Determination of Dipicolinic Acid through the Antenna Effect of Eu(III) Coordination Polymer.

Bacillus anthracis is a Gram-positive bacterium that can cause acute infection and anthracnose, which is a serious concern for human health. Determining Bacillus anthracis through its spore biomarker dipicolinic acid (DPA) is crucial, and there is a strong need for a method that is rapid, sensitive, and selective. Here, we created Eu(III)-coordination polymers (Eu-CPs) with surfaces that have abundant carboxyl and hydroxyl groups. This was achieved by using citric acid and europium nitrate hexahydrate as precursors in a straightforward one-pot hydrothermal process. These Eu-CPs were then successfully utilized for highly sensitive DPA determination. The fluorescence (FL) emission of Eu-CPs, which is typically weak due to the coordination of Eu(III) with water molecules, was significantly enhanced in the presence of DPA. This enhancement is attributed to the competitive binding between DPA's carboxyl or hydroxyl groups and water molecules. As a result, the absorbed energy of DPA, when excited by 280 nm ultraviolet light, is transferred to Eu-CPs through an antenna effect. This leads to the emission of the characteristic red fluorescence of Eu3+ at 618 nm. A strong linear relationship was observed between the enhanced FL intensity and DPA concentration in the range of 0.5-80 µM. This relationship allowed for a limit of detection (LOD) of 15.23 nM. Furthermore, the Eu-CPs we constructed can effectively monitor the release of DPA from Bacillus subtilis spores, thereby further demonstrating the potential significance of this strategy in the monitoring and management of anthrax risk. This highlights the novelty of this approach in practical applications, provides a valuable determination technique for Bacillus anthracis, and offers insights into the development cycle of microorganisms.

White light-driven enhanced cerium-doped carbon dots activity to combat multidrug-resistant bacterial infection.

Infections caused by multidrug-resistant (MDR) bacteria are increasing and becoming an urgent global health crisis. The discovery and development of novel antibacterial agents to combat MDR are highly desirable. Here, we report the fabrication of cerium-doped carbon dots (CeCDs) with a simple hydrothermal method, which exhibit intrinsic broad efficacy against MDR bacteria including clinical isolates while maintaining low cytotoxicity and hemolytic effects. Importantly, the antibacterial activity of CeCDs is dramatically improved owing to the generation of reactive oxygen species (ROS) upon white light irradiation. Comprehensive analyses revealed that the CeCDs can penetrate the bacterial wall, disrupt the cell membrane, and prevent the biofilm formation, possibly hindering the bacterial resistance development. And the interaction of CeCDs with lipopolysaccharide (LPS) may contribute to the higher activity against Gram-negative bacteria strains. The treatment of CeCDs in a murine skin infection model can significantly reduce the number of bacteria on infected sites and accelerate wound healing by irradiation with light. Overall, CeCDs show great promise as low-cost and efficient antibacterial agents for chronic wounds and may be served as a powerful weapon to fight against the growing threat of MDR bacterial infection.

Extracellular vesicle-packaged lncRNA from cancer-associated fibroblasts promotes immune evasion by downregulating HLA-A in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterised by immune evasion that contribute to poor prognosis. Cancer-associated fibroblasts (CAFs) play a pivotal role in orchestrating the PDAC tumour microenvironment. We investigated the role of CAF-derived extracellular vesicle (EV)-packaged long non-coding RNAs (lncRNAs) in immune evasion and explored gene therapy using engineered EVs loading small interfering RNAs (siRNAs) as a potential therapeutic strategy. Our findings highlight the significance of EV-packaged lncRNA RP11-161H23.5 from CAF in promoting PDAC immune evasion by downregulating HLA-A expression, a key component of antigen presentation. Mechanistically, RP11-161H23.5 forms a complex with CNOT4, a subunit of the mRNA deadenylase CCR4-NOT complex, enhancing the degradation of HLA-A mRNA by shortening its poly(A) tail. This immune evasion mechanism compromises the anti-tumour immune response. To combat this, we propose an innovative approach utilising engineered EVs as natural and biocompatible nanocarriers for siRNA-based gene therapy and this strategy holds promise for enhancing the effectiveness of immunotherapy in PDAC. Overall, our study sheds light on the critical role of CAF-derived EV-packaged lncRNA RP11-161H23.5/CNOT4/HLA-A axis in PDAC immune evasion and presents a novel avenue for therapeutic intervention.

Bimetallic Ag/Fe-MOG derived flake-like Ag2O/Fe2O3 p-n heterojunction for efficient photodegradation organic pollutants within a wide pH range.

In this paper, we reported a facile and clean strategy to prepare the flake-like Ag2O/Fe2O3 bimetallic p-n heterojunction composites for photodegradation organic pollutants. The surface morphology, crystal structure, chemical composition and optical properties of Ag2O/Fe2O3 were characterized by SEM, high-resolution TEM images with EDX spectra, XRD, XPS, FT-IR and UV-vis DRS spectra respectively. The formation of Ag2O/Fe2O3 p-n heterojunction facilitated the interfacial transfer of electrons as well as the separation of charge carries. Hence, the as-synthesized Ag2O/Fe2O3-3 composites exhibited ultra-high photocatalytic activity. Under the experimental conditions of catalyst dosage of 0.4 mg mL-1 and irradiation time of 60 min, the degradation conversion rate of rhodamine B reached 96.1 %, which was 5.0 and 2.8 times of pure phase Ag2O and Fe2O3, respectively. Meanwhile, the degradation performance of Ag2O/Fe2O3-3 was not limited by pH, and it can achieve high degradation efficiency under 3-11. In addition, Ag2O/Fe2O3-3 also showed superb degradation ability for other common anionic dyes, cationic dyes and antibiotics. XPS and FT-IR spectra showed that Ag2O/Fe2O3-3 retained a carbon skeleton that facilitated electron transport and light absorption conversion. And the analyses of quenching experiment and EPR demonstrated •O2-, •OH and h+ were crucial reactive oxidant species contributing to the rapid organic pollutant degradation. This work provides new insights into obtaining p-n photocatalysts heterojunction with excellent catalytic activity for removing organic pollutants from wastewater.

Coreactant-Free Zirconium Metal-Organic Framework with Dual Emission for Ratiometric Electrochemiluminescence Detection of HIV DNA.

Owing to the limitations of dual-signal luminescent materials and coreactants, constructing a ratiometric electrochemiluminescence (ECL) biosensor based on a single luminophore is a huge challenge. This work developed an excellent zirconium metal-organic framework (MOF) Zr-TBAPY as a single ECL luminophore, which simultaneously exhibited cathodic and anodic ECL without any additional coreactants. First, Zr-TBAPY was successfully prepared by a solvothermal method with 1,3,6,8-tetra(4-carboxyphenyl)pyrene (TBAPY) as the organic ligand and Zr4+ cluster as the metal node. The exploration of ECL mechanisms confirmed that the cathodic ECL of Zr-TBAPY originated from the pathway of reactive oxygen species (ROS) as the cathodic coreactant, which is generated by dissolved oxygen (O2), while the anodic ECL stemmed from the pathway of generated Zr-TBAPY radical itself as the anodic coreactant. Besides, N,N-diethylethylenediamine (DEDA) was developed as a regulator to ECL signals, which quenched the cathodic ECL and enhanced the anodic ECL, and the specific mechanisms of its dual action were also investigated. DEDA can act as the anodic coreactant while consuming the cathodic coreactant ROS. Therefore, the coreactant-free ratiometric ECL biosensor was skillfully constructed by combining the regulatory role of DEDA with the signal amplification reaction of catalytic hairpin assembly (CHA). The ECL biosensor realized the ultrasensitive ratio detection of HIV DNA. The linear range was 1 fM to 100 pM, and the limit of detection (LOD) was as low as 550 aM. The outstanding characteristic of Zr-TBAPY provided new thoughts for the development of ECL materials and developed a new way of fabricating the coreactant-free and single-luminophore ratiometric ECL platform.

Dual-emission Tb-based coordination polymer as a ratiometric fluorescence probe for the detection of phosphate.

A simple, sensitive dual-emission probe was developed for the detection of phosphate (Pi). The probe Tb-BTB/DPA was synthesized by mixing dual-ligand, 1,3,5-tri(4-carboxyphenyl) benzene (H3BTB) and dipicolinic acid (DPA), with metal ions Tb3+ in ethanol-water solution at 40℃ for 2 h. Tb-BTB/DPA exhibits two emission peaks, the emission at 362 nm is attributed to H3BTB, an energy transfer between Tb3+ nodes, and DPA further enhances the fluorescence of Tb3+ at 544 nm. Pi competes with ligand H3BTB to coordinate Tb3+, resulting in partial collapse of the Tb-BTB/DPA structure and interrupting the electron transfer between H3BTB and Tb3+. Therefore, the emission at 362 nm is enhanced, while the emission at 544 nm is unchanged, and a ratiometric fluorescence method is developed to detect Pi. Tb-BTB/DPA exhibits good linearity within the Pi concentration range (0.1-50 µmol/L), and the detection limit was 25.8 nmol/L. This study provides a new way to prepare probes with dual emission sensing properties.

CPE correlates with poor prognosis in gastric cancer by promoting tumourigenesis.

Aims: To investigate the potential functions and mechanisms of tumourigenesis in carboxypeptidase E (CPE) and its prognostic value in gastric cancer, and to develop a predictive model for prognosis based on CPE. Results: Transcriptome level variation and the prognostic value of CPE in different types of cancers were investigated using bioinformatics analyses. The association between CPE and clinicopathological characteristics was specifically explored in gastric cancer. Elevated CPE expression was associated with poor survival and recurrence prognosis and was found in cases with a later clinical stage of gastric cancer. The CPE was considered an independent prognostic factor, as assessed using Cox regression analysis. The prognostic value of CPE was further verified through immunohistochemistry and haematoxylin staining. Enrichment analysis provided a preliminary confirmation of the potential functions and mechanisms of CPE. Immune cell infiltration analysis revealed a significant correlation between CPE and macrophage infiltration. Eventually, a prognosis prediction nomogram model based on CPE was developed. Conclusion: CPE was identified as an independent biomarker associated with poor prognosis in gastric cancer. This suggests that CPE overexpression promoted epithelial-mesenchymal transition via the activation of the Erk/Wnt pathways, leading to proliferation, invasion, and metastasis. Targeted therapeutic strategies for gastric cancer may benefit from these findings.

Survival prognostic in different age groups of patients undergoing local versus radical excision for rectal cancer: a study based on the SEER database.

Age significantly affects the prognosis of patients with rectal cancer after radical excision (RE), and local excision (LE) is an alternative surgical procedure to RE. To compare the survival prognosis in different age groups of LE versus RE for rectal cancer. Patients diagnosed with rectal adenocarcinoma treated by LE or RE from 2010 to 2017 were obtained from the SEER database. The primary outcomes are 5-year OS and CSS. A total of 11,170 patients were eventually included, and there were 490 patients in LE and RE groups, respectively, after 1:1 propensity score matching. The 5-year OS and CSS after LE were significantly better in < 50 years and 50-66 years groups than in > 66 years group (5-year OS: 95.70% vs 88.40% vs 67.00%, P < 0.001; 5-year CSS: 95.70% vs 96.30% vs 82.60%, P < 0.001). No statistical significance was found for the differences in 5-year OS and CSS between LE and RE in < 50, 50-66, and > 66 years group (P > 0.05). Multivariate analysis showed age > 66 years, poorly differentiated or undifferentiated (Grade III/IV), and tumor size 3 to 5 cm was independent risk factors for 5-year OS after LE; age > 66 years, perineural invasion, and tumor size 3 to 5 cm were the 5-year CSS independent risk factors for after LE. We found that the survival prognosis of younger rectal cancer patients treated with LE was significantly better than older (> 66 years) patients, and the survival prognosis of rectal cancer patients in the three age groups was similar between LE and RE.

Coreactant-free aggregation-induced electrochemiluminescence system based on the novel zinc-luminol metal-organic gel for ultrasensitive detection of PiRNA-823.

Aggregation-induced electrochemiluminescence (AIECL) technology has aroused widespread interest due to the significant improve in ECL response by solving the problems of aggregation-caused quenching and poor water solubility of the luminophore. However, the existing AIECL emitters still suffer from low ECL efficiency, additional coreactants and complex synthesis steps, which greatly limit their applications. Herein, luminol, as a kind of AIE molecule, was assembled with Zn2+ nodes to obtain a novel microflower-like Zinc-luminol metal-organic gel (Zn-MOG) by one-step method. In the light of the strong affinity of N atoms in luminol ligand to Zn2+, Zn-MOG with vigorous viscosity and stability can be formed immediately after vortex oscillation, overcoming the main difficulties of the complicated synthesis steps and poor film-forming performance encountered in current AIECL materials. Impressively, an AIECL resonance energy transfer (RET) biosensor was constructed using Zn-MOG as a donor and Alexa Fluor 430 as an acceptor in combination with DNA-Fuel-driven target recycling amplification for the ultrasensitive detection of PiRNA-823. The fabricated biosensor exhibited a wide linear relationship in the range of 100 aM to 100 pM and a detection limit as low as 60.0 aM. This work is the first to realize the construction of ECL emitters using the AIE effect of luminol, which provides inspiration for the design of AIECL systems without adding coreactants.

Catalytic hairpin assembly triggering amplified DNAzyme-feedback for sensitive detection of hepatitis C virus genotype 1b.

Developing a simple, reliable, and sensitive hepatitis C virus (HCV) genetic sensing platform is of great significance for diagnosing diseases and selecting appropriate antiviral treatments. Herein, a tandem nucleic acid amplification strategy for sensitive detection of HCV genotype 1b (HCV-1b) was developed by stringing the catalytic hairpin assembly (CHA) and the triggered DNAzyme amplifier. The hairpin reactants were initiated by the target to produce lots of triggering double-stranded DNA sequences which can efficiently activate the subsequent blocked DNAzyme. Thereby, the continuous cleavage of substrate was realized, resulting in the fluorescence signal amplification. The DNA-based isothermal CHA-DNAzyme (CDz) sensing platform was successfully applied for sensitive detection of HCV-1b with the limit of detection (84 pM) and showed good selectivity. Moreover, the practical detection of target DNA in the complex biologic matrix indicated that the developing strategy had good potential for early HCV infection diagnosis.

DNA-Based Fluorescent Nanoprobe for Cancer Cell Membrane Imaging.

As an important barrier between the cytoplasm and the microenvironment of the cell, the cell membrane is essential for the maintenance of normal cellular physiological activities. An abnormal cell membrane is a crucial symbol of body dysfunction and the occurrence of variant diseases; therefore, the visualization and monitoring of biomolecules associated with cell membranes and disease markers are of utmost importance in revealing the biological functions of cell membranes. Due to their biocompatibility, programmability, and modifiability, DNA nanomaterials have become increasingly popular in cell fluorescence imaging in recent years. In addition, DNA nanomaterials can be combined with the cell membrane in a specific manner to enable the real-time imaging of signal molecules on the cell membrane, allowing for the real-time monitoring of disease occurrence and progression. This article examines the recent application of DNA nanomaterials for fluorescence imaging on cell membranes. First, we present the conditions for imaging DNA nanomaterials in the cell membrane microenvironment, such as the ATP, pH, etc. Second, we summarize the imaging applications of cell membrane receptors and other molecules. Finally, some difficulties and challenges associated with DNA nanomaterials in the imaging of cell membranes are presented.

Prognostic impact of tumor budding in rectal cancer after neoadjuvant therapy: a systematic review and meta-analysis.

BACKGROUND: Tumor budding (TB) is a negative prognostic factor in colorectal cancer; however, its prognostic impact following neoadjuvant therapy for patients with rectal cancer remains unclear. This study aims to assess the prognostic impact of TB and the correlation between TB and other pathological features in patients with rectal cancer after neoadjuvant therapy. METHODS: A comprehensive search of PubMed, Embase, Cochrane, Scopus, CNKI, Wanfang, and ClinicalKey databases was conducted for studies on the prognosis of TB in rectal cancer after neoadjuvant therapy from the inception of the databases to January 2023, and the final literature included was determined using predefined criteria. Quality assessment of the studies included, extraction of general and prognostic information from them, and meta-analyses were carried out progressively. RESULTS: A total of 11 studies were included, and the results of the meta-analysis showed that high-grade tumor budding (TB-1) increased the risk of poor 5-year disease-free survival (HR = 1.75, 95% CI 1.38-2.22, P < 0.00001), 5-year overall survival (HR = 1.77, 95% CI 1.21-2.59, P = 0.003), local recurrence (OR = 4.15, 95% CI 1.47-11.75, P = 0.007), and distant metastasis (OR = 5.36, 95% CI 2.51-11.44, P < 0.0001) in patients with rectal cancer after neoadjuvant therapy. TB-1 was significantly associated with poor differentiation and lymphatic, perineural, and venous invasion. CONCLUSION: Tumor budding is significantly correlated with unfavorable prognosis and poor pathological characteristics following neoadjuvant therapy for rectal cancer. We anticipate more high-quality, prospective studies in the future to confirm our findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022377564.

Facile synthesis of dual-ligand europium-metal organic gels for ratiometric electrochemiluminescence detecting I27L gene.

Metal organic gels (MOGs) are a new kind of intelligent soft materials with excellent luminescence properties. However, MOGs with dual electrochemiluminescence (ECL) properties have not been reported. In this study, using Eu3+ as metal node, 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine (Hcptpy) and Luminol as organic ligands, a novel dual-ligand Europium-organic gels (Eu-L-H MOGs) were prepared by simple mixing at room temperature. On the one hand, Eu-L-H MOGs could exhibit strong and stable anodic ECL signals in the phosphate buffered saline (PBS) without the addition of co-reactants, which came from the blue emission of Luminol. On the other hand, using K2S2O8 as a cathodic co-reactant, Eu-L-H MOGs produced cathodic signals, which were derived from the red emission of Eu sensitized by Hcptpy through the antenna effect. Based on the independent dual ECL signals of Eu-L-H MOGs, we selected Alexa Flour 430 as the receptor and anodic ECL emission of Eu-L-H MOGs as the donor to construct the ECL resonance energy transfer (ECL-RET) ratio biosensor, which utilized exonuclease III assisted DNA cycle amplification to achieve ultrasensitive detection of the I27L gene. The detection linearity of I27L ranged from 1 fM to 10 nM, with a detection limit as low as 284 aM. This study developed a straightforward technique for obtaining a single luminescent material with dual signals, and further broadened the analytical application of MOGs in the realm of ECL.

Ratiometric Electrochemiluminescence of Zirconium Metal-Organic Framework as a Single Luminophore for Sensitive Detection of HPV-16 DNA.

This study developed a new zirconium metal-organic framework (MOF) luminophore named Zr-DPA@TCPP with dual-emission electrochemiluminescence (ECL) characteristics at a resolved potential. First, Zr-DPA@TCPP with a core-shell structure was effectively synthesized through the self-assembly of 9,10-di(p-carboxyphenyl)anthracene (DPA) and 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP) as the respective organic ligands and the Zr cluster as the metal node. The reasonable integration of the two organic ligands DPA and TCPP with ECL properties into a single monomer, Zr-DPA@TCPP, successfully exhibited synchronous anodic and cathodic ECL signals. Besides, due to the impressively unique property of ferrocene (Fc), which can quench the anodic ECL but cannot affect the cathodic ECL signal, the ratiometric ECL biosensor was cleverly designed by using the cathode signal as an internal reference. Thus, combined with DNA recycle amplification reactions, the ECL biosensor realized sensitive ratiometric detection of HPV-16 DNA with the linear range of 1 fM-100 pM and the limit of detection (LOD) of 596 aM. The distinctive dual-emission properties of Zr-DPA@TCPP provided a new idea for the development of ECL luminophores and opened up an innovative avenue of fabricating the ratiometric ECL platform.

Nanozyme Rich in Oxygen Vacancies Derived from Mn-Based Metal-Organic Gel for the Determination of Alkaline Phosphatase.

Vacancy engineering as an effective strategy has been widely employed to regulate the enzyme-mimic activity of nanomaterials by adjusting the surface, electronic structure, and creating more active sites. Herein, we purposed a facile and simple method to acquire transition metal manganese oxide rich in oxygen vacancies (OVs-Mn2O3-400) by pyrolyzing the precursor of the Mn(II)-based metal-organic gel directly. The as-prepared OVs-Mn2O3-400 exhibited superior oxidase-like activity as oxygen vacancies participated in the generation of O2•-. Besides, steady state kinetic constant (Km) and catalytic kinetic constant (Ea) suggested that OVs-Mn2O3-400 had a stronger affinity toward 3,3',5,5'-tetramethylbenzidine and possessed prominent catalytic performance. By taking 2-phospho-l-ascorbic acid as the substrate, which can be converted into reducing substance ascorbic acid in the presence of alkaline phosphatase (ALP), OVs-Mn2O3-400 can be applied as an efficient nanozyme for ALP colorimetric analysis without the help of destructive H2O2. The colorimetric sensor established by OVs-Mn2O3-400 for ALP detection showed a good linearity from 0.1 to 12 U/L and a lower limit of detection of 0.054 U/L. Our work paves the way for designing enhanced enzyme-like activity nanozymes, which is of significance in biosensing.

Endogenous Adenosine Triphosphate-Assisted Three-Dimensional DNA Walker Assembled on Soft Nanoparticles for Intracellular MicroRNA Imaging.

DNA walkers, a sophisticated type of nanomachines, exhibit intelligent application in biosensing with high programmability and flexibility but usually need additional auxiliary driving force, particularly when walking on hard surfaces. Herein, we construct a three-dimensional (3D) DNA walker on the soft surface of DNA nanospheres (DSs) by using a single-stranded DNA (ssDNA), which is powered by endogenous adenosine triphosphate (ATP) of live cells, so as to sensitively image microRNA (miRNA) in the tumor microenvironment. When the DS walker enters into live cells, miR-21, a general overexpressed biomarker in cancer cells, binds with the blocking strand (B), releasing the walking strand (W) and triggering an ATP-propelled walking reaction. The walking of the DS walker then generates an increasing Cy3 fluorescence signal that indicates the content of miR-21 with about 2.73-fold increase in sensitivity and about 157-fold decrease in the detection limit. Notably, the assembly of the DS walker on soft nanoparticles needs just an easy hybridization process, which facilitates the operation. Meanwhile, this endogenous ATP-powered 3D DNA walker walking on the soft surface performs real-time in situ imaging of miR-21 in live cells, which not only avoids the complex cell treatment and signal error induced by additional auxiliary factors, but also shows high promise of designing programmable DNA nanomachines.

Development of a prognostic model based on ferroptosis-related genes for colorectal cancer patients and exploration of the biological functions of NOS2 in vivo and in vitro.

Background: Ferroptosis is involved in many malignant tumors and has been implicated in important mechanisms of colorectal cancer (CRC) suppression. However, the prognostic and predictive values of the ferroptosis activation pattern in CRC patients have not been noted. Here, we aimed to construct and validate a prediction model based on ferroptosis-related genes (FRGs) for CRC patients and investigated the expression pattern and biological function of the most significantly altered gene. Methods: A total of 112 FRGs were obtained from the FerrDb website, and the clinical characteristics of 545 CRC patients and their global gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. Survival-related FRGs were identified by Cox proportional hazards regression analysis. Finally, the expression pattern and biological function of NOS2, the most implicated gene was explored in vitro and in vivo. Results: The prediction model was established based on 8 FRGs. Patients in the high- or low-risk group were stratified based on the median risk value calculated by our model, and patients in the high-risk group experienced poor overall survival (p<0.01). Further validation demonstrated that the FRG model acted as an independent prognostic indicator for CRC patients (HR=1.428, 95% CI, 1.341-1.627; p<0.001). The area under the receiver operating characteristic (ROC) curve (AUC) for 5-year survival was 0.741. NOS2 was one of the most significantly affected FRGs and was highly expressed in malignant tissue, but it inhibited tumor growth and induced tumor cell death in vitro and in vivo, possibly by repressing the NF-κB pathway. Conclusion: Our study revealed that FRGs have potential prognostic value in CRC patients and that NOS2 suppresses tumor progression, providing a novel therapeutic target for CRC treatment based on ferroptosis.

Dual-ligand two-dimensional terbium-organic frameworks nanosheets for ratiometric fluorescence detection of phosphate.

Here, we reported a ratiometric fluorescence strategy for the detection of phosphate (Pi) in artificial wetland water. The strategy was based on dual-ligand two-dimensional terbium-organic frameworks nanosheets (2D Tb-NB MOFs). 2D Tb-NB MOFs were prepared through blending 5-boronoisophthalic acid (5-bop), 2-aminoterephthalic acid (NH2-BDC) and Tb3+ ions at room temperature in the presence of triethylamine (TEA). The dual-ligand strategy realized dual emission originated from ligand NH2-BDC and Tb3+ ions at 424 and 544 nm, respectively. Pi could compete with ligands to coordinate Tb3+ due to the strong binding ability between Pi and Tb3+, resulting in structural destruction of 2D Tb-NB MOFs, so static quenching and antenna effect between ligands and metal ions were interrupted, and emission at 424 nm was enhanced and emission at 544 nm was weakened. This novel probe had excellent linearity with Pi concentrations from 1 to 50 µmol/L; the detection limit was 0.16 µmol/L. This work revealed that mixed ligands improved sensing efficiency of MOFs by enhancing the sensitivity of the coordination between the analyte and MOFs.

Plasmonic scattering imaging of single Cu2-xSe nanoparticle for Hg2+ detection.

The development of new efficient contrast nanoprobe has been greatly concerned in the field of scattering imaging for sensitive and accurate detection of trace analytes. In this work, the non-stoichiometric Cu2-xSe nanoparticle with typical localized surface plasmon resonance (LSPR) properties originating from their copper deficiency as a plasmonic scattering imaging probe was developed for sensitive and selective detection of Hg2+ under dark-field microscopy. Hg2+ can compete with Cu(I)/Cu(II) which were sources of optically active holes coexisting in these Cu2-xSe nanoparticles for its higher affinity with Se2-. The plasmonic properties of Cu2-xSe were adjusted effectively. Thus, the color scattering images of Cu2-xSe nanoparticles was changed from blue to cyan, and the scattering intensity was obviously enhanced with the dark-field microscopy. There was a linear relationship between the scattering intensity enhancement and the Hg2+ concentration in the range of 10-300 nM with a low detection limit of 1.07 nM. The proposed method has good potential for Hg2+ detection in the actual water samples. This work provides a new perspective on applying new plasmonic imaging probe for the reliable determination of trace heavy metal substances in the environment at a single particle level.

Delivery of Engineered Primary Tumor-Derived Exosomes Effectively Suppressed the Colorectal Cancer Chemoresistance and Liver Metastasis.

Liver metastasis is one of the major causes of colorectal cancer (CRC)-related morbidity and mortality. Delivering small interfering RNAs (siRNAs) or noncoding RNAs has been reported as a promising method to target liver metastasis and chemoresistance in CRC. Here, we report a noncoding RNA delivery system using exosomes derived from primary patient cells. Coiled-coil domain-containing protein 80 (CCDC80) was strongly associated with CRC liver metastasis and chemoresistance, a finding validated by bioinformatic analysis and clinical specimens. Silencing CCDC80 significantly increased sensitivity to chemotherapy agents in OXA-resistant cell lines and a mouse model. The primary cell-derived exosome delivery system was designed to simultaneously deliver siRNAs targeting CCDC80 and increase chemotherapy sensitivity in the distant CRC liver metastasis mouse models and patient-derived xenograft mouse models. We further validated the antitumor effect in an ex vivo model of chemoresistant CRC organoids and a patient-derived organoid xenograft model. Tumor-bearing mice treated with the siRNA-delivering exosomes and hepatectomy showed ideal overall survival. Our results provide a therapeutic target and represent a possible therapeutic alternative for patients with CRC and distant metastasis and in cases of chemoresistance.