Paper-Supported Photoelectrochemical Biosensor for Dual-Mode miRNA-106a Assay: Integration of Luminescence-Confined Upconversion-Actuated Fluorescent Resonance Energy Transfer and CRISPR/Cas13a-Powered Cascade DNA Circuits.

Near-infrared (NIR)-responsive bioassays based on upconversion nanoparticle (UCNP) incorporating high-performance semiconductors have been developed by researchers, but most lack satisfactory ultrasensitivity for exceedingly trace amounts of target. Herein, for the first time, the CRISPR/Cas13a system is combined with cascade DNA circuits, fluorescent resonance energy transfer (FRET) effect, and luminescence-confined UCNPs-bonded CuInS2/ZnO p-n heterostructures-functionalized paper-working electrode to construct dual-signal-on paper-supported NIR-irradiated photoelectrochemical (PEC) (NIR-PEC) and upconversion luminescence (UCL) bioassay for high-sensitive quantification of miRNA-106a (miR-106a). By constructing an ideal FAM-labeled aminating molecular beacon (FAM-H2) model, a relatively good FRET ratio between the UCNP and FAM (≈85.3%) can be achieved. In the existence of miR-106a, the hairpin-structure FAM-H2 was unwound, bringing about the distance increase of UCNP and FAM and the restraint of FRET. Accordingly, both the NIR-PEC signal and the UCL intensity gradually recovered distinctly. Unlike conventional single-mode PEC sensors, with NIR excitation, the designed dual-mode sensing system could implement minimized misdiagnose assay and quantitative miR-106a determination with low detection limits, that is, 76.54 and 51.36 aM for NIR-PEC and UCL detection, respectively. This work not only broadens the horizon of application of the CRISPR/Cas13a strategy toward biosensing but also constructs a new structure of the UCNP-semiconductor in the exploration of efficient NIR-responsive tools and inspires the construction of a no-misdiagnosed and novel biosensor for dual-mode liquid biopsy.

Ultrasensitive Microfluidic Paper-Based Electrochemical/Visual Analytical Device via Signal Amplification of Pd@Hollow Zn/Co Core-Shell ZIF67/ZIF8 Nanoparticles for Prostate-Specific Antigen Detection.

An effective signal amplification strategy is essential to enhance the analytical performance of microfluidic paper-based analytical devices (µPADs) for tracing biomarkers. Here, a simple but efficient approach with superior electrocatalytic performance of Pd@hollow Zn/Co core-shell ZIF67/ZIF8 nanoparticles for regulating the efficacious signal amplification process was utilized to realize the detection of prostate-specific antigen (PSA). By rationally designing the core-shell structure of ZIF67/ZIF8 with hollow characteristics on the nanoscale and introducing the noble metal element Pd into the cavity, the diffusion limitation and porous confinement reduction of the obtained nanomaterials with uniform morphology and satisfactory chemical stability could be realized, which endowed it with better catalytic performance than solid metal-organic frameworks (MOFs) and ensured effective signal amplification of H2O2 reduction for achieving enhanced electrochemical signals. Moreover, with the assistance of signal probes, the remaining H2O2 could flow to the color area to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine to form a colored product by changing the spatial configuration of the µPAD, thus realizing the visual detection of PSA. On the basis of this novel analytical device, dual-mode ultrasensitive detection of PSA could be achieved with a lower limit of detection of 0.78 pg/mL (S/N = 3) and a wider linear range from 5 pg/mL to 50 ng/mL. This work provided the opportunity of introducing the noble metal element Pd into the cavity of the MOF hollow structure to improve its electrocatalytic efficiency and construct a high-performance µPAD for clinical detection of other biomarkers.

Phthalates promote the invasion of hepatocellular carcinoma cells by enhancing the interaction between Pregnane X receptor and E26 transformation specific sequence 1.

Phthalates (PAEs) are considered endocrine-disrupting chemicals (EDCs), a series of compounds able to disrupt the normal regulation of the human endocrine-system. In the present study, we investigated the roles of four PAEs, butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), dimethyl phthalate (DMP), and diethyl phthalate (DEP), in hepatocellular carcinoma (HCC) cells. We define novel roles for the PAEs on the migration of HCC cells via their enhancing of the interaction between the pregnane X receptor (PXR) and E26 transformation specific sequence 1 (ETS-1). Our results indicate that PAEs induced the transcriptional activation of ETS-1 and PXR. PXR activated by PAEs could bind to ETS-1 directly and enhanced the activity of ETS-1, which resulted in the induction of invasion-related ETS-1 target genes. The "LXXLL" motif in the ETS-1C-terminal was essential for the interaction between PXR and ETS-1 induced by PAEs. Treatment of PAEs promoted the nuclear accumulation of ETS-1 or the recruitment of ETS-1, but not in cells expressing ETS-1 with a mutated LXXLL motif in its downstream gene promoter region, or following transfection of PXR siRNA. Treatment with the PXR antagonist ketoconazole almost completely inhibited the effects of PAEs. Moreover, PAEs enhanced the in vitro or in vivo invasion of HCC cells via PXR/ETS-1. Therefore, our results not only contribute to a better understanding of HCC, but also extended the roles of EDCs regulating human malignancies.

Ultrasensitive Paper-Based Photoelectrochemical Sensing Platform Enabled by the Polar Charge Carriers-Created Electric Field.

Efficient separation of electron-hole pairs is vitally crucial to enhancing the analytical performance of paper-based photoelectrochemical (PEC) bioanalysis. Herein, a simple but effective strategy is developed to modulate the effective separation of photogenerated electrons and holes via introducing a polar charge carriers-created (PCC) electric field induced by a classical perovskite ferroelectric BaTiO3 (BTO). By inserting it between the n-type WO3 nanoflakes and p-type Cu2O (WO3 nanoflakes/BTO/Cu2O), the photoelectrode is endowed with a renewable PCC electric field, as a sustaining driving force, to guarantee the realization of directional separation of charge carrier (DSCC) strategy in PEC bioanalysis. The enduring PCC electric field can attract the electrons of Cu2O and holes of WO3, respectively, thereby regulating the directional migration of charge carriers and achieving an enhanced PEC photocurrent for the ultrasensitive quantification based on the highly efficient separation of electron-hole pairs. Consequently, with respect to WO3 nanoflakes/Cu2O and WO3 nanoflakes photoelectrode, the polarized WO3 nanoflakes/BTO/Cu2O photoelectrode exhibits 1.7 and 10.9 times higher photocurrent density, respectively. Benefiting from this, the prominent photocurrent density is obtained which is extremely beneficial for enhancing the sensitivity of PEC bioanalysis. Ultimately, the ultrasensitive detection of model prostate specific antigen (PSA) is realized and presents a linear range of 0.1 pg/mL-50 ng/mL with the detection limitation of 0.036 pg/mL. This work provides the basis for understanding the role of the polarized electric field induced by ferroelectric in tuning the charge separation as well as insights on strategies for constructing high-performance paper-based PEC bioanalysis.

Ambient Bistable Single Dipole Switching in a Molecular Monolayer.

Reported here is a molecular dipole that self-assembles into highly ordered patterns at the liquid-solid interface, and it can be switched at room temperature between a bright and a dark state at the single-molecule level. Using a scanning tunneling microscope (STM) under suitable bias conditions, binary information can be written at a density of up to 41 Tb cm-2 (256 Tb/in2 ). The written information is stable during reading at room temperature, but it can also be erased at will, instantly, by proper choice of tunneling conditions. DFT calculations indicate that the contrast and switching mechanism originate from the stacking sequence of the molecular dipole, which is reoriented by the electric field between the tip and substrate.

Low-Power and High-Performance Trimethylamine Gas Sensor Based on n-n Heterojunction Microbelts of Perylene Diimide/CdS.

In this work, low-power and high-performance gas sensors toward trimethylamine (TMA) are presented for the food quality control in the Internet of Things. An amphiphilic perylene diimide derivative (1,6,7,12-tetra-chlorinated perylene- N-(2-hydroxyethyl)- N'-hexylamine-3,4,9,10-tetracarboxylic bisimide, TC-PDI) is synthesized and further employed to construct the organic microrods of TC-PDI and organic/inorganic microbelts of TC-PDI/CdS by a phase transfer method. Due to the formation of n-n heterojunctions, the TC-PDI/CdS microbelts exhibit higher conductivity than the TC-PDI microrods alone, which present an efficient gas sensing platform for TMA determination at room operating temperature with high reproducibility and selectivity. Remarkably, the limit of detection, stability, and selectivity of the TC-PDI/CdS gas sensor are significantly improved, which ascribes to the efficient charge separation of n-n heterojunctions. More importantly, the fabricated gas sensor provides potential application of "on-site" and "on-line" TMA identification in real systems and suggests an efficient way to develop new hybrid n-n heterojunctions for a low-power and high-performance gas sensor.

Triggerable H2O2-Cleavable Switch of Paper-Based Biochips Endows Precision of Chemometer/Ratiometric Electrochemical Quantification of Analyte in High-Efficiency Point-of-Care Testing.

In this work, a triggerable H2O2-cleavable fluid switch mediated paper-based biochip, being amenable to multiplexing and quantitative analysis with the dual-response output of visual screening and ratiometric electrochemistry, was developed for sensitive detection of target on-site. By properly implanting hydrophobic Ag-H2O2 responsive material in specific zone to form a programmable fluid switch, the biochip could achieve different modes of blocking/connecting switching automatically. In order to improve the test performance, a ratiometric electrochemical signal readout was designed, which was enhanced by a secondary in situ growth method fabricating trepang-shaped Au modified paper working electrode. In virtue of hybridization chain reaction, classic competitive recognition interactions of aptamer and target, and ratiometric internally calibrated mechanisms, ultrasensitive detection of the target was realized. To acquire a more quantitative and straightforward naked eye visual screening, the hydrophobic Ag switch was triggered by stimulating instructions from H2O2, thus reconnecting the electrochemical and ratiometric units automatically and resulting in a "signal on" visual fluidic flow on the chemometer characterized by the accurate distance of color development as a detection motif. With MCF-7 and K562 cells as models, wider linear detection ranges from 150 to 1.0 × 107 and 220 to 7.0 × 106 cells mL-1 for MCF-7 and K562 cells, respectively, were achieved. Meanwhile, thanks to the paper fluid chemometer, an acceptable screening detection limit of 103 cells mL-1 was obtained in the quantitative colorimetric assays. The proposed paper-based biochips opened up new horizons for designing of integratable, easy-to-use, and precise point-of-care testing devices.

Long noncoding RNA DIO3OS interacts with miR-122 to promote proliferation and invasion of pancreatic cancer cells through upregulating ALDOA.

BACKGROUND: Long noncoding RNA (lncRNA) has been implicated in numerous tumors, including pancreatic cancer (PC). However, the precise cellular roles and molecular mechanisms of lncRNA DIO3OS on PC development remains to be fully clarified. METHODS: We performed the meta-analysis on PC samples and non-tumor samples retrieved from the TCGA database, and measured the levels of DIO3OS in PC cell lines and a normal pancreatic duct epithelial cell line HPDE6-C7. Cell proliferation was evaluated via CCK-8 assay. Cell invasion in vitro was investigated by transwell assay. The RNA immunoprecipitation assay and luciferase reporter assay was utilized to confirm the putative miR-122-binding site in DIO3OS. The effects of DIO3OS on PC progression were tested using in vivo subcutaneous xenografts. RESULTS: Our results showed that DIO3OS was highly expressed in human PC tissues and PC cell lines. DIO3OS exhibited oncogenic properties in stimulating PC cell proliferation and invasion in vitro and promoting cancer growth in vivo. Through online predictive tools and functional experiments, we found that DIO3OS could bind directly to microRNA-122 (miR-122) and inhibited its expression, which functioned as a tumor suppressor in PC cells. We also verified that ALDOA was the direct target of miR-122, and the tumor suppressive effects caused by DIO3OS knockdown or miR-122 overexpression could be rescued by re-expression of ALDOA in PC cells. CONCLUSIONS: Overall, our study suggested that lncRNA DIO3OS promotes PC cell growth and invasion by competing for miR-122 to modulate the expression of ALDOA. These findings yield a better understanding of the potential mechanisms by which gain of DIO3OS expression accelerates PC progression.

Addressable TiO2 Nanotubes Functionalized Paper-Based Cyto-Sensor with Photocontrollable Switch for Highly-Efficient Evaluating Surface Protein Expressions of Cancer Cells.

Inspired by the well-known "Wheel of Fortune", a rotatable paper-photocontrollable switch (RPPS) was designed to form an addressable paper-based photoelectrochemical (PEC) cyto-sensor for ultrasensitive detection of a cell-surface protein. By simply rotating the RPPS, a light source can selectively activate the desired working zones of the cyto-sensor. To realize the high-performance paper-based PEC cyto-sensor, a cascaded photoactive interface consisting of neat TiO2 nanotubes arrays, Pt nanoparticles (NPs), and nitrogen-carbon dots was introduced into paper fibers, gaining signal-on PEC state (NTPP for short). Then the NTPP fixed with a hairpin probe H1 allowed the hybridization chain reaction (HCR) to happen with CuS NPs-labeled hairpin probe H2 by the free primer strand (PS) triggering; hence, the CuS NPs as the emulative sensitizers were introduced onto the NTPP with the photocurrent intensity decrement for signal-off PEC state. During this process, the PS carefully designed with specific sequences can recognize the target strand (TS) of MCF-7 cells and stimulate HCR by its trigger zone. The presence of MCF-7 cells destroyed the interaction between PS and ZnFe2O4 functionalized TS, causing the PS release from the mixture of PS and TS under the help of a magnet. Then, the released PS, acting as a primer probe, realized ultrasensitive detection of a cell-surface protein. On the basis of this novel protocol, multiple-signal amplification was skillfully imported into the addressable paper PEC chip, resulting in ultrasensitive quantification of carcinoembryonic antigen in the surface of MCF-7 cells. Given the fascinating analytical performances of the developed cyto-sensor, ultralow expression of antigens for MCF-7, A549, and PC 3 cells was discriminated effectively.

Paper-Based Origami Photoelectrochemical Sensing Platform with TiO2/Bi4NbO8Cl/Co-Pi Cascade Structure Enabling of Bidirectional Modulation of Charge Carrier Separation.

A bidirectional modulation of photoinduced charge carrier separation strategy based on TiO2/Bi4NbO8Cl/Co-Pi was proposed in microfluidic paper based photoelectrochemical analytical device (µ-POAD). Perovskite Bi4NbO8Cl with high charge carrier mobility was employed as visible light absorber, sandwiching between electron transporting material (ETM) and hole transporting material (HTM). Paper based TiO2 nanosheet arrays (PTNAs) serve as the ETM to provide a direct pathway for electron transport and Co-Pi works as the HTM to extract holes. Driven by a built-in electric field, the generated electrons of Bi4NbO8Cl are extracted by PTNAs, while holes are drawn toward Co-Pi, achieving efficient carrier separation. Remarkably, it is the first time that the HTM was introduced into µ-POAD to efficiently output holes and enhance the sensitivity. With the aid of ETM and HTM, 2.59 and 14.6 times higher photocurrent density was obtained compared with PTNAs/Bi4NbO8Cl and Bi4NbO8Cl photoelectrode, respectively. Benefiting from this dramatic photocurrent signal, ultrasensitive detection of ß human chorionic gonadotrophin is realized with the linear range of 0.01-3000 IU L-1 and detection limitation of 0.005 IU L-1. This work demonstrates the importance of efficient carrier separation to the sensitivity of µ-POAD and paves the way for developing a high-performance analytical device.

Stackable Lab-on-Paper Device with All-in-One Au Electrode for High-Efficiency Photoelectrochemical Cyto-Sensing.

Highly conductive, robust, and multifunctional integrated paper-supported electrodes are requisite to fulfill the promise of paper-based analytical application. Herein, an all-in-one Au electrode comprising of detection zone, waterproof electronic bridge, and signal output contactor was engineered via combining the double-sided growth method with the secondary wax-printing. Benefiting from the strongly omnidirectional conductivity and desirably mechanical robustness of the as-prepared electrode, a stackable lab-on-paper cyto-device integrated with high-efficiency photoelectrochemical strategy was developed for the MCF-7 cells assay. Specifically, the detection zone of the electrode, serving as the signal generator, was functionalized with a low-toxic cosensitized structure composed of corn-like ZnO nanorods, graphene quantum dots (GQDs), and Ag2Se QDs. With the proximity control of DNA hairpin-based aptamer probe (DHAP), a strong photocurrent could be promoted by the activated cosensitization effect and collected on the signal output contactor via the electron transport of waterproof electronic bridge. Upon the MCF-7 cells recognition, the DHAP switched from closed to open state with the formation of DNA-cell bioconjugates and the spatial separation of Ag2Se QDs linked on the terminal of DHAP from the electrode surface. The photocurrent was noticeably decreased due to the double inhibition of steric hindrance effect and vanished cosensitization effect. Based on the target-triggered photocurrent attenuation, the sensitive detection of target cells was achieved. This work not only provided a unique method for paper-based electrode preparation but also offered a powerful platform for the highly sensitive photoelectrochemical bioanalysis.

"On-Off-On" Photoelectrochemical/Visual Lab-on-Paper Sensing via Signal Amplification of CdS Quantum Dots@Leaf-Shape ZnO and Quenching of Au-Modified Prism-Anchored Octahedral CeO2 Nanoparticles.

An effective "on-off-on" photoelectrochemical (PEC)/visual sensing system based on cleaning-switchable lab-on-paper device was designed to achieve ultrasensitive detection of analytes. The first amplified "signal-on" PEC state was gained by CdS quantum dots sensitized leaf-shape ZnO (CdS QDs/leaf-shape ZnO) structure, which was assembled on reduced graphene oxide (rGO) modified paper electrode. Then Au-modified prism-anchored octahedral CeO2 nanoparticles (Au@PO-CeO2 NPs), as an efficient signal quencher, were immobilized on the CdS QDs/leaf-shape ZnO with the assistance of DNA hybridization, resulting in a noticeable photocurrent response decrement with the "signal-off" PEC state. With the addition of analytes, the quencher Au@PO-CeO2 NPs were immediately released from the sensing surface and robust PEC response was recovered to the signal-on state again. Meanwhile, the disengaged quencher in electrolyte solution flowed to the colorimetric detection area of lab-on-paper device and catalyzed oxidation of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine in the presence of H2O2 to form the colored product, making the analytes detection more convincing with the visual discrimination. Under optimal conditions, the proposed PEC/visual lab-on-paper device possessed the detection limits toward adenosine and potassium ion as low as 0.15 and 0.06 nM, respectively. With ingenious design of actuating conversion process between hydrophilicity and hydrophobicity by slipping paper tab to solve cleaning issue in the assay procedures, the cleaning-switchable lab-on-paper device was constructed for high-performance biosensing applications. It provides an unambiguous simplicity and portable operation for exploring high reliability and sensitivity of novel point-of-care diagnostic tool with dual-signal readout.

Transcriptome profiling reveals the genetic basis of alkalinity tolerance in wheat.

BACKGROUND: Soil alkalinity shows significant constraints to crop productivity; however, much less attention has been paid to analyze the effect of soil alkalinity on plant growth and development. Shanrong No. 4 (SR4) is an alkalinity tolerant bread wheat cultivar selected from an asymmetric somatic hybridization between the bread wheat cultivar Jinan 177 (JN177) and tall wheatgrass (Thinopyrum ponticum), which is a suitable material for studying alkalinity tolerant associate genes. RESULTS: The growth of SR4 plant seedlings was less inhibited than that of JN177 when exposed to alkalinity stress conditions. The root cytosolic Na+/K+ ratio in alkalinity stressed SR4 was lower than in JN177, while alkalinity stressed SR4 contained higher level of nutrient elements than in JN177. SR4 plant seedlings accumulated less malondialdehyde (MDA) and reactive oxygen species (ROS), it also showed higher activity of ROS scavenging enzymes than JN177 under alkalinity stress. The root intracellular pH decreased in both alkalinity stressed JN177 and SR4, however, it was much lower in SR4 than in JN177 under alkalinity stress. The transcriptomes of SR4 and JN177 seedlings exposed to alkalinity stress were analyzed by digital gene expression tag profiling method. Alkalinity stress conditions up- and down-regulated a large number of genes in the seedling roots that play the functions in the categories of transcription regulation, signal transduction and protein modification. CONCLUSIONS: SR4 expresses a superior tolerance to alkaline stress conditions which is due to its strong absorbing ability for nutrient ions, a strong regulating ability for intracellular and rhizosphere pH and a more active ROS scavenging ability.

Reversible Anion-Driven Switching of an Organic 2D Crystal at a Solid-Liquid Interface.

Ionic self-assembly of charged molecular building blocks relies on the interplay between long-range electrostatic forces and short-range, often cooperative, supramolecular interactions, yet has been seldom studied in two dimensions at the solid-liquid interface. Here, we demonstrate anion-driven switching of two-dimensional (2D) crystal structure at the Au(111)/octanoic acid interface. Using scanning tunneling microscopy (STM), three organic salts with identical polyaromatic cation (PQPC6+ ) but different anions (perchlorate, anthraquinonedisulfonate, benzenesulfonate) are shown to form distinct, highly ordered self-assembled structures. Reversible switching of the supramolecular arrangement is demonstrated by in situ exchange of the anion on the pre-formed adlayer, by changing the concentration ratio between the incoming and outgoing anion. Density functional theory (DFT) calculations reveal that perchlorate is highly mobile in the adlayer, and corroborate why this anion is only resolved transiently in STM. Surprisingly, the templating effect of the anion persists even where it does not become part of the adlayer 2D fabric, which we ascribe to differences in stabilization of cation conformations by the anion. Our results provide important insight into the structuring of mixed anion-cation adlayers. This is essential in the design of tectons for ionic self-assembled superstructures and biomimetic adaptive materials and valuable also to understand adsorbate-adsorbate interactions in heterogeneous catalysis.

Multicomponent self-assembly with a shape-persistent N-heterotriangulene macrocycle on Au(111).

Multicomponent network formation by using a shape-persistent macrocycle (MC6) at the interface between an organic liquid and Au(111) surface is demonstrated. MC6 serves as a versatile building block that can be coadsorbed with a variety of organic molecules based on different types of noncovalent interactions at the liquid-solid interface. Scanning tunneling microscopy (STM) reveals the formation of crystalline bicomponent networks upon codeposition of MC6 with aromatic molecules, such as fullerene (C60) and coronene. Tetracyanoquinodimethane, on the other hand, was found to induce disorder into the MC6 networks by adsorbing on the rim of the macrocycle. Immobilization of MC6 itself was studied in two different noncovalently assembled host networks. MC6 assumed a rather passive role as a guest and simply occupied the host cavities in one network, whereas it induced a structural transition in the other. Finally, the central cavity of MC6 was used to capture C60 in a complex three-component system. Precise immobilization of organic molecules at discrete locations within multicomponent networks, as demonstrated here, constitutes an important step towards bottom-up fabrication of functional surface-based nanostructures.

Coal-burning endemic fluorosis is associated with reduced activity in antioxidative enzymes and Cu/Zn-SOD gene expression.

To study the effect of fluorine on the oxidative stress in coal-burning fluorosis, we investigated the environmental characteristics of coal-burning endemic fluorosis combined with fluorine content surveillance in air, water, food, briquette, and clay binder samples from Bijie region, Guizhou Province, southwest of China. The activities of antioxidant enzymes including copper/zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and level of lipid peroxidation such as malondialdehyde (MDA) were measured in serum samples obtained from subjects residing in the Bijie region. Expression of the Cu/Zn-SOD gene was assessed by quantitative reverse transcriptase PCR (qRT-PCR). Our results showed that people suffering from endemic fluorosis (the high and low exposure groups) had much higher MDA level. Their antioxidant enzyme activities and Cu/Zn-SOD gene expression levels were lower when compared to healthy people (the control group). Fluorosis can decrease the activities of antioxidant enzymes, which was associated with exposure level of fluorine. Down-regulation of Cu/Zn-SOD expression may play an important role in the aggravation of oxidative stress in endemic fluorosis.

Squeezing, then stacking: from breathing pores to three-dimensional ionic self-assembly under electrochemical control.

We demonstrate the spontaneous and reversible transition between the two- and three-dimensional self-assembly of a supramolecular system at the solid-liquid interface under electrochemical conditions, using in situ scanning tunneling microscopy. By tuning the interfacial potential, we can selectively organize our target molecules in an open porous pattern, fill these pores to form an auto-host-guest structure, or stack the building blocks in a stratified bilayer. Using a simple electrostatic model, we rationalize which charge density is required to enable bilayer formation, and conversely, which molecular size/charge ratio is necessary in the design of new building blocks. Our results may lead to a new class of electrochemically controlled dynamic host-guest systems, artificial receptors, and smart materials.

Gene mutation profiling in microsatellite instability colorectal cancer and its association with the efficacy of immunotherapy: A retrospective study.

BACKGROUND: Microsatellite instability-high (MSI-H) colorectal cancer (CRC) is known for its heightened responsiveness to immunotherapy. However, establishing robust predictive markers for immunotherapy efficacy remains imperative. This retrospective study aimed to elucidate the genetic landscape of MSI-H CRC and correlate these genetic alterations with immunotherapy outcomes in a cohort of 121 patients. METHODS: We analyzed clinical and molecular data from 121 patients with MSI-H CRC. We conducted a thorough genetic analysis of MSI-H CRC patients, with a specific emphasis on the APC, TP53, RAS, and MMR genes. We further analyzed the relationship between gene mutations and immunotherapy efficacy. The primary endpoints analyzed were objective response rate (ORR) and progression-free survival (PFS). All statistical analysis was conducted using SPSS26.0 and R 4.2.0 software. RESULTS: Our findings underscored the complexity of the genetic landscape in MSI-H CRC, shedding light on the intricate interplay of these genes in CRC development. Notably, mutations in MMR genes exhibited a distinctive pattern, providing insights into the underlying mechanisms of MSI-H. Furthermore, our results revealed correlations between specific genetic alterations and immunotherapy outcomes, with a particular focus on treatment response rates and progression-free survival. CONCLUSION: This study represents a significant step toward unraveling the genetic nuances of MSI-H CRC. The distinctive pattern of MMR gene mutations not only adds depth to our understanding of MSI-H CRC but also hints at potential avenues for targeted therapies. This research sets the stage for future investigations aimed at refining therapeutic strategies and improving outcomes for patients with MSI-H CRC.

Biological upcycling of nickel and sulfate as electrocatalyst from electroplating wastewater.

Upcycling nickel (Ni) to useful catalyst is an appealing route to realize low-carbon treatment of electroplating wastewater and simultaneously recovering Ni resource, but has been restricted by the needs for costly membranes or consumption of large amount of chemicals in the existing upcycling processes. Herein, a biological upcycling route for synchronous recovery of Ni and sulfate as electrocatalysts, with certain amount of ferric salt (Fe3+) added to tune the product composition, is proposed. Efficient biosynthesis of bio-NiFeS nanoparticles from electroplating wastewater was achieved by harnessing the sulfate reduction and metal detoxification ability of Desulfovibrio vulgaris. The optimal bio-NiFeS, after further annealing at 300 °C, served as an efficient oxygen evolution electrocatalyst, achieving a current density of 10 mA·cm-1 at an overpotential of 247 mV and a Tafel slope of 60.2 mV·dec-1. It exhibited comparable electrocatalytic activity with the chemically-synthesized counterparts and outperformed the commercial RuO2. The feasibility of the biological upcycling approach for treating real Ni-containing electroplating wastewater was also demonstrated, achieving 99.5 % Ni2+removal and 41.0 % SO42- removal and enabling low-cost fabrication of electrocatalyst. Our work paves a new path for sustainable treatment of Ni-containing wastewater and may inspire technology innovations in recycling/ removal of various metal ions.

Z-Scheme Heterojunction Excited by DNA-Programmed Upconversion Nanotransducers for a Near-Infrared Light-Actuated Lab-on-Paper Device.

Herein, a flexible near-infrared (NIR) light-actuated photoelectrochemical (PEC) lab-on-paper device was constructed toward miRNA-122 detection, utilizing the combination of DNA-programmed NaYF4/Yb,Tm upconversion nanoparticles (UCNPs) and the Z-scheme AgI/WO3 heterojunction grown in situ on gold nanoparticle-decorated 3D cellulose fibers. The UCNPs were employed as light transducers for converting NIR light into ultraviolet/visible (UV/vis) light to excite the nanojunction. The multiple diffraction of NaYF4/Yb,Tm matched the absorption band of the Z-scheme AgI/WO3 heterojunction, resulting in enhanced PEC photocurrent output. This prepared Z-scheme heterojunction effectively directed charge migration and highly facilitated the electron-hole pair separation. Target miRNA-122 activated the nonenzyme catalytic hairpin assembly signal amplification strategy, generating duplexes which caused the exfoliation of NaYF4/Yb,Tm UCNPs from the biosensor electrode and lowered the photocurrent under 980 nm irradiation. Under optimized circumstances, the proposed NIR-actuated PEC lab-on-paper device presented accurate miRNA-122 detection within a wide linear range of 10 fM-100 nM with a low limit of detection of 2.32 fM, providing a reliable strategy in the exploration of NIR-actuated PEC biosensors for low-cost, high-performance bioassay in clinical applications.