AptaDiff: de novo design and optimization of aptamers based on diffusion models.

Aptamers are single-stranded nucleic acid ligands, featuring high affinity and specificity to target molecules. Traditionally they are identified from large DNA/RNA libraries using $in vitro$ methods, like Systematic Evolution of Ligands by Exponential Enrichment (SELEX). However, these libraries capture only a small fraction of theoretical sequence space, and various aptamer candidates are constrained by actual sequencing capabilities from the experiment. Addressing this, we proposed AptaDiff, the first in silico aptamer design and optimization method based on the diffusion model. Our Aptadiff can generate aptamers beyond the constraints of high-throughput sequencing data, leveraging motif-dependent latent embeddings from variational autoencoder, and can optimize aptamers by affinity-guided aptamer generation according to Bayesian optimization. Comparative evaluations revealed AptaDiff's superiority over existing aptamer generation methods in terms of quality and fidelity across four high-throughput screening data targeting distinct proteins. Moreover, surface plasmon resonance experiments were conducted to validate the binding affinity of aptamers generated through Bayesian optimization for two target proteins. The results unveiled a significant boost of $87.9\%$ and $60.2\%$ in RU values, along with a 3.6-fold and 2.4-fold decrease in KD values for the respective target proteins. Notably, the optimized aptamers demonstrated superior binding affinity compared to top experimental candidates selected through SELEX, underscoring the promising outcomes of our AptaDiff in accelerating the discovery of superior aptamers.

Broadband sensitized near-infrared emission in Eu2+-Nd3+ co-doped BaAl2O4 as a potential spectral modulator for silicon solar cells.

The near-infrared (NIR) down-conversion process for broadband sensitization has been studied in Eu2+-Nd3+ co-doped BaAl2O4. This material has a broad absorption band of 200-480 nm and can convert photons in the visible region into NIR photons. The NIR emission at 1064 nm, attributed to the Nd3+:4F3/2 → 4I11/2 transition, matches the bandgap of Si, allowing Si solar cells to utilize the solar spectrum better. The energy transfer (ET) process between Eu2+ and Nd3+ was demonstrated using photoluminescence spectra and luminescence decay curves, and Eu2+ may transfer energy to Nd3+ through the cooperative energy transfer (CET) to achieve the down-conversion process. The energy transfer efficiency (ETE) and theoretical quantum efficiency (QE) were 68.61% and 156.34%, respectively, when 4 mol% Nd3+ was introduced. The results indicate that BaAl2O4:Eu2+-Nd3+ can serve as a potential modulator of the solar spectrum and is expected to be applied to Si solar cells.

Building synergistic multiple active sites in branch-leaf nanostructured carbon nanofiber derived from MOF/COF hybrid for flexible wearable Zn-air battery.

Covalent organic frameworks (COFs) and metal-organic frameworks (MOFs) have attracted growing attention in electrochemical energy storage and conversion systems (e.g., Zn-air batteries, ZABs) owing to their structural tunability, ordered porosity and high specific surface area. In this work, for the first time, the three-dimensional (3D) highly open catalyst (CNFs/CoZn-MOF@COF) possessing hierarchical porous structure and high-density active sites of uniform cobalt (Co) nanoparticles and metal-Nx (M-Nx, M = Co and Zn) is demonstrated, which is fabricated using electrospinning technique in combination with MOF/COF hybridization strategy and direct pyrolysis. Benefiting from the well-designed branch-leaf nanostructures, plentiful and uniform active sites on the MOF/COF-derived carbon frameworks, as well as the synergistic effect of multiple active sites, CNFs/CoZn-MOF@COF catalyst achieves superior electrocatalytic activity and stability towards both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) with a small potential gap (ΔE = 0.75 V). In situ Raman spectroscopy and X-ray photoelectron spectroscopy results indicate that the CoOOH intermediates are the main active species during OER/ORR. Significantly, both aqueous and all-solid-state rechargeable ZABs assembled with CNFs/CoZn-MOF@COF as the air cathode show high open-circuit potential, outstanding peak power density, large capacity and long cycle life. More impressively, the obtained all-solid-state ZAB also displays superb mechanical flexibility and device stability under different, showcasing great application deformations potential in portable and wearable electronics. This work provides a new insight into the design and exploitation of bifunctional catalysts from MOF/COF hybrid materials for energy storage and conversion devices.

MOF-derived low Ru-loaded high entropy alloy as an efficient and durable self-supporting electrode in rechargeable liquid/flexible Zn-air batteries.

Exploiting the high-entropy alloy (HEA) electrocatalysts with the synergistic effect of multi-metal components is an effective approach to address the slow kinetics and undesirable stability of the oxygen evolution reaction (OER) in Zn-air batteries (ZABs), but still faces many challenges. In this study, a multimetallic Metal-organic framework (MOF)-derived HEA catalyst was successfully fabricated on carbon fiber as a flexible self-supporting electrode (denoted as CC@FeCoNiMoRu-HEA/C) for high-performance liquid/flexible ZABs using a facile and cost-effective strategy. The three-dimensional (3D) highly open network framework and hierarchical porous structure accelerate the mass transport of OH-/O2 and charge transfer. The electronic structure adjustment, lattice defects and high entropy effects enable the CC@FeCoNiMoRu-HEA/C catalysts to perform high OER catalytic activity and strong durability while reducing the Ru content and lowering the economic cost. In situ Raman spectra and XPS results reveal the generation of metal-OOH intermediates on the HEA surface during the OER process. In a practical demonstration, the liquid ZAB assembled with CC@FeCoNiMoRu-HEA/C + Pt/C as the air electrode offers stable open-circuit voltage, large power density, excellent specific capacity and satisfactory cycle life, outperforming the commercial RuO2 + Pt/C-based reference ZAB. More attractively, the flexible solid-state ZAB also achieves fast dynamic response, high peak power density, robust cycling stability as well as favorable mechanical flexibility, indicating a promising application prospect in future flexible electronics and wearable devices. This work provides a viable pathway to develop low precious metal-loaded HEAs as advanced OER self-supporting electrocatalysts and realize high-performance flexible energy storage devices.

Corrigendum: Identification of DYNLT1 associated with proliferation, relapse, and metastasis in breast cancer.

[This corrects the article DOI: 10.3389/fmed.2023.1167676.].

Identification and validation of the cellular senescence-related molecular subtypes of triple negative breast cancer via integrating bulk and single-cell RNA sequencing data.

Patients with triple-negative breast cancer (TNBC) reportedly benefit from immune checkpoint blockade (ICB) therapy. However, the subtype-specific vulnerabilities of ICB in TNBC remain unclear. As the complex interplay between cellular senescence and anti-tumor immunity has been previously discussed, we aimed to identify markers related to cellular senescence that may serve as potential predictors of response to ICB in TNBC. We used three transcriptomic datasets derived from ICB-treated breast cancer samples at both scRNA-seq and bulk-RNA-seq levels to define the subtype-specific vulnerabilities of ICB in TNBC. Differences in the molecular features and immune cell infiltration among the different TNBC subtypes were further explored using two scRNA-seq, three bulk-RNA-seq, and two proteomic datasets. 18 TNBC samples were collected and utilized to verify the association between gene expression and immune cell infiltration by multiplex immunohistochemistry (mIHC). A specific type of cellular senescence was found to be significantly associated with response to ICB in TNBC. We employed the expression of four senescence-related genes, namely CDKN2A, CXCL10, CCND1, and IGF1R, to define a distinct senescence-related classifier using the non-negative matrix factorization approach. Two clusters were identified, namely the senescence-enriching cluster (C1; CDKN2A high CXCL10 high CCND1 low IGF1R low) and proliferating-enriching cluster (C2; CDKN2A low CXCL10 low CCND1 high IGF1R high). Our results indicated that the C1 cluster responds better to ICB and behaves with higher CD8+ T cell infiltration than the C2 cluster. Altogether, in this study, we developed a robust cellular senescence-related classifier of TNBC based on the expression of CDKN2A, CXCL10, CCND1, and IGF1R. This classifier act as a potential predictor of clinical outcomes and response to ICB.

Semi-automated and efficient parallel SELEX of aptamers for multiple targets.

In this study, we constructed and optimized a semi-automatic instrument to perform aptamer SELEX targeting multiple proteins simultaneously. Our work provides a simple SELEX platform characterized by real-time feedback, which is time efficient and can reduce human intervention. A number of aptamers were rapidly screened by this method. Moreover, the binding affinities of these aptamers were verified by various methods, including SPR and flow cytometry, which supports the applicability and reliability of our newly established aptamer SELEX system.

Identification of DYNLT1 associated with proliferation, relapse, and metastasis in breast cancer.

Background: Breast cancer (BC) is the most common malignant disease worldwide. Although the survival rate is improved in recent years, the prognosis is still bleak once recurrence and metastasis occur. It is vital to investigate more efficient biomarkers for predicting the metastasis and relapse of BC. DYNLT1 has been reported that participating in the progression of multiple cancers. However, there is still a lack of study about the correlation between DYNLT1 and BC. Methods: In this study, we evaluated and validated the expression pattern and prognostic implication of DYNLT1 in BC with multiple public cohorts and BC tumor microarrays (TMAs) of paraffin-embedded tissues collected from the Affiliated Hospital of Jining Medical University. The response biomarkers for immune therapy, such as tumor mutational burden (TMB), between different DYNLT1 expression level BC samples were investigated using data from the TCGA-BRCA cohort utilizing public online tools. In addition, colony formation and transwell assay were conducted to verify the effects of DYNLT1 in BC cell line proliferation and invasion. Results: The results demonstrated that DYNLT1 overexpressed in BC and predicted poor relapse-free survival in our own BC TMA cohort. In addition, DYNLT1 induced BC development by promoting MDA-MB-231 cell proliferation migration, and metastasis. Conclusion: Altogether, our findings proposed that DYNLT1 could be a diagnostic and prognostic indicator in BC.

Identification and Validation of a Prognostic Signature Based on Methylation Profiles and Methylation-Driven Gene DAB2 as a Prognostic Biomarker in Differentiated Thyroid Carcinoma.

Recurrence is the major death cause of differentiated thyroid carcinoma (DTC), and a better understanding of recurrence risk at early stage may lead to make the optimal medical decision to improve patients' prognosis. The 2015 American Thyroid Association (ATA) risk stratification system primary based on clinic-pathologic features is the most commonly used to describe the initial risk of persistent/recurrent disease. Besides, multiple prognostics models based on multigenes expression profiles have been developed to predict the recurrence risk of DTC patients. Recent evidences indicated that aberrant DNA methylation is involved in the initiation and progression of DTC and can be useful biomarkers for clinical diagnosis and prognosis prediction of DTC. Therefore, there is a need for integrating gene methylation feature to assess the recurrence risk of DTC. Gene methylation profile from The Cancer Genome Atlas (TCGA) was used to construct a recurrence risk model of DTC by successively performed univariate Cox regression, LASSO regression, and multivariate Cox regression. Two Gene Expression Omnibus (GEO) methylation cohorts of DTC were utilized to validate the predictive value of the methylation profiles model as external cohort by receiver operating characteristic (ROC) curve and survival analysis. Besides, CCK-8, colony-formation assay, transwell, and scratch-wound assay were used to investigate the biological significance of critical gene in the model. In our study, we constructed and validated a prognostic signature based on methylation profiles of SPTA1, APCS, and DAB2 and constructed a nomogram based on the methylation-related model, age, and AJCC_T stage that could provide evidence for the long-term treatment and management of DTC patients. Besides, in vitro experiments showed that DAB2 inhibited proliferation, colony-formation, and migration of BCPAP cells and the gene set enrichment analysis and immune infiltration analysis showed that DAB2 may promote antitumor immunity in DTC. In conclusion, promoter hypermethylation and loss expression of DAB2 in DTC may be a biomarker of unfavorable prognosis and poor response to immune therapy.

Cationic recognition by tert-butylcalix[4]arene-functionalized nanoprobes.

A nanoparticle-based strategy has been demonstrated using structurally-tailored tert-butylcalixarenes immobilized on gold nanoparticles to tune the guest access to the calixarene cone cavity for cationic recognition. This strategy exploits the interparticle charge-induced aggregation upon selective capture of metal cations into the nanoparticle-immobilized tert-butylcalixarenes, which produces calorimetric changes for the detection. A possible pathway for the binding of M(n+) into the t-BCA structure and the interparticle interaction is proposed for the formation of an electric double layer inducing the interparticle association responsible for the red-shifted surface plasmon resonance band of the nanoparticles. The value of this class of calorimetric nanoprobes will be in the area of designing advanced host-guest probes using a variety of calixarene ligands for ionic recognition in a simplistic detection format.