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Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with limited response to chemotherapy. Histone acetylation is reduced in DLBCL. Chidamide, a histone deacetylase inhibitor, shows promise in lymphomas but needs further investigation for DLBCL. Our study indicated that chidamide effectively suppresses DLBCL both in vitro and in vivo. High-throughput RNA sequencing analysis provided comprehensive evidence that chidamide markedly influences crucial signaling pathways in DLBCL, including the MAPK, MYC and p53 pathway. Additionally, we observed substantial variability in the sensitivity of DLBCL cells to chidamide, and identified that elevated expression of BCL6 might confer resistance to chidamide in DLBCL. Moreover, our investigations revealed that BCL6 inhibited chidamide-induced histone acetylation by recruiting histone deacetylase (HDACs), leading to drug resistance in DLBCL cells. Furthermore, we found that lenalidomide targeted BCL6 degradation through the ubiquitination pathway and restore the sensitivity of drug-resistant DLBCL to chidamide. Collectively, these findings provided valuable insights into the global impact of chidamide on DLBCL and highlight the potential of targeting HDACs as a therapeutic strategy for DLBCL. Identifying BCL6 as a biomarker for predicting the response to chidamide and the combination therapy with BCL6 inhibition has the potential to lead to more personalized and effective treatments for DLBCL patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Developing biosensors with antifouling properties is essential for accurately detecting low-concentration biomarkers in complex biological matrix, which is imperative for effective disease diagnosis and treatment. Herein, an antifouling electrochemical aptasensor qualifying for probing targets in human serum was explored based on newly-devised peptides that could form inverted U-shaped structures with long-term stability., Results: The inverted U-shaped peptides (U-Pep) with two terminals of thiol groups grafted onto the Au-modified electrode showcase superior antifouling properties in terms of high stability against enzymatic hydrolysis and long acting against biofouling in actual biofluids. The construction of the outlined antifouling electrochemical aptasensor just involved the fabrication of Au-deposited poly(3,4 ethylenedioxythiophene) (Au/PEDOT) modified electrode, followed by one-step co-incubation in the peptides and the aptamer probes with the Au/PEDOT electrode. Taking a typical biomarker of alpha-fetoprotein (AFP) for detection, this elegant antifouling aptasenor demonstrated a nice response for probing the target AFP with a low detection limit of 0.27 pg/mL and a wide linear scope of 1.0 pg/mL to 1.0 μg/mL, and furthermore qualified for assaying of AFP in human serum samples with satisfactory accuracy and feasibility., Significance: This engineering strategy of U-Pep with long-lasting antifouling efficacy opens a new horizon for high-performance antifouling biosensors suitable for detection in complex bifluids, and it could spark more inspiration for a follow-up exploration of other featured antifouling biomaterials., Competing Interests: Declaration of competing interest We hereby declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. Furthermore, we affirm that there are no professional or personal interests of any kind in any products, services, or companies that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Growing evidence indicated that to develop of atherosclerosis observed more often by people with Alzheimer's disease (AD), but the underlying mechanism is not fully clarified. Considering that amyloid-β (Aβ) deposition in the brain is the key pathophysiology of AD and plasma Aβ is closely relate to Aβ deposition in the brain, in the present study, we investigated the relationships between atherosclerosis and plasma Aβ levels., Methods: This was a population based cross-sectional study. Patients with high risk of atherosclerosis from Qubao Village, Xi'an were underwent carotid ultrasound for assessment of atherosclerosis. Venous blood was collected on empty stomach in the morning and plasma Aβ 1-40 and Aβ 1-42 levels were measured using ELISA. Multivariate logistic regression analysis was performed to investigate the relationships between carotid atherosclerosis (CAS) and plasma Aβ levels., Results: Among 344 patients with high risk of atherosclerosis, 251(73.0%) had CAS. In the univariate analysis, the plasma Aβ levels had no significant differences between CAS group and non-CAS group (Aβ 1-40 : 53.07 ± 9.24 pg/ml vs. 51.67 ± 9.11pg/ml, p = 0.211; Aβ 1-42 : 40.10 ± 5.57 pg/ml vs. 40.70 pg/ml ± 6.37pg/ml, p = 0.285). Multivariate logistic analysis showed that plasma Aβ levels were not associated with CAS (Aβ 1-40 : OR = 1.019, 95%CI: 0.985-1.054, p = 0.270;Aβ 1-42 : OR = 1.028, 95%CI: 0.980-1.079, p = 0.256) in the total study population. After stratified by hypertension, CAS was associated with plasma Aβ 1-40 positively (OR = 1.063, 95%CI: 1.007-1.122, p = 0.028) in the non-hypertension group, but not in hypertensive group. When the plasma Aβ concentrations were classified into four groups according to its quartile, the highest level of plasma Aβ 1-40 group was associated with CAS significantly (OR = 4.465, 95%CI: 1.024-19.474, p = 0.046)., Conclusion: Among patients with high risk of atherosclerosis, CAS was associated with higher plasma Aβ 1-40 level in non-hypertension group, but not in hypertension group. These indicated that atherosclerosis is associated with plasma Aβ level, but the relationship may be confounded by hypertension., (© 2024. The Author(s).)

Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of "transmembrane" and "in-cell target encounter", bypassing the need of multistep signal conversion. The MTD system comprises two intelligent nanorobots capable of independently sensing three molecular markers (MUC1, EpCAM, and miR-21), resulting in comprehensive analysis. Our AND-AND logic-gated system (MTD AND-AND ) demonstrates exceptional specificity, allowing targeted release of drug-DNA specifically in MCF-7 cells. Furthermore, the transformed OR-AND logic-gated system (MTD OR-AND ) exhibits broader adaptability, facilitating the release of drug-DNA in three positive cancer cell lines (MCF-7, HeLa, and HepG2). Importantly, MTD AND-AND and MTD OR-AND , while possessing distinct personalized therapeutic potential, share the ability of outputting three imaging signals without any intermediate conversion steps. This feature ensures precise classification cross diverse cells (MCF-7, HeLa, HepG2, and MCF-10A), even in mixed populations. This study provides a straightforward yet effective solution to augment the versatility and precision of DNA computing systems, advancing their potential applications in biomedical diagnostic and therapeutic research.

Heat stress (HS) poses a substantial threat to animal growth and development, resulting in declining performance and economic losses. The intestinal system is susceptible to HS and undergoes intestinal hyperthermia and pathological hypoxia. Hypoxia-inducible factor-1α (HIF-1α), a key player in cellular hypoxic adaptation, is influenced by prolyl-4-hydroxylase 2 (PHD2) and heat shock protein 90 (HSP90). However, the comprehensive regulation of HIF-1α in the HS intestine remains unclear. This study aims to explore the impact of HS on pig intestinal mucosa and the regulatory mechanism of HIF-1α. Twenty-four Congjiang Xiang pigs were divided into the control and five HS-treated groups (6, 12, 24, 48, and 72 h). Ambient temperature and humidity were maintained in a thermally-neutral state (temperature-humidity index (THI) < 74) in the control group, whereas the HS group experienced moderate HS (78 < THI <84). Histological examination revealed villus exfoliation after 12 h of HS in the duodenum, jejunum, and ileum, with increasing damage as HS duration extended. The villus height to crypt depth ratio (V/C) decreased and goblet cell number increased with prolonged HS. Quantitative real-time PCR, Western blot, and immunohistochemistry analysis indicated increased expression of HIF-1α and HSP90 in the small intestine with prolonged HS, whereas PHD2 expression decreased. Further investigation in IPEC-J2 cells subjected to HS revealed that overexpressing PHD2 increased PHD2 mRNA and protein expression, while it decreases HIF-1α. Conversely, interfering with HSP90 expression substantially decreased both HSP90 and HIF-1α mRNA and protein levels. These results suggest that HS induces intestinal hypoxia with concomitant small intestinal mucosal damage. The expression of HIF-1α in HS-treated intestinal epithelial cells may be co-regulated by HSP90 and PHD2 and is possibly linked to intestinal hyperthermia and hypoxia., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. The author confirms that the work described has not been published before and its publication has been approved by all co-authors., (Copyright © 2024. Published by Elsevier Ltd.)

A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC 50 value of 3.94 ± 0.17 µmol L -1 (NCI-H1299), 3.16 ± 0.11 µmol L -1 (A549), and 1.83 ± 0.13 µmol L -1 (NCI-H1437) for 7a, and an IC 50 value of 3.84 ± 0.22 µmol L -1 (NCI-H1299), 3.86 ± 0.38 µmol L -1 (A549), and 1.69 ± 0.25 µmol L -1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer., (© 2024. The Author(s).)

Antifouling biosensors capable of preventing protein nonspecific adhesion in real human bodily fluids are highly sought-after for precise disease diagnosis and treatment. In this context, an enhanced split-type photoelectrochemical (PEC) aptasensor was developed incorporating a four-armed polyethylene glycol (4A-PEG) to construct a robust antifouling coating, enabling accurate and sensitive bioanalysis. The split-type PEC system involved the photoelectrode and the biocathode, effectively separating signal converter with biorecogniton events. Specifically, the TiO 2 electrode underwent sequential modification with ZnIn 2 S 4 (ZIS) and polydopamine (PDA) to form the PDA/ZIS/TiO 2 photoelectrode. The cathode substrate was synthesized as a hybrid of N-doped graphene loaded with Pt nanoparticles (NG-Pt), and subsequently modified with 4A-PEG to establish a robust antifouling coating. Following the anchoring of probe DNA (pDNA) on the 4A-PEG-grafted antifouling coating, the biocathode for model target of cancer antigen 125 (CA125) was obtained. Leveraging pronounced photocurrent output of the photoelectrode and commendable antifouling characteristics of the biocathode, the split-type PEC aptasensor showcased exceptional detection performances with high sensitivity, good selectivity, antifouling ability, and potential feasibility., Competing Interests: Declaration of competing interest We hereby declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. Furthermore, we affirm that there are no professional or personal interests of any kind in any products, services, or companies that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Peptides with distinct physiochemical properties and biocompatibility hold significant promise across diverse domains including antifouling biosensors. However, the stability of natural antifouling peptides in physiological conditions poses significant challenges to their viability for sustained practical applications. Herein, a unique antifouling peptide FFFGGGEKEKEKEK was designed and self-assembled to form peptide nanoparticles (PNPs), which possessed enhanced stability against enzymatic hydrolysis in biological fluids. The PNP-coated interfaces exhibited superior stability and antifouling properties in preventing adsorption of nonspecific materials, such as proteins and cells in biological samples. Moreover, a highly sensitive and ultralow fouling electrochemical biosensor was developed through the immobilization of the PNPs and specific aptamers onto the polyaniline nanowire-modified electrode, achieving the biomarker carcinoembryonic antigen detection in complex biofluids with reliable accuracy. This research not only addresses the challenge of the poor proteolytic resistance observed in natural peptides but also introduces a universal strategy for constructing ultralow fouling sensing devices.

Recently, organic photoelectrochemical transistor (OPECT) bioanalysis has become a prominent technique for the high-performance detection of biomolecules. However, as a sensitive index of the OPECT, the dynamic regulation transconductance ( g m ) is still severely deficient. Herein, this work reports a new photosensitive metal-organic framework (MOF-on-MOF) heterostructure for the effective modulation of maximum g m and natural bienzyme interfacing toward choline detection. Specifically, the bidentate ligand MOF (b-MOF) was assembled onto the UiO-66 MOF (u-MOF) by a modular assembly method, which could facilitate the charge separation and generate enhanced photocurrents and offer a biophilic environment for the immobilization of choline oxidase (ChOx) and horseradish peroxidase (HRP) through hydrogen-bonded bridges. The transconductance of the OPECT could be flexibly altered by increased light intensity to maximal value at zero gate bias, and sensitive choline detection was achieved with a detection limit of 0.2 μM. This work reveals the potential of MOF-on-MOF heterostructures for futuristic optobioelectronics.

Advanced antifouling biosensors have garnered considerable attention for their potential for precise and sensitive analysis in complex human bodily fluids. Herein, a pioneering approach was utilized to establish a robust and versatile photoelectrochemical aptasensor by conjugating a zwitterionic peptide with a DNA strand. Specifically, the branched zwitterionic peptide (BZP) was efficiently linked to complementary DNA (cDNA) through a click reaction, forming the BZP-cDNA conjugate. This intriguing conjugate exploited the BZP domain to create an antifouling biointerface, while the cDNA component facilitated subsequent hybridization with probe DNA (pDNA). To advance the development of the aptasensor, an upgraded PDA/HOF-101/ZnO ternary photoelectrode was designed as the signal converter for the modification of the BZP-cDNA conjugate, while a bipyridinium (MCEPy) molecule with strong electron-withdrawing properties was labeled at the front end of the pDNA to form the pDNA-MCEPy signal probe. Targeting the model of mucin-1, a remarkable enhancement in the photocurrent signal was achieved through exonuclease-I-aided target recycling. Such an engineered zwitterionic peptide-DNA conjugate surpasses the limitations imposed by conventional peptide-based sensing modes, exhibiting unique advantages such as versatility in design and capability for signal amplification.

Artificial solid-state nanochannels have aroused intense interests in biosensors and bioelectronics because of their special architectures. Herein, we pioneered an ingenious approach of target-triggered cascade signal amplification in porous anodic aluminum oxide (AAO) nanochannels for ultrasensitive photoelectrochemical (PEC) DNA bioanalysis. In the design, AAO nanochannels were modified initially with capture DNA (cDNA) and then incorporated with a photoelectrode, yielding the desired architecture of highly ordered nanoarrays on top of the signal transducer. For target DNA (tDNA) probing, exonuclease III (Exo-III) mediated target recycling (ETR) was first activated to generate plenty of output DNA (oDNA) fragments. After oDNA and the conjugate of Au-labeled probe DNA (Au-pDNA) were anchored within the nanochannels via DNA hybridization, in-situ synthesis of Ag shells on tethered Au nanoparticles was conducted. The resulting large-sized Au@Ag core-shell nanostructure within the nanochannels would cause conspicuous blocking effect to hinder the transportation of electrons accessing the photoelectrode. Since the signal inhibition was directly related to tDNA concentration, an innovative nanochannels PEC DNA assay was exploited and qualified for ultrasensitive detection. The anti-interference ability of this platform was also emphasized by the split AAO membrane for biological incubation without participation of the photoelectrode. This featured nanochannels PEC strategy with cascade amplification launched a novel detecting platform for trace levels of DNA, and it could spark more inspiration for a follow-up exploration of other smart nanochannels PEC bioassays., Competing Interests: Declaration of competing interest We hereby declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. Furthermore, we affirm that there are no professional or personal interests of any kind in any products, services, or companies that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The challenge of heavy biofouling in complex sweat environments limits the potential of electrochemical sweat sensors for noninvasive physiological assessment. In this study, a novel semi-interpenetrating hydrogel of PSBMA/PEDOT:PSS was engineered by interlacing PEDOT:PSS conductive polymer with zwitterionic PSBMA network. This versatile hydrogel served as the foundation for developing an anti-fouling wearable molecular imprinting sensor capable of sensitive and robust detection of tryptophan (Trp) in complex sweat. The incorporation of PEDOT:PSS conductive polymer into the semi-interpenetrating hydrogel introduced diverse physical crosslinks, including hydrogen bonding, electrostatic interactions, and chain entanglement. This incorporation considerably boosted the hydrogel's mechanical robustness and imparted commendable self-healing property. At the same time, the synergistic coupling between the well-balanced charge of the zwitterionic network and the high conductivity of the PEDOT:PSS polymer facilitated efficient charge transfer. The formation of the desired molecular imprinting membrane of semi-interpenetrating hydrogel was triggered by self-polymerization of dopamine (DA) in the presence of Trp. The designed biosensor demonstrated good sensitivity, selectivity and stability in detecting the target Trp. Notably, it also exhibited exceptional anti-fouling abilities, allowing for accurate Trp detection in complex real sweat samples, yielding results comparable to commercial enzyme-linked immunoassay (ELISA)., Competing Interests: Declaration of competing interest We hereby declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. Furthermore, we affirm that there are no professional or personal interests of any kind in any products, services, or companies that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We report an electrochemiluminescence (ECL) sensor for Salmonella detection based on allosteric probe as a bio-recognition element and CRISPR/Cas12a as a signal amplification strategy. In the presence of Salmonella, the structure switching occurs on allosteric probes, resulting in their hybridization with primers to trigger isothermal amplification. Salmonella is then released to initiate the next reaction cycle accompanying by generating a large amount of dsDNA, which are subsequently recognized by CRISPR-gRNA for activating the trans-cleavage activity of Cas12a. Furthermore, the activated Cas12a can indiscriminately cut the ssDNA which is bound to the electrode, enabling the release of the ECL emitter porphyrinic Zr metal - organic framework (MOF, PCN-224) and exhibiting a decreased ECL signal accordingly. The linear range is 50 CFU·mL -1 -5 × 10 6 CFU·mL -1 and the detection limit is calculated to be 37 CFU·mL -1 . This method sensitively detects Salmonella in different types of real samples, indicating it is a promising strategy for Salmonella detection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Catalytic decomposition of methane offers a viable solution for producing pure hydrogen and nanocarbon without emitting carbon dioxide. However, conventional thermal catalytic processes and catalysts have limitations in terms of poor carbon quality and catalyst deactivation due to carbon deposition. The newly developed electrochemical splitting of methane (ESM) in molten salt has emerged as a promising alternative that allows for the separate production of hydrogen at the anode and carbon deposition at the cathode. In this study, hydrogen produced via ESM while generating nanocarbon with diverse structures through manipulations of the cathode material and kinetics. Carbon nanotubes grown on Ni cathode, possessing high specific surface area and abundant functional groups, displayed excellent adsorptive capacity for dye adsorption. The open hollow nanocarbon grown on the Ag cathode displayed good capacitance performance. ESM technology has immense potential to enhance the utilization value of carbon by-products and the commercial production of green hydrogen., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The building of practical biosensors that have anti-interference abilities against biofouling of nonspecific proteins and biooxidation of reducing agents in actual biological matrixes remains a great challenge. Herein, a robust photoelectrochemical (PEC) biosensor capable of accurate detection in human serum was pioneered through the integration of a new engineered branching peptide (EBP) into a synergetic dual-photoelectrode system. The synergetic dual-photoelectrode system involved the tandem connection of a C 3 N 4 /TiO 2 photoanode and a AuPt/PANI photocathode, while the EBP as a dual-functional antifouling and recognition probe featured an inverted Y-shaped configuration with one recognition backbone and two antifouling branches. Such an EBP enables a simple procedure for electrode modification and an enhanced antifouling nature compared to a regular linear peptide (LP), as theoretically supported by the results from molecular dynamics simulations. The as-developed PEC biosensor had a higher photocurrent response and a good antioxidation property inherited from the photoanode and photocathode, respectively. Targeting the model protein biomarker of cardiac troponin I (cTnI), this biosensor achieved good performances in terms of high sensitivity, specificity, and anti-interference.

CRISPR/Cas12a has been believed to be powerful in molecular detection and diagnostics due to its amplified trans-cleavage feature. However, the activating specificity and multiple activation mechanisms of the Cas12a system are yet to be elucidated fully. Herein, a "synergistic activator effect" is discovered, which supports an activation mechanism that a synergistic incorporation of two short ssDNA activators can promote the trans-cleavage of CRISPR/Cas12a, while either of them is too short to work independently. As a proof-of-concept example, the synergistic activator-triggered CRISPR/Cas12a system has been successfully harnessed in the AND logic operation and the discrimination of single-nucleotide variants, requiring no signal conversion elements or other amplified enzymes. Moreover, a single-nucleotide specificity has been achieved for the detection of single-nucleotide variants by pre-introducing a synthetic mismatch between crRNA and the "helper" activator. The finding of "synergistic activator effect" not only provides deeper insight into CRISPR/Cas12a but also may facilitate its expanded application and power the exploration of the undiscovered properties of other CRISPR/Cas systems.

Accurate identification of cancer cells is an essential prerequisite for cancer diagnosis and subsequent effective curative interventions. The logic-gate-assisted cancer imaging system that allows a comparison of expression levels between biomarkers, rather than just reading biomarkers as inputs, returns a more comprehensive logical output, improving its accuracy for cell identification. To fulfill this key criterion, we develop a compute-and-release logic-gated double-amplified DNA cascade circuit. This novel system, CAR-CHA-HCR, consists of a compute-and-release (CAR) logic gate, a double-amplified DNA cascade circuit (termed CHA-HCR), and a MnO 2 nanocarrier. CAR-CHA-HCR, a novel adaptive logic system, is designed to logically output the fluorescence signals after computing the expression levels of intracellular miR-21 and miR-892b. Only when miR-21 is present and its expression level is above the threshold C miR-21 > C miR-892b , the CAR-CHA-HCR circuit performs a compute-and-release operation on free miR-21, thereby outputting enhanced fluorescence signals to accurately image positive cells. It is capable of comparing the relative concentrations of two biomarkers while sensing them, thus allowing accurate identification of positive cancer cells, even in mixed cell populations. Such an intelligent system provides an avenue for highly accurate cancer imaging and is potentially envisioned to perform more complex tasks in biomedical studies.

To establish protein enzyme-free and simple approach for sensitive detection of single nucleotide polymorphisms (SNPs), the nucleic acid amplification reactions were developed to reduce the dependence on protein enzymes (polymerase, endonuclease, ligase). These methods, while enabling highly amplified analysis for the short sequences, cannot be generalized to long genomic sequences. Herein, we develop a protein enzyme-free and general SNPs assay based on asymmetric MNAzyme probes. The multi-arm probe (MNAzyme-9 M -13) with two asymmetric recognition arms, containing a short (9 nt) and a long (13 nt) arm, is designed to detect EGFR T790 M mutation (MT). Owing to the excellent selectivity of short recognition arm, MNAzyme-9 M -13 probe can efficiently avoid interferences from wild-type target (WT) and various single-base mutations. Through a one-pot mixing, MNAzyme-9 M -13 probe enables the sensitive detection of MT, without protein enzyme or multi-step operation. The calculated detection limit for MT is 0.59 nM and 0.83%. Moreover, this asymmetric MNAzyme strategy can be applied for SNPs detection in long genomic sequences as well as short microRNAs (miRNAs) only by changing the low-cost unlabeled recognition arms. Therefore, along with simple operation, low-cost, protein enzyme-free and strong versatility, our asymmetric MNAzyme strategy provides a novel solution for SNPs detection and genes analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

An ingenious strategy with the integration of a zwitterionic peptide into a two-photoelectrode system was reported to construct an advanced photoelectrochemical immunosensing platform. The strategy has endowed the platform with both excellent photoelectric properties and an antifouling ability, and was capable of accurate and sensitive detection of target biomarkers in biological specimens.

Photocathodic immunosensors generally exhibit fortified anti-interference abilities than photoanodic ones against the detection in biological specimens. Yet, the weak photocurrent signals of the photocathodes have limited evidently the detection performance. Herein, an efficient and feasible photoelectrochemical (PEC) immunosensor was developed on the basis of the featured photocathode-photoanode operating system. In the proposal, the elaborated PEC immunosensor integrated photocathode with photoanode, and the immune recognition occurred just on the photocathode. To illustrate the performance, α-fetoprotein (AFP) was selected as a target antigen (Ag) for detection. TiO 2 nanoparticles were decorated with AgInS 2 quantum dots (AIS QDs) to fabricate the TiO 2 /AIS photoanode, and the carbon nanotubes (CNTs) were modified with CuInS 2 nanoflowers (CIS NFs) to prepare the CNT/CIS photocathode for the capture AFP antibody (Ab) anchoring. Target Ag detection depended on significant decrease of the photocurrent signal produced by large steric hindrance of the captured AFP molecules. Coupling excellent photoelectric property with anti-interference ability in this elegant PEC immunosensor, sensitive and specific probing of target Ag was realized. The proposed photocathode-photoanode integrating strategy provides a promising way to explore other high-performance PEC immunosensors against the detection in biological matrixes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We conducted a two-factor split-plot experiment to examine the alteration of soil inorganic phosphorus forms and phosphorus availability under straw mulching and phosphorus fertilizer rates. The main factor was straw mulching and non-mulching, while the sub-factor was phosphorus supply rates, including 0, 75, and 120 kg·hm -2 . We analyzed the characteristics of phosphorus adsorption-desorption, the content of inorganic phosphorus components and their relationship with available phosphorus in hilly upland purple soil in Sichuan. Results showed that compared with the non-mulching, the maximum phosphorus adsorption capacity of straw mulching was notably decreased by 7.7% and 7.4% in the two experimental years from 2018 to 2020. The degree of phosphorus saturation and readily desorbable phosphorus of straw mulching were remarkably increased by 35.4% and 21.6% in 2019 and 18.6% and 35.2% in 2020, respectively. The maximum buffer capacity of phosphorus was not different between straw mulching and non-mulching. The maximum phosphorus adsorption capacity and maximum buffer capacity of phosphorus were significantly lower, and the degree of phosphorus saturation was notably higher in the phosphorus application treatment than that under no phosphorus treatment. The readily desorbable phosphorus increased with the increases of phosphorus rates. The contents of dicalcium phosphate (Ca 2 -P), octa-calcium phosphate (Ca 8 -P) and iron phosphorus (Fe-P) in straw mulching treatment were notably higher than those in non-mulching treatment, whereas the content of aluminum phosphorus (Al-P) significantly lower under the straw mulching. Meanwhile, the contents of occluded phosphate (O-P) and apatite (Ca 10 -P) tended to decrease in the straw mulching compared with that under the non-mulching. Phosphorus application increased the content of different inorganic phosphorus components. Compared with the non-mulching, soil available phosphorus content and the phosphorus activation coefficient of straw mulching remarkably increased by 23.2% and 21.3% in 2019, and 9.6% and 8.9% in 2020, respectively. Soil available phosphorus content and phosphorus activation coefficient increased with the increases of phosphorus rate. Results of regression analysis showed that the contribution of inorganic phosphorus components to the availability of available phosphorus in purple soil was Ca 2 -P > Fe-P > Al-P > Ca 8 -P > Ca 10 -P > O-P. Therefore, straw mulching combined with a reasonable phosphorus fertilizer rate could promote the decomposition and transformation of insoluble soil phosphorus to moderately active or easily absorbed phosphorus forms, reduce soil phosphorus adsorption, stimulate soil phosphorus desorption, and improve soil phosphorus availability. Based on the economic benefits, phosphate fertilizer application at the rate of 75 kg·hm -2 combined with straw mulching was recommended in Sichuan hilly dryland, which would be more beneficial in improving soil phosphorus availability.

Rabies is caused by the infection of Rabies virus, it leads to fatal encephalitis, developing a highly sensitive and specific detection method for Rabies virus remains a challenge. Herein, we report an electrochemiluminescence (ECL) biosensor for Rabies viral RNA based on dual-signal amplification and DNA nanotweezers (DTs). Dual-signal amplification process includes target binding induced isothermal amplification and CRISPR-based amplification. In the presence of target RNA, two assisted probes simultaneously hybridized with it to trigger isothermal amplification with the help of polymerase and nicking enzyme. This process generated a large amount of single-stranded DNA (ssDNA) as products. The products hybridized with CRISPR RNA to activate the trans-cleavage activity of Cas12a to indiscriminately cleave predesigned single-stranded trigger (ST) strands. After mixing the cleavage products with DTs and hemin molecules, DTs cannot be closed by cleaved ST strands to capture hemin to the electrode to quench the ECL signal. Therefore, the higher concentration of the target, the stronger intensity of the ECL signal. The detection limit is as low as 2.8 pM and the detection range is from 5 pM to 5 nM with excellent specificity and stability. The proposed method provides a promising strategy for Rabies detection, and can be easily adapted to other analytes via reasonable design as a valuable and versatile tool in bioanalysis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

SignificanceThere is a common consensus that lode gold deposits mostly precipitated from metamorphic fluids via fluid boiling and/or fluid-rock interaction, but whether magmatic hydrothermal fluids and the mixing of such fluids with an external component have played a vital role in the formation of lode gold deposits remains elusive. We use garnet secondary ion mass spectrometry oxygen isotope analysis to demonstrate that the world-class Dongping lode gold deposit has been formed by multiple pulses of magmatic hydrothermal fluids and their mixing with large volumes of meteoric water. This study opens an opportunity to tightly constrain the origin of lode gold deposits worldwide and other hydrothermal systems that may have generated giant ore deposits in the Earth's crust.

Target biomarker detection with high accuracy in biological sample is necessary for the constructed immunoassays. Herein, a novel and enhanced cathodic immunosensor supported by photoanode was designed for sensitive and specific detection of human chorionic gonadotropin (HCG). Specifically, the electrode of TiO 2 nanotube with N doping (TiO 2 :N) was fabricated and assembled with AgInS 2 quantum dots (QDs) to acquire the TiO 2 :N/AgInS 2 photoanode. For the sensing cathode, Pt nanoparticles (NPs) were decorated on carbon nanotubes (CNTs) to prepare the CNT/Pt cathodic matrix and was used to modify capture HCG antibody (Ab). In this photoelectrochemical (PEC) sensing system, the TiO 2 :N/AgInS 2 photoanode served as the signal-converting element to produce prominent current signal, while the immune recognition events occurred on the sensing cathode to evidently change the initial current signal from steric hindrance effect. Profiting by excellent photoelectric property and good anti-interference ability of this featured PEC system, the developed cathodic immunosensor demonstrated high sensitivity and specificity for the detection of target HCG antigen (Ag). This photoanode-supported cathodic sensing strategy provided a potential path forward to exploit other enhanced PEC immunosensors in the application of biological samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

DNA nanotweezers (DTs) are reversible DNA nanodevices that can optionally switch between opened and closed states. Due to their excellent flexibility and high programmability, they have been recognized as a promising platform for constructing a diversity of biosensors and logic gates, as well as a versatile tool for molecular biology studies. In this review, we provide an overview of biosensing applications using DTs. First, the design and working principle of DTs are introduced. Next, the signal producing principles of DTs are summarized. Furthermore, biosensing applications of DTs for varying targets and purposes, both in buffers and complex biological environments, are highlighted. Finally, we provide potential opportunities and challenges for the further development of DTs.

Taking the maximum fluorescence of an identical fluorophore as a reference, a DNAzyme-based normalized strategy is developed to unify the output signals under external interferences. This makes it possible to directly quantify endogenous zinc in living cells by in situ fluorescence imaging, implying promising potential in fundamental study and early disease diagnosis.

Ionic chiral selectors have been received much attention in the field of asymmetric catalysis, chiral recognition, and preparative separation. It has been shown that the addition of ionic chiral selectors can enhance the recognition efficiency dramatically due to the presence of multiple intermolecular interactions, including hydrogen bond, π-π interaction, van der Waals force, electrostatic ion-pairing interaction, and ionic-hydrogen bond. In the initial research stage of the ionic chiral selectors, most of work center on the application in chromatographic separation (capillary electrophoresis, high-performance liquid chromatography, and gas chromatography). Differently, more and more attention has been paid on the spectroscopy (nuclear magnetic resonance, fluorescence, ultraviolet and visible absorption spectrum, and circular dichroism spectrum) and electrochemistry in recent years. In this tutorial review as regards the ionic chiral selectors, we discuss in detail the structural features, properties, and their application in chromatography, spectroscopy, and electrochemistry., (© 2021 Wiley-VCH GmbH.)

Epigenetic alterations have been previously shown to contribute to multiple myeloma (MM) pathogenesis via DNA methylations and histone modifications. RNA methylation, a novel epigenetic modification, is required for cancer cell survival, and targeting this pathway has been proposed as a new therapeutic strategy. The extent to the N6-methyladenosine (m6A)-regulatory pathway functions in MM remains unknown. Here, we show that an imbalance of RNA methylation may underlies the tumorigenesis of MM. Mechanistically, isocitrate dehydrogenase 2 (IDH2) is highly expressed in CD138 + cells from MM and its levels appear a progressive increase in the progression of plasma cell dyscrasias. Downregulation of IDH2 increases global m6A RNA levels and reduces myeloma cell growth in vitro, decreases the burden of disease and prolongs overall survival in vivo. IDH2 regulates RNA methylation by activating the RNA demethylase FTO, which is an α-KG-dependent dioxygenase. Furthermore, IDH2-mediated FTO activation decreases the m6A level on WNT7B transcripts, then increases WNT7B expression and thus activated Wnt signaling pathway. Moreover, survival analysis indicates that the elevated expression of IDH2 predicts a poor prognosis. Higher expression of FTO is related to higher International Staging System (ISS) stage and higher Revised-ISS (R-ISS) stage of MM. Collectively, our studies reveal that IDH2 regulates global m6A RNA modification in MM via targeting RNA demethylases FTO. The imbalance of m6A methylation activates the Wnt signaling pathway by enhancing the WNT7B expression, and thus promoting tumorigenesis and progression of MM. IDH2 might be used as a therapeutic target and a possible prognostic factor for MM., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

A nanoflare, a conjugate of Au nanoparticles (NPs) and fluorescent nucleic acids, is believed to be a powerful nanoplatform for diagnosis and therapy. However, it highly suffers from the nonspecific detachment of nucleic acids from the AuNP surface because of the poor stability of Au-S linkages, thereby leading to the false-positive signal and serious side effects. To address these challenges, we report the use of covalent amide linkage and functional Au@graphene (AuG) NP to fabricate a covalent conjugate system of DNA and AuG NP, label-rcDNA-AuG. Covalent coating of abundant amino groups (-NH 2 ) onto the graphitic shell of AuG NP efficiently facilitates the coupling with carboxyl-labeled capture DNA sequences through simple, but strong, amide bonds. Importantly, such an amide-bonded nanoflare possesses excellent stability and anti-interference capability against the biological agents (nuclease, DNA, glutathione (GSH), etc.). By accurately monitoring the intracellular miR-21 levels, this covalent nanoflare is able to identify the positive cancer cells even in a mix of cancer and normal cells. Moreover, it allows for efficient photodynamic therapy of the targeted cancer cells with minimized side effects on normal cells. This work provides a facile approach to develop a superstable nanosystem showing promising potential in clinical diagnostics and therapy.

Background: Secondary plasma cell leukaemia (sPCL) is an aggressive form of multiple myeloma (MM), but the mechanism underlying MM progresses into PCL remains unknown., Methods: Gene expression profiling of MM patients and PCL patients was analysed to identify the molecular differences between the two diseases. Cox survival regression and Kaplan-Meier analysis were performed to illustrate the impact of integrin subunit alpha 6 (ITGA6) on prognosis of MM. Invasion assays were performed to assess whether ITGA6 regulated the progression of MM to PCL., Results: Gene expression profiling analyses showed that cell metastasis pathways were enriched in PCL and ITGA6 was differentially expressed between PCL and MM. ITGA6 expression was an independent prognostic factor for event-free survival (EFS) and overall survival (OS) of MM patients. Moreover, the stratification ability of the International Staging System (ISS) of MM was improved when including ITGA6 expression. Functional studies uncovered that increased ITGA6 reduced the myeloma cell invasion. Additionally, low expression of ITGA6 resulted from epigenetic downregulating of its anti-sense non-coding RNA, ITGA6-AS1., Conclusion: Our data reveal that ITGA6 gradually decreases during plasma cell dyscrasias progression and low expression of ITGA6 contributes to myeloma metastasis. Moreover, ITGA6 abundance might help develop MM prognostic stratification.

The initiation and progression of diffuse large B-cell lymphoma (DLBCL) is governed by genetic and epigenetic aberrations. As the most abundant eukaryotic messenger RNA (mRNA) modification, N6-methyladenosine (m6A) is known to influence various fundamental bioprocesses by regulating the target gene; however, the function of m6A modifications in DLBCL is unclear. PIWI-interacting RNAs (piRNAs) have been indicated to be epigenetic effectors in cancer. Here, we show that high expression of piRNA-30473 supports the aggressive phenotype of DLBCL, and piRNA-30473 depletion decreases proliferation and induces cell cycle arrest in DLBCL cells. In xenograft DLBCL models, piRNA-30473 inhibition reduces tumor growth. Moreover, piRNA-30473 is significantly associated with overall survival in a univariate analysis and is statistically significant after adjusting for the National Comprehensive Cancer Network-International Prognostic Index in the multivariate analysis. Additional studies demonstrate that piRNA-30473 exerts its oncogenic role through a mechanism involving the upregulation of WTAP, an m6A mRNA methylase, and thus enhances the global m6A level. Integrating transcriptome and m6A-sequencing analyses reveals that WTAP increases the expression of its critical target gene, hexokinase 2 (HK2), by enhancing the HK2 m6A level, thereby promoting the progression of DLBCL. Together, the piRNA-30473/WTAP/HK2 axis contributes to tumorigenesis by regulating m6A RNA methylation in DLBCL. Furthermore, by comprehensively analyzing our clinical data and data sets, we discover that the m6A regulatory genes piRNA-30473 and WTAP improve survival prediction in DLBCL patients. Our study highlights the functional importance of the m6A modification in DLBCL and might assist in the development of a prognostic stratification and therapeutic approach for DLBCL., (© 2021 by The American Society of Hematology.)

β-Cyclodextrin (β-CD) modified silver nanoparticles (AgNPs), denoted as β-CD/AgNPs, were prepared by a simple one-pot method. Due to the inherent chirality of β-CD, the developed β-CD/AgNPs exhibited higher affinity toward l-tyrosine (l-Tyr) than d-tyrosine (d-Tyr), leading to serious aggregation of AgNPs in the presence of l-Tyr. Consequently, the l-Tyr induced aggregation of AgNPs can result in signal amplification in the differential pulse voltammograms (DPVs) of l-Tyr, which can be applied for the electrochemical chiral discrimination of the Tyr enantiomers. Other chiral amino acids including tryptophan and phenylalanine can also be successfully discriminated with the β-CD/AgNPs, suggesting high universality of the developed chiral sensor.

Nucleic acid lateral flow sensing has drawn great research attention since it has the advantages of being simple, rapid, and cost-effective. However, considering the trace amounts of the nucleic acid targets, its sensitivity is still limited. Although enormous efforts have been devoted to enhancing its sensitivity, developing a simple lateral flow sensing platform with high sensitivity remains challenging. We report a novel lateral flow microRNA-21 biosensing platform based on a portable surface enhanced Raman scattering (SERS) reader coupled with a catalytic hairpin assembly signal amplification strategy. Hairpin DNA probes were anchored on Au@Ag nanotags, and the presence of microRNA-21 triggered the formation of numerous double-stranded DNAs along with the exposure of the biotin groups. By this means, the target was recycled and signal amplification was achieved. The Au@Ag nanoprobes with exposed biotin can be captured on the test line via its interaction with streptavidin. By scanning the strip with a portable SERS reader, the sensitive quantification of microRNA-21 was realized with a detection limit as low as 84 fM. The proposed strategy was employed to detect the target in a serum sample, demonstrating its great potential in amplified point-of-care biosensing for clinical diagnosis.

Accurate and sensitive detection of targets in practical biological matrixes such as blood, plasma, serum, or tissue fluid is a frontier issue for most biosensors since the coexistence of both potential reducing agents and protein molecules has the possibility of causing signal interference. Herein, aiming at detection in a complex environment, an advanced and robust peptide-based photocathodic biosensor, which integrated a recognition peptide with an antifouling peptide in one probe electrode, was first proposed. Selecting human chorionic gonadotropin (hCG) as a model target, the recognition peptide with the sequence PPLRINRHILTR was first anchored on the CuBi 2 O 4 /Au (CBO/Au) photocathode and then the antifouling peptide with the sequence EKEKEKEPPPPC was further anchored to generate an antifouling biointerface. The peptide-based photocathodic biosensor demonstrated excellent anti-interference to both nonspecific proteins and reducing agents because of the capability of the antifouling peptide. It also exhibited good sensitivity owing to the utilization of the recognition peptide rather than an antibody probe. This peptide-integrated method offers a new perspective for practical applications of photocathodic biosensors.

The trade-off between leaf size and number is the basis for plant growth strategies. It is of great significance to study the underlying mechanism of leaf size and number trade-offs for well understanding plant growth strategies. In this study, leaf size was expressed by the dry mass of single leaf, while leafing intensity was expressed by the number of leaves per unit stem volume. We used standardized major axis regression analysis method to examine the trade-off relationship between leaf size and number in Hulunbuir grassland. There was a significant negative isometric-growth trade-off between leaf size and number in Chenqicuogang (typical steppe) and Chenqibayi (meadow steppe). There was a significant negative allometric-growth trade-off between leaf size and number in Xeltala (meadow steppe). The underlying mechanism of the relationship between leaf size and number depended on the leaf and stem biomass allocation mechanism and the changes of the stem tissue density.

Photocathodic bioassays have shown great potential to apply in real bio-sample detection owning to their intrinsic abilities against interference from reductive species. However, the pursuit of photocathodic bioassays with excellent detection performance is still in the infancy. Herein, an advanced signal amplifier of platinum-based nanocatalyst with efficient oxygen reduction capability was explored to build a high-performance photocathodic immunoassay. The target model of carbohydrate antigen 19-9 (CA19-9, Ag) was used for describing the sensing platform. Specifically, the nontoxic Au/CuBi 2 O 4 photocathode was first prepared by decorating Au nanoparticles on CuBi 2 O 4 nanofilm and was used as the matrix to anchor capture CA19-9 antibody (Ab 1 ). Platinum (Pt) nanoparticles were loaded on graphene (GR) nanosheet to form Pt/GR nanocomposite, which was utilized as signal amplifier conjugating with signal CA19-9 antibody (Ab 2 ). When specific sandwich immunoreaction happened, the Pt/GR played the role of an efficient nanocatalyst to accelerate the reduction reaction of electron acceptor of oxygen in the electrolyte, causing evidently enhanced cathodic photocurrent signal. By incorporating this superior signal amplification strategy into the anti-interference photocathodic immunoassay, highly sensitive and specific detection of target Ag was realized. This work pioneers a new perspective for the design of advanced photocathodic bioanalysis for various targets of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

For SERS analysis in living cells, the inevitable desorption of Raman molecule on the substrate surface is a key challenge. To ensure high stability, SERS systems with Raman molecules protected inside the core-Raman molecule-shell (C-M-S) structures have been designed, but at the expense of sacrificed sensing performances. Here a shell-switchable SERS blocking strategy is developed for the reliable SERS analysis in living cells, relying on the shell blockers to regulate the SERS sensing signal without affecting the internal Raman molecules. After several C-M-S structures were investigated, the SERS blocking mechanism confirmed that thick shells (Au, Ag, ZnO, and MnO 2 ) can cause a significant reduction in the internal SERS signal by obstructing the penetration of the laser or signal. The C Au -Mpy-S Au -S MnO 2 nanoprobe is designed for the ratiometric SERS sensing in living cells, which retains sensing performances even though the Raman molecule is protected inside the nanostructure. This SERS strategy makes the turn-on sensing achievable in living cells with the MnO 2 shell as a signal switch and a Raman reference. Additionally, it allows for accurate monitoring of the degradation of MnO 2 carriers in living cells, even without fluorescent labels.

Pathogenic bacterial fouling in agriculture and food-associated products poses mounting food safety concerns today. Efficient integration of precise tracking and on-demand bacterial killing to achieve the source control of pathogenic bacteria at the single-cell level is one of the most valuable antifouling methods for safeguarding food safety but remains unexplored. Here, we report an all-in-one design strategy as a proof of concept to establish a stimuli-responsive nanoprobe PDANSs-FAM-Apt for the detection of Staphylococcus aureus ( S. aureus ) at the single-cell level, which could be capable of guiding the on-demand photothermal killing of bacteria upon near-infrared (NIR) light irradiation. By examining the size-dependent modulation of the fluorescence resonance energy transfer efficiency to polydopamine nanospheres (PDANSs), PDANSs-FAM-Apt was finally assembled by 6-carboxyfluorescein-terminated S. aureus, binding the aptamer (FAM-Apt) and PDANSs at ∼258 nm through π-π stacking interactions. As a result, PDANSs-FAM-Apt exhibits a remarkable fluorescence enhancement (∼261-fold) to S. aureus with a satisfactory detection limit of 1.0 cfu/mL, allowing for assay at the single-cell level and thus ultralow background fluorescence imaging of S. aureus as well as its biofilms. Moreover, PDANSs-FAM-Apt shows a high photothermal bactericidal property upon NIR light irradiation, endowing it with the strong capacity to efficiently produce heat for destroying S. aureus and its biofilms with the guidance of imaging results. This work emphasizes the versatility of using the combination of stimuli-responsive fluorescence imaging dependent on the PDANS size modulation and NIR light-activated photothermal antibacterial activity to design stimuli-responsive nanoprobes with an improved precision for pathogenic bacteria monitoring and source controlling, which opens a promising antifouling avenue to eliminate bacteria and disrupt bacterial biofilms in agriculture and food-related industries.

As nonspecific adsorption or biofouling has obvious side effects on the selectivity, it is a great challenge for cytosensors to detect target cells in practical biological samples. In this study, we first propose the design and synthesis of an antifouling photoelectrode. The antifouling photoelectrode not only has the desired photocurrent response, but also possesses an unexpected antifouling capability of resisting nonspecific adsorption of biomolecules. Herein, the PEDOT-HPG/SnS/ZnO-NT antifouling photoelectrode was formed and a robust photoelectrochemical cytosensor with enhanced sensitivity and selectivity has been demonstrated.

Fluoroquinolone antibiotics (FQs), a new class of pollutants that seriously threaten human health through environmental and food residues, have aroused wide public concern. However, little attention has been paid to the potential toxicity of FQs' metal complex. Here, we firstly explore the proof-of-concept study of FQs' metal complex to bind bovine serum albumin (BSA) using systematical spectroscopic approaches. In detail, we have found that the complex of Al 3+ with gatifloxacin (Al(III)-GFLX complex) can effectively bind to BSA via electrostatic interaction in PBS buffer (pH = 7.4, 1×), resulting in the formation of Al(III)-GFLX-BSA complex. The negative value of ΔG shows that the binding of Al(III)-GFLX complex to BSA is a spontaneous process. Circular dichroism spectra verify that Al(III)-GFLX complex effectively triggers the conformation changes of BSA's secondary structure. It has been proved that the interaction of small molecule with serum albumin has a significant effect on their in vivo biological effects such as absorption, distribution, metabolism, and excretion, and etc. Therefore, the results of this paper may offer a valuable theoretical basis for establishing safety standards of FQs' metal complex to ensure food and environmental health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

An efficient signaling on-off mechanism was first proposed by integrating exciton-plasmon coupling and exciton energy transfer into cathodic PEC bioassays. This signaling on-off mechanism has endowed the cathodic PEC biosensor with powerful capability for ultrasensitive and specific detection of target DNA.

This work reports a customized methodology for the fabrication of 3D CdS nanosheet (NS)-enwrapped carbon fiber framework (CFF) and its utilization for sensitive split-type CuO-mediated PEC immunoassay. Specifically, the 3D CdS NS-CFF was fabricated via a solvothermal process, while the sandwich immunocomplexing was allowed in a 96 well plate with CuO nanoparticles (NPs) as the signaling labels. The subsequent release of the Cu 2+ ions was directed to interact with the CdS NS, generating trapping sites and thus inhibiting its photocurrent generation. In such a protocol, the 3D CdS NS-CFF photoelectrode could not only guarantee its sufficient contact with the Cu 2+ -containing solution but also supply plenty CdS surface for the Cu 2+ ions. Because of the target-dependent release of the Cu 2+ ions and its proper coupling with the 3D CdS NS-CFF photoelectrode, a sensitive split-type PEC immunoassay was achieved for the detection of brain natriuretic peptide (BNP). This proposed system exhibited good stability and selectivity, and its applicability for real sample analysis was also demonstrated via comparison with the commercial BNP enzyme-linked immunosorbent assay (ELISA) kit. We expect this work could stimulate more interest in the design and utilization of 3D photoelectrodes for novel PEC bioanalysis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this study, an electroactive rotaxane, (S,S)-crown-3, consisting of a polymeric chiral ionic liquid as a flexible axle and 18-crown-6 as the wheel, was designed and synthesized. It is worth noting that a stimuli-responsive system was developed, in which the wheel could switch its location between the chiral carbamido group and ionic pair of the ionic polymers under an external force. Next, (S,S)-crown-3 was employed as a modification on the surface of glassy electrode. In contrast to previous study, the developed probe presented a clear discrimination of an electrochemical signal in the absence of Cu(ii). Under the external force (different pH values), l-isomers of amino acids (tryptophan, tyrosine, and cysteine) could form stable host-guest interactions with the chiral carbamido group, producing higher peak currents than the d-isomers. Compared to the absence of the crown, (S,S)-crown-3 showed much better recognition efficiency. The value of I L /I D for tryptophan could reach 39.8. In brief, the present study describes a powerful method for the synthesis of an electroactive rotaxane with great enantiorecognition capability.

Currently, one of important research directions of photoelectrochemical (PEC) bioanalysis is to exploit innovative photoactive species and their elegant implementations for selective detection and signal transduction. Different from existing candidates for photoelectrode development, this study, exemplified by the cationic dipeptide nanoparticles (CDNPs), reports the first demonstration of self-assembled peptide nanostructures (SAPNs) for the PEC bioanalysis. Specifically, the CDNPs were prepared as representative materials and then immobilized onto the indium tin oxide (ITO) electrode for the PEC differentiation of several commonly involved biomolecules such as ascorbic acid (AA) and l-cysteine. Significantly, the experimental results disclosed that the CDNPs possessed unique photocathodic responses and good analytical performance toward AA detection in terms of rapid response, high stability, and excellent selectivity. This work demonstrates the great potential of the large SAPN family for the future PEC bioanalysis development and has not been reported to our knowledge.

Low fouling electrochemical immunosensors with both "signal-off" and "signal-on" analytical methods were developed for the highly sensitive and efficient detection of cancer antigen 15-3 (CA 15-3) in human serum samples. The antifouling sensing interfaces were constructed by assembling multifunctional polyethylene glycol on gold electrodes, followed by covalent conjugation with CA 15-3 antibody. Pure antigens and Fe 3 O 4 @Ag will competitively bind to the immobilized antibody on the electrode. Fe 3 O 4 magnetic nanoparticles attached to the working electrode and collected by a magnetic electrode were treated via electrochemical conversion to generate electroactive Prussian blue as a signal readout. Therefore, these two signals measured independently were complementary, and this design allowed one to choose the assay method according to real situations so as to ensure accuracy of the immunosensor. Moreover, owing to its good antifouling property, the immunosensor was capable of detecting CA 15-3 even in complex human serum samples, demonstrating potential application in quantitative analysis of real patient serum samples.

Uracil-DNA glycosylase (UDG) is a typical initiator for base excision repair (BER) process. Since aberrant expression of UDG is relevant to a variety of cancers, analysis of UDG activity with high sensitivity and accuracy is of great importance. We reported herein a sensitive and reliable dual-signal bioassay for UDG activity by coupling photoelectrochemical (PEC) and electrochemical (EC) strategies in one probe electrode. The Au/TiO 2 hybrid was used as a matrix to immobilize substrate DNA (sDNA), which modified with AgInS 2 quantum dot (AIS QD) on the terminal. When UDG exist, the base of uracil was eliminated from the sDNA, and the produced apyrimidinic (AP) site could be cleaved by endonuclease IV (Endo. IV) immediately. Under this situation, the PEC labels of AIS QDs were detached from the electrode, resulting in a "signal-off" trend for PEC signal. After assistant DNA (aDNA) was then assembled, the hybridization chain reaction (HCR) was triggered, and EC labels of ferrocene molecules were introduced, producing a "signal-on" trend for EC signal. Besides, as the produced long double-stranded DNA by the HCR had evident steric hindrance, the PEC signal further decreased. Based on this meticulous design, the dual-signal bioassay for UDG activity showed low detection limits of 4.3 × 10 -5 and 1.9 × 10 -4 U/mL with PEC and EC detection, and accurate analysis of UDG activity in living cells was realized. By just changing the recognition site, this sensitive and reliable dual-signal strategy can be extended to diagnose other DNA repair-related enzymes in the real samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A "signal-off" surface-enhanced Raman scattering (SERS) platform has been constructed for ultrasensitive detection of miRNA-21 by integrating exonuclease-assisted target recycling amplification with a plasmon coupling enhancement effect. On this platform, Raman-labeled Au nanostar (AuNS) probes can be covalently linked with the thiolated aptamer (Apt) on the Au-decorated silicon nanowire arrays (SiNWAs/Au) substrate, creating a coupled electromagnetic field between the substrate and the probes to enhance Raman signal. In the presence of miRNA-21, T7 exonuclease specifically hydrolyzed Apt on Apt/miRNA duplex to release miRNA-21. The regenerated element could then initiate another cycle of Apt/miRNA duplex formation and Apt cleavage. Correspondingly, the capture ability of substrate toward probes and the plasmon coupling effect between them were both diminished, giving a prominent attenuation of Raman intensity that can work as the detection signal. Due to the cascading integration between the target cycle process and the plasmon coupling effect, the present platform displayed a very low detection limit (0.34 fM, 3σ) for miRNA-21 detection. Furthermore, it was proven to be effective for analyzing miRNA-21 in biological samples and distinguishing the expression levels of miRNA-21 in MCF-7 cells and NIH3T3 cells, which became a promising tool to monitor miRNA-21 in cancer auxiliary diagnosis and drug screening.

Solid-state nanochannels have great potentials in the vibrant field of photoelectrochemical (PEC) bioanalysis. This work herein demonstrates the innovative use of DNA-decorated nanoporous anodic alumina (NAA) nanochannels for sensitive PEC bioanalysis of telomerase (TE) activity. Specifically, telomerase primer sequences (TS) were initially immobilized within the NAA nanochannels and then extended by TE in the presence of deoxyribonucleoside triphosphates (dNTPs). The as formed single-strand DNA was then directed to hybrid with many partially matched single-strand assisting DNA (aDNA), leading to the formation of multiple DNAzymes by the unmatched parts and the subsequent DNAzyme-stimulated biocatalytic precipitation (BCP) within the nanochannels. Because the inhibited signals of the photoelectrode could be correlated with TE-enabled TS extension, an innovative nanochannels PEC bioanalysis could be realized for probing TE activity. This work features the ingenious use of DNA-associated nanochannels for PEC bioanalysis of TE activity. Given the versatile functions of DNA molecules, the extension of this strategy easily allows for addressing numerous other targets of interest. Also, we envision this work could inspire more interest for the further development of nanochannels PEC bioanalysis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this report, enhanced organic-inorganic heterojunction of polypyrrole@Bi 2 WO 6 was fabricated and applied for sensitive photoelectrochemical (PEC) immunoassay of creatine kinase-MB (CK-MB). Specifically, heterostructured polypyrrole@Bi 2 WO 6 photoelectrode was prepared and sandwich immunorecognition were integrated for the CK-MB immunoassay. In the detection, with the aid of alkaline phosphate (ALP)-induced biocatalytic precipitation (BCP), the precipitation-dependent suppression of the photocurrent can be recorded due to the impediment of the interfacial mass and electron transfer. On the basis of target-controlled BCP formation, a novel PEC immunoassay could be developed for the sensitive and specific CK-MB detection. This work manifested the great potential of polypyrrole@Bi 2 WO 6 heterojunction as a novel platform for PEC bioanalysis development and also a PEC method for CK-MB detection. This work is expected to stimulate more interest in the design and implementation of numerous other organic-inorganic heterojunction for advanced PEC bioanalysis development., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This work reports the innovative design and application of a three-dimensional (3D) TiO 2 @Cu 2 O@nickel foam electrode synergized with enzyme catalysis toward the proof-of-concept study for oxygen-independent photocathodic enzymatic detection. Specifically, a 3D-nanostructured photoelectrode has great potential in the semiconductor-based photoelectrochemical (PEC) biological analysis. On the other hand, using various photocathodes, cathodic PEC bioanalysis, especially the photocathodic enzymatic detection, represents an attractive frontier in the field. Different from state-of-the-art photocathodic enzymatic studies that are oxygen-dependent, herein, we present the ingenious design, characterization, and implementation of 3D TiO 2 @Cu 2 O@nickel foam photocathodes for the first oxygen-independent example. In such a configuration, the Cu 2 O acted as the visible-light absorber, while the TiO 2 shell would simultaneously function as a protective layer for Cu 2 O and as a desirable substrate for the immobilization of enzyme biomolecules. Especially, because of the proper band positions, the as-designed photocathode exhibited unique O 2 -independent PEC property. Exemplified by glucose oxidases, the as-developed sensor exhibited positive response to glucose with good performance. Because various oxidases could be integrated with the system, this protocol could serve as a universal O 2 -independent platform for many other targets. This work is also anticipated to catalyze more studies in the advanced 3D photoelectrodes toward innovative enzymatic applications.