Clinical characteristics, genetic alterations, and prognosis of adult T-cell leukemia/lymphoma: an 11-year multicenter retrospective study in China.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis, and there is little data available from the Chinese population. This retrospective study included 115 patients diagnosed with ATLL who were treated across five hospitals in China from June 2011 to December 2022. The median age at diagnosis was 53 years. Several genes involved in T-cell receptor-induced nuclear factor κB (TCR-NF-κB) signaling were commonly mutated, including PLCG1, CIC, PRKCB, CARD11, and IRF4. Eighty-seven patients received chemotherapy. Of these, 13 received a hematopoietic stem cell transplant (HSCT) (allogeneic-HSCT, n=9; autologous-HSCT, n=4) after chemotherapy. Following initial multiagent chemotherapy using EPOCH/CHOEP and other regimens, the overall response rates were 80.6% (complete response [CR], 44.4%) and 42.8% (CR, 14.2%), respectively. The 4-year survival rates (median survival time in days) for EPOCH/CHOEP (n=43), HSCT (n=13), and CHOP-based regimens (n=31) were 12.7% (138), 30.8% (333), and 0% (66), respectively. Lymphadenopathy, EPOCH/CHOEP, and hematopoietic stem cell transplantation were independent prognostic protective factors in patients with aggressive ATLL. Chinese patients exhibit a higher incidence of aggressive-type ATLL, sharing similar genetic alterations with Japanese patients. Etoposide-based chemotherapy (EPOCH or CHOEP) remains the preferred choice for aggressive ATLL, and upfront allogeneic HSCT should be considered in all eligible patients.

Genetic prediction of causal association between serum bilirubin and hematologic malignancies: a two-sample Mendelian randomized and bioinformatics study.

Introduction: An increasing number of cohort studies have shown a correlation between serum bilirubin and tumors, but no definitive causal relationship has been established between serum bilirubin and hematological malignancies.Therefore, the aim of the present study was to assess the causal relationship of serum bilirubin, including total bilirubin (TBIL) and direct bilirubin (DBIL), with hematological malignancies, including leukemia, lymphoma, and myeloma. Methods: We used a genome-wide association study (GWAS) collection of TBIL, DBIL, and hematological malignancies data. Using two-sample Mendelian randomization(MR), we assessed the impact of TBIL and DBIL on hematological malignancies. For this study, the inverse variance weighting method (IVW) was the primary method of MR analysis. In the sensitivity analysis, the weighted median method, MR Egger regression, and MR-PRESSO test were used. To understand the mechanisms behind TBIL and DBIL, we used three different approaches based on screening single nucleotide polymorphisms (SNPs) and their associated genes, followed by bioinformatics analysis. Results: The IVW test results showed evidence of effects of TBIL (odds ratio [OR]: 4.47, 95% confidence interval [CI]: 1.58-12.62) and DBIL (OR: 3.31, 95% CI: 1.08-10.18) on the risk of acute myeloid leukemia (AML).The findings from bioinformatics indicated that TBIL could potentially undergo xenobiotic metabolism through cytochrome P450 and contribute to chemical carcinogenesis. Discussion: In this study, two-sample MR analysis revealed a causal relationship between TBIL, DBIL, and AML.

High expression of SLC27A2 predicts unfavorable prognosis and promotes inhibitory immune infiltration in acute lymphoblastic leukemia.

Solute carrier family 27 member 2 (SLC27A2) is involved in fatty acid metabolism in tumors and represents a prospective target for cancer therapy. However, the role and mechanism of action of SLC27A2 in acute lymphoblastic leukemia (ALL) remain unclear. In this study, we aimed to explore the intrinsic associations between SLC27A2 and ALL and evaluate the prognostic significance, biological functions, and correlation with immune infiltration. We used the transcriptome and clinical data from the TARGET dataset. Differentially expressed genes (DEGs) in the SLC27A2 low- and high-expression groups were analyzed for prognostic implications and functional enrichment. Furthermore, we analyzed the relationship between SLC27A2 gene expression and immune cell infiltration using the ESTIMATE method, which was evaluated using the TIGER platform. Finally, we knocked down SLC27A2 in the Jurkat ALL cell line and conducted cell proliferation, western blotting, flow cytometry, and CCK-8 assays to elucidate the biological function of SLC27A2 in ALL. Patients with ALL who have higher expression levels of SLC27A2 have poorer overall survival and event-free survival. According to gene set enrichment analysis, the DEGs were primarily enriched with immune system processes and the PI3K-Akt signaling pathway. There was an inverse relationship between SLC27A2 expression and immune cell invasion, suggesting involvement of the former in tumor immune evasion. In vitro experiments showed that knockdown of SLC27A2 inhibited cell proliferation and protein expression and altered the Akt pathway, with a reduced proportion of B cells. In conclusion, SLC27A2 plays a vital role in the development of ALL.

High-precision 3D printing of multi-branch vascular scaffold with plasticized PLCL thermoplastic elastomer.

Three-dimensional (3D) printing has emerged as a transformative technology for tissue engineering, enabling the production of structures that closely emulate the intricate architecture and mechanical properties of native biological tissues. However, the fabrication of complex microstructures with high accuracy using biocompatible, degradable thermoplastic elastomers poses significant technical obstacles. This is primarily due to the inherent soft-matter nature of such materials, which complicates real-time control of micro-squeezing, resulting in low fidelity or even failure. In this study, we employ Poly (L-lactide-co-ϵ-caprolactone) (PLCL) as a model material and introduce a novel framework for high-precision 3D printing based on the material plasticization process. This approach significantly enhances the dynamic responsiveness of the start-stop transition during printing, thereby reducing harmful errors by up to 93%. Leveraging this enhanced material, we have efficiently fabricated arrays of multi-branched vascular scaffolds that exhibit exceptional morphological fidelity and possess elastic moduli that faithfully approximate the physiological modulus spectrum of native blood vessels, ranging from 2.5 to 45 MPa. The methodology we propose for the compatibilization and modification of elastomeric materials addresses the challenge of real-time precision control, representing a significant advancement in the domain of melt polymer 3D printing. This innovation holds considerable promise for the creation of detailed multi-branch vascular scaffolds and other sophisticated organotypic structures critical to advancing tissue engineering and regenerative medicine.

In Situ Unveiling of the Resistive Switching Mechanism of Halide Perovskite-Based Memristors.

The organic-inorganic halide perovskite has become one of the most promising candidates for next-generation memory devices, i.e. memristors, with excellent performance and solution-processable preparation. Yet, the mechanism of resistive switching in perovskite-based memristors remains ambiguous due to a lack of in situ visualized characterization methods. Here, we directly observe the switching process of perovskite memristors with in situ photoluminescence (PL) imaging microscopy under an external electric field. Furthermore, the corresponding element composition of conductive filaments (CFs) is studied, indicating that the metallic CFs with respect to the activity of the top electrode are essential for device performance. Finally, electrochemical impedance spectroscopy (EIS) is conducted to reveal that the transition of ion states is associated with the formation of metallic CFs. This study provides in-depth insights into the switching mechanism of perovskite memristors, paving a pathway to develop and optimize high-performance perovskite memristors for large-scale applications.

Investigation of the temperature gradient control in the printing space for the material extrusion of medical biodegradable hydrogel.

Material extrusion has shown promise in the fabrication of biocompatible scaffolds for tissue engineering using medical biodegradable hydrogel materials. However, the uncontrollable shape of prepared 3D architecture decelerates the development of large-size complex hydrogel models for the fabrication of human-scale tissue or organs. A primary cause of the collapse as well as shrinkage of prepared architectures is the uncontrollable ambient temperature distribution during the extruding process for hydrogel materials. Therefore, there is a need to accurately control the temperature gradient in the printing space during the material extrusion. The study proposed a novel temperature-controlled substrate configuration with a multilayered enclosure, by which the temperature gradient in the printing space can be regulated by varying the height as well as the internal diameter of the enclosure. Subsequently, a finite element simulation model, as well as a self-developed temperature measuring device, was established to numerically and experimentally investigate the temperature distribution in the printing space. Furthermore, printing trials were implemented on the novel substrate. The collapse of 3D architectures was successfully avoided, and the height of scaffolds was improved obviously from 2.21 mm to 13.24 mm.

Influence of different caregiving styles on fundamental movement skills among children.

Purpose: This study investigated the influence of parenting and grandparenting caregiving styles on fundamental motor skills (FMS) of preschool children. Method: A total of 1,326 preschool children (698 boys, 628 girls) aged 4-6 years were recruited from the kindergartens of Jinhua City, China. Locomotor skills (LM), ball skills (BS), and total fundamental movement skills (TS) of children were assessed by the Test of Gross Motor Development-3rd edition (TGMD-3). Results: There were 978 children in parenting and 348 children in grandparenting caregiving styles. The LM, BS and TS scores of children were considerably (p < 0.001) increased with age (irrespective of sex or caregiving style). For the sex comparisons, BS scores of boys were significantly higher than girls (p < 0.001), while LM and TS scores were not different between boys and girls. For the caregiving style comparison, parenting is superior to grandparenting in developing of children's FMS. Parenting boys of 4-, 5-, and 6-years old showed better BS compared to age-matched parenting girls, whereas boys of 5-years old in grandparenting only showed better BS compared to same-age grandparenting girls (p < 0.05). Furthermore, parenting boys of 6-years reported higher LM (p < 0.01), BS (p < 0.001), and TS (p < 0.001) scores compared to grandparenting boys, but girls' FMS at all ages were not significantly different between the caregiving styles. Conclusion: Parenting caregiving style is positively associated with proper development of FMS among children. Girl children with poor FMS in grandparenting may need a special care or intervention programs to promote their FMS.

Computational investigation of a 3D-printed skin substitute with orthotropy in mechanical property.

As a promising treatment for third-degree burns, grafting with bioengineering skin substitutes shows a capability to overcome the deficiency of donor skin. Similar mechanical properties with human skin are required for employed skin substitutes to avoid secondary damage to patients. Given the representativeness of orthotropy in mechanical properties, there is a need for developing orthotropic skin substitutes. This paper presents computational investigation as well as structural design for the fabrication of orthotropic skin substitutes. A finite element method (FEM) based mechanics simulation model for analyzing the stress field in the skin substitute was developed, by which the stress distribution in mimetic structures of the epidermis and dermis can be acquired. Moreover, the equation of Young's modulus was deduced based on the simulation result, which expressed the mechanical property of designed skin substitutes. Furthermore, several structures of skin substitutes were proposed and their calculated Young's modulus ranged from 21.87 kPa to 213.32 kPa, which was similar to the human skin. Ultimately, uniaxial tensile tests were performed for three types of 3D-printed orthotropic skin substitutes, which validates the feasibility to regulate Young's modulus by regulating the structure of fabricated skin substitutes.

Highly Active Single-Atom Nanozymes with High-Loading Iridium for Sensitive Detection of Pesticides.

Single-atom nanozymes (SAzymes) are novel mimic-enzyme materials with atomically doped active sites. They play a pivotal role in the field of nanozymes because of their excellent catalytic activities, high utilization efficiency of the metal atoms, and simple model of active sites. Herein, the peroxidase (POD)-like SAzymes with high-loading iridium (Ir) (5.31%) on graphene oxide (GO) nanosheets [Ir(III)/GO] were prepared through a coordination reaction between the Ir(III) complex and the oxygen-containing groups in GO. The preparation strategy avoids nitrogen doping and pyrolysis procedures which are the usually used strategies to improve the GO-based enzyme mimic activity. Ascribed to the highly active Ir atoms, Ir(III)/GO SAzymes demonstrate outstanding POD-like activity without the oxidase-like activity. In advantage of the excellent POD-like activity, a simple and sensitive colorimetric pesticide detection platform is established. The developed sensing platform offers an excellent "switch-on" pirimicarb (PIB) detection in the linear range of 10-300 nM with a limit of detection (LOD) of 2.81 nM. Moreover, the detection platform was fabricated into a portable test kit, which is composed of a test swab and sample processing tube. In the aid of a color-reading APP, the test kit can detect PIB with the LOD of 3.31 nM. It is astonishing to get this excellent detection sensitivity just using the simple colorimetric strategy. This work not only provides a novel strategy to synthesize Ir-based SAzymes but also exhibits the super capability of Ir(III)/GO in the biosensing field.

All-solution-processed perovskite/gallium nitride particles hybrid visible-blind ultraviolet photodetectors.

Last decades have witnessed the rapid development of ultraviolet (UV) photodetectors in diversity of applications. The III-nitride semiconductor and metal halide perovskite have both performed promising UV-sensing optoelectronic properties. However, they are still suffering from either the high temperature epitaxial-growth or low photocurrent generated in UV range. In this work, we demonstrate an innovative MAPbCl3/GaN particle hybrid device with all-solution-processed deposition methods. Comparing to the control MAPbCl3photoconductors, the photo-sensing ability of the hybrid device with the optimal concentration of GaN particles is more than one order of magnitude enhanced, and report a responsivity of 86 mA W-1, a detectivity of 3.1 × 1011Jones and a rise/fall time of 1.1/10.7 ms at 360 nm. The photocurrent increment could be attributed to the enhanced UV absorption of GaN particles and facilitated charge separation and photoconductive gain at MAPbCl3/GaN heterojunction. This work paves a pathway towards the large-scale low-cost UV photodetectors in versatile applications.

Ultrasonographic classification of 26 cases of fetal umbilical-portal-systemic venous shunts and the correlations with fetal chromosomal abnormalities.

OBJECTIVE: To investigate the ultrasonographic classification of fetal umbilical-portal-systemic venous shunts (UPSVS) and the correlations with fetal chromosomal abnormalities. METHODS: We retrospectively analyzed the ultrasound characteristics and the corresponding chromosomal abnormalities of 26 cases of fetal UPSVS prenatally diagnosed. RESULTS: A total of 26 fetuses diagnosed as UPSVS were included, including four cases of type I UPSVS, ten of type II, three of type IIIA, and nine of type IIIB. Four cases of type I were all complicated by fetal heart enlargement and heart insufficiency, of which one case had multiple malformations, and all four cases terminated pregnancies. Six of ten cases of type II terminated pregnancies, including four of Down's syndrome, one of twin reversed arterial perfusion sequence, one of fetal edema but with normal copy number variation (CNV) by chorionic villus sampling. The other four of ten cases were isolated type II with normal chromosomes, which were delivered at full term and were normal in growth and development when followed up 34 months after birth. Three cases of type IIIA all terminated pregnancies, of which one had multiple malformations, one had right multicystic dysplastic kidney, and one had fetal heart enlargement and heart failure. Among nine of type IIIB, seven with chromosomal abnormalities and/ or complicated malformations terminated pregnancies, and two with isolated type IIIB and normal chromosomes were delivered at full term, and were normal in growth and development (one was followed up to 33 months after birth and the other 20 months after birth). CONCLUSION: Fetal UPSVS can be clearly diagnosed and typed by prenatal ultrasonography. Fetal prognosis is determined by the types of UPSVS and complicated malformations and/ or chromosomal abnormalities. The probability of fetal chromosomal abnormalities in UPSVS fetuses is related to the ultrasonographic classification.

Surface Cleanliness Maintenance with Laminar Flow Based on the Characteristics of Laser-Induced Sputtering Particles in High-Power Laser Systems.

In high-power laser systems, the primary cause of contamination of optical components and degradation of spatial cleanliness is laser-induced sputtering of particles. To mitigate this problem, laminar flow is frequently utilized to control the direction and transport of these particles. This study characterizes the properties of laser-induced sputtering particles, including their flying trend, diameter range, and velocity distribution at varying time intervals. A time-resolved imaging method was employed to damage the rear surface of fused silica using a 355 nm Nd: YAG pump laser. The efficacy of laminar flow in controlling these particles was then assessed, with a particular focus on the influence of laminar flow direction, laminar flow velocity, particle flight height, and particle diameter. Our results indicate that the optimal laminar flow velocity for preventing particle invasion is highly dependent on the maximum particle attenuation distance (or safety distance), which can vary by up to two orders of magnitude. Furthermore, a laminar flow velocity of 0.5 m/s can effectively prevent particle sedimentation. Future research will aim to optimize laminar flow systems based on these findings to achieve high surface cleanliness in high-power laser systems with minimal energy consumption.

Influence of reactive oxygen species concentration and ambient temperature on the evolution of chemical bonds during plasma cleaning: a molecular dynamics simulation.

The research on plasma chemistry involved in the formation and dissociation of abundant chemical bonds is fundamental to developing plasma cleaning. To understand the influence of reactive oxygen species' concentration and ambient temperature on the evolution behavior of the chemical bond during plasma cleaning, microscopic reaction models between organic contaminants and reactive oxygen species were established and performed by reactive molecular dynamics. Dibutyl phthalate, as a representative organic contaminant, was selected as the research object. The simulation results suggested that hydrogen bonds between hydroxyl radicals reduced the mobility of reactive species, resulting in the cleaning ability of hydroxyl radicals being much lower than atomic oxygen and ozone radicals. The concentration of reactive species dominated the efficiency of plasma cleaning, and the increase in ambient temperature further improved the cleaning ability. C-H, C-C and C-O bonds were gradually oxidized to C[double bond, length as m-dash]C, C-O, C[double bond, length as m-dash]O and O-H bonds by hydrogen abstraction reaction during the reaction of reactive species with organic contaminants. An increase in ambient temperature induced the possibility of benzene ring destruction under the action of reactive species, which was considered a method of complete dissociation of aromatic hydrocarbons.

Investigation on the Temperature Distribution Uniformity of an Extrusion-Based 3D Print Head and Its Temperature Control Strategy.

Extrusion-based 3D printing for thermoplastic polymers manifests potential for the fabrication of biocompatible and biodegradable scaffolds. However, the uncontrollable shape of printed filaments usually negatively impacts on the printing processes. Non-uniform temperature in the print head is a primary cause of inaccuracy in the diameter of filaments formed during the process of extruding thermoplastic polymers. Therefore, the temperature distribution inside the print head must be controlled accurately. This study developed a novel print head configuration with two groups of controllable heat sources for extrusion-based printing of thermoplastic polymers. Subsequently, a numerical thermal analysis based on the finite element method (FEM) was conducted to investigate the temperature field in the print head during the heating process. Moreover, a temperature control strategy is proposed under which the temperature distribution of the print head can be regulated. The temperature uniformity can be improved with the proposed temperature control strategy. Lastly, groups of printing trials were implemented, and the printed filaments showed excellent uniformity of diameter when temperature distribution uniformity was controlled in the print head.

LPS activates neuroinflammatory pathways to induce depression in Parkinson's disease-like condition.

Aim: This study aimed to observe the effects of lipopolysaccharide (LPS) intraperitoneal (i.p.) injection on rats and investigate how neuroinflammation contributes to the pathogenesis of depression in Parkinson's disease (dPD). Methods: Rats were administered LPS (0.5 mg/kg, i.p.) for either 1, 2, or 4 consecutive days to establish a rat model of dPD. The sucrose preference test (SPT), the open field test (OFT), and the rotarod test evaluated depression-like and motor behaviors. Magnetic resonance imaging was used to detect alterations in the intrinsic activity and the integrity of white matter fibers in the brain. The expression of c-Fos, ionized calcium-binding adapter molecule (Iba-1), and tyrosine hydroxylase (TH) was evaluated using immunohistochemistry. The concentration of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and interleukin-10 (IL-10) was measured using Luminex technology. Results: LPS i.p. injections decreased sucrose preference in the SPT, horizontal and center distance in the OFT, and standing time in the rotarod test. The intrinsic activities in the hippocampus (HIP) were significantly reduced in the LPS-4 d group. The integrity of white matter fibers was greatly destroyed within 4 days of LPS treatment. The expression of c-Fos and Iba-1 in the prefrontal cortex, HIP, and substantia nigra increased dramatically, and the number of TH+ neurons in the substantia nigra decreased considerably after LPS injection. The levels of IL-6, TNF-α, and IL-10 were higher in the LPS-4 d group than those in the control group. Conclusion: Injection of LPS (0.5 mg/kg, i.p.) for 4 consecutive days can activate microglia, cause the release of inflammatory cytokines, reduce intrinsic activities in the HIP, destroy the integrity of white matter fibers, induce anhedonia and behavioral despair, and finally lead to dPD. This study proved that LPS injection (0.5 mg/kg, i.p.) for 4 consecutive days could be used to successfully create a rat model of dPD.

Exploring the fluorescence enhancement of the split G-quadruplex towards DNA-templated AgNCs and their application in omethoate detection.

Herein, the fluorescent enhancement of the split G-quadruplex (G4) towards DNA-templated AgNCs (DNA-AgNCs) was systematically studied. It was shown that the two G-rich probes with the ratio of the guanine (G) bases of 6 : 6 was the best split mode, and the spacer length of the zero T base at both two sides could present the optimal distance between the AgNCs and split G4. In light of these results, a split G4 coupled with DNA-AgNCs for omethoate (OME) detection was successfully fabricated. The developed fluorescent aptasensor could sense OME in the concentration range of 5-200 nM with a detection limit of 4.16 nM. Moreover, the aptasensor performed well in real-sample detection.

Diagnostic value of reflux episodes in gastroesophageal reflux-induced chronic cough: a novel predictive indicator.

Background: Multichannel intraluminal impedance and pH-monitoring (MII-pH) is an essential testing modality for gastroesophageal reflux-induced chronic cough (GERC), while the existing diagnostic criteria still have some inherent defects. This study aimed to explore the diagnostic value of a direct and objective index, reflux episodes, and related parameters in MII-pH in different types of GERC. Methods: Patients with chronic cough suspected of gastroesophageal reflux disease who successfully received MII-pH were enrolled. The differences in MII-pH parameters were analyzed among patients with different etiologies and the predictive diagnostic value of reflux episodes and related parameters were analyzed in patients with GERC, acid GERC, and non-acid GERC, and compared with existing diagnostic criteria. Results: A total of 190 patients with suspected GERC who underwent MII-pH were enrolled; 131 of these patients were finally diagnosed with GERC. When the reflux episodes were used to diagnose GERC, the area under the curve (AUC) was 0.684; when the acid reflux episodes and the ratio of acid reflux episodes were used to diagnose acid GERC, the AUCs were 0.769 and 0.854; when the non-acid reflux episodes and the ratio of non-acid reflux episodes were used to diagnose non-acid GERC, the AUCs were 0.735 and 0.705, respectively. When the non-acid reflux episodes > 58 and the proportion of non-acid reflux episodes > 68.18% were used alone or in combination to diagnose non-acid GERC, their diagnostic value was significantly better than SAP or SI (all ps < 0.05). Conclusion: The number of reflux episodes has a good diagnostic value for GERC, especially in the diagnosis of non-acid GERC.

Investigation on the Temperature Control Accuracy of a Print Head for Extrusion 3D Printing and Its Improved Design.

For the extrusion 3D printing process, the printing temperature has a significant impact on the filament formation process because the rheological properties of the printed materials are extremely thermal sensitive, which requires a high temperature control accuracy of the print head. This paper presents a numerical and experimental investigation on the temperature field of a homemade print head. A finite element simulation model for analyzing the temperature field of the print head was established, by which the temperature distribution inside the print head can be acquired. Moreover, to improve the temperature control accuracy, an improved configuration was proposed, and two schemes were compared. The temperature control error dropped from 28% to 6.2% with the improved print head, which was verified experimentally. Furthermore, printing trials were conducted by the optimized print head. The filament diameter could be regulated by changing the temperature of the print head, which validates the feasibility to control the filament diameter during the extrusion process via temperature regulation.

Analysis of the Effect of Exercise Combined with Diet Intervention on Postoperative Quality of Life of Breast Cancer Patients.

To analyze the effect of exercise combined with diet intervention on postoperative quality of life of breast cancer patients, a total of 104 breast cancer patients randomly selected from October 2019 to September 2020 who received systemic adjuvant endocrine drug therapy in our hospital for the first time were divided into the observation group and control group as the research subjects. The control group was given exercise and exercise intervention on the basis of routine nursing, and the observation group was given exercise and exercise combined with diet intervention on the basis of basic nursing. Nutritional indexes, anxiety and depression, sleep quality, cancer-induced fatigue, and life quality were observed in both groups. The nutritional indicators of the observation group were slightly different from the control group after exercise and diet intervention, indicating that the observation group's data was higher than the control group (P > 0.05). The HAMA (human anti-mouse antibody) and HAMD (Hamilton depression scale) ratings of the two groups did not differ significantly (P > 0.05). Both groups' HAMA and HAMD ratings improved after intervention; although, the control group's increase was bigger than the observation group (P < 0.05). Both groups' poor sleep quality assessment (PSQI) scores improved after intervention, with the observation group's increase rate being lower than the control group (P < 0.05); the control group's sleep time fell more than the observation group (P < 0.05).

Ratiometric detection of transcription factor based on Europium(III) complex-doped silicon nanoparticles and a G-quadruplex-selective Iridium(III) complex.

To sensitively detect transcription factor (TF) in complicated biological systems, a ratiometric luminescent detection system based on europium(III) complex-doped silicon nanoparticles (SiNPs) and a G-quadruplex (G4)-selective iridium(III) complex has been successfully constructed. During the biosensor fabrication, the G-rich hairpin DNA H1 was immobilized on the surface of SiNPs which was doped with the europium(III) complex Eu(III)(EDTA)(DPA). The dsDNA (S1/S2) contains TF recognition site, and one of its ssDNA S2 is protected by TF from the digestion of exonuclease III (Exo III). The survived S2 starts a signal amplification process at the aid of Exo III, then a lot of G4 DNA was generated which can be recognized by the G4-selective iridium(III) complex (Ir(III)-2G). So, the emission intensity of Ir(III)-2G is enhanced with the increase of TF concentration, while the emission of Eu(III)(EDTA)(DPA) keeps stable. Ascribed to the long lifetimes of both metal complexes, the constructed detection platform can perform time-resolved emission spectroscopy (TRES) measurement in complicated biological systems. The ratiometric TF detection platform not only can detect NF-κB P50 in buffered system in the linear range of 0.05-5 nM with the limit of detection (LOD) 0.014 nM, but also is able to monitor NF-κB P50 in 10% human serum in the linear range of 0.05-5 nM with the LOD of 0.010 nM through TRES measurement. The two-metal complex-based ratiometric TF biosensor provides new strategy for low concentrations of biomarker detection in the complicated biological systems.