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The chiral recognition and separation of enantiomers are of great importance for biological research and the pharmaceutical industry. Preparing homochiral materials with adjustable size and chiral binding sites is beneficial for achieving an efficient chiral recognition performance. Here, a homochiral covalent organic framework membrane modified with β-cyclodextrin (CD-COF) was constructed, which was subsequently utilized as an electrochemical sensor for the enantioselective sensing of tryptophan (Trp) molecules. The preferential adsorption of l-Trp over d-Trp at the β-CD sites can enhance the surface charge density and hydrophilicity of the CD-COF membrane, resulting in an increased transmembrane ionic current. Trp enantiomers with concentrations down to 0.28 nM can be effectively discriminated. The l-/d-Trp recognition selectivity increases with the Trp concentration and reaches a value of 19.2 at 1 mM. The selective adsorption of l-Trp to the CD-COF membrane will also hinder its transport, resulting in a l-/d-Trp permeation selectivity of 15.3. This study offers a new strategy to construct homochiral porous membranes and achieve efficient chiral sensing and separation.

Magnolia sieboldii , an important ornamental tree native to East Asia, comprises two subspecies in distinct regions, with wild populations facing suboptimal survival. This study aimed to understand the potential habitat distribution of these subspecies under future climate-change conditions to support climate-adaptive conservation. The maximum entropy (MaxEnt) model was used with occurrence and environmental data to simulate the current and future suitable habitats under various climate scenarios. Precipitation in the warmest quarter played a crucial role in shaping the potential habitats of both subspecies; however, they exhibited different sensitivities to temperature-related variables and altitude. Magnolia sieboldii subsp. sieboldii is more sensitive to temperature seasonality and annual mean temperature, whereas Magnolia sieboldii subsp. japonica is more affected by altitude, mean temperature in the driest quarter, and isothermality. Currently, the subsp. sieboldii is predicted to have larger, more contiguous suitable habitats across northeastern China, the Korean Peninsula, and Japan, whereas the subsp. japonica occupies smaller, more disjunct habitats scattered in central and western Japan and the southern Chinese mountains. These two subspecies will respond differently to future climate change. Potentially suitable habitats for subsp. sieboldii are expected to expand significantly northward over time, especially under the SSP585 scenario compared with the SSP126 scenario. In contrast, moderately and highly suitable habitats for the subsp. japonica are projected to contract southward significantly. Therefore, we recommend prioritizing the conservation of the subsp. japonica over that of the subsp. sieboldii . Strategies include in situ and ex situ protection, introduction and cultivation, regional hybridization, and international cooperation. Our study offers valuable insights for the development of targeted conservation strategies for both subspecies of M. sieboldii to counteract the effects of climate change.

Photosensitizers with near-infrared (NIR) excitation, especially above 800 nm which is highly desired for phototherapy, remain rare due to the fast nonradiative relaxation process induced by exciton-vibration coupling. Here, a diketopyrrolopyrrole-derived photosensitizer (DTPA-S) is developed via thionation of carbonyl groups within the diketopyrrolopyrrole skeleton, which results in a large bathochromic shift of 81 nm, endowing the photosensitizer with strong NIR absorption at 712 nm. DTPA-S is then introduced with a functional biomolecule (N 3 -PEG 2000 -RGD) via click reaction for the construction of integrin αvβ3 receptor-targeted nano-micelles (NanoDTPA-S/RGD), which endows the photosensitizer with a further superlarge absorption redshift of 138 nm, thus extending the absorption maxima to ≈850 nm. Remarkably, thiocarbonyl substitution increases the nonbonding characters in frontier molecular orbitals, which can effectively suppress the nonradiative vibrational relaxation process via reducing the reorganization energy, enabling efficient reactive oxygen species (ROS) generation under 880 nm excitation. Screened by in vitro and in vivo assays, NanoDTPA-S/RGD with high water solubility, excellent tumor-targeting ability, and photodynamic/photothermal therapy synergistic effect exhibits satisfactory phototherapeutic performance. Overall, this study demonstrates a new design of efficient NIR-triggered diketopyrrolopyrrole photosensitizer with facile installation of functional biomolecules for potential clinical applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The performance and stability of organic metal halide perovskite (OMHP) optoelectronic devices have been associated with ion migration. Understanding of nanoscale resolved organic cation migration mechanism would facilitate structure engineering and commercialization of OMHP. Here, we report a three-dimensional approach for in situ nanoscale infrared imaging of organic ion migration behavior in OMHPs, enabling to distinguish migrations along grain boundary and in crystal lattice. Our results reveal that organic cation migration along OMHP film surface and grain boundaries (GBs) occurs at lower biases than in crystal lattice. We visualize the transition of organic cation migration channels from GBs to volume upon increasing electric field. The temporal resolved results demonstrate the fast MA + migration kinetics at GBs, which is comparable to diffusivity of halide ions. Our findings help understand the role of organic cations in the performance of OMHP devices, and the proposed approach holds broad applicability for revealing migration mechanisms of organic ions in OMHPs based optoelectronic devices., (© 2024 Wiley-VCH GmbH.)

Enzyme-free single-molecule sequencing has the potential to significantly expand the application of nanopore technology to DNA, proteins, and saccharides. Despite their advantages over biological nanopores and natural suitability for enzyme-free single-molecule sequencing, conventional solid-state nanopores have not yet achieved single-molecule DNA sequencing. The biggest challenge for the accuracy of single-molecule sequencing using solid-state nanopores lies in the precise control of the pore size and conformity. In this study, we fabricated nanopore devices by covering the tip of a quartz nanopipette with ultrathin two-dimensional (2D) covalent organic framework (COF) nanosheets (pore size ≈ 1.1 nm). The size of the periodically arranged nanopores in COF is comparable to that of protein nanopores, and the structure of each COF nanopore is consistent at the atomic scale. The COF nanopore device could roughly distinguish dAMP, dCMP, dGMP, and dTMP. Furthermore, a certain percentage of the current blockades originating from 150 nucleotides model DNA molecules (13.5% for dA 50 dC 50 dA 50 and 11.1% for dC 50 dA 50 dC 50 ) show distinct DNA sequence-specific concave and convex resistive current patterns. The finite element simulation confirmed that the current blockade pattern of a DNA molecule passing through a COF nanopore is dependent on the relative location of the nanopore with respect to the wall of the nanopipette. Our study is a significant step toward single-molecule DNA sequencing by solid-state nanopores.

Objectives: To investigate the changes in the serum levels of oxidized phospholipids (OxPLs) and endothelial nitric oxide synthase (eNOS) and their association with coronary artery disease (CAL) in children in the acute stage of Kawasaki disease (KD), as well as the clinical significance of OxPLs and eNOS., Methods: A prospective study was conducted on 95 children in the acute stage of KD (KD group). According to the presence of absence of CAL, the KD group was further divided into a CAL subgroup and a non-CAL (NCAL) subgroup. Thirty children with fever due to lower respiratory tract infection were enrolled as the fever group. Thirty healthy children who underwent physical examination were enrolled as the healthy control group. The above groups were compared in terms of general information and serum levels of OxPLs, eNOS and other laboratory indexes, and the correlation between OxPLs level and eNOS level was analyzed., Results: The KD group had a significantly higher level of OxPLs and a significantly lower level of eNOS compared with the fever group and the healthy control group ( P <0.05). After treatment, the children with KD had a significantly decreased OxPLs level and a significantly increased eNOS level ( P <0.05). Compared with the NCAL subgroup, the CAL subgroup had a significantly higher level of OxPLs and a significantly lower level of eNOS ( P <0.05). Among the children of KD, the level of OxPLs was negatively correlated with that of eNOS ( r s =-0.353, P <0.05)., Conclusions: Serum OxPLs and eNOS in the acute stage of KD may be involved in the development of CAL in children with KD, and therefore, they may be used as the biomarkers to predict CAL in these children.

The combination of closed bipolar electrodes (cBPE) with electrochemiluminescence (ECL) imaging has demonstrated remarkable capabilities in the field of bioanalysis. Here, we established a cBPE-ECL platform for ultrasensitive detection of alkaline phosphatase (ALP) and two-dimensional imaging of epidermal growth factor receptor (EGFR). This cBPE-ECL system consists of a high-density gold nanowire array in anodic aluminum oxide (AAO) membrane as the cBPE coupled with ECL of highly luminescent cadmium selenide quantum dots (CdSe QDs) luminophores to achieve cathodic electro-optical conversion. When an enzyme-catalyzed amplification effect of ALP with 4-aminophenyl phosphate monosodium salt hydrate (p-APP) as the substrate and 4-aminophenol (p-AP) as the electroactive probe is introduced, a significant improvement of sensing sensitivity with a detection limit as low as 0.5 fM for ALP on the cBPE-ECL platform can be obtained. In addition, the cBPE-ECL sensing system can also be used to detect cancer cells with an impressive detection limit of 50 cells/mL by labeling ALP onto the EGFR protein on A431 human epidermal cancer cell membranes. Thus, two-dimensional (2D) imaging of the EGFR proteins on the cell surface can be achieved, demonstrating that the established cBPE-ECL sensing system is of high resolution for spatiotemporal cell imaging.

Simultaneous detection and structural characterization of protein variants on a single platform are highly desirable but technically challenging. Herein, we present a single-molecule spectral system based on a gold plasmonic nanopore for analyzing two peptides and their single-point mutated variants. The gold plasmonic nanopore enabled the high-throughput acquisition of surface-enhanced Raman scattering (SERS) spectra at the single-molecule level by electrically driving analytes into hot spots. Furthermore, a statistical method based on Boolean operations was developed to extract prominent features from fluctuated single-molecule SERS spectra. The effects of the single-amino acid substitutions on both the intramolecular interactions and the peptide conformations were directly characterized by the nanopore system, and the results agreed with the predictions by AlphaFold2. This study highlights the mutual benefits of spectroscopy and nanopore technology, whereby the gold plasmonic nanopore offers a powerful tool for the structural analysis of single-molecule proteins.

Synthesis of ammonia by electrochemical nitrogen reduction reaction (NRR) is a promising alternative to the Haber-Bosch process. However, it is commonly obstructed by the high activation energy. Here, we report the design and synthesis of an Al-Al bonded dual atomic catalyst stabilized within an amorphous nitrogen-doped porous carbon matrix (Al 2 NC) with high NRR performance. The dual atomic Al 2 -sites act synergistically to catalyze the complex multiple steps of NRR through adsorption and activation, enhancing the proton-coupled electron transfer. This Al 2 NC catalyst exhibits a high Faradaic efficiency of 16.56±0.3 % with a yield rate of 29.22±1.2 μg h -1  mg cat -1 . The dual atomic Al 2 NC catalyst shows long-term repeatable, and stable NRR performance. This work presents an insight into the identification of synergistic dual atomic catalytic site and mechanistic pathway for the electrochemical conversion of N 2 to NH 3 ., (© 2024 Wiley-VCH GmbH.)

Structural complexity brings a huge challenge to the analysis of sugar chains. As a single-molecule sensor, nanopores have the potential to provide fingerprint information on saccharides. Traditionally, direct single-molecule saccharide detection with nanopores is hampered by their small size and weak affinity. Here, a carbon nitride nanopore device is developed to discern two types of trisaccharide molecules (LeA pN and SLeC pN ) with minor structural differences. The resolution of LeA pN and SLeC pN in the mixture reaches 0.98, which has never been achieved in solid-state nanopores so far. Monosaccharide (GlcNAc pN ) and disaccharide (LacNAc pN ) can also be discriminated using this system, indicating that the versatile carbon nitride nanopores possess a monosaccharide-level resolution. This study demonstrates that the carbon nitride nanopores have the potential for conducting structure analysis on single-molecule saccharides.

Background: Previous epidemiological studies about the relationship between per- and polyfluoroalkyl substances (PFAS) concentrations and adolescent asthma have typically examined single PFAS, without considering the mixtures effects of PFAS., Methods: Using data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES), 886 adolescents aged 12-19 years were included in this study. We explored the association between PFAS mixture concentrations and adolescent asthma using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models, respectively., Results: After adjusting for confounders, the results of the WQS regression and BKMR models were consistent, with mixed exposure to the five PFAS not significantly associated with asthma in all adolescents. The association remained nonsignificant in the subgroup analysis by sex., Conclusions: Our study demonstrated no significant association between mixed exposure to PFAS and adolescent asthma, and more large cohort studies are needed to confirm this in the future., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The photoinduced dipole force (PiDF) is an attractive force arising from the Coulombic interaction between the light-induced dipoles on the illuminated tip and the sample. It shows extreme sample-tip distance and refractive index dependence, which is promising for nanoscale infrared (IR) imaging of ultrathin samples. However, the existence of PiDF in the mid-IR region has not been experimentally demonstrated due to the coexistence of photoinduced thermal force (PiTF), typically one to two orders of magnitude higher than PiDF. In this study, we demonstrate that, with the assistance of surface phonon polaritons, the PiDF of c-quartz can be enhanced to surpass its PiTF, enabling a clear observation of PiDF spectra reflecting the properties of the real part of permittivity. Leveraging the detection of the PiDF of phonon polaritonic substrate, we propose a strategy to enhance the sensitivity and contrast of photoinduced force responses in transmission images, facilitating the precise differentiation of the heterogeneous distribution of ultrathin samples., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Developing cost-effective and high-performance electrocatalysts for oxygen reduction reaction (ORR) is critical for clean energy generation. Here, we propose an approach to the synthesis of iron phthalocyanine nanotubes (FePc NTs) as a highly active and selective electrocatalyst for ORR. The performance is significantly superior to FePc in randomly aggregated and molecularly dispersed states, as well as the commercial Pt/C catalyst. When FePc NTs are anchored on graphene, the resulting architecture shifts the ORR potentials above the redox potentials of Fe 2+/3+ sites. This does not obey the redox-mediated mechanism operative on conventional FePc with a Fe 2+ -N moiety serving as the active sites. Pourbaix analysis shows that the redox of Fe 2+/3+ sites couples with HO - ions transfer, forming a HO-Fe 3+ -N moiety serving as the ORR active sites under the turnover condition. The chemisorption of ORR intermediates is appropriately weakened on the HO-Fe 3+ -N moiety compared to the Fe 2+ -N state and thus is intrinsically more ORR active., Competing Interests: Competing interests statement:The authors declare no competing interest.

IR spectroelectrochemistry (EC-IR) is a cutting-edge operando method for exploring electrochemical reaction mechanisms. However, detection of interfacial molecules is challenged by the limited sensitivity of existing EC-IR platforms due to the lack of high-enhancement substrates. Here, we propose an innovative plasmon-enhanced infrared spectroelectrochemistry (EC-PEIRS) platform to overcome this sensitivity limitation. Plasmonic antennae with ultrahigh IR signal enhancement are electrically connected via monolayer graphene while preserving optical path integrity, serving as both the electrode and IR substrate. The [Fe(CN) 6 ] 3- /[Fe(CN) 6 ] 4- redox reaction and electrochemical CO 2 reduction reaction (CO 2 RR) are investigated on the EC-PEIRS platform with a remarkable signal enhancement. Notably, the enhanced IR signals enable a reconstruction of the electrochemical curve of the redox reactions and unveil the CO 2 RR mechanism. This study presents a promising technique for boosting the in-depth understanding of interfacial events across diverse applications., (© 2024 Wiley-VCH GmbH.)

Membrane consisting of ordered sub-nanochannels has been pursued in ion separation technology to achieve applications including desalination, environment management, and energy conversion. However, high-precision ion separation has not yet been achieved owing to the lack of deep understanding of ion transport mechanism in confined environments. Biological ion channels can conduct ions with ultrahigh permeability and selectivity, which is inseparable from the important role of channel size and "ion-channel" interaction. Here, inspired by the biological systems, we report the high-precision separation of monovalent and divalent cations in functionalized metal-organic framework (MOF) membranes (UiO-66-(X) 2 , X = NH 2 , SH, OH and OCH 3 ). We find that the functional group (X) and size of the MOF sub-nanochannel synergistically regulate the ion binding affinity and dehydration process, which is the key in enlarging the transport activation energy difference between target and interference ions to improve the separation performance. The K + /Mg 2+ selectivity of the UiO-66-(OCH 3 ) 2 membrane reaches as high as 1567.8. This work provides a gateway to the understanding of ion transport mechanism and development of high-precision ion separation membranes., (© 2024. The Author(s).)

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Atomic force microscopy (AFM)-based nanoscale infrared (nano-IR) techniques have found extensive application in the fields of chemistry, physics, and materials science, enabling the visualization of nanoscale features that surpass the optical diffraction limit. More recently, tentative investigations have been conducted into the use of these techniques in the field of catalysis, particularly in studying interfacial processes involving molecular monolayer samples. IR nanoimaging and nanospectroscopy offer unique perspectives on catalytic processes. Considering the specific characteristics of catalytic processes, this Perspective highlights the need for and reviews the current status of AFM-based nano-IR techniques for catalysis investigations, which aims to contribute to a deeper understanding of the nanoscale mechanisms underlying the catalytic processes.

Plasmon-enhanced electrochemistry (PEEC) has been observed to facilitate energy conversion systems by converting light energy to chemical energy. However, comprehensively understanding the PEEC mechanism remains challenging due to the predominant use of ensemble-based methodologies on macroscopic electrodes, which fails to measure electron-transfer kinetics due to constraints from mass transport and the averaging effect. In this study, we have employed nanoparticle impact electrochemistry (NIE), a newly developed electroanalytical technique capable of measuring electrochemical dynamics at a single-nanoparticle level under optimal mass transport conditions, along with microscopic electron-transfer theory for data interpretation. By investigating the plasmon enhanced hydrogen evolution reaction (HER) at individual silver nanoparticles (AgNPs), we have clearly revealed the previously unknown influence of solvent effects within the PEEC mechanism. This finding suggests an additional approach to optimize plasmon-assisted electrocatalysis and electrosynthesis systems.

Enzyme-prodrug therapies have shown unique advantages in efficiency, selectivity, and specificity of in vivo prodrug activation. However, precise spatiotemporal control of both the enzyme and its substrate at the target site, preservation of enzyme activity, and in situ substrate depletion due to low prodrug delivery efficiency continue to be great challenges. Here, we propose a novel core-shell reactor partitioning enzyme and prodrug by ZIF-8, which integrates an enzyme with its substrate and increases the drug loading capacity (DLC) using a prodrug as the building ligand to form a Zn-prodrug shell. Cytochrome P450 (CYP450) is immobilized in ZIF-8, and the antitumor drug dacarbazine (DTIC) is coordinated and deposited in its outer layer with a high DLC of 43.6±0.8 %. With this configuration, a much higher prodrug conversion efficiency of CYP450 (36.5±1.5 %) and lower IC 50 value (26.3±2.6 μg/mL) are measured for B16-F10 cells with a higher NADPH concentration than those of L02 cells and HUVECs. With the tumor targeting ability of hyaluronic acid, this core-shell enzyme reactor shows a high tumor suppression rate of 96.6±1.9 % and provides a simple and versatile strategy for enabling in vivo biocatalysis to be more efficient, selective, and safer., (© 2023 Wiley-VCH GmbH.)

In recent years, sex-controlled breeding has emerged as an effective strategy to enhance the yields of economic animals with different growth characteristics, while increasing the economic benefits of aquaculture. It is known that the NF-κB pathway participates in gonadal differentiation and reproduction. Therefore, we used the large-scale loach as a research model for the present study and selected an effective inhibitor of the NF-κB signaling pathway (QNZ). This, to investigates the impacts of the NF-κB signaling pathway on gonadal differentiation during a critical period of gonad development and after maturation. Simultaneously, the sex ratio bias and the reproductive capacities of adult fish were analyzed. Our results indicated that the inhibition of the NF-κB signaling pathway influenced the expression of genes related to gonad development, regulated the gene expression related to the brain-gonad-liver axis of juvenile loaches, and finally impacted the gonadal differentiation of the large-scale loach and promoted a male-biased sex ratio. Meanwhile, high QNZ concentrations affected the reproductive abilities of adult loaches and inhibited the growth performance of offspring. Thus, our results deepened the exploration of sex control in fish and provided a certain research basis for the sustainable development of the aquaculture industry., Competing Interests: Declaration of competing interest The authors have no conflicts of interest related to this research., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The recognition and separation of chiral molecules with similar structure are of great industrial and biological importance. Development of highly efficient chiral recognition systems is crucial for the precise application of these chiral molecules. Herein, a homochiral zeolitic imidazolate frameworks (c-ZIF) functionalized nanochannel device that exhibits an ideal platform for electrochemical enantioselective recognition is reported. Its distinct chiral binding cavity enables more sensitive discrimination of tryptophan (Trp) enantiomer pairs than other smaller chiral amino acids owing to its size matching to the target molecule. It is found that introducing neighboring aldehyde groups into the chiral cavity will result in an inferior chiral Trp recognition due to the decreased adsorption-energy difference of D- and L-Trp on the chiral sites. This study may provide an alternative strategy for designing efficient chiral recognition devices by utilizing the homochiral reticular materials and tailoring their chiral environments., (© 2023 Wiley-VCH GmbH.)

Plasmonic materials enabling sunlight as an energy input to catalyze the hydrogen evolution reaction (HER) have become the research focus of artificial photosynthesis. Upon visible photoexcitation, there are both intraband transition and interband transition hot carriers generated, and which of them dominates the catalytic reaction remains elusive. Here, the contributions of hot electrons from intraband and interband transitions to the photoelectrocatalytic HER on plasmonic Au triangle nanoprisms (AuTNPs) have been studied. Compared with the dark reaction, the exchange current density increases by 9-fold and 3-fold under intraband and interband excitation, respectively, which is attributed to the higher energy level of intraband transition hot electrons. By calculation of the reaction activation energy with and without illumination, the contributions of the hot electrons from the two photoexcitation modes to the photoenhanced electroreduction reaction (PEER) are quantitatively analyzed, proposing the general standard to measure the effect of different hot electrons in different reactions.

More anomalous transport behaviors have been observed with the rapid progress in nanofabrication technology and characterization tools. The ions/molecules inside nanochannels can act dramatically different from those in the bulk systems and exhibit novel mechanisms. Here, we have reported the fabrication of a nanodevice, covalent organic frameworks covered theta pipette (CTP), that combine the advantages of theta pipette (TP), nanochannels framework, and field-effect transistors (FETs) for controlling and modulating the anomalous transport. Our results show that ammonia, a weak base, causes a continuous supply of ions inside covalent organic framework (COF) nanochannels, leading to an abnormally high current depending on the ionic/molecular size and the pore size of the nanochannel. Furthermore, CTP can distinguish different concentrations of ammonia and have all of the qualities of a nanosensor.

A label-free magnetic surface enhanced Raman scattering (SERS) platform was constructed, which was composed of superparamagnetic Fe 3 O 4 nanoparticles as cores for separation and Au layers as shells for label-free SERS detection. Our method could effectively distinguish exosomes from different cell sources for cancer diagnosis and showed high sensitivity and specificity within a 95% confidence interval. As a low-cost and efficient exosome analysis method, the designed integrated platform for separation and detection has promising applicability in clinical diagnostics.

Development of highly efficient near-infrared (NIR)-excited photosensitizers is hampered by the fast nonradiative vibrational relaxation process regulated by the energy gap law. Here, from the fundamental perspective we propose that the intermolecular coupling of well-designed photosensitizers has the potential to facilitate exciton delocalization and hence reduce the exciton-vibration coupling, thereby boosting their phototherapeutic efficacy via inhibition of the vibrational relaxation pathway. Such conceived NIR-excited metallo-photosensitizers (IrHA1 and IrHA2) were prepared and studied for experimental validation. The resulting iridium complexes exhibited a little singlet oxygen ( 1 O 2 ) production in the monomeric state, but produced substantially enhanced 1 O 2 generation efficiency via benefiting from the exciton-vibration decoupling in the self-assembly state. Particularly, IrHA2 exhibits an unprecedented high 1 O 2 quantum yield of 54.9% (FDA-approved NIR dye indocyanine green: Φ Δ = 0.2%) under 808 nm laser irradiation with negligible heat generation, probably attributed to the suppression of vibronic couplings from the stretching mode of the acceptor ligand. In phototherapy, IrHA2-NPs with high biocompatibility and low dark toxicity can induce substantial tumor regression with 92.9% tumor volume reduction in vivo. This self-assembly-induced vibronic decoupling strategy would offer an effective approach to the design of high-performance NIR-excited photosensitizers.

The unique ion-transport properties in nanoconfined pores enable nanofluidic devices with great potential in harvesting osmotic energy. The energy conversion performance could be significantly improved by the precise regulation of the "permeability-selectivity" trade-off and the ion concentration polarization effect. Here, we take the advantage of electrodeposition technique to fabricate a Janus metal-organic framework (J-MOF) membrane that possesses rapid ion-transport capability and impeccable ion selectivity. The asymmetric structure and asymmetric surface charge distribution of the J-MOF device can suppress the ion concentration polarization effect and enhance the ion charge separation, exhibiting an improved energy harvesting performance. An output power density of 3.44 W/m 2 has been achieved with the J-MOF membrane at a 1000-fold concentration gradient. This work provides a new strategy for fabricating high-performance energy-harvesting devices.

The simultaneous and accurate detection of intracellular pH (pH i ) and extracellular pH (pH e ) is essential for studying the complex physiological activities of cancer cells and exploring pH-related therapeutic mechanisms. Here, we developed a super-long silver nanowire-based surface-enhanced Raman scattering (SERS) detection strategy for simultaneous sensing of pH i and pH e . A surface-roughened silver nanowire (AgNW) with a high aspect ratio is prepared at a nanoelectrode tip using a Cu-mediated oxidation process, which is then modified by pH-sensitive 4-mercaptobenzoic acid (4-MBA) to form 4-MBA@AgNW as a pH sensing probe. With the assistance of a 4D microcontroller, 4-MBA@AgNW is efficient in simultaneously detecting pH i and pH e in both 2D and 3D culture cancer cells by SERS, with minimal invasiveness, high sensitivity, and spatial resolution. Further investigation proves that the surface-roughened single AgNW can also be used in monitoring the dynamic variation of pH i and pH e of cancer cells upon stimulation with anticancer drugs or under a hypoxic environment.

Pancreatic adenocarcinoma (PAAD) has a poor prognosis and is relatively unresponsive to immunotherapy. Gasdermin C (GSDMC) induces pyroptosis in cancer cells and inflammation in the tumor microenvironment. However, whether GSDMC expression in PAAD is associated with survival or response to immunotherapy remains unknown. GSDMC expression and the relationship between GSDMC and patient survival or immune infiltration in PAAD were examined using data in the The Cancer Genome Atlas (TCGA), Gene Expression Ominbus (GEO), Genotype-Tissue Expression (GTEx) and Cancer Cell Line Encyclopedia (CCLE) databases. The TCGA PAAD cohort could be divided into two distinct risk groups based on the expression of GSDMC-related genes (GRGs). The TIDE algorithm predicted that the low-risk group was more responsive to immune checkpoint blockade therapy than the high-risk group. A novel 15-gene signature was constructed and could predict the prognosis of PAAD. In addition, the 15-gene signature model predicted the infiltration of immune cells and Immune checkpoint blockade (ICB) treatment response. Immunohistochemical staining assessment of patient-derived human tissue microarray (TMA) from 139 cases of local PAAD patients revealed a positive correlation between GSDMC expression and PD-L1 expression but a negative correlation between GSDMC expression and infiltration of low CD8+ T cells. Moreover, the overexpression of GSDMC was related to poor overall survival (OS). This study suggests that GSDMC is a valuable biomarker for predicting PAAD prognosis and predicts the immunotherapy response of PAAD., Competing Interests: None., (AJCR Copyright © 2023.)

Obtaining sequential and conformational information on proteins is vital to understand their functions. Although the nanopore-based electrical detection can sense single molecule (SM) protein and distinguish among different amino acids, this approach still faces difficulties in slowing down protein translocation and improving ionic current signal-to-noise ratio. Here, we observe the unfolding and multistep sequential translocation of SM cytochrome c (cyt c) through a surface enhanced Raman scattering (SERS) active conical gold nanopore. High bias voltage unfolds SM protein causing more exposure of amino acid residues to the nanopore, which slows down the protein translocation. Specific SERS traces of different SM cyt c segments are then recorded sequentially when they pass through the hotspot inside the gold nanopore. This study shows that the combination of SM SERS with a nanopore can provide a direct insight into protein segments and expedite the development of nanopore toward SM protein sequencing.

Direct structural and dynamic characterization of protein conformers in solution is highly desirable but currently impractical. Herein, we developed a single molecule gold plasmonic nanopore system for observation of protein allostery, enabling us to monitor translocation dynamics and conformation transition of proteins by ion current detection and SERS spectrum measurement, respectively. Allosteric transition of calmodulin (CaM) was elaborately probed by the nanopore system. Two conformers of CaM were well-resolved at a single-molecule level using both the ion current blockage signal and the SERS spectra. The collected SERS spectra provided structural evidence to confirm the interaction between CaM and the gold plasmonic nanopore, which was responsible for the different translocation behaviors of the two conformers. SERS spectra revealed the amino acid residues involved in the conformational change of CaM upon calcium binding. The results demonstrated that the excellent spectral characterization furnishes a single-molecule nanopore technique with an advanced capability of direct structure analysis.

Cell surface proteins, as important components of biological membranes, cover a wide range of important markers of diseases and even cancers. In this regard, precise detection of their expression levels is of crucial importance for both cancer diagnosis and the development of responsive therapeutic strategies. Herein, a size-controlled core-shell Au@ Copper(II) benzene-1,3,5-tricarboxylate (Au@Cu-BTC) nanomaterial was synthesized for specific and simultaneous imaging of multiple protein expression levels on cell membranes. The porous shell of Cu-BTC constructed on Au nanoparticles enabled effective loading of Raman reporter molecules, followed by further modification of the targeting moieties, which equipped the nanoprobe with good specificity and stability. Additionally, given the flexibility of the types of Raman reporter molecules available for loading, the nanoprobes were also demonstrated with good multichannel imaging capabilities. Ultimately, the present strategy of electromagnetic and chemical dual Raman scattering enhancement was successfully applied for the simultaneous detection of varied proteins on cell surfaces with high sensitivity and accuracy. The proposed nanomaterial holds promising applications in biosensing and therapeutic fields, which could not only provide a general strategy for the synthesis of metal-organic framework-based core-shell surface-enhanced Raman scattering nanoprobes but also enable further utilization in multitarget and multichannel cell imaging.

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

This review centers on a closed bipolar electrode (BPE) array using an electro-fluorochromism (EFC) or electro-chemiluminescence (ECL) reaction as the reporting reaction. Electrochemical signals at one pole of the closed BPE array can be transduced into the EFC or ECL signals at the opposite pole. Therefore, the current signal of a redox reaction can be easily detected and imaged by monitoring the luminescence signal. Recent developments in closed BPE array-based EFC and ECL sensing and imaging are summarized and discussed in detail. Finally, we consider the challenges and opportunities for improving the spatial resolution of closed BPE array-based electrochemical imaging, and emphasize the important application of this technique to the imaging of cellular activities at the single-cell level., (© 2022 Wiley-VCH GmbH.)

Based on transcriptome sequencing technology, the mouse model of prediabetes treated with Huangjing Qianshi Decoction was sequenced to explore the possible mechanism of treating prediabetes. First of all, transcriptome sequencing was performed on the normal BKS-DB mouse group, the prediabetic model group, and the Huangjing Qianshi Decoction treatment group(treatment group) to obtain differentially expressed genes in the skeletal muscle samples of mice. The serum biochemical indexes were detected in each group to screen out the core genes of Huangjing Qianshi Decoction in prediabetes. Gene Ontology(GO) database and Kyoto Encyclopedia of Genes and Genomes(KEGG) database were used to conduct signaling pathway enrichment analysis of differentially expressed genes, and real-time quantitative polymerase chain reaction(RT-qPCR) was used to verify them. The results showed that the levels of fasting blood glucose(FBG), fasting insulin(FINS), insulin resistance index(HOMA-IR), total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in the mouse model were significantly decreased after treatment with Huangjing Qianshi Decoction. In the results of differential gene screening, there were 1 666 differentially expressed genes in the model group as compared with the normal group, and there were 971 differentially expressed genes in the treatment group as compared with the model group. Among them, interleukin-6(IL-6) and NR3C2 genes, which were closely related to the regulation of insulin resis-tance function, were significantly up-regulated between the model group and the normal group, and vascular endothelial growth factor A(VEGFA) genes were significantly down-regulated between the model group and the normal group. However, the expression results of IL-6, NR3C2, and VEGFA genes were adverse between the treatment group and the model group. GO functional enrichment analysis found that the biological process annotation mainly focused on cell synthesis, cycle, and metabolism; cell component annotation mainly focused on organelles and internal components; and molecular function annotation mainly focused on binding molecular functions. KEGG pathway enrichment analysis found that it involved the protein tyrosine kinase 6(PTK6) pathway, CD28-dependent phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) pathway, p53 pathway, etc. Therefore, Huangjing Qianshi Decoction can improve the state of prediabetes, and the mechanism may be related to cell cycle and apoptosis, PI3K/AKT pathway, p53 pathway, and other biological pathways regulated by IL-6, NR3C2, and VEGFA.

Herein, a nanopipette-based thermocouple probe that possesses high temperature resolution, rapid response, good reversibility and stability was constructed and successfully applied for single-cell temperature sensing. Different intracellular temperatures were observed in diverse types of cells, which reveals differences in their metabolism levels. Temperature responses of cancer and normal cells against various exogenous drugs were also demonstrated. The spatially resolved temperature sensing of three-dimensional cell culture models unveils the existence of their inner temperature gradients. This work would facilitate drug screening and disease diagnosis.

An indole-related molecules have been considered as the potential fluorescent probes for biological and electrochemical sensing. However, most of the indole probes have been usually used in a single detection mode. Indolium probes that enable accurate detection in complex environments are rarely reported. Here, four novel indole derivatives including the phenyl group substituted with different functional moieties were designed on the basis of the donor-π-acceptor (D-π-A) concept. These derivatives exhibit positive solvatochromism owing to their varied molecular conformations upon contacting to various solvents and the different HOMO-LUMO gaps caused by the difference in electronic push-pull capability of the substituents. Their solid-state fluorescence emissions and multiple chromisms are observed due to the inherent twisted geometries and aggregation modes. In addition, these derivatives show dramatic color and fluorescence responses due to the protonation of the nitrogen and oxygen containing groups, and thus novel colorimetric pH sensors, fluorescent papers and logic gates have been designed.

Establishing a systematic molecular information analysis strategy for cell culture models is of great significance for drug development and tissue engineering technologies. Here, we fabricated single silver nanowires with high surface-enhanced Raman scattering activity to extract SERS spectra in situ from two-dimensional (2D) and three-dimensional (3D) cell culture models. The silver nanowires were super long, flexible and thin enough to penetrate through multiple cells. A single silver nanowire was used in combination with a four-dimensional microcontroller as a cell endoscope for spectrally analyzing the components in cell culture models. Then, we adopted a machine learning algorithm to analyze the obtained spectra. Our results show that the abundance of proteins differs significantly between the 2D and 3D models, and that nucleic acid-rich and protein-rich regions can be distinguished with satisfactory accuracy.

To enhance the fluorescence efficiency of semiconductor nanocrystal quantum dots (QDs), strategies via enhancing photo-absorption and eliminating non-radiative relaxation have been proposed. In this study, we demonstrate that fluorescence efficiency of molybdenum disulfide quantum dots (MoS 2 QDs) can be enhanced by single-atom metal (Au, Ag, Pt, Cu) modification. Four-fold enhancement of the fluorescence emission of MoS 2 QDs is observed with single-atom Au modification. The underlying mechanism is ascribed to the passivation of non-radiative surface states owing to the new defect energy level of Au in the forbidden band that can trap excess electrons in n-type MoS 2 , increasing the recombination probability of conduction band electrons with valence band holes of MoS 2 . Our results open an avenue for enhancing the fluorescence efficiency of QDs via the modification of atomically dispersed metals, and extend their scopes and potentials in a fundamental way for economic efficiency and stability of single-atom metals., (© 2022 Wiley-VCH GmbH.)

A crack-free micrometer-sized compact structure of 1,3,5-tris(4-aminophenyl)benzene-terephthaldehyde-covalent organic frameworks (TAPB-PDA-COFs) was constructed in situ at the tip of a theta micropipette (TMP). The COF-covered theta micropipette (CTP) then created a stable liquid-gas interface inside COF nanochannels, which was utilized to electrochemically analyze the content and distribution of ammonia gas in the microenvironments. The TMP-based electrochemical ammonia sensor (TEAS) shows a high sensing response, with current increasing linearly from 0 to 50,000 ppm ammonia, owing to the absorption of ammonia gas in the solvent meniscus that connects both barrels of the TEAS. The TEAS also exhibits a short response and recovery time of 5 ± 2 s and 6 ± 2 s, respectively. This response of the ammonia sensor is remarkably stable and repeatable, with a relative standard deviation of 6% for 500 ppm ammonia gas dispensing with humidity control. Due to its fast, reproducible, and stable response to ammonia gas, the TEAS was also utilized as a scanning electrochemical microscopy (SECM) probe for imaging the distribution of ammonia gas in a microspace. This study unlocks new possibilities for using a TMP in designing microscale probes for gas sensing and imaging.

Ultrathin nanosheets of two-dimensional covalent organic frameworks covered a quartz nanopipette and then acted as a nanopore device for single-molecule DNA sensing. Our results showed that a single DNA homopolymer as short as 6 bases could be detected. The dwell times of 30-mer DNA homopolymers were obviously longer than the times of 10- or 6-mer ones. For different bases, poly(dA) 6 showed the slowest transport speed (∼595 μs/base) compared with cytosine (∼355 μs/base) in poly(dC) 6 and thymine (∼220 μs/base) in poly(dT) 6 . Such translocation speeds are the slowest ever reported in two-dimensional material-based nanopores. Poly(dA) 6 also showed the biggest current blockade (94.74 pA) compared with poly(dC) 6 (79.54 pA) and poly(dT) 6 (71.41 pA). However, the present difference in blockade current was not big enough to distinguish the four DNA bases. Our study exhibits the shortest single DNA molecules that can be detected by COF nanopores at the present stage and lights the way for DNA sequencing based on solid-state nanopores.

Ion transport in nanochannels of a size comparable to that of hydrated ions exhibits unique properties due to the synergistic effect of various forces. Here, we design a nanochannel/ion channel composite (NIC) membrane that shows a high ion current rectification (ICR) ratio in different electrolytes. Experimental and theoretical results demonstrate that the synergistic effect of electrostatic interaction and ionic dehydration plays an important role in regulating the ICR behavior of the NIC membrane. We find that electrostatic attraction between ions and the channel surface in the ultraconfined space increases the probability of ionic dehydarion, resulting in different dehydration energy costs for different ions. This further alters the driving force for ion transport and thus regulates ICR of the NIC membrane. This work provides fundamental knowledge of ion transport in ion channels, which aids in the understanding of the function of biological systems and the design of high-performance nanochannel devices.

Effective photosensitizers are of particular importance for the widespread clinical utilization of phototherapy. However, conventional photosensitizers are usually plagued by short-wavelength absorption, inadequate photostability, low reactive oxygen species (ROS) quantum yields, and aggregation-caused ROS quenching. Here, we report a near-infrared (NIR)-supramolecular photosensitizer (RuDA) via self-assembly of an organometallic Ru(II)-arene complex in aqueous solution. RuDA can generate singlet oxygen ( 1 O 2 ) only in aggregate state, showing distinct aggregation-induced 1 O 2 generation behavior due to the greatly increased singlet-triplet intersystem crossing process. Upon 808 nm laser irradiation, RuDA with excellent photostability displays efficient 1 O 2 and heat generation in a 1 O 2 quantum yield of 16.4% (FDA-approved indocyanine green: Φ Δ  = 0.2%) together with high photothermal conversion efficiency of 24.2% (commercial gold nanorods: 21.0%, gold nanoshells: 13.0%). In addition, RuDA-NPs with good biocompatibility can be preferably accumulated at tumor sites, inducing significant tumor regression with a 95.2% tumor volume reduction in vivo during photodynamic therapy. This aggregation enhanced photodynamic therapy provides a strategy for the design of photosensitizers with promising photophysical and photochemical characteristics., (© 2022. The Author(s).)

High ion selectivity and permeability, as two contradictory aspects for the membrane design, highly hamper the development of osmotic energy harvesting technologies. Metal-organic frameworks (MOFs) with ultra-small and high-density pores and functional surface groups show great promise in tackling these problems. Here, we propose a facile and mild cathodic deposition method to directly prepare crack-free porphyrin MOF membranes on a porous anodic aluminum oxide for osmotic energy harvesting. The abundant carboxyl groups of the functionalized porphyrin ligands together with the nanoporous structure endows the MOF membrane with high cation selectivity and ion permeability, thus a large output power density of 6.26 W m -2 is achieved. The photoactive porphyrin ligands further lead to an improvement of the power density to 7.74 W m -2 upon light irradiation. This work provides a promising strategy for the design of high-performance osmotic energy harvesting systems., (© 2022 Wiley-VCH GmbH.)

Various S-bonding configurations existing in sulfur-doped reduced graphene oxide (S-rGO) show different electronic structures and physiochemical properties. Thus, understanding the properties of unique S-bonding configurations requires the construction of S-rGO with only single configuration. Here, we synthesized S-rGO with a pure thiophene-sulfur configuration through a simple and low-cost hydrothermal method by simply controlling the oxidation degree of the graphene oxide (GO) precursor. Through the use of a GO precursor with a high content of C-O groups, pure doping of the thiophene-sulfur configuration in the rGO can be achieved. Further electrochemical characterization reveals an increased electrocatalytic activity of the pure thiophene-sulfur-doped S-rGO in the oxygen reduction reaction, indicating the important role of thiophene-sulfur. The present work deepens the understanding of the functions of doped nonmetal elements in carbon materials in electrocatalysis and helps in the design of high performance electrocatalysts.