A Review of Design Strategies in SiO/C Composite Anodes for Rechargeable Lithium-Ion Batteries.

Lithium-ion batteries (LIBs) are widely used in electric vehicles, portable electronic devices, clean energy storage, and other fields due to their long service life, high energy density, and low self-discharge rate, which also puts forward higher requirements for the performance of lithium-ion batteries. As an anode for lithium-ion batteries, SiO materials have garnered significant attention from researchers due to its high specific capacity (2400 mAh·g-1), abundance of raw materials, and simple preparation. However, its large volume change (~ 200%) and poor electrical conductivity hinder its large-scale commercial application. Researchers employ various methods to reduce the volume change of SiO during lithium intercalation and improve its structural stability during cycling. This work mainly reviews the chemical structure and lithium storage mechanism of SiO, as well as the latest research progress on the preparation methods of SiO/C anode materials, focusing on summarizing the following preparation strategies: chemical vapor deposition, mechanical ball milling, spray drying, and in-situ reduction/oxidation methods. The obtained SiO-based anode materials' structural characteristics and electrochemical properties are compared and summarized. Finally, this review discusses the advantages and disadvantages of the current preparation methods, the future research directions, and the development prospects of SiO-based anode materials.

Genomics of hybrid parallel origin in Aquilegia ecalcarata.

BACKGROUND: The parallel evolution of similar traits or species provides strong evidence for the role of natural selection in evolution. Traits or species that evolved repeatedly can be driven by separate de novo mutations or interspecific gene flow. Although parallel evolution has been reported in many studies, documented cases of parallel evolution caused by gene flow are scarce by comparison. Aquilegia ecalcarata and A. kansuensis belong to the genus of Aquilegia, and are the closest related sister species. Mutiple origins of A. ecalcarata have been reported in previous studies, but whether they have been driven by separate de novo mutations or gene flow remains unclear. RESULTS: In this study, We conducted genomic analysis from 158 individuals of two repeatedly evolving pairs of A. ecalcarata and A. kansuensis. All samples were divided into two distinct clades with obvious geographical distribution based on phylogeny and population structure. Demographic modeling revealed that the origin of the A. ecalcarata in the Eastern of China was caused by gene flow, and the Eastern A. ecalcarata occurred following introgression from Western A. ecalcarata population. Analysis of Treemix and D-statistic also revealed that a strong signal of gene flow was detected from Western A. ecalcarata to Eastern A. ecalcarata. Genetic divergence and selective sweep analyses inferred parallel regions of genomic divergence and identified many candidate genes associated with ecologically adaptive divergence between species pair. Comparative analysis of parallel diverged regions and gene introgression confirms that gene flow contributed to the parallel evolution of A. ecalcarata. CONCLUSIONS: Our results further confirmed the multiple origins of A. ecalcarata and highlighted the roles of gene flow. These findings provide new evidence for parallel origin after hybridization as well as insights into the ecological adaptation mechanisms underlying the parallel origins of species.

Design, synthesis and biological evaluation of 1-aryldonepezil analogues as anti-Alzheimer's disease agents.

Aim: To design and synthesize a novel series of 1-aryldonepezil analogues. Materials & methods: The 1-aryldonepezil analogues were synthesized through palladium/PCy3-catalyzed Suzuki reaction and were evaluated for cholinesterase inhibitory activities and neuroprotective effects. In silico docking of the most effective compound was conducted. Results: The 4-tert-butylphenyl analogue exhibited good inhibitory potency against acetylcholinesterase and butyrylcholinesterase and had a favorable neuroprotective effect on H2O2-induced SH-SY5Y cell injury. Conclusion: The 4-tert-butylphenyl derivative is a promising lead compound for anti-Alzheimer's disease drug development.

[Box: see text].

Urease-producing bacteria with plant growth-promoting ability that may tolerate and remove cadmium from aqueous solution.

Urease-producing bacteria (UPB) are widely present in soil and play an important role in soil ecosystems. In this study, 65 UPB strains were isolated from cadmium (Cd)-polluted soil around a lead-zinc mine in Yunnan Province, China. The Cd tolerance, removal of Cd from aqueous solution, production of indoleacetic acid (IAA) and plant growth-promoting effects of these materials were investigated. The results indicate that among the 65 UPB strains, four strains with IAA-producing ability were screened and identified as Bacillus thuringiensis W6-11, B. cereus C7-4, Serratia marcescens W11-10, and S. marcescens C5-6. Among the four strains, B. cereus C7-4 had the highest Cd tolerance, median effect concentration (EC50) of 59.94 mg/L. Under Cd 5 mg/L, S. marcescens C5-6 had the highest Cd removal from aqueous solution, up to 69.83%. Under Cd 25 mg/kg, inoculation with B. cereus C7-4 significantly promoted maize growth in a sand pot by increasing the root volume, root surface area, and number of root branches by 22%, 29%, and 20%, respectively, and plant height and biomass by 16% and 36%, respectively, and significantly increasing Cd uptake in the maize roots. Therefore, UPB is a potential resource for enhancing plant adaptability to Cd stress in plants with Cd-polluted habitats.

This study utilized urease-producing bacteria screened from the soil of lead zinc mining areas in Yunnan, China as the research object, enriching the microbial resources in Yunnan. In addition, this article verified the IAA production ability and cadmium removal ability of urease-producing bacteria, and screened out bifunctional urease-producing bacteria that have potential in cadmium pollution control and plant growth promotion.

A high-performance C@Na5V12O32 nanowire electrode derived from the reconstruction of carbon quantum dots.

Vanadate electrodes are potential candidates for lithium-ion batteries (LIBs) due to their large theoretical specific capacity. However, their easy dissolution in the electrolyte, large structural changes, low conductivity and capacity decay during cycling hinder their further application. Herein, a lithium-ion battery electrode of Na5V12O32 (NVO) nanowires covered with a carbon film and formed by the reconstruction of carbon quantum dots (CDs) was obtained using an in situ capping strategy. Remarkably, the carbon film could prevent direct contact between the NVO nanowires and the electrolyte, thus slowing down the occurrence of side reactions and avoiding the dissolution of the NVO nanowires. Among the electrodes treated at different temperatures, the C@NVO-400 electrode exhibits high capacity and excellent cycling stability as the electrode of LIBs, with a discharge specific capacity of 779.1 and 315.5 mAh g-1 after 400 and 1000 cycles at a current density of 0.1 and 2 A g-1, respectively. An in situ coating strategy is proposed here to contribute to the further development of coated vanadate electrodes for high-performance LIBs.

Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) protect against diabetic cardiovascular diseases and nephropathy. However, their activity in diabetic retinopathy (DR) remains unclear. Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications, suggesting their advantage in DR treatment. By single-cell RNA-sequencing analysis and immunostaining, we observed a high expression of GLP-1R in retinal endothelial cells, which was down-regulated under diabetic conditions. Treatment of GLP-1 RAs significantly restored the receptor expression, resulting in an improvement in retinal degeneration, vascular tortuosity, avascular vessels, and vascular integrity in diabetic mice. GO and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 RAs. Additionally, the treatment attenuated STING signaling activation in retinal endothelial cells, which is typically activated by leaked mitochondrial DNA. Expression of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular membranes. Further investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING signaling. This study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

Unveiling the luminescence property of Li2MgGeO4:Mn4+ featuring the tetrahedral crystallographic-site occupancy of Mn4.

Owing to the occupying tendency of Mn4+ at octahedral sites, doping Mn4+ activators in tetrahedral structures poses challenges and hence is seldom reported. In this work, tetrahedrally sited Mn4+ phosphors were studied. By combining X-ray diffraction (XRD) data with Rietveld refinement analysis, the location of Mn4+ was determined. It was found that by adding excessive raw MgO, the phosphor synthesis temperature can be improved, enhancing the crystallinity of the crystal and thus improving the emission performance of the phosphor. In addition, excessive raw MgO forms a second phase in an LMGO matrix, which does not change the doping site for Mn4+. The Tanabe-Sugano diagram of Mn4+ in the tetrahedral field and the energy-level diagram of these phosphors were constructed for the first time, and the excitation and emission mechanisms are discussed in detail. With 1.2-fold excess of raw MgO, the prepared sample (LMGO-Mn-1.2) shows the best luminescence, demonstrating red emissions peaked at 656 nm and affording an emission intensity enhancement of over 50 times compared to a stoichiometric LMGO:Mn4+ system. At 150 °C, LMGO-Mn-1.2 keeps 90% emission intensity compared to that at room temperature. Finally, a high-efficiency warm white light-emitting diode was built. This work provides new insights into the study of Mn4+-activated phosphors in a tetrahedron crystal field.

Preorganization Effects on Eu(III) Ion Coordination by Dipyridyl-Phenanthroline Ligands: A Combined Experimental and Theoretical Analysis.

Although 1,10-phenanthroline has been proven to hold a strong complexing capacity for f-block elements and their derivatives have been applied in many fields, research on more highly or completely rigid phenanthroline ligands is still rare due to the challenging syntheses. Here, we reported three tetradentate ligands 2,9-di(pyridin-2-yl)-1,10-phenanthroline (L1), 12-(pyridin-2-yl)-5,6-dihydroquinolino[8,7b][1,10]phenanthroline (L2), and 5,6,11,12-tetrahydrobenzo[2,1-b:3,4-b']bis([1,10]phenanthroline) (L3) with increasing preorganization on the side chain; among which, L3 is fully preorganized. Their complexation reactions with Eu(III) were systematically investigated by electrospray ionization mass spectrometry (ESI-MS), UV-vis titrations, and single-crystal structures. It is found that all three ligands form only 1:1 M/L complexes with Eu(III). The single-crystal structures revealed that the three ligands hold similar coordination modes, while their stability constants determined by UV-vis titrations were L3 (4.80 ± 0.01) > L2 (4.38 ± 0.01) > L1 (3.88 ± 0.01). This trend is supported not only by the thermodynamic stability of rigid ligands compared to free ligands but also by the conclusion that rigid ligands exhibit faster reaction rates (lower energy barrier) than free ligands kinetically. This work is helpful in providing theoretical guidance for the subsequent development of highly preorganized chelating ligands with strong coordination ability and high selectivity for f-block elements.

Epimerization effects on coordination behaviours of phenanthroline-based phosphine-oxide ligands with uranyl ions.

Epimers of the (1,10-phenanthroline-2,9-diyl)bis(ethyl(phenyl)phosphine oxide) (Et-Ph-BPPhen) ligand with two chiral centers (R,R/S,S and R,S) were synthesized. The configurational effects on the coordination ability and mechanism between these epimeric ligands and uranyl ions were thoroughly investigated. This work is helpful to reveal the effects of different conformations of epimeric ligands on their coordination properties.

Nuclear KRT19 is a transcriptional corepressor promoting histone deacetylation and liver tumorigenesis.

BACKGROUND AND AIMS: Epigenetic reprogramming and escape from terminal differentiation are poorly understood enabling characteristics of liver cancer. Keratin 19 (KRT19), classically known to form the intermediate filament cytoskeleton, is a marker of stemness and worse prognosis in liver cancer. This study aimed to address the functional roles of KRT19 in liver tumorigenesis and to elucidate the underlying mechanisms. APPROACH AND RESULTS: Using multiplexed genome editing of hepatocytes in vivo, we demonstrated that KRT19 promoted liver tumorigenesis in mice. Cell fractionation revealed a previously unrecognized nuclear fraction of KRT19. Tandem affinity purification identified histone deacetylase 1 and REST corepressor 1, components of the corepressor of RE-1 silencing transcription factor (CoREST) complex as KRT19-interacting proteins. KRT19 knockout markedly enhanced histone acetylation levels. Mechanistically, KRT19 promotes CoREST complex formation by enhancing histone deacetylase 1 and REST corepressor 1 interaction, thus increasing the deacetylase activity. ChIP-seq revealed hepatocyte-specific genes, such as hepatocyte nuclear factor 4 alpha ( HNF4A ), as direct targets of KRT19-CoREST. In addition, we identified forkhead box P4 as a direct activator of aberrant KRT19 expression in liver cancer. Furthermore, treatment of primary liver tumors and patient-derived xenografts in mice suggest that KRT19 expression has the potential to predict response to histone deacetylase 1 inhibitors especially in combination with lenvatinib. CONCLUSIONS: Our data show that nuclear KRT19 acts as a transcriptional corepressor through promoting the deacetylase activity of the CoREST complex, resulting in dedifferentiation of liver cancer. These findings reveal a previously unrecognized function of KRT19 in directly shaping the epigenetic landscape in cancer.

Flexural Performance and Stress Calculation of External Prestressed Fiber-Reinforced Polymer-Bar-Strengthened One-Way Concrete Slabs.

External prestressing is widely employed in structural strengthening engineering due to its numerous advantages. However, external prestressed steel bars are prone to corrosion when exposed to the service environment. This paper is dedicated to examining the use of fiber-reinforced polymer (FRP) bars as external prestressing materials to strengthen one-way concrete slabs. Five one-way concrete slabs were strengthened with externally prestressed FRP bars with different prestress levels and different amounts of FRP bars, while one non-strengthened slab was used for comparison. The effects of strengthening on the flexural behavior, specifically the cracking load, ultimate load, stiffness and failure mode, were analyzed systematically. Moreover, the ductility and cost-benefit optimizing properties of the reinforcing design were discussed. The results show that external prestressed FRP bars significantly improve the cracking load, ultimate load and stiffness of one-way concrete slabs. The absence of a bond between the concrete and FRP bars overcomes the brittleness of the FRP bars, while the strengthened slabs exhibit satisfactory ductility and a higher post-yield stiffness and bearing capacity. Additionally, the cost/benefit ratio is optimized by increasing the prestress level, while a higher number of prestressed FRP bars is beneficial to ductility. Finally, a method for calculating the stress in prestressed FRP bars at ultimate loads was proposed. Irrespective of the prestressing material, this method is applicable to both strengthened beams and one-way slabs.

FUS reads histone H3K36me3 to regulate alternative polyadenylation.

Complex organisms generate differential gene expression through the same set of DNA sequences in distinct cells. The communication between chromatin and RNA regulates cellular behavior in tissues. However, little is known about how chromatin, especially histone modifications, regulates RNA polyadenylation. In this study, we found that FUS was recruited to chromatin by H3K36me3 at gene bodies. The H3K36me3 recognition of FUS was mediated by the proline residues in the ZNF domain. After these proline residues were mutated or H3K36me3 was abolished, FUS dissociated from chromatin and bound more to RNA, resulting in an increase in polyadenylation sites far from stop codons genome-wide. A proline mutation corresponding to a mutation in amyotrophic lateral sclerosis contributed to the hyperactivation of mitochondria and hyperdifferentiation in mouse embryonic stem cells. These findings reveal that FUS is an H3K36me3 reader protein that links chromatin-mediated alternative polyadenylation to human disease.

Morphologic and Functional Assessment of Photoreceptors in Laser-Induced Retinopathy Using Adaptive Optics Scanning Laser Ophthalmoscopy and Microperimetry.

PURPOSE: To assess the cone photoreceptors' morphology and associated retinal sensitivity in laser-induced retinopathy (LIR) using adaptive optics scanning laser ophthalmoscopy (AO-SLO) and microperimetry (MP). DESIGN: Cohort study. METHODS: This study included 13 patients (15 eyes) with LIR and 38 age-matched healthy volunteers (38 eyes). Participants underwent comprehensive evaluations including AO-SLO, MP, and spectral-domain OCT. Lesion morphology, cone density, dispersion, and regularity in AO-SLO were assessed and correlated with visual function. RESULTS: In AO-SLO images, LIR lesions were predominantly characterized by hyporeflective regions, suggesting potential cone loss at the fovea, accompanied by the presence of sizable clumps of hyperreflective material within these lesions. The average size of lesions in affected eyes was 97,128±107,478 µm², ranging from 6705 to 673,348 µm². Compared with the healthy contralateral eye and control group, LIR demonstrated significantly reduced cone density, increased cone dispersion, and notably decreased cone regularity in all 4 quadrants at 3° eccentricity (all P values < .05). Lesion morphology in AO-SLO correlated with ellipsoid zone defects observed in OCT, showing a positive correlation in size (r = 0.84, P < .001) but not with retinal sensitivities (P = .09). Similarly, cone density at 3° eccentricity did not correlate with retinal sensitivities (P = .13). CONCLUSIONS AND RELEVANCE: The study provides crucial insights into the morphologic and functional impacts of LIR on cone photoreceptors, revealing significant morphologic changes in cones that do not consistently align with functional outcomes. This research highlights the need for continued exploration into the relationship between retinal structure and function in LIR, and the importance of heightened public awareness and preventive strategies to mitigate the risk of LIR.

Enzymatic-related network of catalysis, polyamine, and tumors for acetylpolyamine oxidase: from calculation to experiment.

The regulation of enzymes and development of polyamine analogs capable of controlling the dynamics of endogenous polyamines to achieve anti-tumor effects is one of the biggest challenges in polyamine research. However, the root of the problem remains unsolved. This study represents a significant milestone as it unveils, for the first time, the comprehensive catalytic map of acetylpolyamine oxidase that includes chemical transformation and product release kinetics, by utilizing multiscale simulations with over six million dynamical snapshots. The transportation of acetylspermine is strongly exothermic, and high binding affinity of enzyme and reactant is observed. The transfer of hydride from polyamine to FAD is the rate-limiting step, via an H-shift coupled electron transfer mechanism. The two products are released in a detour stepwise mechanism, which also impacts the enzymatic efficiency. Inspired by these mechanistic insights into enzymatic catalysis, we propose a novel strategy that regulates the polyamine level and catalytic progress through the action of His64. Directly suppressing APAO by mutating His64 further inhibited growth and migration of tumor cells and tumor tissue in vitro and in vivo. Therefore, the network connecting microcosmic and macroscopic scales opens up new avenues for designing polyamine compounds and conducting anti-tumor research in the future.

Assessing the Role of BN-Embedding Position in B2N2-Perylenes.

Incorporating heteroatoms can effectively modulate the molecular optoelectronic properties. However, the fundamental understanding of BN doping effects in BN-embedded polycyclic aromatic hydrocarbons (PAHs) is underexplored, lacking rational guidelines to modulate the electronic structures through BN units for advanced materials. Herein, a concise synthesis of novel B2N2-perylenes with BN doped at the bay area is achieved to systematically explore the doping effect of BN position on the photophysical properties of PAHs. The shift of BN position in B2N2-perylenes alters the π electron conjugation, aromaticity and molecular rigidness significantly, achieving substantially higher electron transition abilities than those with BN doped in the nodal plane. It is further clarified that BN position dominates the photophysical properties over BN orientation. The revealed guideline here may apply generally to novel BN-PAHs, and aid the advancement of BN-PAHs with highly-emissive performance.

The identification and classification of candidate genes during the zygotic genome activation in the mammals.

Zygotic genome activation (ZGA) is a critical event in early embryonic development, and thousands of genes are involved in this delicate and sophisticated biological process. To date, however, only a handful of these genes have revealed their core functions in this special process, and therefore the roles of other genes still remain unclear. In the present study, we used previously published transcriptome profiling to identify potential key genes (candidate genes) in minor ZGA and major ZGA in both human and mouse specimens, and further identified the conserved genes across species. Our results showed that 887 and 760 genes, respectively, were thought to be specific to human and mouse in major ZGA, and the other 135 genes were considered to be orthologous genes. Moreover, the conserved genes were most enriched in rRNA processing in the nucleus and cytosol, ribonucleoprotein complex biogenesis, ribonucleoprotein complex assembly and ribosome large subunit biogenesis. The findings of this first comprehensive identification and characterization of candidate genes in minor and major ZGA provide relevant insights for future studies on ZGA.

Achieving Ideal and Environmentally Stable n-Type Charge Transport in Polymer Field-Effect Transistors.

Realizing ideal charge transport in field-effect transistors (FETs) of conjugated polymers is crucial for evaluating device performance, such as carrier mobility and practical applications of conjugated polymers. However, the current FETs using conjugated polymers as the active layers generally show certain non-ideal transport characteristics and poor stability. Here, ideal charge transport of n-type polymer FETs is achieved on flexible polyimide substrates by using an organic-inorganic hybrid double-layer dielectric. Deposited conjugated polymer films show highly ordered structures and low disorder, which are supported by grazing-incidence wide-angle X-ray scattering, near-edge X-ray absorption fine structure, and molecular dynamics simulations. Furthermore, the organic-inorganic hybrid double-layer dielectric provides low interfacial defects, leading to excellent charge transport in FETs with high electron mobility (1.49 ± 0.46 cm2 V-1 s-1) and ideal reliability factors (102 ± 7%). Fabricated polymer FETs show a self-encapsulation effect, resulting in high stability of the FET charge transport. The polymer FETs still work with high mobility above 1 cm2 V-1 s-1 after storage in air for more than 300 days. Compared with state-of-the-art conjugated polymer FETs, this work simultaneously achieves ideal charge transport and environmental stability in n-type polymer FETs, facilitating rapid device optimization of high-performance polymer electronics.

Association between choroidopathy and photoreceptors during the early stage of diabetic retinopathy: a cross-sectional study.

PURPOSE: To explore the role of choroidopathy in diabetic retinopathy (DR) by investigating the correlation between alterations of choroidal vessel and photoreceptors during the early stage of DR. METHODS: We performed a cross-sectional comparison of diabetic patients without DR (NDR group; n=16) and those with mild nonproliferative diabetic retinopathy (NPDR group; n=39). Optical coherence tomography (OCT) images of choroidal vessel alterations and photoreceptor structures were evaluated using the choroidal vascularity index (CVI) and adjusted ellipsoid zone (EZ) reflectivity, respectively. To evaluate the function of cone photoreceptors, the fundamental, harmonic amplitudes, the parameters S and Rmp3 were calculated from the electroretinogram (ERG). These factors were compared between groups. The correlation between the CVI and parameters describing the function and structure of the photoreceptors was evaluated. RESULTS: The significant decrease was observed in the CVI in the NPDR group compared to the NDR group (0.67 ± 0.04 vs. 0.70 ± 0.06; p = 0.028), but not in the adjusted EZ reflectivity or ERG parameters. In NPDR group and merging the 2 groups, CVI was moderately positively correlated with the fundamental amplitude obtained by the flicker ERG (NPDR only: r = 0.506; p = 0.001; merge the 2 groups: r = 0.423; p = 0.001), which was regulated by the response of the cone photoreceptors. The CVI was positively and moderately correlated with the logS (NPDR only: r = 0.462; p = 0.003; merge the 2 groups: r = 0.355; p = 0.008), indicating the sensitivity of cone cell light transduction. CONCLUSION: Compared to eyes without DR, CVI decreased representing choroidal vascular changes in eyes with mild NPDR. These changes may be related to the functional impairment of cone photoreceptors, especially phototransduction sensitivity, as the DR develops.

Development and Comprehensive Benchmark of a High-Quality AMBER-Consistent Small Molecule Force Field with Broad Chemical Space Coverage for Molecular Modeling and Free Energy Calculation.

Biomolecular simulations have become an essential tool in contemporary drug discovery, and molecular mechanics force fields (FFs) constitute its cornerstone. Developing a high quality and broad coverage general FF is a significant undertaking that requires substantial expert knowledge and computing resources, which is beyond the scope of general practitioners. Existing FFs originate from only a limited number of groups and organizations, and they either suffer from limited numbers of training sets, lower than desired quality because of oversimplified representations, or are costly for the molecular modeling community to access. To address these issues, in this work, we developed an AMBER-consistent small molecule FF with extensive chemical space coverage, and we provide Open Access parameters for the entire modeling community. To validate our FF, we carried out benchmarks of quantum mechanics (QM)/molecular mechanics conformer comparison and free energy perturbation calculations on several benchmark data sets. Our FF achieves a higher level of performance at reproducing QM energies and geometries than two popular open-source FFs, OpenFF2 and GAFF2. In relative binding free energy calculations for 31 protein-ligand data sets, comprising 1079 pairs of ligands, the new FF achieves an overall root-mean-square error of 1.19 kcal/mol for ΔΔG and 0.92 kcal/mol for ΔG on a subset of 463 ligands without bespoke fitting to the data sets. The results are on par with those of the leading commercial series of OPLS FFs.

LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment.

BACKGROUND: Malignant melanoma is a highly heterogeneous skin cancer with the highest mortality rate among dermatological cancers. Catenins form functional networks in the nucleus to regulate gene expression and determine cell fate. Dysregulation of catenin expression correlates with the malignant characteristics of the tumor. We aimed to investigate the regulatory mechanisms of catenins in melanoma and to further define the function of catenin-related molecular signaling in the tumor microenvironment. METHODS: In this study, a bioinformatics approach combined with experimental validation was used to explore the potential tumor biology mechanisms of catenin-related signaling. RESULTS: Melanoma patients can be divided into two catenin clusters. Patients defined by high Junction Plakoglobin (JUP), Plakophilin 1 (PKP1), Plakophilin 3 (PKP3) levels (C2) had shorter survival time than other patients (C1). We demonstrated that JUP regulates Anterior Gradient 2 (AGR2)/LY6/PLAUR Domain Containing 3 (LYPD3) to maintain melanoma stemness and promotes glycolysis. We also found that LYPD3 was co-expressed with S100A9 and associated with immunosuppressive tumor microenvironment (TME). CONCLUSION: The JUP/AGR2/LYPD3 signaling axis plays an important role in the malignant features of melanoma. Targeting the JUP/AGR2/LYPD3 signaling axis can help develop promising drugs.