Dynamic Interface-Assisted Rapid Self-Assembly of DNA Origami-Framed Anisotropic Nanoparticles.

The ordered arrangement of nanoparticles can generate unique physicochemical properties, rendering it a pivotal direction in the field of nanotechnology. DNA-based chemical encoding has emerged as an unparalleled strategy for orchestrating precise and controlled nanoparticle assemblies. Nonetheless, it is often time-consuming and has limited assembly efficiency. In this study, we developed a strategy for the rapid and ordered assembly of DNA origami-framed nanoparticles assisted by dynamic interfaces. By assembling Au nanoparticles (AuNPs) onto DNA origami with different sticky ends in various directions, we endowed them with anisotropic specific affinities. After assembling DNA origami-framed AuNPs onto supported lipid bilayers with freely diffusing single-stranded DNA via DNA hybridization, we found that DNA origami-framed AuNPs could form larger ordered assemblies than those in 3D solution within equivalent time frames. Furthermore, we also achieved rapid and ordered assembly of liposome nanoparticles by employing the aforementioned strategy. Our work provides a novel avenue for efficient and rapid assembly of nanoparticles across two-dimensional interfaces, which is expected to promote the application of ordered nanoparticle assemblies in sensor and biomimetic system construction.

Tumor-associated antigen-specific cell imaging based on upconversion luminescence and nucleic acid rolling circle amplification.

Tumor-associated antigen (TAA)-based diagnosis has gained prominence for early tumor screening, treatment monitoring, prognostic assessment, and minimal residual disease detection. However, limitations such as low sensitivity and difficulty in extracting non-specific binding membrane proteins still exist in traditional detection methods. Upconversion luminescence (UCL) exhibits unique physical and chemical properties under wavelength near-infrared light excitation. Rolling circle amplification (RCA) is an efficient DNA amplification technique with amplification factors as high as 105. Therefore, the above two excellent techniques can be employed for highly accurate imaging analysis of tumor cells. Herein, we developed a novel nanoplatform for TAA-specific cell imaging based on UCL and RCA technology. An aptamer-primer complex selectively binds to Mucin 1 (MUC1), one of TAA on cell surface, to trigger RCA reaction, generating a large number of repetitive sequences. These sequences provide lots of binding sites for complementary signal probes, producing UCL from lanthanide-doped upconversion nanoparticles (UCNPs) after releasing quencher group. The experimental results demonstrate the specific attachment of upconversion nanomaterials to cancer cells which express a high level of MUC1, indicating the potential of UCNPs and RCA in tumor imaging.

Urine-derived exosomes and their role in modulating uroepithelial cells to prevent hypospadias.

PURPOSE: Urethral hypospadias, a common congenital malformation in males, is closely linked with disruptions in uroepithelial cell (UEC) processes. Evidence exists reporting that urine-derived exosomes (Urine-Exos) enhance UEC proliferation and regeneration, suggesting a potential role in preventing hypospadias. However, the specific influence of Urine-Exos on urethral hypospadias and the molecular mechanisms involved are not fully understood. This study focuses on investigating the capability of Urine-Exos to mitigate urethral hypospadias and aims to uncover the underlying molecular mechanisms. METHODS: Bioinformatics analysis was performed to identify key gene targets in Urine-Exos potentially involved in hypospadias. Subsequent in vitro and in vivo experiments were conducted to validate the regulatory effects of Urine-Exos on hypospadias. RESULTS: Bioinformatics screening revealed syndecan-1 (SDC1) as a potential pivotal gene for the prevention of hypospadias. In vitro experiments demonstrated that Urine-Exos enhanced the proliferation and migration of UECs by transferring SDC1 and inhibiting cell apoptosis. Notably, Urine-Exos upregulated ß-catenin expression through SDC1 transfer, further promoting UEC proliferation and migration. These findings were confirmed in a congenital hypospadias rat model induced by di(2-ethylhexyl) phthalate (DEHP). CONCLUSION: This study reveals the therapeutic potential of Urine-Exos in hypospadias, mediated by the SDC1/ß-catenin axis. Urine-Exos promote UEC proliferation and migration, thereby inhibiting the progression of hypospadias. These findings offer new insights and potential therapeutic targets for the management of congenital malformations.

Pluripotency state transition of embryonic stem cells requires the turnover of histone chaperone FACT on chromatin.

The differentiation of embryonic stem cells (ESCs) begins with the transition from the naive to the primed state. The formative state was recently established as a critical intermediate between the two states. Here, we demonstrate the role of the histone chaperone FACT in regulating the naive-to-formative transition. We found that the Q265K mutation in the FACT subunit SSRP1 increased the binding of FACT to histone H3-H4, impaired nucleosome disassembly in vitro, and reduced the turnover of FACT on chromatin in vivo. Strikingly, mouse ESCs harboring this mutation showed elevated naive-to-formative transition. Mechanistically, the SSRP1-Q265K mutation enriched FACT at the enhancers of formative-specific genes to increase targeted gene expression. Together, these findings suggest that the turnover of FACT on chromatin is crucial for regulating the enhancers of formative-specific genes, thereby mediating the naive-to-formative transition. This study highlights the significance of FACT in fine-tuning cell fate transition during early development.

Inhibitory effects of catalpol on DNCB-induced atopic dermatitis and IgE-mediated mast cells reaction.

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation. Catalpol is an iridoids, possessing anti-inflammatory, antioxidant, and neuroprotective activities. It can be added to food as a dietary supplement. To evaluate the effects and mechanisms of catalpol on AD, both in vitro and in vivo studies were conducted. It was found that catalpol downregulated the phosphorylation of Lyn and Syk to inhibit various downstream pathways, including intracellular Ca2+ elevation, cytokines generation, and histamine release, which ultimately controlled mast cell (MCs) degranulation. The results showed that catalpol alleviated AD-like skin lesions and MC infiltration via regulation of pro-Th2 and Th2 cytokines in vivo. Furthermore, this compound reduced the levels of IgE in AD mice and improved allergic reactions in PCA mice. The results provided that catalpol was potentially developed as a dietary supplement to improve AD and other atopic diseases.

Metabolic Glycoengineering-Programmed Nondestructive Capture of Circulating Tumor Cells.

Circulating tumor cells (CTCs) are the "seeds" for malignant tumor metastasis, and they serve as an ideal target for minimally invasive tumor diagnosis. Abnormal glycolysis in tumor cells, characterized by glycometabolism disorder, has been reported as a universal phenomenon observed in various types of tumors. This provides a potential powerful tool for universal CTC capture. However, to the best of our knowledge, no metabolic glycoengineering-based CTC capture strategies have been reported. Here, we proposed a nondestructive CTC capture method based on metabolic glycoengineering and a nanotechnology-based proximity effect, allowing for highly specific, sensitive, and universal CTC capture. To achieve this goal, cells are first labeled with DNA tags through metabolic glycoengineering and then captured through a DNA tetrahedra-functionalized dual-tentacle magnetic nanodevice. Due to the difference in metabolic performance, only tumor cells are labeled with more densely packed DNA tags and captured through enhanced intermolecular interaction mediated by the proximity effect. In summary, we have constructed a versatile platform for nondestructive CTC capture, offering a novel perspective for the application of CTC liquid biopsy in tumor diagnosis and treatment.

Gold-Catalyzed C-O Cross-Coupling Reactions of Aryl Iodides with Silver Carboxylates.

We have developed a C-O cross-coupling reaction of (hetero)aryl iodides with silver carboxylates via a AuI/AuIII catalytic cycle. The transformation featured exclusive chemoselectivity and moisture/air insensitivity. Aromatic and aliphatic (including primary, secondary, and tertiary) silver carboxylates are all suitable substrates. Moreover, this protocol worked well intermolecularly and intramolecularly. Most importantly, good yields were obtained regardless of the substrates' electronic effect and steric hindrance.

Establishment of Digital PCR Method and Reference Material for Adenoviruses 40 and 41.

Coinfection with human adenovirus (HAdV) and SARS-CoV-2 has been associated with acute hepatitis in children with unknown etiology. Similar cases have been reported in many countries, and HAdV 40 and HAdV 41 have been identified. The quantification method is established based on digital PCR (dPCR) for HAdV 40/41, which is more convenient for low-concentration virus detection. The limit of detections of HAdV 40/41 dPCR were 4 and 5 copies/µL. Pseudovirus reference material (RM) that contains the highly conserved HEXON gene was developed and quantified with the dPCR method. The assigned values with expanded uncertainty were (1.43 ± 0.35) × 103 copies/µL for HAdV 40 RM and (1.21 ± 0.28) × 103 copies/µL for HAdV 41 RM. The values could be reproduced on multiple platforms. The dPCR method and pseudovirus RMs contribute to the improved accuracy of HAdV 40/41 detection, which is crucial for clinical diagnosis.

Comprehensive analysis of the RSK gene family in acute myeloid leukemia determines a prognostic signature for the prediction of clinical prognosis and treatment responses.

OBJECTIVE: The prognosis of acute myeloid leukemia (AML) remains poor although the basic and translational research has been highly productive in understanding the genetics and pathopoiesis of AML and a plethora of targeted therapies have been developed. Consequently, it is crucial to deepen the knowledge of molecular pathogenesis underlying AML for the advancement of new treatment options. METHOD: A RSK gene family-related signature was constructed to investigate whether RSK gene family members were useful in predicting the prognosis of AML patients. The relationship between the RSK gene family-related signature and the infiltration of immune cells was further assessed using the CIBERSORT algorithm. The 'oncoPredict' package was used to analyze relationships between the RSK gene family-related signature and the sensitivity to drugs or small molecules. RESULTS: Patients were classified into two groups using the RSK gene family-related signature following the median risk score. Overall survival (OS) was significantly longer in patients with low-risk scores than that in patients with high-risk scores as showed by both training and validation datasets. Moreover, the signature was helpful in predicting 1-year, 3-year, and 5-year OS in training and validation datasets. In addition, it was identified that low-risk patients exhibited greater sensitivity to 20 drugs or small molecules and that high-risk patients had higher sensitivity to 38 drugs or small molecules. CONCLUSION: RSK gene family members, particularly RPS6KA1 and RPS6KA4, may help to predict prognosis for AML patients. Furthermore, RPS6KA1 may serve as a novel drug target for AML.

A portable and partitioned DNA hydrogel chip for multitarget detection.

A DNA hydrogel, owing to its dual properties of liquid and solid, is considered to be an ideal material for constructing biosensors that can integrate the advantages of both wet chemistry and dry chemistry. Nevertheless, it has struggled to cope with the demands of high-throughput analysis. A partitioned and chip-based DNA hydrogel is a potential avenue to achieve this, but currently remains a formidable challenge. Here, we developed a portable and partitioned DNA hydrogel chip that can be used for multitarget detection. The partitioned and surface-immobilized DNA hydrogel chip was formed by inter-crosslinking amplification by incorporating target-recognizing fluorescent aptamer hairpins into multiple rolling circle amplification products, which can achieve portable and simultaneous detection of multiple targets. This approach expands the application of semi-dry chemistry strategies, which can realize high throughput and point of care testing (POCT) of different targets, improving the development of hydrogel-based bioanalysis and providing new potential solutions for biomedical detection.

Synthetic biology-based bioreactor and its application in biochemical analysis.

In the past few years, synthetic biologists have established some biological elements and bioreactors composed of nucleotides under the guidance of engineering methods. Following the concept of engineering, the common bioreactor components in recent years are introduced and compared. At present, biosensors based on synthetic biology have been applied to water pollution monitoring, disease diagnosis, epidemiological monitoring, biochemical analysis and other detection fields. In this paper, the biosensor components based on synthetic bioreactors and reporters are reviewed. In addition, the applications of biosensors based on cell system and cell-free system in the detection of heavy metal ions, nucleic acid, antibiotics and other substances are presented. Finally, the bottlenecks faced by biosensors and the direction of optimization are also discussed.

The Role of Nomogram Based on the Combination of Ultrasound Parameters and Clinical Indicators in the Degree of Pathological Remission of Breast Cancer.

Background: The mortality rate of breast cancer (BC) ranks first among female tumors worldwide and presents a trend of younger age, which poses a great threat to women's health and life. Neoadjuvant chemotherapy (NAC) for breast cancer is defined as the first step of treatment for breast cancer patients without distant metastasis before planned surgical treatment or local treatment with surgery and radiotherapy. According to the current NCCN guidelines, patients with different molecular types of BC should receive neoadjuvant chemotherapy (NAC), which can not only achieve tumor downstaging, increase the chance of surgery, and improve the breast-conserving rate. In addition, it can identify new genetic pathways and drugs related to cancer, improve patient survival rate, and make new progress in breast cancer management. Objective: To explore the role of the nomogram established by the combination of ultrasound parameters and clinical indicators in the degree of pathological remission of breast cancer. Methods: A total of 147 breast cancer patients who received neoadjuvant chemotherapy and elective surgery in the Department of Ultrasound, Nantong Cancer Hospital, from May 2014 to August 2021 were retrospectively included. Postoperative pathological remission was divided into two groups according to Miller-Payne classification: no significant remission group (NMHR group, n = 93) and significant remission group (MHR group, n = 54). Clinical characteristics of patients were recorded and collected. The multivariate logistic regression model was used to screen the information features related to the MHR group, and then, a nomogram model was constructed; ROC curve area, consistency index (C-index, CI), calibration curve, and H-L test were used to evaluate the model. And the decision curve is used to compare the net income of the single model and composite model. Results: Among 147 breast cancer patients, 54 (36.7%) had pathological remission. Multivariate logistic regression showed that ER, reduction/disappearance of strong echo halo, Adler classification after NAC, PR + CR, and morphological changes were independent risk factors for pathological remission (P < 0.05). Based on these factors, the nomogram was constructed and verified. The area under the curve (AUC) and CI were 0.966, the sensitivity and specificity were 96.15% and 92.31%, and the positive predictive value (PPV) and negative predictive value (NPV) were 87.72% and 97.15%, respectively. The mean absolute error of the agreement between the predicted value and the real value is 0.026, and the predicted risk is close to the actual risk. In the range of HRT of about 0.0∼0.9, the net benefit of the composite evaluation model is higher than that of the single model. H-L test results showed that χ 2 = 8.430, P=0.393 > 0.05. Conclusion: The nomogram model established by combining the changes of ultrasound parameters and clinical indicators is a practical and convenient prediction model, which has a certain value in predicting the degree of pathological remission after neoadjuvant chemotherapy.

Development of highly accurate digital PCR method and reference material for monkeypox virus detection.

Human monkeypox has attracted attention recently. Monkeypox virus (MPXV) keeps evolving as it spreading around the world rapidly, which may threaten the health of more and more people. Here, we have developed a high order reference method based on digital PCR (dPCR) for MPXV detection, of which the limits of quantification (LoQ) and detection (LoD) are 38 and 6 copies/reaction, respectively. Pseudovirus reference materials (RM) containing the conserved F3L gene has been developed, and the homogeneity assessment showed that the RM was homogeneous. The reference value with its expanded uncertainty determined by the established dPCR is (2.74 ± 0.46) × 103 copies/µL. Six different MPXV test kits were accessed by the RM. Four out of six test kits cannot reach their claimed LoDs. The poor analytical sensitivity might cause false-negative results, which lead to incorrect diagnosis and treatment. The establishment of a high order reference method of dPCR and pseudovirus RM is very useful for improving the accuracy and reliability of MPXV detection.

Recent advances in tumor biomarker detection by lanthanide upconversion nanoparticles.

Early tumor diagnosis could reliably predict the behavior of tumors and significantly reduce their mortality. Due to the response to early cancerous changes at the molecular or cellular level, tumor biomarkers, including small molecules, proteins, nucleic acids, exosomes, and circulating tumor cells, have been employed as powerful tools for early cancer diagnosis. Therefore, exploring new approaches to detect tumor biomarkers has attracted a great deal of research interest. Lanthanide upconversion nanoparticles (UCNPs) provide numerous opportunities for bioanalytical applications. When excited by low-energy near-infrared light, UCNPs exhibit several unique properties, such as large anti-Stoke shifts, sharp emission lines, long luminescence lifetimes, resistance to photobleaching, and the absence of autofluorescence. Based on these excellent properties, UCNPs have demonstrated great sensitivity and selectivity in detecting tumor biomarkers. In this review, an overview of recent advances in tumor biomarker detection using UCNPs has been presented. The key aspects of this review include detection mechanisms, applications in vitro and in vivo, challenges, and perspectives of UCNP-based tumor biomarker detection.

Microfluidics for diagnosis and treatment of cardiovascular disease.

Cardiovascular disease (CVD), a type of circulatory system disease related to the lesions of the cardiovascular system, has become one of the main diseases that endanger human health. Currently, the clinical diagnosis of most CVDs relies on a combination of imaging technology and blood biochemical test. However, the existing technologies for diagnosis of CVDs still have limitations in terms of specificity, detection range, and cost. In order to break through the current bottleneck, microfluidic with the advantages of low cost, simple instruments and easy integration, has been developed to play an important role in the early prevention, diagnosis and treatment of CVDs. Here, we have reviewed the recent various applications of microfluidic in the clinical diagnosis and treatment of CVDs, including microfluidic devices for detecting CVD markers, the cardiovascular models based on microfluidic, and the microfluidic used for CVDs drug screening and delivery. In addition, we have briefly looked forward to the prospects and challenges of microfluidics in diagnosis and treatment of CVDs.

CaCl2 mitigates chilling injury in loquat fruit via the CAMTA5-mediated transcriptional repression of membrane lipid degradation genes.

Loquat fruit is vulnerable to chilling injury (CI) under long-term low temperature storage. The application of calciumchloride (CaCl2) can alleviate CI in loquat fruit, however, the molecular mechanisms remain unclear. In this study, the loquat fruit were immersed in 1 % CaCl2 solution for 10 min and then stored at 1 ± 1 ℃ for 35 d. The results showed that CaCl2 treatment suppressed the increases in internal browning index, electrolyte leakage, and malonaldehyde content in loquat fruit under chilling stress. The internal browning index in CaCl2-treated loquat fruit was 33.34 % lower than that in the control at the end of storage. Meanwhile, CaCl2 treatment delayed the phospholipids degradation, and retained high level of unsaturated/saturated fatty acid ratio, which was 15.21 % higher than that in the control fruit at the end of storage. The CaCl2 treatment also decreased the enzymatic activities and gene expressions of phospholipase D (PLD), phospholipase C (PLC), and lipoxygenase (LOX) in loquat fruit during cold storage. Moreover, a calmodulin-binding transcription activator (CAMTA) transcription factor (TF), EjCAMTA5, was cloned from loquat fruit. The EjCAMTA5 expression was up-regulated by cold stress and CaCl2 treatment. Further investigation revealed that EjCAMTA5 directly bound to the promoters of EjPLC6-like and EjLOX5 to repress their transcription. Taken together, these findings implied that CaCl2 application could activate the EjCAMTA5-mediated transcriptional repression of EjPLC6-like and EjLOX5 genes, which contributed to delaying the degradation of membrane lipid and maintaining the integrity of cell membrane, thereby inhibiting the occurrence of browning in loquat fruit under chilling stress.

A peptide-DNA hybrid bio-nanomicelle and its application for detection of caspase-3 activity.

Bio-nanomicelles based on biomaterials such as nucleic acids, peptides, glycans, and lipids have developed rapidly in the field of bioanalysis. Although DNA and peptides have unique advantages, unfortunately, there are few bio-nanomicelles integrating DNA with peptides. Here, we designed a peptide-DNA hybrid bio-nanomicelle for the activity detection of caspase-3. The detection mechanism is based on caspase-3 specific recognition and cleavage of peptide substrates, which owns high sensitivity and selectivity. Under optimal conditions, the detection of caspase-3 activity can be achieved using our designed bio-nanomicelles and the detection limit is 0.72 nM. Furthermore, the proposed method was also successfully applied for the detection of caspase-3 in cell lysate samples after apoptosis-inducing.

Series of TM-OFs as a Platform for Efficient Catalysis and Multifunctional Luminescence Sensing.

Three novel porous transition-metal-organic frameworks (TM-OFs), formulated as [Co3(DCPN)2(µ2-OH2)4(H2O)4](DMF)2 (1), [Cd3(DCPN)2(µ2-OH2)4(H2O)4](DMF)2 (2), and [CdK(DCPN)(DMA)] (3), have been successfully prepared via solvothermal conditions based on a 5-(3',6'-dicarboxylic phenyl) nicotinic carboxylic acid (H3DCPN) ligand. 1 and 2 both have the same porous 3D network structure with the point symbol of {410·614·84}·{45·6}2 based on trinuclear ({Co3} or {Cd3}) clusters, indicating a one-dimensional porous channel, and possess excellent water and thermal stability; 3 also displays a porous 3D network structure with a 4-connected sra topology based on the heteronuclear metal cluster {CdK}. Complex 1 can be used to load Pd nanoparticles (Pd NPs) via a wetness impregnation strategy to obtain Pd@1. The reduction of nitrophenols (2-NP, 3-NP, 4-NP) by Pd@1 in aqueous solution shows outstanding conversion, excellent rate constants (k), and remarkable cycling stability due to the synergistic effect of complex 1 and Pd NPs. Luminescence sensing tests confirmed that 2 is a reliable multifunctional chemical sensor with high selectivity and sensitivity for low concentrations of Fe3+, Cr2O72-, CPFX, and NFX. Specifically, 2 shows a fluorescence enhancement behavior toward fluoroquinolone antibiotics (CPFX and NFX), which has not been reported previously in the literature. Moreover, the rational mechanism of fluorescence sensing was also systematically investigated by various detection means and theoretical calculations.

Characteristics of prefrontal activity during emotional and cognitive processing in patients with bipolar disorder: A multi-channel functional near-infrared spectroscopy study.

Bipolar disorder (BD) is a recurrent chronic mental disorder with a broad profile of functional deficits including disturbed emotional processing and cognitive impairments. The goal of the current study was to further explore the underlying neural mechanism of dysfunction in patients with BD from a comprehensive perspective of both cognition and emotion. Forty-six clinical patients with BD and forty-five healthy controls performed emotion induction task and verbal fluency task (VFT), with frontal activity measured by functional near-infrared spectroscopy (fNIRS). Our results show distinct hemodynamic activity in the prefrontal region during emotional and cognitive processing between patients with BD and healthy controls. Patients with BD exhibit valence-dependent prefrontal cortex (PFC) hemodynamic response to emotional stimuli, with bilateral frontal hypoactivity indicating decreased positive reactivity and left frontal hyperactivity indicating increased negative reactivity. On the other hand, patients with BD showed impaired performance with bilateral frontal hypoactivity during VFT. Taken together, frontal dysfunction of cognition and emotionality in patients with BD probed by fNIRS would be a potential biomarker in clinical assessment.

Effect of Fraxetin on Oxidative Damage Caused by Isoproterenol-Induced Myocardial Infarction in Rats.

At present, cardiovascular disorders are the most prominent factors for the high morbidity rate globally. The occurrence of myocardial infarction followed by myocardial ischemia is the important cause of high death rates. Various medical treatments are available, yet the mortality and morbidity rate is high. In the present investigation, the cardioprotective property of fraxetin (Fx) is evaluated in myocardial infarction-induced experimental rats. Fraxetin, a phytochemical known as coumarin isolated from Fraxinus rhynchophylla. Fraxetin has numerous pharmacological activities including antioxidant, apoptosis inhibitor, anti-inflammatory, and antimicrobial agent. The experimental mice were split into 4 groups each comprising six animals. Group I was considered the control group; 0.1% NaCl solution was given as dosage. Group II received only Fx; group III was treated with ISO. Group IV was treated with Fx followed by ISO to induce myocardial infarction. In ISO administrated rats, there were changes in the heart weight, activities of cardiac markers, transmembrane protein activity, antioxidant enzymes, pro-inflammatory proteins, lipid profile, and myocardial structures. Pre-treatment of fraxetin in group IV experimental rats resulted in decreased cardiac weight, diminished level of cardiac markers (cardiac troponin T (cTnT), creatine kinase, creatine kinase-MB, and cardiac troponin I (cTnI)), reduced level of oxidative stress biomarkers (LOOH and TBARS) in the plasma and cardiac tissue, amplified level of enzymes in antioxidant defense system (catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPx)) in the plasma and heart tissue, and elevated level of ATPase activities. The histopathological studies also revealed the potent activity of fraxetin in protecting the cardiac tissues from inflammation and damage. ISO-administrated experimental rats treated with fraxetin exhibit increased antioxidants activity and decreased free radicals. Our study revealed that the administration of fraxetin significantly reduced the extent of myocardial damage during myocardial infarction in rats caused by isoproterenol. Thus, the results prove the cardioprotective effect of fraxetin in MI-induced rats.