 5.21% (25.86% vs. 2.89% in the third month; 29.77% vs. 2.28% in the sixth month; 24.77% vs. 3.27% in the 12th month). The body mass index Z scores decreased from the initial values after the first month (-0.56 (-1.47, 0.23) vs. -0.44 (-1.29, 0.41)) but improved later and decreased again at 6 months. The children in the undernutrition group had longer hospital stays (p < 0.001), higher hospitalization costs (p < 0.001), higher antibiotic costs (p < 0.001), a higher risk of neutropenia (OR = 4.781 (95% CI: 1.571-14.553), p = 0.006), and a higher risk of ICU transfers (OR = 1.498 (95% CI: 1.010-2.224), p = 0.044). No significant differences in those associations by malnutrition and infection, ICU duration, or length of parenteral nutrition were observed. CONCLUSION: There is a considerable prevalence of malnutrition in children with solid tumors. Malnutrition is related to adverse clinical outcomes and increases in total hospital expenses and antibiotic costs.

Deep skin diseases diagnostic system with Dual-channel Image and Extracted Text.

Background: Due to the lower reliability of laboratory tests, skin diseases are more suitable for diagnosis with AI models. There are limited AI dermatology diagnostic models combining images and text; few of these are for Asian populations, and few cover the most common types of diseases. Methods: Leveraging a dataset sourced from Asia comprising over 200,000 images and 220,000 medical records, we explored a deep learning-based system for Dual-channel images and extracted text for the diagnosis of skin diseases model DIET-AI to diagnose 31 skin diseases, which covers the majority of common skin diseases. From 1 September to 1 December 2021, we prospectively collected images from 6,043 cases and medical records from 15 hospitals in seven provinces in China. Then the performance of DIET-AI was compared with that of six doctors of different seniorities in the clinical dataset. Results: The average performance of DIET-AI in 31 diseases was not less than that of all the doctors of different seniorities. By comparing the area under the curve, sensitivity, and specificity, we demonstrate that the DIET-AI model is effective in clinical scenarios. In addition, medical records affect the performance of DIET-AI and physicians to varying degrees. Conclusion: This is the largest dermatological dataset for the Chinese demographic. For the first time, we built a Dual-channel image classification model on a non-cancer dermatitis dataset with both images and medical records and achieved comparable diagnostic performance to senior doctors about common skin diseases. It provides references for exploring the feasibility and performance evaluation of DIET-AI in clinical use afterward.

A robust and tunable Luttinger liquid in correlated edge of transition-metal second-order topological insulator Ta2Pd3Te5.

The interplay between topology and interaction always plays an important role in condensed matter physics and induces many exotic quantum phases, while rare transition metal layered material (TMLM) has been proved to possess both. Here we report a TMLM Ta2Pd3Te5 has the two-dimensional second-order topology (also a quadrupole topological insulator) with correlated edge states - Luttinger liquid. It is ascribed to the unconventional nature of the mismatch between charge- and atomic- centers induced by a remarkable double-band inversion. This one-dimensional protected edge state preserves the Luttinger liquid behavior with robustness and universality in scale from micro- to macro- size, leading to a significant anisotropic electrical transport through two-dimensional sides of bulk materials. Moreover, the bulk gap can be modulated by the thickness, resulting in an extensive-range phase diagram for Luttinger liquid. These provide an attractive model to study the interaction and quantum phases in correlated topological systems.

Intrinsic surface p-wave superconductivity in layered AuSn4.

The search for topological superconductivity (TSC) is currently an exciting pursuit, since non-trivial topological superconducting phases could host exotic Majorana modes. However, the difficulty in fabricating proximity-induced TSC heterostructures, the sensitivity to disorder and stringent topological restrictions of intrinsic TSC place serious limitations and formidable challenges on the materials and related applications. Here, we report a new type of intrinsic TSC, namely intrinsic surface topological superconductivity (IS-TSC) and demonstrate it in layered AuSn4 with Tc of 2.4 K. Different in-plane and out-of-plane upper critical fields reflect a two-dimensional (2D) character of superconductivity. The two-fold symmetric angular dependences of both magneto-transport and the zero-bias conductance peak (ZBCP) in point-contact spectroscopy (PCS) in the superconducting regime indicate an unconventional pairing symmetry of AuSn4. The superconducting gap and surface multi-bands with Rashba splitting at the Fermi level (EF), in conjunction with first-principle calculations, strongly suggest that 2D unconventional SC in AuSn4 originates from the mixture of p-wave surface and s-wave bulk contributions, which leads to a two-fold symmetric superconductivity. Our results provide an exciting paradigm to realize TSC via Rashba effect on surface superconducting bands in layered materials.

Comparative effectiveness and safety of drug therapy for chronic urticaria: a network meta-analysis and risk-benefit assessment.

BACKGROUND: Chronic urticaria (CU) is a prevalent chronic skin condition characterized by recurrent wheals. Clinical guidelines recommend multiple drugs for CU treatment. Our study aims to compare the effectiveness and safety of drug therapy for CU. METHODS: We conducted a comprehensive search of randomized controlled trials (RCTs) and real-world studies (RWSs) in PubMed, EMBASE, and Cochrane. A network meta-analysis (NMA) was conducted to assess the response rate, decline in Urticaria Activity Score over 7 Days (UAS7), Dermatology Life Quality Index (DLQI), and adverse event rates of standard-dose and high-dose H1 antihistamine (H1AH), omalizumab (OMA) 75, 150, and 300 mg, cyclosporine and placebo. The risk-benefit assessment was conducted by probabilistic simulation and stochastic multicriteria acceptability analysis (SMAA). RESULTS: A total of 39 studies were identified, including 37 RCTs and 2 RWSs. OMA 300 mg and 150 mg both had significantly higher response rate than standard-dose H1AH (p < 0.05, respectively). OMA 300 mg and 150 mg both consistently led to a huge drop in UAS7 and DLQI compared to standard-dose H1AH and high-dose H1AH (p < 0.05). CONCLUSION: Regarding risk-benefit assessment, OMA 300 mg emerges as the optimal pharmacological intervention for CU, while OMA 150 mg stands as a secondary alternative compared to H1 antihistamines and cyclosporine.

Decreased TAX1BP1 participates in systemic lupus erythematosus by regulating monocyte/macrophage function.

Systemic lupus erythematosus (SLE) involves disorders of innate and adaptive immune pathways. Tax1-binding protein 1 (TAX1BP1) modulates the production of antibodies in B cells and the T-cell cycle by regulating the NF-κB signaling pathway. However, the potential association of TAX1BP1 with SLE and its role in monocytes/macrophages have not been fully elucidated. In this study, we utilized whole-exome sequencing (WES) in combination with Sanger sequencing and identified 16 gene mutations, including in TAX1BP1, in an SLE family. TAX1BP1 protein expression with western blotting detection was reduced in SLE patients and correlated with disease activity negatively. Furthermore, RNA sequencing and 4D Label-Free Phosphoproteomic analysis were employed to characterize the transcriptome and phosphoproteome profiles in THP-1 and THP-1-differentiated M1 macrophages with TAX1BP1 knockdown. Silencing of TAX1BP1 in THP-1 and THP-1-differentiated M1 macrophages led to an increase in cluster of differentiation 80 (CD80) expression and differential changes in CD14 and CD16 expression, as assessed by flow cytometry. Additionally, western blot analysis showed that knockdown of TAX1BP1 led to a reduction in TRAF6 and p-p65 in THP-1-differentiated macrophages, with or without lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α stimulation. Taken together, our findings suggest that TAX1BP1 participates in SLE activity by regulating antigen presentation in monocytes and inflammatory responses in M1 macrophages.

High-flux wavelength tunable XUV source in the 12-40.8†eV photon energy range with adjustable energy and time resolution for Tr-ARPES applications.

High-order harmonic generation (HHG) has a broad spectrum covering vacuum ultraviolet to extreme ultraviolet (XUV) bands, which is useful for applications involving material analyses at different information depths. Such an HHG light source is perfect for time- and angle-resolved photoemission spectroscopy. Here, we demonstrate a high-photon flux HHG source driven by a two-color field. Applying a fused silica compression stage to reduce the driving pulse width, we obtained a high XUV photon flux of 2 × 1012 phs/s @21.6 eV on target. We designed a classical diffraction mounted (CDM) grating monochromator that can achieve a wide range of photon energy from 12 to 40.8 eV, while the time resolution is improved by reducing the pulse front tilt after the harmonic selection. We designed a spatial filtering method to adjust the time resolution using the CDM monochromator and significantly reduced the pulse front tilt of the XUV pulses. We also demonstrate a detailed prediction of the energy resolution broadening which is caused by the space charge effect.

Effect of nutritional status on outcomes in children receiving umbilical cord blood stem cell transplantation.

BACKGROUND AND OBJECTIVES: The impacts of nutritional status on clinical outcomes in children receiving umbilical cord blood stem cell transplantation (UCBT) are not fully described. We evaluated the risk for malnutrition before transplantation admission and influence of weight loss during hospitalization on short-term clinical outcomes in children with UCBT. METHODS AND STUDY DESIGN: We conducted a retrospective study of pediatric patients up to age 18 years who received UCBT and were treated at the Children's Hospital of Fudan University between January 2019 and December 2020. RESULTS: The mean age of the 91 patients was 1.3 years, with 78 (85.7%) men and 13 (14.3%) women (p<0.001). UCBT was performed mostly for primary immunodeficiency disease (PID) (83, 91.2%). The weight loss differences among children with different primary diseases were statistically significant (p=0.003). Children with a large amount of weight loss during hospitalization (n = 24) had higher risks of skin graft-versus-host disease (GVHD) (multivariate OR=5.01, 95% CI: 1.35-18.65), intestinal GVHD (multivariate OR=7.27, 95% CI: 1.74-30.45), a longer median hospital stay (p=0.004), higher antibiotic costs (p=0.008) and higher total hospitalization costs (p=0.004). Malnutrition on admission was significantly positively correlated with longer parenteral nutrition (PN) time (p=0.008). Early nutritional intervention effects on clinical outcomes need further assessment. CONCLUSIONS: Underweight recipient child and excessive weight loss during transplantation increases the length and cost of hospital stay, and is associated with a high incidence of GVHD, which affects the prognosis of transplantation and medical resources consumption.

Charge instability of topological Fermi arcs in chiral crystal CoSi.

Topological boundary states emerged at the spatial boundary between topological non-trivial and trivial phases, are usually gapless, or commonly referred as metallic states. For example, the surface state of a topological insulator is a gapless Dirac state. These metallic topological boundary states are typically well described by non-interacting fermions. However, the behavior of topological boundary states with significant electron-electron interactions, which could turn the gapless boundary states into gapped ordered states, e.g., density wave states or superconducting states, is of great interest theoretically, but is still lacking evidence experimentally. Here, we report the observation of incommensurable charge density wave (CDW) formed on the topological boundary states driven by the electron-electron interactions on the (001) surface of CoSi. The wavevector of CDW varies as the temperature changes, which coincides with the evolution of topological surface Fermi arcs with temperature. The orientation of the CDW phase is determined by the chirality of the Fermi arcs, which indicates a direct association between CDW and Fermi arcs. Our finding will stimulate the search of more interactions-driven ordered states, such as superconductivity and magnetism, on the boundaries of topological materials.

Potential application of let-7a antagomir in injured peripheral nerve regeneration.

Neurotrophic factors, particularly nerve growth factor, enhance neuronal regeneration. However, the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages, such as its short biological half-life, its contribution to pain response, and its inability to cross the blood-brain barrier. Considering that let-7 (human miRNA) targets and regulates nerve growth factor, and that let-7 is a core regulator in peripheral nerve regeneration, we evaluated the possibilities of let-7 application in nerve repair. In this study, anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship, and functional screening. Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve, including Schwann cells, fibroblasts and macrophages. Use of hydrogel effectively achieved controlled, localized, and sustained delivery of let-7a antagomir. Finally, let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft, which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection. Our study provides an experimental basis for potential in vivo application of let-7a.

Efficacy of abrocitinib for atopic dermatitis: a meta-analysis of randomized controlled trials.

Introduction: The efficacy of abrocitinib for atopic dermatitis remains controversial. Aim: We conducted a systematic review and meta-analysis to explore the influence of abrocitinib versus placebo on the treatment of atopic dermatitis. Material and methods: We searched PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases up to June 2021 for randomized controlled trials (RCTs) assessing the effect of abrocitinib versus placebo for patients with atopic dermatitis. This meta-analysis was performed using a random-effect model. Results: Four RCTs involving 932 patients were included in the meta-analysis. Overall, compared with the control group for atopic dermatitis, abrocitinib has a remarkably positive impact on IGA response (OR = 6.60; 95% CI: 4.41-9.87; p < 0.00001), EASI-75 (OR = 9.19; 95% CI: 6.20-13.61; p < 0.00001), EASI-90 (OR = 10.50; 95% CI: 5.54-19.93; p < 0.0001), NRS response (OR = 6.99; 95% CI: 4.43-11.01; p < 0.00001) and adverse events (OR = 1.76; 95% CI: 1.23-2.52; p = 0.002), but showed no obvious influence on serious adverse events (OR = 0.53; 95% CI: 0.20-1.44; p = 0.22). Conclusions: Abrocitinib exerts a favorable effect on the treatment of atopic dermatitis.

Protecting nonlocal quantum correlations in correlated squeezed generalized amplitude damping channel.

Nonlocal quantum correlations, such as quantum entanglement, quantum steering, and Bell nonlocality, are crucial resources for quantum information tasks. How to protect these quantum resources from decoherence is one of the most urgent problems to be solved. Here, we investigate the evolution of these correlations in the correlated squeezed generalized amplitude damping (SGAD) channel and propose a scheme to protect them with weak measurement (WM) and quantum measurement reversal (QMR). Compared with the results of the uncorrelated SGAD channel, we find that when [Formula: see text], correlation and squeezing effects can prolong the survival time of quantum entanglement, Bell nonlocality, and quantum steering by about 152 times, 207 times, and 10 times, respectively. In addition, local WM and QMR can effectively recover the disappeared nonlocal quantum correlations either in uncorrelated or completely correlated SGAD channels. Moreover, we find that these initial nonlocal quantum correlations could be drastically amplified under the correlated channel. And the steering direction can be flexibly manipulated either by changing the channel parameters or the strength of WM and QMR. These results not only make a step forward in suppressing decoherence and enhancing quantum correlation in noise channels, but also help to develop relevant practical applications.

Comprehensive assessment of growth factors, inflammatory mediators, and cytokines in vitreous from patients with proliferative diabetic retinopathy.

AIM: To assess alterations in growth factors, inflammatory mediators, and cytokines associated with vitreous-retinal diseases in vitreous humor from patients with proliferative diabetic retinopathy (PDR), and to identify potential new treatment targets and strategies. METHODS: Control vitreous samples were collected from patients with macular hole, epiretinal membranes, or rhegmatogenous retinal detachments, and PDR samples from patients with complications of PDR, who required pars plana vitrectomy. Specimens were stored at -80°C and then investigated by Luminex multi-factor assay. Parametric and nonparametric analyses of demographic characteristics and cytokine expression levels were conducted using SPSS. RESULTS: There were no significant differences in demographic characteristics between patients with and without PDR. Expression levels of growth factors [platelet-derived growth factor (PDGF)-AA, glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor A (VEGFA)], inflammatory mediators [interleukin (IL)-8, IL-11, and tumor necrosis factor-α (TNF-α)] and cytokines [chemokine C-X-C ligand (CXCL)10, interferon-γ (IFN-γ), and granulocyte macrophage-colony stimulating factor (GM-CSF)] were significantly elevated in vitreous humor from patients with PDR compared with those in the control group (all P<0.05). Further, VEGFA levels were lower in patients with PDR treated with anti-VEGF injection than those who were not (P<0.05), and there was no difference between the PDR group treated with anti-VEGF and controls (P>0.05). CONCLUSION: This proof-of-concept study demonstrates the potential for combinational therapeutic strategies to ameliorate diabetic retinopathy progression by targeting growth factors, inflammatory factors, and cytokines, in addition to VEGFA.

Construction and validation of a m6A RNA methylation and ferroptosis-related prognostic model for pancreatic cancer by integrated bioinformatics analysis.

Background: Both N6-methyladenosine (m6A) ribonucleic acid (RNA) methylation and ferroptosis regulators are demonstrated to have significant effects on the malignant clinicopathological characteristics of pancreatic adenocarcinoma (PAAD) patients. However, the currently available clinical indexes are not sufficient to predict precise prognostic outcomes pf PAAD patients accurately. This study aims to examine the clinicopathologic features of m6A RNA methylation and ferroptosis regulators in predicting the outcomes of different types of cancer. Methods: As the foundation for this research, the differentially expressed genes (DEGs) between PAAD tissues and adjacent normal tissues were first identified. Next, dimensional reduction analysis (DCA) based on m6A RNA methylation regulators and ferroptosis regulators were performed and DEGs between good/poor prognosis PAAD patient clusters were identified. DEGs were then screened by Cox analysis, and finally a risk signature was established by least absolute shrinkage and selection operator (LASSO) analyses. The prediction model based on risk score was further evaluated by a validation set from Gene Expression Omnibus (GEO) database. Results: In total, 4 m6A RNA methylation regulator genes and 29 ferroptosis regulator genes were found to have close causal relationships with the prognosis of PAAD, and a risk score with 3 m6A methylation regulators (i.e., IGF2BP2, IGF2BP3, and METTL16) and 4 ferroptosis regulators (i.e., ENPP2, ATP6V1G2, ITGB4, and PROM2) was constructed and showed to be highly involved in PAAD progression and could serve as effective markers for prognosis with AUC value equaled 0.753 in training set and 0.803 in validation set. Conclusions: The combined prediction model, composed of seven regulators of m6A methylation and ferroptosis, in this study more effectively reflects the progression and prognosis of PAAD than previous single genome or epigenetic analysis. Our study provides a broader perspective for the subsequent establishment of prognostic models and the patients may benefit from more precision management.