Nab-paclitaxel plus S-1 versus nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer: a multicenter, randomized, phase II study.

BACKGROUND: Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC). METHODS: In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Between July 16, 2019, and September 9, 2022, 62 patients (AS, n = 32; AG, n = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group. CONCLUSION: The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308).

Stable Halide Perovskite CsPbBr3 Nanocrystals Assisted by Covalent-Organic Frameworks for Electrochemiluminescence Analysis in an Aqueous Medium.

Lead halide perovskites have garnered attention as promising electrochemiluminescence (ECL) emitters owing to their superior photophysical characteristics. However, their poor water stability severely restricts their application in aqueous media for ECL. In this study, inorganic perovskite CsPbBr3 was assembled in situ in the imine-linked covalent-organic framework (COF-LZU1) as a novel ECL emitter. The expansive surface area and robust hydrophobic architecture of COF-LZU1 not only improved the water stability of CsPbBr3 but also guaranteed its exceptional ECL performance. The novel composite nanoluminescent material was coated onto an indium tin oxide (ITO) electrode via spin-coating and calcination processes to serve as an electrochemiluminescence (ECL) platform. A sensor was developed by combining a DNA hydrogel target-induced release system with a platform using ascorbic acid (AA) as a coreactant and T-2 toxin as the target analyte model. This method achieved a detection limit as low as 3.56 fg·mL-1 and was successfully applied to the analysis of the T-2 toxin content in corn samples. This study offers a novel path for the advancement of perovskite-based ECL emitters and their utilization in aqueous environments within the ECL field.

Multiple Enzyme-Mimicking CuMOF-Driven Self-Cascading Antioxidant Reaction for Synergistic Electrochemiluminescence Modulation in Ultrasensitive Biosensing.

Developing nanozyme-based free radical scavenging is a promising signal modulation approach for ECL sensing. Nevertheless, the relatively low antioxidant activity and inherent pro-oxidant activity of numerous nanozymes have significantly hindered the development of this strategy. Here a biofunctional copper-based metal-organic framework (CuMOF) with multiple enzyme-mimicking activities was employed for the modulation of the ECL immunosensor, guided by the self-cascade antioxidant reaction. The inherent SOD, CAT, and the capacity to eliminate ·OH endow CuMOF with powerful synergistic antioxidant effects while little pro-oxidant activities were displayed, enabling efficient scavenging of the O2·- produced during the electrochemical oxidation of H2O2. Subsequently, the nanoconfinement effect of the layered double hydroxide was introduced to ensure a steady ECL signal. The suggested ECL immunosensor, using aflatoxin B1 as a proof-of-concept target, demonstrated a detection range spanning from 0.001 pg/mL to 10 ng/mL, with the detection limit calculated to be 0.18 fg/mL. This exceptional achievement greatly broadens the range of possible uses for nanozyme-based radical scavenging modulated ECL analysis.

Electrochemiluminescence Biosensor for Ascorbic Acid Based on Target Transformation of Cell-Free RNA Transcription System and Duplex-Specific Nuclease-Assisted Recycling Amplification.

A cell-free RNA transcription system had been coupled with electrochemiluminescence (ECL) detection technology for the first time to develop an ascorbic acid (AA, acting as a model target) biosensor. The biosensor is composed of single-stranded DNA (ssDNA) sequences modified with alkynyl and azido groups, respectively, alongside an incomplete gene circuit framework. The addition of target AA and copper ions will cause the linkage of the two ssDNA sequences through a click chemistry reaction. This results in the subsequent reconstruction of a complete gene circuit. The reconstituted gene circuit, in conjunction with the T7 RNA polymerase, drives the transcription of substantial quantities of RNA. ssDNA labeled with ferrocene (Fc) (Fc-DNA) had been immobilized on a tris(2,2'-bipyridyl) ruthenium(II) chloride hexahydrate-doped SiO2 nanoparticle (Ru@SiO2 NPs) modified electrode first. The quenching effect of Fc on Ru@SiO2 causes the low ECL detected. The transcribed RNA sequence assisted double-stranded specific nuclease (DSN) to cut the ssDNA-Fc and the ECL of the system was enhanced. Optimal experimental conditions reveal that the ECL signal exhibits a linear correlation with the logarithmic concentration of AA, spanning a detection range from 100 nM to 1 mM, with a detection limit of 45 nM. This innovative methodology expands the utility of a cell-free RNA transcription system within the realm of biosensing applications.

High-Sensitivity Homogeneous Detection of miRNA-155 Governed by DNA Walker-Regulated Surface DNA Density of Magnetic Electrochemiluminescence Nanoparticles.

Homogeneous electrochemiluminescence (ECL) has gained attention for its simplicity and stability. However, false positives due to solution background interference pose a challenge. To address this, magnetic ECL nanoparticles (Fe3O4@Ru@SiO2 NPs) were synthesized, offering easy modification, magnetic separation, and stable luminescence. These were utilized in an ECL sensor for miRNA-155 (miR-155) detection, with locked DNAzyme and substrate chain (mDNA) modified on their surface. The poor conductivity of long-chain DNA significantly impacts the conductivity and electron transfer capability of Fe3O4@Ru@SiO2 NPs, resulting in weaker ECL signals. Upon target presence, unlocked DNAzyme catalyzes mDNA cleavage, leading to shortened DNA chains and reduced density. In contrast, the presence of short-chain DNA has minimal impact on the conductivity and electron transfer capability of Fe3O4@Ru@SiO2 NPs. Simultaneously, the material surface's electronegativity decreases, weakening the electrostatic repulsion with the negatively charged electrode, resulting in the system detecting stronger ECL signals. This sensor enables homogeneous ECL detection while mitigating solution background interference through magnetic separation. Within a range of 100 fM to 10 nM, the sensor exhibits a linear relationship between ECL intensity and target concentration, with a 26.91 fM detection limit. It demonstrates high accuracy in clinical sample detection, holding significant potential for clinical diagnostics. Future integration with innovative detection strategies may further enhance sensitivity and specificity in biosensing applications.

Conductivity-Regulated Bipolar Electrochemiluminescence Sensing Platform for Indicator-Free Homogeneous Bioassay.

Electrochemiluminescence (ECL) sensors have been widely developed because of their high sensitivity and low background. However, most of them suffered from tedious probe modification on the electrode and cross-interferences within the sensing and reporting reactions. The bipolar electrode based ECL (BPE-ECL) can effectively eliminate interference by physically separating the sensing and reporting cells, but there is still a need for exogenous electroactive indicators to transduce the variations between two poles of a BPE. Herein, based on the discovery that conductivity can be regulated in aqueous medium by homogeneous bioreaction, we showed a novel BPE-ECL sensing platform that combined the conductivity-based biosensing technology with ECL reporting system for the first time. Compared to many short nucleic acids, the target induced a hybridization chain reaction to produce the long nucleic acid aggregates, resulting in a conductivity decrease of the sensing cell and finally reducing the ECL response in the reporting cell. The BPE-ECL platform has already been applied to detect microRNA-21 for a demonstration. This innovative system not only separates the target sensing and reporting reactions but also avoids the use of electrochemical indicators for measurement. The BPE-ECL biosensing platform can be developed to detect different targets by changing the probe used.

Charge Density-Regulated Microchannel-Based Electrochemiluminescence Sensor for Hydrogen Sulfide Detection with a Highly Efficient Accumulation Strategy.

The electrochemiluminescence (ECL) intensity can be regulated by ionic current passing through the microchannel, which broadened the regulation of the ECL sensors. But in the early reported sensors, the electrostatic repulsion and steric hindrance caused few targets to approach the interface of the microchannel driven by concentration difference, which reduced the detection efficiency and prolonged the detection period. In this study, different accumulation strategies, such as a positive electric field and different polarity electric fields, were designed to accumulate targets in the microchannel. The interaction of azide groups and hydrogen sulfide served as a research model. Hydrogen sulfide can react with the negatively charged azide groups in the microchannel surface to produce positively charged amino groups, decreasing the negative charge density of the microchannel and thus altering the ionic current and ECL intensity. The accumulation of hydrogen sulfide at the microchannel tip can increase the collision probability with azide groups to improve the detection efficiency, and the integration of accumulation and reaction can shorten the detection period to 28 min. The hydrogen sulfide concentration on the microchannel tip accumulated by applying different polarity electric fields was 22.3-fold higher than that accumulated by applying a positive electric field. The selected research model broadened the application range of a microchannel-based ECL sensor and confirmed the universality of the microchannel-based ECL sensor.

Photoelectrochemical Sensor for H2S Based on a Lead-Free Perovskite/Metal-Organic Framework Composite.

Halide perovskites have emerged as a highly promising class of photoelectric materials. However, the application of lead-based perovskites has been hindered by their toxicity and relatively weak stability. In this work, a composite material comprising a lead-free perovskite cesium copper iodide (CsCu2I3) nanocrystal and a metal-organic framework (MOF-801) has been synthesized through an in situ growth approach. The resulting composite material, denoted as CsCu2I3/MOF-801, demonstrates outstanding stability and exceptional optoelectronic characteristics. MOF-801 may serve a dual role by acting as a protective barrier between CsCu2I3 nanocrystals and the external environment, as well as promoting the efficient transfer of photogenerated charge carriers, thereby mitigating their recombination. Consequently, CsCu2I3/MOF-801 demonstrates its utility by providing both stability and a notably high initial photocurrent. Leveraging the inherent reactivity between H2S and the composite material, which results in the formation of Cu2S and structural alteration, an exceptionally sensitive photoelectrochemical sensor for H2S detection has been designed. This sensor exhibits a linear detection range spanning from 0.005 to 100 µM with a remarkable detection limit of 1.67 nM, rendering it highly suitable for precise quantification of H2S in rat brains. This eco-friendly sensor significantly broadens the application horizon of perovskite materials and lays a robust foundation for their future commercialization.

Added value of histogram analysis of intravoxel incoherent motion and diffusion kurtosis imaging for the evaluation of complete response to neoadjuvant therapy in locally advanced rectal cancer.

OBJECTIVE: To evaluate how intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) histogram analysis contribute to assessing complete response (CR) to neoadjuvant therapy (NAT) in locally advanced rectal cancer (LARC). MATERIAL AND METHODS: In this prospective study, participants with LARC, who underwent NAT and subsequent surgery, with adequate MR image quality, were enrolled from November 2021 to March 2023. Conventional MRI (T2WI and DWI), IVIM, and DKI were performed before NAT (pre-NAT) and within two weeks before surgery (post-NAT). Image evaluation was independently performed by two experienced radiologists. Pathological complete response (pCR) was used as the reference standard. An IVIM-DKI-added model (a combination of IVIM and DKI histogram parameters with T2WI and DWI) was constructed. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic performance of conventional MRI and the IVIM-DKI-added model. RESULTS: A total of 59 participants (median age: 58.00 years [IQR: 52.00, 62.00]; 38 [64%] men) were evaluated, including 21 pCR and 38 non-pCR cases. The histogram parameters of DKI, including skewness of kurtosis post-NAT (post-KSkewness) and root mean squared of change ratio of diffusivity (Δ%DDKI-root mean squared), were entered into the IVIM-DKI-added model. The area under the ROC curve (AUC) of the IVIM-DKI-added model for assessing CR to NAT was significantly higher than that of conventional MRI (0.855 [95% CI: 0.749-0.960] vs 0.685 [95% CI: 0.565-0.806], p < 0.001). CONCLUSION: IVIM and DKI provide added value in the evaluation of CR to NAT in LARC. KEY POINTS: Question The current conventional imaging evaluation system lacks adequacy for assessing CR to NAT in LARC. Findings Significantly improved diagnostic performance was observed with the histogram analysis of IVIM and DKI in conjunction with conventional MRI. Clinical relevance IVIM and DKI provide significant value in evaluating CR to NAT in LARC, which bears significant implications for reducing surgical complications and facilitating organ preservation.

Eu MOF-enhanced FeNCD nanozymes for fluorescence and highly sensitive colorimetric detection of tetracycline.

The constrained enzymatic activity and aggregation challenges encountered by small-sized nanozymes pose obstacles to their practical utility, necessitating a strategy to mitigate aggregation and boost enzymatic catalytic efficiency. In this work, a negatively charged Eu MOF was utilized as the encapsulation matrix, encapsulating the small-sized nanozymes FeNCDs into the Eu MOF to synthesize an FeNCDs@Eu MOF. The dispersibility of the encapsulated FeNCDs was increased, and owing to the negative charge of the FeNCDs@Eu MOF, electrostatic pre-concentration of the positively charged target molecule tetracycline (TC) was facilitated, thereby amplifying the enzymatic catalytic efficiency of the FeNCDs. The response of the FeNCDs to TC increased by nearly 6 times upon encapsulation. The TC detection limit (LOD) of the FeNCDs@Eu MOF-based sensor is as low as 11.63 nM. The incorporation of fluorescence detection expanded the linear range of the sensor, rendering it more suitable for practical sample detection.

Nanozyme catalysis pressure-powered intuitive distance variation for portable quantitative detection of H2S with the naked eye.

As a representative gas of food spoilage, the development of rapid hydrogen sulfide (H2S) analysis strategies for food safety control is in great demand. Despite traditional methods for H2S detection possessing great achievements, they are still incapable of meeting the requirement of portability and quantitative detection at the same time. Herein, a nanozyme catalysis pressure-powered sensing platform that enables visual quantification with the naked eye is proposed. In this methodology, Pt nanozyme inherits the catalase-like activity to facilitate the decomposition of H2O2 to O2, which can significantly improve the pressure in the closed container, further pushing the movement of indicator dye. Furthermore, H2S was found to effectively inhibit the catalytic activity of Pt nanozyme, indicating that the catalase-like activity of PtNPs may be regulated by varying concentrations of H2S. Therefore, by utilizing a self-designed pressure-powered microchannel device, the concentration of H2S was successfully converted into a distinct signal variation in distance. The effectiveness of the as-designed sensor in assessing the spoilage of red wine by H2S determination has been demonstrated. It exhibits a strong correlation between the change in dye distance and H2S concentration within the range of 1-250 µM, with a detection limit of 0.17 µM. This method is advantageous as it enhances the quantitative detection of H2S with the naked eye based on the portable pressure-powered sensing platform, as compared to traditional H2S biosensors. Such a pressure-powered distance variation platform would greatly broaden the application of H2S-based detection in food spoilage management.

Electrolytic growth of phenyl-modified silica isoporous membrane for non-polar extraction and electrochemical detection of pentachloronitrobenzene.

A phenyl-modified silica isoporous membrane (Ph-SIM) was prepared on the indium-tin-oxide (ITO) electrode using the electrochemically assisted self-assembly (EASA) method. The resulting Ph-SIM preserved vertically ordered nanochannels while exhibiting outstanding hydrophobicity due to the incorporation of phenyl groups within the nanochannels. As a result, the Ph-SIM/ITO sensor exhibited a remarkable affinity for PCNB extraction through hydrophobic interactions, leading to high detection sensitivity. The electrochemical response showed a linear enhancement with the logarithmic concentration of PCNB ranging from 0.1 to 20.0 µM, and the limit of detection was 4.64 nM. Practical results demonstrated that the Ph-SIM/ITO sensor possessed good anti-fouling capability and robust stability, making it a promising candidate for portable detection of non-polar contaminants.

Screening and Application of DNA Aptamers for Heparin-Binding Protein.

Rapid detection of heparin-binding protein (HBP) is essential for timely intervention in sepsis cases. Current detection techniques are usually antibody-based immunological methods, which have certain problems, such as complexity and slow detection, and fall short in meeting the urgency of clinical needs. The application of an aptamer can address these concerns well. In this study, HBP-specific DNA aptamers were screened first. Among which, Apt-01, Apt-02, and Apt-13 had a high affinity for HBP, exhibiting impressive KD values of 3.42, 1.44, and 1.04 nmol/L, respectively. Then, the aptamer of HBP and its partially complementary primer probe were combined to form double-stranded DNA (dsDNA) and synthesize a circular DNA template. The template is complementary to the primer probe, but due to the presence of dsDNA, ExoIII cleaves C2-13 as an RCA primer probe, rendering the template unable to recognize the primer probe and preventing the RCA reaction from proceeding. When the target is present, it competes with the adapter for recognition and releases C2-13, exposing its 3' end. After initiating the RCA at room temperature and reacting with SYBR GreenII at 37 °C for 20 min, fluorescence changes can be observed and quantitatively analyzed at a 530 nm wavelength, achieving quantitative biological analysis. Apt-01 was used to develop a fluorescent biosensor for HBP detection, which exhibited a good linear range (0.01 nmol/L to 10 nmol/L) and detection limit (0.0056 nmol/L). This advancement holds the potential to lay a solid groundwork for pioneering sensitive and specific methods for HBP detection and to significantly enhance the diagnostic processes for sepsis.

Low-Background Signal-On Homogeneous Electrochemiluminescence Biosensor for Hepatitis B Virus Detection Based on the Regulation of the Length of DNA Modified on the Nanoparticles by CRISPR/Cas12a and Hybridization Chain Reaction.

In this work, combined with the high amplification efficiency of hybridization chain reaction (HCR), high specificity of the CRISPR/Cas12a system, and convenience of the homogeneous electrochemiluminescence (ECL) assay based on the regulation of negative charge on the reporting probes, a sensitive ECL biosensor for hepatitis B virus DNA (chosen as a model target) had been developed. The initiator chain trigger DNA that can induce HCR amplification is modified on the surface of ruthenium bipyridine-doped silica nanoparticles (Ru@SiO2 NPs) first, and large amounts of negative charges modified on the particles were achieved through the HCR amplification reaction. The efficiency of the nanoparticles reaching the negatively charged working electrode can be regulated and realize the change of the ECL signal. In addition, long DNA on the surface of the luminescent body may prevent the coreactant from entering the pore to react with ruthenium bipyridine. These factors combine to produce a low-background system. The presence of the target can activate the CRISPR/Cas12a system and make trigger DNA disappear from the nanoparticle surface, and strong ECL can be detected. The sensor does not require a complex electrode modification; therefore, it has better reproducibility. Additionally, due to dual signal amplification, the sensor has a high sensitivity. In the range of 10 fM to 10 nM, the ECL intensity exhibits a strong linear relationship with the logarithm of the target concentration, and the detection limit is 7.41 fM. This sensor has shown high accuracy in detecting clinical samples, which holds significant potential for application in clinical testing.

Multicolor Biosensor for Trypsin Detection Based on the Regulation of the Peroxidase Activity of Bovine Serum Albumin-Coated Gold Nanoclusters and Etching of Gold Nanobipyramids.

The detection of trypsin is significantly important for both clinical diagnosis and disease treatment. In this study, an innovative multicolor sensor for trypsin detection has been established based on the regulation of the peroxidase activity of bovine serum albumin-coated gold nanoclusters (BSA-Au NCs) and efficient etching of gold nanobipyramids (Au NBPs). BSA-Au NCs have slight peroxidase enzyme activity and can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to generate TMB+, while trypsin can hydrolyze BSA ligands on the surface of BSA-Au NCs, thus exposing more catalytic active sites of BSA-Au NCs and resulting in the enhancement of the peroxidase activity of BSA-Au NCs, hence more TMB+ is generated. Under acidic conditions, TMB+ can etch Au NBPs efficiently, consequently affecting the aspect ratio of Au NBPs accompanied by the ultraviolet-visible (UV-vis) spectra blue shifting of the system. Furthermore, this also results in color variations that can be distinguished and recognized by naked eyes without any expensive and sophisticated instruments. This multicolor sensor has an available linear relationship with the logarithm of the trypsin concentration in the range of 0.1-100 µg/mL, and the detection limit is 0.045 µg/mL. The designed sensor has been used to detect the concentration of trypsin in human serum samples from healthy individuals and pancreatitis patients with satisfactory results.

Dual Self-Amplification Homogeneous Electrochemiluminescence Biosensor for Terminal Deoxynucleotidyl Transferase Activity Based on Controlling the Surface Morphology and Charge of Reporter Nanoparticles.

Terminal deoxynucleotidyl transferase (TdT) is upregulated in several types of leukemia and is considered a disease biomarker and a potential therapeutic target for leukemia. In this research, a homogeneous electrochemiluminescence (ECL) method based on the control of surface charge and morphology of tris (2,2'-bipyridine) ruthenium(II) chloride hexahydrate-doped silica nanoparticles (Ru@SiO2 NPs) has been designed for TdT activity detection. A small amount of short single-stranded DNA (ssDNA) was modified onto the surface of Ru@SiO2 NPs, and the nanoparticles with a slight positive charge experienced electrostatic attraction with the indium tin oxide (ITO) electrode with a negative charge, so relatively high ECL signals had been detected. Under the action of TdT, the ssDNA was significantly elongated, carrying numerous negative charges on its phosphate backbone, so the overall negative charge of the reporter nanoparticles was enhanced, resulting in a strong electrostatic repulsion with the ITO electrode. Simultaneously, the long ssDNA wrapped around the nanoparticles hindered the approach of the coreactant. Due to the dual effects, the ECL response of the system decreased. The constructed biosensor exhibited excellent sensitivity toward TdT over a range spanning from 1 to 100 U/L. The limit of detection is as low as 1.78 U/L. The developed approach was effectively applied to detect TdT activity in leukemic patients' leukocyte extracts.

Dual-Signal Mode Ratiometric Photoelectrochemical Sensor Based on G-Quadruplex Hole Transport for Rapid and Sensitive Detection of miRNA-210.

For rapid and sensitive detection of miRNA-210, which is important for improving the reliability of clinical diagnosis of breast cancer, a dual-signal mode ratiometric photoelectrochemical (PEC) sensor based on a Au/GaN photoanode is proposed. First, a DNA probe was designed that could complement the target miRNA-210. Then, another G-rich DNA sequence was designed to mismatch the probe and form a double-stranded DNA (dsDNA). Upon addition of the target, the dsDNA unwinds from its binding site and releases G-rich single-stranded DNA. In the presence of Mg2+ and K+, this single-stranded DNA molecule spontaneously forms a G-quadruplex structure, facilitating the rapid transport of photogenerated holes, thereby increasing the photocurrent response of Au/GaN and enabling sensitive label-free detection of miRNA-210. By control of different pH values, a response signal was generated at pH 8, while a reference signal was produced at pH 5. The designed PEC system shows a high potential for the development of miRNA-210 detection. Ultimately, the response signal-to-reference signal ratio was used as the variable, and a broad linear span ranging from 10 fM to 1 nM (R2 = 0.993) has been exhibited, with a detection threshold of 3 fM (S/N = 3). The designed PEC platform shows potential for the development of other disease markers.

Electrochemiluminescence Biosensor for Estrogen-Related Receptor Alpha (ERRα) Based on Target-Induced Change of the Steric Hindrance Effect of an Antibody-Modified Electrode.

In this work, a simple and sensitive electrochemiluminescence (ECL) biosensor has been devised based on target-induced steric hindrance of an antibody-modified electrode surface. Estrogen-related receptor alpha (ERRα) is closely related to estrogen-dependent tumors, which had been chosen as a model target. The ERRα antigen can bind to the antibody modified on the electrode surface with high specificity and results in the increase of steric hindrance, which prevented the ECL indicators (tris(2,2'-bipyridine) dichlororuthenium(II) hexahydrate) from approaching the electrode surface, and the ECL intensity of the system decreased. The ECL response of the system has a good linear relationship with ERRα concentration in the range of 1.0-60 ng/L, and the limit of detection is 0.5 ng/L. Different from the traditional sandwiched immune ECL detection system, which need the modification of ECL indicators on the secondary antibody, only one antibody had been used in this system. The system is easy to operate and has good sensitivity. The designed biosensor has been applied to detect ERRα in the serum and different cell line samples with satisfied results.

KIAA1199 drives immune suppression to promote colorectal cancer liver metastasis by modulating neutrophil infiltration.

BACKGROUND AND AIMS: Metastasis is the primary cause of cancer mortality, and colorectal cancer (CRC) frequently metastasizes to the liver. Our previous studies demonstrated the critical role of KIAA1199 in tumor invasion and metastasis in CRC. In the present study, we described an immune regulatory effect of KIAA1199 that creates a permissive environment for metastasis. APPROACH AND RESULTS: Flow cytometry was used to examine the effects of KIAA1199 on the infiltration of tumor immune cells. Neutrophils and T cells were isolated, stimulated, and/or cultured for in vitro function assays. In the patients with CRC, high expression levels of KIAA1199 were associated with an increased neutrophil infiltration into the liver. This result was further validated in mouse metastasis models. The increased influx of neutrophils contributed to the KIAA1199-driven CRC liver metastasis. Mechanistically, KIAA1199 activated the TGFß signaling pathway by interacting with the TGFBR1/2 to stimulate CXCL1 and CXCL3 production, thereby driving the aggregation of immunosuppressive neutrophils. Genetic blockade or pharmacologic inhibition of KIAA1199 restored tumor immune infiltration, impeded tumor progression, and potentiated response to immune checkpoint blockade (ICB). CONCLUSIONS: These findings indicated that KIAA1199 could facilitate the liver infiltration of immunosuppressive neutrophils via the TGFß-chemokine (C-X-C motif) ligand (CXCL)3/1-CXCR2 axis, which might be clinically targeted for the treatment of hepatic metastasis.

A photoelectrochemical aptasensor for tetracycline based on the self-assembly of 2D MoS2 on a 3D ZnO/Au/ITO electrode.

Two-dimensional (2D) layered MoS2 has good dispersion and adsorption properties, but being a narrow bandgap semiconductor limits its application in photoelectric sensing. In this study, a homogeneous photoelectrochemical sensor based on three-dimensional (3D) ZnO/Au/2D MoS2 is proposed for the ultrasensitive detection of tetracycline (TET). MoS2 is uniformly embedded on the 3D ZnO/Au surface by ordered self-assembly. The physical method of π-π interaction of MoS2 replaces the conventional use of chemically modifying aptamers on the electrode material surface. Under optimal conditions, this method has been successfully applied to the detection of TET in milk, honey, pig kidney and pork samples with reliable results. We believe that this study presents a method for the preparation of sensing carriers and target detection with great potential for application.