In situ generated CdTe quantum dot-encapsulated hafnium polymer membrane to boost electrochemiluminescence analysis of tumor biomarkers.

Exploring the construction of an interface with bright emission, fabulous stability, and good function to develop high-performance electrochemiluminescence (ECL) biosensors for tumor biomarkers is in high demand but faces a huge challenge. Herein, we report an oriented attachment and in situ self-assembling strategy for one-step fabrication of CdTe QD-encapsulated Hf polymer membrane onto an ITO surface (Hf-CP/CdTe QDs/APS/ITO). Hf-CP/CdTe QDs/APS/ITO is fascinating with excellent stability, high ECL emission, and specific adsorption toward ssDNA against dsDNA and mononucleotides (mNs). These interesting properties make it an ideal interface to rationally develop an immobilization-free ECL biosensor for cancer antigen 125 (CA125), used as a proof-of-concept analyte, based on target-aptamer recognition-promoted exonuclease III (Exo III)-assisted digestion. The recognition of ON by CA125 leads to the formation of CA125@ON, which hybridizes with Fc-ssDNA to switch Exo III-assisted digestion, decreasing the amount of Fc groups anchored onto the electrode's surface and blocking electron transfer. As compared to the case where CA125 was absent, significant ECL emission recovery is determined and relies on CA125 concentration. Thus, highly sensitive analysis of CA125 against other biomarkers was achieved with a limit of detection down to 2.57 pg/mL. We envision this work will provide a new path to develop ECL biosensors with excellent properties, which shows great potential for early and accurate diagnosis of cancer.

Greenhouse gas emissions from U.S. crude oil pipeline accidents: 1968 to 2020.

Crude oil pipelines are considered as the lifelines of energy industry. However, accidents of the pipelines can lead to severe public health and environmental concerns, in which greenhouse gas (GHG) emissions, primarily methane, are frequently overlooked. While previous studies examined fugitive emissions in normal operation of crude oil pipelines, emissions resulting from accidents were typically managed separately and were therefore not included in the emission account of oil systems. To bridge this knowledge gap, we employed a bottom-up approach to conducted the first-ever inventory of GHG emissions resulting from crude oil pipeline accidents in the United States at the state level from 1968 to 2020, and leveraged Monte Carlo simulation to estimate the associated uncertainties. Our results reveal that GHG emissions from accidents in gathering pipelines (~720,000 tCO2e) exceed those from transmission pipelines (~290,000 tCO2e), although significantly more accidents have occurred in transmission pipelines (6883 cases) than gathering pipelines (773 cases). Texas accounted for over 40% of total accident-related GHG emissions nationwide. Our study contributes to enhanced accuracy of the GHG account associated with crude oil transport and implementing the data-driven climate mitigation strategies.

HMGB3 promotes the malignant phenotypes and stemness of epithelial ovarian cancer through the MAPK/ERK signaling pathway.

BACKGROUND: Ovarian cancer, particularly epithelial ovarian cancer (EOC), is the leading cause of cancer-related mortality among women. Our previous study revealed that high HMGB3 levels are associated with poor prognosis and lymph node metastasis in patients with high-grade serous ovarian carcinoma; however, the role of HMGB3 in EOC proliferation and metastasis remains unknown. METHODS: MTT, clonogenic, and EdU assays were used to assess cell proliferation. Transwell assays were performed to detect cell migration and invasion. Signaling pathways involved in HMGB3 function were identified by RNA sequencing (RNA-seq). MAPK/ERK signaling pathway protein levels were evaluated by western blot. RESULTS: HMGB3 knockdown inhibited ovarian cancer cell proliferation and metastasis, whereas HMGB3 overexpression facilitated these processes. RNA-seq showed that HMGB3 participates in regulating stem cell pluripotency and the MAPK signaling pathway. We further proved that HMGB3 promotes ovarian cancer stemness, proliferation, and metastasis through activating the MAPK/ERK signaling pathway. In addition, we demonstrated that HMGB3 promotes tumor growth in a xenograft model via MAPK/ERK signaling. CONCLUSIONS: HMGB3 promotes ovarian cancer malignant phenotypes and stemness through the MAPK/ERK signaling pathway. Targeting HMGB3 is a promising strategy for ovarian cancer treatment that may improve the prognosis of women with this disease. Video Abstract.

Photofuel cell-based self-powered biosensor for HER2 detection by integration of plasmonic-metal/conjugated molecule hybrids and electrochemical sandwich structure.

Human epidermal growth factor receptor 2 (HER2) has been regarded as the considerable biomarker of breast and gastric cancer. Thus, precise detection of HER2 is of significance for the early diagnosis and treatment. Here, a photofuel cell-based self-powered biosensor (PFC-SPB) was constructed for the ultrasensitive HER2 detection, which was composed of a plasmonic gold nanoparticles (Au NPs)/organic semiconductor hybrid photoanode and a cathode with biosensing strategy of electrochemical sandwich structure. The localized surface plasmon resonance effect of Au NPs can obviously enhance the separation efficiency of photo-generated electron/hole pair, which was beneficial to the sensitivity and stability of PFC-SPB. Meanwhile, the cathodic sandwich structure not only was used for the target recognition, but also can guarantee the enrichment of electroactive molecules (molybdophosphate). Consequently, with the open circuit voltage (EOCV) as the output signal, the PFC-SPB can achieve the HER2 detection in the range of 0.1-500 pg mL-1 with a low detection limit of 0.02 pg mL-1. Moreover, the as-proposed bioassay can be applied in cell lysate sample without any pretreatment, providing a promising and powerful tool early clinical diagnosis of cancer.

Highly sensitive and stable self-powered biosensing for exosomes based on dual metal-organic frameworks nanocarriers.

Biofuel cells (BFCs)-based self-powered biosensors suffer from the limited stability of bioenzymes. Meanwhile, the poor performance of self-powered biosensors affects the sensitivity of biosensing, thus, it is significant and challenging to improve their stability and sensitivity. In our work, a BFC-based self-powered biosensor, with simultaneously enhanced stability and sensitivity, was constructed utilizing dual metal-organic frameworks (MOFs) as the carriers of the bioenzyme and the electroactive probe, respectively. Anodic enzyme, glucose dehydrogenase (GDH), was encapsulated in zeolitic imidazolate framework-8 (ZIF-8) to form GDH@ZIF-8 composites, enhancing the catalytic activity and stability of GDH. Meanwhile, another zirconium metal-organic frameworks (UiO-66-NH2) loaded with electroactive molecules (K3[Fe(CN)6]) served as nano-enrichment carriers and improved the capability of the cathode to accept electrons from the anode, further improving the sensitivity of the as-proposed biosensor. Herein, the "signal-on" BFC-based self-powered biosensing of exosomes, the model analyte, with excellent stability and outstanding sensitivity was realized with the assistance of dual MOFs, and the detection limit was down to 300 particles mL-1 (based on 3s/k), which was superior to those previously reported in literatures. Furthermore, the developed protocol was capable of detecting exosomes derived from cancer cells in complex biological samples. Overall, in this work the enhancement of both stability and sensitivity has been achieved by utilizing two types of MOFs, which laid the foundation for expanding the applications of BFC-based self-powered biosensors.

Self-Powered Biosensing Platform Based on "Signal-On" Enzymatic Biofuel Cell for DNA Methyltransferase Activity Analysis and Inhibitor Screening.

Aberrant DNA methylation catalyzed by DNA methyltransferases (MTase) has proved to be associated with human diseases such as cancers. Thus, the development of an efficient strategy to accurately detect DNA MTase is highly desirable in medical diagnostics. Herein, we proposed a robust "signal-on" enzymatic biofuel cell (EBFC)-based self-powered biosensing platform with excellent anti-interference ability for DNA MTase activity analysis and inhibitor screening. In the presence of target MTase, the MTase-catalyzed DNA methylation occurred and hindered the HpaII endonuclease-catalyzed dsDNA dissociation, which enabled more bilirubin oxidase (BOD) to immobilize at the cathode surface via amidation. Then, BOD-catalyzed oxygen reduction took place by accepting electrons generated at the anode via glucose oxidation, thus leading to an elevated open-circuit voltage value, the amplitude of which was directly related to MTase concentration. The direct detection limit of the M.SssI assay was down to 0.005 U/mL, which was lower than that of those reported results. Notably, the as-proposed protocol was competent to detect DNA MTase activity directly in human serum samples without enrichment and separation, and applicable to the screening of M.SssI inhibitors. Considering the virtues of the excellent anti-interference ability, no requirement of external power, simplicity, and high accuracy, the biosensing platform would hold great potential in DNA MTase bioassay and clinical diagnosis of cancers.

A label-free homogeneous electrochemical cytosensor for the ultrasensitive detection of cancer cells based on multiaptamer-functionalized DNA tetrahedral nanostructures.

We developed a label-free homogeneous electrochemical cytosensor for ultrasensitive detection of cancer cells based on multiaptamer-functionalized DNA tetrahedral nanostructures, which avoided expensive labeling and sophisticated immobilization procedures, providing opportunities for precisely detecting cancer cells in clinical applications.

Solar-Powered Organic Semiconductor-Bacteria Biohybrids for CO2 Reduction into Acetic Acid.

An organic semiconductor-bacteria biohybrid photosynthetic system is used to efficiently realize CO2 reduction to produce acetic acid with the non-photosynthetic bacteria Moorella thermoacetica. Perylene diimide derivative (PDI) and poly(fluorene-co-phenylene) (PFP) were coated on the bacteria surface as photosensitizers to form a p-n heterojunction (PFP/PDI) layer, affording higher hole/electron separation efficiency. The π-conjugated semiconductors possess excellent light-harvesting ability and biocompatibility, and the cationic side chains of organic semiconductors could intercalate into cell membranes, ensuring efficient electron transfer to bacteria. Moorella thermoacetica can thus harvest photoexcited electrons from the PFP/PDI heterojunction, driving the Wood-Ljungdahl pathway to synthesize acetic acid from CO2 under illumination. The efficiency of this organic biohybrid is about 1.6 %, which is comparable to those of reported inorganic biohybrid systems.

Light-driven ultrasensitive self-powered cytosensing of circulating tumor cells via integration of biofuel cells and a photoelectrochemical strategy.

Herein, a light-driven, membrane-less and mediator-less self-powered cytosensing platform via integration of biofuel cells (BFCs) and a photoelectrochemical strategy was developed for ultrasensitive detection of circulating tumor cells (CTCs). To construct cytosensors, an elaborately designed SH-Sgc8c aptamer/AuNP/g-C3N4 photoelectrode was used as an alternative anode for glucose oxidation, avoiding the introduction of anodic enzymes. Initially, glucose could favorably reach the photoanode surface and be easily oxidized by the photogenerated holes, while the photogenerated electrons would transfer to the biocathode and achieve biocatalytic reduction of O2, leading to a high EOCV. However, in the presence of CTCs, they could preferentially interact with the Sgc8c aptamer via specific recognition, and then complexes with large steric hindrance were immobilized on the photoanode surface, which could greatly affect the electron transfer between glucose and the photoanode surface. In this case, the EOCV decreased sharply. Encouragingly, this self-powered cytosensor exhibited an ultrasensitive response to the target CTCs in a wide concentration range from 20 to 2 × 105 cells mL-1 with a low detection limit of 10 cells mL-1 (S/N = 3), being superior to those of the reported methods. Moreover, this as-proposed self-powered cytosensor integrated with a photoelectrochemical strategy possessed unique advantages of not requiring an external power source, being anodic enzyme-free, having a simple construction process, facile miniaturization, and high selectivity and sensitivity, providing a promising and powerful tool for fundamental biochemical research and clinical diagnosis.

Enzymatic biofuel cell-based self-powered biosensing of protein kinase activity and inhibition via thiophosphorylation-mediated interface engineering.

We developed a facile and ultrasensitive enzymatic biofuel cell (EBFC)-based self-powered biosensor of protein kinase A (PKA) activity and inhibition via thiophosphorylation-mediated interface engineering. The detection limit was down to 0.00022 U mL-1 (S/N = 3). In addition, the PKA activities from MCF-7 and A549 cell lysates were analyzed and achieved reliable results.

Label-Free and Ultrasensitive Biomolecule Detection Based on Aggregation Induced Emission Fluorogen via Target-Triggered Hemin/G-Quadruplex-Catalyzed Oxidation Reaction.

Fluorescence biosensing strategy has drawn substantial attention due to their advantages of simplicity, convenience, sensitivity, and selectivity, but unsatisfactory structure stability, low fluorescence quantum yield, high cost of labeling, and strict reaction conditions associated with current fluorescence methods severely prohibit their potential application. To address these challenges, we herein propose an ultrasensitive label-free fluorescence biosensor by integrating hemin/G-quadruplex-catalyzed oxidation reaction with aggregation induced emission (AIE) fluorogen-based system. l-Cysteine/TPE-M, which is carefully and elaborately designed and developed, obviously contributes to strong fluorescence emission. In the presence of G-rich DNA along with K+ and hemin, efficient destruction of l-cysteine occurs due to hemin/G-quadruplex-catalyzed oxidation reactions. As a result, highly sensitive fluorescence detection of G-rich DNA is readily realized, with a detection limit down to 33 pM. As a validation for the further development of the proposed strategy, we also successfully construct ultrasensitive platforms for microRNA by incorporating the l-cysteine/TPE-M system with target-triggered cyclic amplification reaction. Thus, this proposed strategy is anticipated to find use in basic biochemical research and clinical diagnosis.

Ultrasensitive Ratiometric Homogeneous Electrochemical MicroRNA Biosensing via Target-Triggered Ru(III) Release and Redox Recycling.

A new label-free and enzyme-free ratiometric homogeneous electrochemical microRNA biosensing platform was constructed via target-triggered Ru(III) release and redox recycling. To design the effective ratiometric dual-signal strategy, [Ru(NH3)6]3+ (Ru(III)), as one of the electroactive probes, was ingeniously entrapped in the pores of the positively charged mesoporous silica nanoparticle (PMSN), and another electroactive probe, [Fe(CN)6]3- (Fe(III)), was selected to facilitate Ru(III) redox recycling due to its distinctly separated reduction potential and different redox properties. Owing to the liberation of the formed RNA-ssDNA complex from PMSN, the target miRNA triggered the Ru(III) release and was quickly electroreduced to Ru(II), and then, the in-site-generated Ru(II) could be chemically oxidized back to Ru(III) by Fe(III). Thus, with the release of Ru(III) and the consumption of Fe(III), a significant enhancement for the ratio of electroreduction current [Ru(NH3)6]3+ over [Fe(CN)6]3- (IRu(III)/IFe(III)) value was observed, which was dependent on the concentration of the target miRNA. Consequently, a simple, accurate, and ultrasensitive method for the miRNA assay was readily realized. Furthermore, the limit of detection (LOD) of our method was down to 33 aM (S/N = 3), comparable or even superior to other approaches reported in literature. More importantly, it also exhibited excellent analytical performance in the complex biological matrix cell lysates. Therefore, this homogeneous biosensing strategy not only provides an ingenious idea for realizing simple, rapid, reliable, and ultrasensitive bioassays but also has a great potential to be adopted as a powerful tool for precision medicine.

Ultrasensitive self-powered cytosensors based on exogenous redox-free enzyme biofuel cells as point-of-care tools for early cancer diagnosis.

An exogenous redox-free, membrane-less enzyme biofuel cell-based ultrasensitive self-powered cytosensing platform was fabricated. With the ultrahigh sensitivity and the merits of not requiring external power sources or exogenous reagents, the device has great potential as a point-of-care tool for early diagnosis of cancer in vivo.

Development and application of a method for analysis of phthalates in ham sausages by solid-phase extraction and gas chromatography-mass spectrometry.

A gas chromatography-mass spectrometry assay was developed and successfully applied for the determination of phthalates in ham sausage migrated from packaging film. The phthalates studied were dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), benzylbutyl phthalate (BBP), bis(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP), with dibutyl adipate (DBA) as internal standard. The sample pre-treatments included extraction with n-hexane, solvent evaporation and reconstitution with acetonitrile before and after solid-phase extraction (SPE). The extraction and cleaning up procedure was carried out with cartridges containing dimethyl butylamine groups, which showed extraction efficiencies over 87.3%. The calibration curves obtained were linear with correlation coefficients greater than 0.99. The method proved to be accurate and precise for the six phthalates used. It was successfully applied to a study on the migration of phthalates from packaging PVC film into ham sausage.

Simultaneous determination of phthalates and adipates in human serum using gas chromatography-mass spectrometry with solid-phase extraction.

A gas chromatography-mass spectrometry assay was developed and validated for the simultaneous determination of phthalates and adipates in human serum. The phthalates and adipates studied were dimethyl phthalate, diethyl phthalate, dibutyl phthalate, benzylbutyl phthalate, di-2-ethylhexyl phthalate, di-n-octyl phthalate, diethyl adipate, dibutyl adipate, diisobutyl adipate, bis(2-butoxyethyl) adipate and di-2-ethylhexyl adipate, with diisooctyl phthalate as internal standard. The extraction and cleaning up procedure was carried out with solid-phase extraction cartridges containing dimethyl butylamine groups, which showed extraction efficiencies over 88% for each analyte and the internal standard. The calibration curves obtained were linear with correlation coefficients greater than 0.98. For all analytes, the assay gave CV% values for intra-day precision from 4.9 to 13.3% and mean accuracy values from 91.4 to 108.4%, while inter-day precision was 5.2-13.4% and mean accuracy 91.0-110.2%. The limits of detection for the assay of phthalates and adipates were in the range 0.7-4.5 ng/mL. The method is simple, sensitive and accurate, and allows for simultaneous determination of nanogram levels of phthalates and adipates in human serum. It was successfully applied to an investigation on the level of phthalates and adipates in a non-occupationally exposed population.