NucleoCraft: The Art of Stimuli-Responsive Precision in DNA and RNA Bioengineering.

Recent advancements in DNA and RNA bioengineering have paved the way for developing stimuli-responsive nanostructures with remarkable potential across various applications. These nanostructures, crafted through sophisticated bioengineering techniques, can dynamically and precisely respond to both physiological and physical stimuli, including nucleic acids (DNA/RNA), adenosine triphosphate, proteins, ions, small molecules, pH, light, and temperature. They offer high sensitivity and specificity, making them ideal for applications such as biomarker detection, gene therapy, and controlled targeted drug delivery. In this review, we summarize the bioengineering methods used to assemble versatile stimuli-responsive DNA/RNA nanostructures and discuss their emerging applications in structural biology and biomedicine, including biosensing, targeted drug delivery, and therapeutics. Finally, we highlight the challenges and opportunities in the rational design of these intelligent bioengineered nanostructures.

PROTAC-mediated vimentin degradation promotes terminal erythroid differentiation of pluripotent stem cells.

BACKGROUND: Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), can undergo erythroid differentiation, offering a potentially invaluable resource for generating large quantities of erythroid cells. However, the majority of erythrocytes derived from hPSCs fail to enucleate compared with those derived from cord blood progenitors, with an unknown molecular basis for this difference. The expression of vimentin (VIM) is retained in erythroid cells differentiated from hPSCs but is absent in mature erythrocytes. Further exploration is required to ascertain whether VIM plays a critical role in enucleation and to elucidate the underlying mechanisms. METHODS: In this study, we established a hESC line with reversible vimentin degradation (dTAG-VIM-H9) using the proteolysis-targeting chimera (PROTAC) platform. Various time-course studies, including erythropoiesis from CD34+ human umbilical cord blood and three-dimensional (3D) organoid culture from hESCs, morphological analysis, quantitative real-time PCR (qRT-PCR), western blotting, flow cytometry, karyotyping, cytospin, Benzidine-Giemsa staining, immunofluorescence assay, and high-speed cell imaging analysis, were conducted to examine and compare the characteristics of hESCs and those with vimentin degradation, as well as their differentiated erythroid cells. RESULTS: Vimentin expression diminished during normal erythropoiesis in CD34+ cord blood cells, whereas it persisted in erythroid cells differentiated from hESC. Depletion of vimentin using the degradation tag (dTAG) system promotes erythroid enucleation in dTAG-VIM-H9 cells. Nuclear polarization of erythroblasts is elevated by elimination of vimentin. CONCLUSIONS: VIM disappear during the normal maturation of erythroid cells, whereas they are retained in erythroid cells differentiated from hPSCs. We found that retention of vimentin during erythropoiesis impairs erythroid enucleation from hPSCs. Using the PROTAC platform, we validated that vimentin degradation by dTAG accelerates the enucleation rate in dTAG-VIM-H9 cells by enhancing nuclear polarization.

Enhancing terminal erythroid differentiation in human embryonic stem cells through TRIB3 overexpression.

Tribbles pseudokinase 3 (TRIB3) expression significantly increases during terminal erythropoiesis in vivo. However, we found that TRIB3 expression remained relatively low during human embryonic stem cell (hESC) erythropoiesis, particularly in the late stage, where it is typically active. TRIB3 was expressed in megakaryocyte-erythrocyte progenitor cells and its low expression was necessary for megakaryocyte differentiation. Thus, we proposed that the high expression during late stage of erythropoiesis could be the clue for promotion of maturation of hESC-derived erythroid cells. To our knowledge, the role of TRIB3 in the late stage of erythropoiesis remains ambiguous. To address this, we generated inducible TRIB3 overexpression hESCs, named TRIB3tet-on OE H9, based on a Tet-On system. Then, we analyzed hemoglobin expression, condensed chromosomes, organelle clearance, and enucleation with or without doxycycline treatment. TRIB3tet-on OE H9 cells generated erythrocytes with a high proportion of orthochromatic erythroblast in flow cytometry, enhanced hemoglobin and related protein expression in Western blot, decreased nuclear area size, promoted enucleation rate, decreased lysosome and mitochondria number, more colocalization of LC3 with LAMP1 (lysosome marker) and TOM20 (mitochondria marker) and up-regulated mitophagy-related protein expression after treatment with 2 µg/mL doxycycline. Our results showed that TRIB3 overexpression during terminal erythropoiesis may promote the maturation of erythroid cells. Therefore, our study delineates the role of TRIB3 in terminal erythropoiesis, and reveals TRIB3 as a key regulator of UPS and downstream mitophagy by ensuring appropriate mitochondrial clearance during the compaction of chromatin.

Interactive effect of air pollution and genetic risk of depression on processing speed by resting-state functional connectivity of occipitoparietal network.

BACKGROUND: Air pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function. METHODS: Eligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months' ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 µm (PM2.5). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility. RESULTS: Using a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM2.5 interactive effect (PFWE = 0.028), indicating that PM2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network (PFDR < 0.05). In those genetically predisposed to MDD, increased PM2.5 exposure positively correlated with resting-state functional connectivity between the left angular gyrus and left cuneus gyrus. This connectivity was negatively associated with processing speed. CONCLUSIONS: Our cross-sectional study suggests that air pollution may be associated with an increased likelihood of cognitive impairment in individuals genetically predisposed to depression, potentially through alterations in the resting-state function of the occipitoparietal and default mode network.

Single-Cell Transcriptomics Applied in Plants.

Single-cell RNA sequencing (scRNA-seq) is a high-tech method for characterizing the expression patterns of heterogeneous cells in the same tissue and has changed our evaluation of biological systems by increasing the number of individual cells analyzed. However, the full potential of scRNA-seq, particularly in plant science, has not yet been elucidated. To explore the utilization of scRNA-seq technology in plants, we firstly conducted a comprehensive review of significant scRNA-seq findings in the past few years. Secondly, we introduced the research and applications of scRNA-seq technology to plant tissues in recent years, primarily focusing on model plants, crops, and wood. We then offered five databases that could facilitate the identification of distinct expression marker genes for various cell types. Finally, we analyzed the potential problems, challenges, and directions for applying scRNA-seq in plants, with the aim of providing a theoretical foundation for the better use of this technique in future plant research.

Acetylation participation in theanine biosynthesis: Insights from transcriptomics, proteomics, and acetylomics.

Acetylation, a crucial post-translational modification, regulates transcriptional activation, enzymatic activity, and protein interactions, playing vital roles in plant physiology and metabolism. However, the regulatory mechanism of acetylation in the biosynthesis of theanine remains unexplored. This study aims to elucidate the regulatory role of acetylation on the biosynthesis of theanine using transcriptomics, proteomics, and acetylomics in tea leaves from three tea plant cultivars with markedly different theanine content. Nineteen theanine biosynthesis-related genes were identified in the transcriptome, with ten showing significant correlation with theanine content. Proteomic analysis revealed elevated expression levels of proteins associated with the biosynthesis of theanine precursor glutamate in leaves with high theanine content, such as GOGAT and GDH. Unexpectedly, the expression level of TS was inversely correlated with the theanine content in leaves. Several highly expressed acetylated proteins and sites, such as TS, GS, and GOGAT, were found in the acetylome of leaves with high theanine content. Acetylation at lysine 304 (K304) of the TS protein may significantly contribute to the abundant accumulation of theanine in leaves. Our findings indicate that acetylation modification may play a pivotal role in theanine biosynthesis, thereby offering novel insights into the development of high-theanine tea plant germplasm resources.

DNA-templated spatially controlled proteolysis targeting chimeras for CyclinD1-CDK4/6 complex protein degradation.

Constraining proximity-based drugs, such as proteolysis-targeting chimeras (PROTACs), into its bioactive conformation can significantly impact their selectivity and potency. However, traditional methods for achieving this often involve complex and time-consuming synthetic procedures. Here, we introduced an alternative approach by demonstrating DNA-templated spatially controlled PROTACs (DTACs), which leverage the programmability of nucleic-acid based self-assembly for efficient synthesis, providing precise control over inhibitors' spacing and orientation. The resulting constructs revealed distance- and orientation-dependent selectivity and degradation potency for the CyclinD1-CDK4/6 protein complex in cancer cells. Notably, an optimal construct DTAC-V1 demonstrated the unprecedented synchronous degradation of entire CyclinD1-CDK4/6 complex. This resulted in the effective cell cycle arrest in G1 phase, and further therapeutic studies showed its potent anti-tumor effects compared to inhibitors alone. These findings present a novel framework for PROTACs design, offering critical insights that may inform the development of other proximity-induced therapeutic modalities.

Superior Hole Injection Material PEGDT/TPF/PVDF with p-Doping Capability for Highly Efficient Solution-Processed Organic Light-Emitting Diode.

The ability to charge injection is a key factor in determining the performance of the organic light-emitting diode (OLED) devices. Improving the work function of the anode surface via interface modification, thus lowering the hole injection barrier, stands as a crucial strategy for enhancing the performance of the OLED device. Herein, we propose an innovative p-doping hole injection material, namely, PEGDT/TPF/PVDF that exhibits excellent performance in OLED devices with the value of maximum current efficiency at 56.4 Cd A-1, maximum luminescence at 25,564 Cd m-2, and a high EQE of 19.8%. The results for PEGDT/TPF/PVDF showed good conductivity, excellent film-forming property, and high transmittance over 98% in the spectrum range of 500-700 nm. Changes in the hole-injection energy barriers observed from the surface of the anode suggest a modified anode with PEGDT/TPF/PVDF deepened the work function at a value of 0.2 eV, which dramatically improves the hole-injection properties. This work not only provides novel structural materials with exceptional hole-injection properties but also proposes a promising alternative to PEDOT/PSS.

Central nervous system dissemination in spinal cord astrocytomas: association with H3 K27M mutation.

OBJECTIVE: Patients with spinal cord astrocytomas (SCAs) are at high risk for CNS dissemination, yet comprehensive data on characteristics of dissemination are lacking. This study depicts the exact incidence and patterns of dissemination by analyzing data from a large-scale dataset of SCA. METHODS: The authors included 94 patients with SCA based on the 2021 WHO classification from 2011 to 2022, retrospectively collected their clinical and pathological characteristics, and analyzed factors influencing SCA dissemination. RESULTS: CNS dissemination, encompassing leptomeningeal spreading and/or subarachnoid seeding, was evaluated in 94 patients with and without H3 K27 alterations, with an overall dissemination rate reaching 85.0% at 5-year follow-up. Patients with altered H3 K27 had a significantly higher 5-year CNS dissemination rate than patients with H3 K27 wildtype status (95.2% vs 68.0%, p = 0.002). The median dissemination-free survival in H3 K27-altered patients was 14.37 (95% CI 2.84-25.89) months, significantly shorter than those with H3 K27 wildtype (statistics not calculated; p < 0.001). Based on univariate Cox regression analysis, H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments) were identified as potential factors associated with CNS dissemination in SCAs. Multivariate Cox regression analysis revealed that H3 K27M alteration appeared to be a risk factor for this phenomenon (HR 2.089, 95% CI 0.940-4.642, p = 0.070). Following dissemination, H3 K27-altered patients had a median postdissemination survival of 8.83 (95% CI 7.13-10.54) months, which was significantly shorter than the 13.40 (95% CI 3.98-34.26) months in those with H3 K27 wildtype (p = 0.008). CONCLUSIONS: Factors indicative of higher SCA malignancy, such as H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments), were similarly suggestive of higher rates of dissemination. The occurrence of dissemination is closely associated with the outcome events in patients with SCA.

Schisandrin C prevents Regorafenib-Induced cardiotoxicity by recovering EPHA2 expression in cardiomyocytes.

Regorafenib, an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor tyrosine kinases, has been approved for the treatment of metastatic colorectal cancer, gastrointestinal stromal tumors and hepatocellular carcinoma by the US Food and Drug Administration and European Medicines Agency. However, regorafenib-induced cardiotoxicity increases the risk of mortality. Despite reports that regorafenib can cause mitochondrial dysfunction in cardiomyocytes, the molecular mechanism of regorafenib-induced cardiotoxicity is much less known and there is an urgent need for intervention strategies. Here, we treated mice with vehicle or 200 mg/kg regorafenib daily for 42 days by gavage or treated cardiomyocyte lines with 8, 16 or 32 µM regorafenib, and we found that regorafenib could cause apoptosis, mitochondrial injury and DNA damage in cardiomyocytes. Mechanistically, regorafenib can reduce the expression of EPHA2, which inhibits AKT signaling, leading to cardiomyocyte apoptosis and cardiotoxicity. In addition, we showed that recovering EPHA2 expression via plasmid-induced overexpression of EPHA2 or schisandrin C, a natural product, could prevent regorafenib-induced cardiotoxicity. These findings demonstrated that regorafenib causes cardiomyocyte apoptosis and cardiac injury by reducing the expression of EPHA2 and schisandrin C could prevent regorafenib-induced cardiotoxicity by recovering EPHA2 expression, which provides a potential management strategy for regorafenib-induced cardiotoxicity and will benefit the safe application of regorafenib in clinic.

Therapeutic applications of RNA nanostructures.

RNA-based therapeutics have gained wide public interest in recent years. RNA is a versatile molecule that exists in many forms including mRNA, siRNA, miRNA, ribozymes, and other non-coding RNAs and is primarily applied for gene therapy. RNA is also used as a modular building block to construct RNA nanostructures. The programmable nature of RNA nanostructures enables the generation of simple, modulable, and multi-functional RNA-based therapeutics. Although the therapeutic application of RNA may be limited due to its structural instability, advances in RNA nanotechnology have improved the stability of RNA nanostructures for greater application. Various strategies have been developed to enhance the stability of RNA nanostructures enabling their application in vivo. In this review, we examine the therapeutic applications of RNA nanostructures. Non-immunogenic RNA nanostructures can be rationally designed with functional RNA molecules to modulate gene expression for gene therapy. On the other hand, nucleic acids can be sensed by cellular receptors to elicit an innate immune response, for which certain DNA and RNA motifs can function as adjuvants. Taking advantage of this adjuvant potential, RNA nanostructures can be used for immunotherapy and be designed for cancer vaccines. Thus, we examine the therapeutic application of immunogenic RNA nanostructures for cancer immunotherapy. RNA nanostructures represent promising platforms to design new nanodrugs, gene therapeutics, immunotherapeutic adjuvants, and cancer vaccines. Ongoing research in the field of RNA nanotechnology will continue to empower the development of RNA nanostructure-based therapeutics with high efficacy and limited toxicity.

Effect of henagliflozin on left ventricular mass index in dialysis patients with HFpEF (HELD-HF): protocol for a multicentre, randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a prevalent comorbidity among patients with end-stage kidney disease. Although sodium-glucose cotransporter 2 inhibitors are validated in treating heart failure and ameliorating left ventricular hypertrophy among non-dialysis patients, the effects on dialysis patients are unknown. We previously investigated the pharmacokinetics of henagliflozin in patients undergoing haemodialysis (HD) or peritoneal dialysis (PD) and clarified its safety. METHODS AND ANALYSIS: This multicentre, randomised, double-blind, placebo-controlled trial is being conducted at three hospitals in Shanghai, China. A target of 108 HD or PD patients with HFpEF are randomly allocated to treatment group (henagliflozin 5 mg/day in addition to standard therapy) or control group (placebo with standard therapy) at a ratio of 1:1. All subjects will be followed up for 24 weeks. The primary outcome is change in echocardiography-measured left ventricular mass index. The secondary interests include changes in left atrial volume index, E/e', e' and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Intergroup comparisons of change in echocardiography-related outcomes from baseline to 24 weeks are based on a linear regression model adjusted for baseline values (analysis of covariance), and repeated measure analysis of variance with Bonferroni adjustment is employed for comparison of change in NT-proBNP. Subgroup analyses of the primary and secondary outcomes are conducted to determine whether the effect of henagliflozin varies according to dialysis modality. The χ2 method is used to compare the occurrence of adverse events and severe adverse events. ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University (LY2023-127-B). All participants provide written informed consent before screening. The results of the trial will be disclosed completely in international peer-reviewed journals. Both positive and negative results will be reported. TRIAL REGISTRATION NUMBER: ChiCTR2300073169.

Machine learning model predicts airway stenosis requiring clinical intervention in patients after lung transplantation: a retrospective case-controlled study.

BACKGROUND: Patients with airway stenosis (AS) are associated with considerable morbidity and mortality after lung transplantation (LTx). This study aims to develop and validate machine learning (ML) models to predict AS requiring clinical intervention in patients after LTx. METHODS: Patients who underwent LTx between January 2017 and December 2019 were reviewed. The conventional logistic regression (LR) model was fitted by the independent risk factors which were determined by multivariate LR. The optimal ML model was determined based on 7 feature selection methods and 8 ML algorithms. Model performance was assessed by the area under the curve (AUC) and brier score, which were internally validated by the bootstrap method. RESULTS: A total of 381 LTx patients were included, and 40 (10.5%) patients developed AS. Multivariate analysis indicated that male, pulmonary arterial hypertension, and postoperative 6-min walking test were significantly associated with AS (all P < 0.001). The conventional LR model showed performance with an AUC of 0.689 and brier score of 0.091. In total, 56 ML models were developed and the optimal ML model was the model fitted using a random forest algorithm with a determination coefficient feature selection method. The optimal model exhibited the highest AUC and brier score values of 0.760 (95% confidence interval [CI], 0.666-0.864) and 0.085 (95% CI, 0.058-0.117) among all ML models, which was superior to the conventional LR model. CONCLUSIONS: The optimal ML model, which was developed by clinical characteristics, allows for the satisfactory prediction of AS in patients after LTx.

Leveraging Pretrained Transformers for Efficient Segmentation and Lesion Detection in Cone-Beam Computed Tomography Scans.

INTRODUCTION: Cone-beam computed tomography (CBCT) is widely used to detect jaw lesions, although CBCT interpretation is time-consuming and challenging. Artificial intelligence for CBCT segmentation may improve lesion detection accuracy. However, consistent automated lesion detection remains difficult, especially with limited training data. This study aimed to assess the applicability of pretrained transformer-based architectures for semantic segmentation of CBCT volumes when applied to periapical lesion detection. METHODS: CBCT volumes (n = 138) were collected and annotated by expert clinicians using 5 labels - "lesion," "restorative material," "bone," "tooth structure," and "background." U-Net (convolutional neural network-based) and Swin-UNETR (transformer-based) models, pretrained (Swin-UNETR-PRETRAIN), and from scratch (Swin-UNETR-SCRATCH), were trained with subsets of the annotated CBCTs. These models were then evaluated for semantic segmentation performance using the Sørensen-Dice coefficient (DICE), lesion detection performance using sensitivity and specificity, and training sample size requirements by comparing models trained with 20, 40, 60, or 103 samples. RESULTS: Trained with 103 samples, Swin-UNETR-PRETRAIN achieved a DICE of 0.8512 for "lesion," 0.8282 for "restorative materials," 0.9178 for "bone," 0.9029 for "tooth structure," and 0.9901 for "background." "Lesion" DICE was statistically similar between Swin-UNETR-PRETRAIN trained with 103 and 60 images (P > .05), with the latter achieving 1.00 sensitivity and 0.94 specificity in lesion detection. With small training sets, Swin-UNETR-PRETRAIN outperformed Swin-UNETR-SCRATCH in DICE over all labels (P < .001 [n = 20], P < .001 [n = 40]), and U-Net in lesion detection specificity (P = .006 [n = 20], P = .031 [n = 40]). CONCLUSIONS: Transformer-based Swin-UNETR architectures allowed for excellent semantic segmentation and periapical lesion detection. Pretrained, it may provide an alternative with smaller training datasets compared to classic U-Net architectures.

Unraveling the Roles of Ionic Size and Hydrogen Bonding in Electric Field-Driven Ion Emission from Hydroxylamine Nitrate-Based Ionic Liquids.

Ionic size and hydrogen bonding (HB) may play significant roles in controlling ion emission from HAN (hydroxylamine nitrate)-based ionic liquids (ILs) but have received little attention. In this paper, the ion emission behavior and mechanism in an external electric field are meticulously investigated using the molecular dynamics (MD) method and density functional theory. We find that the higher the proportion of ionic HAN in the blend of ILs, the longer the delay time of the ion start-up emission. In the positive mode, cations can evaporate directly from the surface of the studied ILs and manifest exclusively as the [EMIM]+ monomers within the simulation time scale, whereas in the negative mode, a variety of complicated anion clusters are emitted. As a result, the average charge-to-mass ratio of the positively charged species remarkably exceeds that of the negatively charged species. This large difference is attributed to the relatively larger size of the [EMIM]+ ion and the absence of substantial HB interactions between the [EMIM]+ ion and any other monomer, leading to diminished binding energies. Conversely, the strong HB interactions, primarily constituted by N-H--O and O-H--O hydrogen bonds, are clearly found in the [EtSO4]--based and HAN-based clusters. In addition, the [NO3]- and [EtSO4]- ions tend to combine with the small-sized [HA]+ ions to form large anion clusters rather than with the [EMIM]+ ions. The energy decomposition results further elucidate that the orbital interaction plays a pivotal role in the [NO3]- and [EtSO4]--based clusters. The findings clearly elucidate the experimental phenomena observed in previous studies and have implications for the formulation of multimode IL propellants.

The relationship between perceived social support, coping style, and the quality of life and psychological state of lung cancer patients.

BACKGROUND: Lung cancer has always a cancer that threatens human health. Quality of life also has been an important research topic. psychological state in patients can influence their quality of life, and perceived social support and coping styles are relevant facilitators of Quality of life, but this specific relationship has not been adequately studied. The purpose of this study is focus on discussing the correlation of these four and understanding their potential mediating pathways. MATERIALS AND METHODS: This is a cross-sectional study. A total of 300 Lung Cancer patients from a cancer hospital in Suzhou were surveyed. The Data was collected using the scales. The collected data was analyzed using SPSS and AMOS software. RESULTS: The study revealed a significant serial mediation model between perceived social support and coping style: Psychological state regulates patients' coping styles by influencing their perceived social support which ultimately has comprehensive impacts on their quality of life. CONCLUSION: Based on the empirical results discussed, this study proposes the following suggestion: Provide good online support to form a related social media intervention matrix. meanwhile, expand the patients' social network offline, provide channels for patients to express their troubles outwardly, and regularly assess the patients' psychological status to improve their level of psychosocial adaptation. This will in turn enhance their negative coping strategies towards the disease and strengthen their ability to buffer against it, ultimately promoting a better quality of life for the patients.

Diagnostic efficacy of the contrast-enhanced ultrasound thyroid imaging reporting and data system classification for benign and malignant thyroid nodules.

Background: The contrasted-enhanced ultrasound thyroid imaging reporting and data system (CEUS TI-RADS) is the first international risk stratification system for thyroid nodules based on conventional ultrasound (US) and CEUS. This study aimed to evaluate the diagnostic efficacy of CEUS TI-RADS for benign and malignant thyroid nodules and to assess the related interobserver agreement. Methods: The study recruited 433 patients who underwent thyroid US and CEUS between January 2019 and June 2023 at the Affiliated Hospital of Guangdong Medical University. A retrospective analysis of 467 thyroid nodules confirmed by fine-needle aspiration (FNA) and/or surgery was performed. Further, a CEUS TI-RADS classification was assigned to each thyroid nodule based on the CEUS TI-RADS scoring criteria for the US and CEUS features of the nodule. The nodules were grouped based on their sizes as follows: size ≤1 cm, group A; size >1 and ≤4 cm, group B; and size >4 cm, group C. Multivariate logistic regression was used to analyze independent risk factors for malignant thyroid nodules. Pathological assessment was the reference standard for establishing the sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) of CEUS TI-RADS in diagnosing malignant thyroid nodules. The area under the curve (AUC) in the receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficacy of the scoring system in predicting malignancy in three groups of nodules. The intragroup correlation coefficient (ICC) was adopted to assess the interobserver agreement of the CEUS TI-RADS score. Results: Out of the 467 thyroid nodules, 262 were malignant and 205 were benign. Logistic regression analysis revealed that the independent risk factors for malignant thyroid nodules included punctate echogenic foci (P<0.001), taller-than-wide shape (P=0.015), extrathyroidal invasion (P=0.020), irregular margins/lobulation (P=0.036), hypoechoicity on US (P=0.038), and hypoenhancement on CEUS (P<0.001). The AUC for the CEUS TI-RADS in diagnosing malignant thyroid nodules was 0.898 for all nodules, 0.795 for group A, 0.949 for group B, and 0.801 for group C, with the optimal cutoff values of the CEUS TI-RADS being 5 points, 6 points, 5 points, and 5 points, respectively. Among these groups of nodules, group B had the highest AUC, with the SEN, SPE, ACC, PPV, and NPV for diagnosing malignant nodules being 95.9%, 88.1%, 92.8%, 92.6%, and 93.2%, respectively. The ICC of the CEUS TI-RADS classification between senior and junior physicians was 0.862 (P<0.001). Conclusions: In summary, CEUS TI-RADS demonstrated significant efficacy in distinguishing thyroid nodules. Nonetheless, there were variations in its capacity to detect malignant nodules across diverse sizes, and it demonstrate optimal performance in 1- to 4-cm nodules. These findings may serve as important insights for clinical diagnoses.

3D DNA origami pincers that multitask on giant unilamellar vesicles.

Proteins self-assemble to function in living cells. They may execute essential tasks in the form of monomers, complexes, or supramolecular cages via oligomerization, achieving a sophisticated balance between structural topology and functional dynamics. The modularity and programmability make DNA origami unique in mimicking these key features. Here, we demonstrate three-dimensional reconfigurable DNA origami pincers (DOPs) that multitask on giant unilamellar vesicles (GUVs). By programmably adjusting their pinching angle, the DOPs can dynamically control the degree of GUV remodeling. When oligomerized on the GUV to form origami cages, the DOP units interact with one another and undergo reorganization, resulting in the capture, compartmentalization, and detachment of lipid fragments. This oligomerization process is accompanied with membrane disruptions, enabling the passage of cargo across the membrane. We envisage that interfacing synthetic cells with engineered, multifunctional DNA nanostructures may help to confer customized cellular properties, unleashing the potential of both fields.

Red blood cell distribution width to albumin ratio associates with prevalence and long-term diabetes mellitus prognosis: an overview of NHANES 1999-2020 data.

Background: Erythrocyte dysfunction is a characteristic of diabetes mellitus (DM). However, erythrocyte-associated biomarkers do not adequately explain the high prevalence of DM. Here, we describe red blood cell distribution width to albumin ratio (RAR) as a novel inflammatory biomarker for evaluating an association with DM prevalence and prognosis of all-cause mortality. Methods: Data analyzed in this study were extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2020. A total of 40,558 participants (non-DM and DM) were enrolled in the study; RAR quartiles were calibrated at Q1 [2.02,2.82] mL/g, Q2 (2.82,3.05] mL/g, Q3 (3.05,3.38] mL/g, and Q4 (3.38,12.08] mL/g. A total of 8,482 DM patients were followed (for a median of 84 months), of whom 2,411 died and 6,071 survived. The prevalence and prognosis associated with RAR and DM were analyzed; age and sex were stratified to analyze the prevalence of RAR in DM and the sensitivity of long-term prognosis. Results: Among non-DM (n=30,404) and DM (n=10,154) volunteers, DM prevalence in RAR quartiles was 8.23%, 15.20%, 23.92%, and 36.39%. The multivariable odds ratio (OR) was significant for RAR regarding DM, at 1.68 (95% CI 1.42, 1.98). Considering Q1 as a foundation, the Q4 OR was 2.57 (95% CI 2.11, 3.13). The percentages of DM morbidity varied across RAR quartiles for dead (n=2,411) and surviving (n=6,071) DM patients. Specifically, RAR quartile mortality ratios were 20.31%, 24.24%, 22.65%, and 29.99% (P<0.0001). The multivariable hazard ratio (HR) for RAR was 1.80 (95% CI 1.57, 2.05). Considering Q1 as a foundation, the Q4 HR was 2.59 (95% CI 2.18, 3.09) after adjusting for confounding factors. Sensitivity analysis revealed the HR of male DM patients to be 2.27 (95% CI 1.95, 2.64), higher than females 1.56 (95% CI 1.31, 1.85). DM patients who were 60 years of age or younger had a higher HR of 2.08 (95% CI1.61, 2.70) as compared to those older than 60 years, who had an HR of 1.69 (95% CI 1.47, 1.94). The HR of RAR in DM patients was optimized by a restricted cubic spline (RCS) model; 3.22 was determined to be the inflection point of an inverse L-curve. DM patients with a RAR >3.22 mL/g suffered shorter survival and higher mortality as compared to those with RAR ≤3.22 mL/g. OR and HR RAR values were much higher than those of regular red blood cell distribution width. Conclusions: The predictive value of RAR is more accurate than that of RDW for projecting DM prevalence, while RAR, a DM risk factor, has long-term prognostic power for the condition. Survival time was found to be reduced as RAR increased for those aged ≤60 years among female DM patients.