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Blockers of pore-forming toxins (PFTs) limit bacterial virulence by blocking relevant channel proteins. However, screening of desired blockers from a large pool of candidate molecules is not a trivial task. Acknowledging its advantages of low cost, high throughput, and multiplicity, DiffusiOptoPhysiology (DOP), an emerging nanopore technique that visually monitors the states of individual channel proteins without using any electrodes, has shown its potential use in the screening of channel blockers. By taking different α-hemolysin (α-HL) mutants as model PFTs and different cyclodextrins as model blockers, we report direct screening of pore blockers solely by using fluorescence microscopy. Different combinations of pores and blockers were simultaneously evaluated on the same DOP chip and a single-molecule resolution is directly achieved. The entire chip is composed of low-cost and biocompatible materials, which is fully disposable after each use. Though only demonstrated with cyclodextrin derivatives and α-HL mutants, this proof of concept has also suggested its generality to investigate other pore-forming proteins.

Chemical reactions of single molecules, caused by rapid formation or breaking of chemical bonds, are difficult to observe even with state-of-the-art instruments. A biological nanopore can be engineered into a single molecule reactor, capable of detecting the binding of a monatomic ion or the transient appearance of chemical intermediates. Pore engineering of this type is however technically challenging, which has significantly restricted further development of this technique. We propose a versatile strategy, “programmable nano-reactors for stochastic sensing” (PNRSS), by which a variety of single molecule reactions of hydrogen peroxide, metal ions, ethylene glycol, glycerol, lactic acid, vitamins, catecholamines or nucleoside analogues can be observed directly. PNRSS presents a refined sensing resolution which can be further enhanced by an artificial intelligence algorithm. Remdesivir, a nucleoside analogue and an investigational anti-viral drug used to treat COVID-19, can be distinguished from its active triphosphate form by PNRSS, suggesting applications in pharmacokinetics or drug screening., Monitoring single molecule chemical reactions can be difficult and nanopore based strategies which have shown promise are technically challenging. Here, the authors report on a technique which allows for the direct observation of different reactions and demonstrate the ability to distinguish clinically relevant analogues.

A mixture of HBPin with KOtBu was found to activate cobalt salt to form a heterotopic cobalt species that is highly active for catalytic intermolecular trimerization of alkynes. This protocol affords 1,2,4-regioisomers in good yields with high regioselectivities under mild conditions. These salient features, together with the operational simplicity and high efficiency, as well as obviating the use of any costly and/or air sensitive ligands, renders the protocol promising for practical applications.

Diverse functions of proteins, including synthesis, catalysis, and signaling, result from their highly variable amino acid sequences. The technology allowing for direct analysis of protein sequences, however, is still unsatisfactory. Recent developments of nanopore sequencing of DNA or RNA have motivated attempts to realize nanopore sequencing of peptides in a similar manner. The core challenge has been to achieve a controlled ratcheting motion of the target peptide, which is currently restricted to a limited choice of compatible enzymes. By constructing peptide-oligonucleotide conjugates (POCs) and measurements with nanopore-induced phase-shift sequencing (NIPSS), direct observation of the ratcheting motion of peptides has been successfully achieved. The generated events show a clear sequence dependence on the peptide that is being tested. The method is compatible with peptides with either a conjugated N- or C-terminus. The demonstrated results suggest a proof of concept of nanopore sequencing of peptide and can be useful for peptide fingerprinting.

Protein nanopores can be engineered as nanoreactors to investigate single-molecule chemical reactions. Recent studies have demonstrated that Mycobacterium smegmatis porin A (MspA) nanopore is a superior engineering template acknowledging its geometrical advantages. However, reported engineering of MspA to form a nanoreactor has focused only on site 91 and mapping of other engineering sites have never been performed before. By taking tetrachloraurate(III) ([AuCl4]-) as a model reactant, potential engineering sites within the pore constriction of MspA have been thoroughly investigated. It is discovered that the produced event amplitude is inversely correlated to the cross-sectional diameter of the pore constriction size at the engineering site, providing evidence that site 91 is actually already the optimum place to introduce the chemical reactivity. Other unavailable engineering sites, which either significantly interfere with the pore assembly or produce reactive sites facing to the pore's exterior instead of to the pore lumen, were also spotted and discussed. All results demonstrated above have provided a complete map of engineering sites within the constriction area of MspA and may be beneficial as a reference in future engineering of corresponding nanoreactors.

Folding of RNA can produce elaborate tertiary structures, corresponding to their diverse roles in the regulation of biological activities. Direct observation of RNA structures at high resolution in their native form however remains a challenge. The large vestibule and the narrow constriction of a Mycobacterium smegmatis porin A (MspA) suggests a sensing mode called nanopore trapping/translocation, which clearly distinguishes between microRNA, small interfering RNA (siRNA), transfer RNA (tRNA) and 5 S ribosomal RNA (rRNA). To further profit from the acquired event characteristics, a custom machine learning algorithm is developed. Events from measurements with a mixture of RNA analytes can be automatically classified, reporting a general accuracy of ~93.4%. tRNAs, which possess a unique tertiary structure, report a highly distinguishable sensing feature, different from all other RNA types tested in this study. With this strategy, tRNAs from different sources are measured and a high structural conservation across different species is observed in single molecule., Nanopores have been used for direct observation of RNA structure in native environments but have limited RNA differentiation capabilities. Here, the authors report on the use of Mycobacterium smegmatis porin A nanopores for the trapping and translocation identification of microRNA, siRNA, tRNA and ribosomal RNA.

Acknowledging its unique conical lumen structure, Mycobacterium smegmatis porin A (MspA) was the first type of nanopore that has successfully sequenced DNA. Recent developments of nanopore single molecule chemistry have also suggested MspA to be an optimum single molecule reactor. However, further investigations with this approach require heavy mutagenesis which is labor intensive and requires high end instruments for purifications. We here demonstrate an efficient and economic protocol which performs rapid and multiplex preparation of a variety of MspA mutants. The prepared MspA mutants were demonstrated in operations such as nanopore insertion, sequencing, optical single channel recording (oSCR), nanopore single molecule chemistry and nanopore rectification. The performance is no different from that of pores however prepared by other means. The time of all human operations and the cost for a single batch of preparation have been minimized to 40 min and 0.4$, respectively. This method is extremely useful in the screening of new MspA mutants, which has an urgent requirement in further investigations of new MspA nanoreactors. Its low cost and simplicity also enable efficient preparations of MspA nanopores for both industrial manufacturing and academic research.

Gold(I) compounds are known to bind sulfur-containing proteins, forming the basis in the design of gold(I)-based drugs. However, the intrinsic molecular mechanism of the chemical reaction is easily hidden when monitored in ensemble. We have previously demonstrated that Mycobacterium smegmatis porin A (MspA) can be engineered (MspA-M) to contain a specialized nanoreactor to probe chemical reactions involving tetrachloroaurate(III). Here, we provide further investigations of coordination interactions between dichloroaurate(I) and MspA-M. Gold compounds of different coordination geometry and valence states are as well probed and evaluated, demonstrating the generality of MspA-M. With single-molecule evidence, MspA-M demonstrates a preference for dichloroaurate(I) than tetrachloroaurate(III), an observation in a single molecule that has never been reported. By counting the maximum number of simultaneous ion bindings, the narrowly confined pore restriction also efficiently distinguishes dichloroaurate(I) and tetrachloroaurate(III) according to their differences in geometry or size. The above demonstration complemented a previous study by demonstrating other possible gold-based single-molecule chemical reactions observable by MspA. These observations bring insights in the understanding of gold-based coordination chemistry in a nanoscale.

MoS2 have recently emerged as alternatives to noble metals as electrocatalysts for the hydrogen evolution reaction (HER) owing to their abundance and low cost. Considering the shortcomings of MoS2 , including insufficient active sites, inert basal plane, and poor conductivity, the electrocatalytic hydrogen evolution properties of MoS2 can be improved in three ways: activating the inert basal plane to improve intrinsic activity, increasing active edge sites, and improving the conductivity. Defects can adjust the surface electronic structure of the crystal to bring the hydrogen adsorption free energy closer to zero. Therefore, current research has mainly used S-vacancies to activate the inert basal surface of MoS2 ; used edge defects to increase the number of active sites; and used defective conductive carbon supports to improve the conductivity of MoS2 -based catalysts. This review introduces researches on improving the performance of MoS2 for HER by considering the purpose, characterization, and preparation of defects.

Reported here for the first time is the Ir-catalyzed γ-selective hydroboration of γ-substituted allylic amides under mild reaction conditions. A variety of functional groups could be compatible with reaction conditions, affording γ-branched amides in good yields with ≤97% γ-selectivity. We have also demonstrated that the obtained borylated products could be used in a series of C-O, C-F, C-Br, and C-C bond-forming reactions.

Recent developments concerning large protein nanopores suggest a new approach to structure profiling of native folded proteins. In this work, the large vestibule of Mycobacterium smegmatis porin A (MspA) and calmodulin (CaM), a Ca2+ -binding protein, were used in the direct observation of the protein structure. Three conformers, including the Ca2+ -free, Ca2+ -bound, and target peptide-bound states of CaM, were unambiguously distinguished. A disease related mutant, CaM D129G was also discriminated by MspA, revealing how a single amino acid replacement can interfere with the Ca2+ -binding capacity of the whole protein. The binding capacity and aggregation effect of CaM induced by different ions (Mg2+ /Sr2+ /Ba2+ /Ca2+ /Pb2+ /Tb3+ ) were also investigated and the stability of MspA in extreme conditions was evaluated. This work demonstrates the most systematic single-molecule investigation of different allosteric conformers of CaM, acknowledging the high sensing resolution offered by the MspA nanopore trap.

Designing polymer-based nanostructures through self-assembly has great practical significance in biomedical applications, especially in drug delivery. In general, hydrophobic chains can induce the self-assembly of amphiphilic copolymer to form polymer-based nanostructures in an aqueous phase. However, the application of polymer-based nanostructures has been prevented due to the insufficient functionality of hydrophobic chains. To address these critical issues, the unique tetraphenylethene (TPE) moiety is employed with aggregation-induced emission (AIE) as functional hydrophobic chains to induce copolymer self-assembly and form polymeric micelles that can show strong fluorescence and a low critical micelle concentration (CMC) in aqueous solution. The novel polymeric micelles can efficiently encapsulate doxorubicin (DOX) molecules, and their favorable stability is demonstrated in a physiological medium. More importantly, the disassembly of polymeric micelles is triggered in the presence of esterase, then causing drug release and fluorescence quenching. It is demonstrated that DOX-loaded polymeric micelles have an obvious toxicity against cancer cells. This work confirms that the combination of AIE and self-assembly is an effective strategy for expanding the application of block copolymers and developing new enzyme-responsive polymeric micelles for cancer therapy.

Polymer self-assembly has attracted intensive technological and scientific consideration due to its intriguing practicability and fascinating versatility. A wide range of morphologies, including micelles, vesicles, cylinders, and many other hierarchical assemblies, have been crafted through polymer self-assembly for many decades. Herein, we report a facile and robust strategy to fabricate polymeric assemblies that possess precisely controllable morphology through copolymer self-assembly. The results show that these copolymers can be self-assembled into two different polymeric assemblies, depending on the choice of polymer structure. In this self-assembly process, the polymerization of dopamine and the coupling between polydopamine and block copolymer are performed in succession (denoted the polymerization-coupling process), which synergistically induces the self-assembly of block copolymer to yield ordered structures, including micelles and vesicles. The key to this strategy is to exploit the self-polymerization of dopamine, which results in polymeric vesicles with cross-linking structures and enhances their stability without additional cross-linking agents. These polymeric vesicles exhibit an ideal drug loading capacity toward doxorubicin (DOX) and bortezomib (BTZ) because of a number of carboxyl groups, conjugated systems, and catechol moieties, while the drug-loaded polymeric vesicles are sensitive to the endogenous weak acidic microenvironment, unloading the drug to fulfil their drug delivery role. Therefore, this strategy provides new insights into the development of molecular self-assembly, and the resultant polymeric assemblies show direct potential applications in the field of drug delivery.

In the formation of coordination interactions between metal ions and amino acids in natural metalloproteins, the bound metal ion is critical either for the stabilization of the protein structure or as an enzyme co-factor. Though extremely small in size, metal ions, when bound to the restricted environment of an engineered biological nanopore, result in detectable perturbations during single channel recordings. All reported work of this kind was performed with engineered α-hemolysin nanopores and the observed events appear to be extremely small in amplitude (∼1–3 pA). We speculate that the cylindrical pore restriction of α-hemolysin may not be optimal for probing extremely small analytes. Mycobacterium smegmatis porin A (MspA), a conical shaped nanopore, was engineered to interact with Ca2+, Mn2+, Co2+, Ni2+, Zn2+, Pb2+ and Cd2+ and a systematically larger event amplitude (up to 10 pA) was observed. The measured rate constant suggests that the coordination of a single ion with an amino acid follows hard–soft-acid–base theory, which has never been systematically validated in the case of a single molecule. By adjusting the measurement pH from 6.8 to 8.0, the duration of a single ion binding event could be modified with a ∼46-fold time extension. The phenomena reported suggest MspA to be a superior engineering template for probing a variety of extremely small analytes, such as monatomic and polyatomic ions, small molecules or chemical intermediates, and the principle of hard–soft-acid–base interaction may be instructive in the pore design.

This Letter reports a novel synthetic methodology for the fabrication of three-dimensional (3D) nanostructured CdS@carbon fiber (CF) networks and the validation of its feasibility for applications as a general platform for photoelectrochemical (PEC) bioanalysis. Specifically, 3D architectures are currently attracting increasing attention in various fields due to their intriguing properties, while CdS has been most widely utilized for PEC bioanalysis applications because of its narrow band gap, proper conduction band, and stable photocurrent generation. Using CdS as a representative material, this work realized the innovative synthesis of 3D CdS@CF networks via a simple solvothermal process. Exemplified by the sandwich immunoassay of fatty-acid-binding protein (FABP), the as-fabricated 3D CdS@CF networks exhibited superior properties, and the assay demonstrated good performance in terms of sensitivity and selectivity. This work features a novel fabrication of 3D CdS@CF networks that can serve as a general platform for PEC bioanalysis. The methodology reported here is expected to inspire new interest for the fabrication of other 3D nanostructured Cd-chalcogenide (S, Se, Te)@CF networks for wide applications in biomolecular detection and beyond.

Cisplatin, which selectively binds to N7 atoms of purines to inhibit normal replication and transcription, is a widely applied chemotherapeutic drug in the treatment of cancer. Though direct identification of cisplatin lesions on DNA is of great significance, existing sequencing methods have issues such as complications of preamplification or enrichment-induced false-positive reports. Direct identification of cisplatin lesions by nanopore sequencing (NPS) is in principle feasible. However, relevant investigations have never been reported. By constructing model sequences (83 nucleotides in length) containing a sole cisplatin lesion, identification of corresponding lesions by NPS is achieved with

Since block copolymers are able to self-assemble into various polymeric architectures, it is intriguing to explore a unique self-assembly strategy for polymers. Two different metallic oxides [manganese dioxide (MnO2) and zinc oxide (ZnO)] are displayed herein to demonstrate this self-assembly mechanism of polymers. In situ generation of metallic oxides induces self-assembly of block copolymers to form polymeric hybrid micelles with tunable stability in aqueous solutions. These final ZnO-cross-linked polymeric micelles exhibited a high drug loading capacity of 0.41 mg mg-1 toward doxorubicin (DOX), whereas DOX-loaded ZnO-cross-linked polymeric micelles could be broken down into Zn2+ and polymer scraps, which facilitated drug release in tumor microenvironments. Both in vitro and in vivo investigations showed that the drug-loaded ZnO-cross-linked polymeric micelles effectively suppressed tumor growth. Accordingly, the present study demonstrates a novel strategy of polymer self-assembly for fabricating polymeric architectures that can potentially provide insight for developing other polymeric architectures.

In the formation of coordination interactions between metal ions and amino acids in natural metalloproteins, the bound metal ion is critical either for the stabilization of the protein structure or as an enzyme co-factor. Though extremely small in size, metal ions, when bound to the restricted environment of an engineered biological nanopore, result in detectable perturbations during single channel recordings. All reported work of this kind was performed with engineered α-hemolysin nanopores and the observed events appear to be extremely small in amplitude (∼1–3 pA). We speculate that the cylindrical pore restriction of α-hemolysin may not be optimal for probing extremely small analytes. Mycobacterium smegmatis porin A (MspA), a conical shaped nanopore, was engineered to interact with Ca2+, Mn2+, Co2+, Ni2+, Zn2+, Pb2+ and Cd2+ and a systematically larger event amplitude (up to 10 pA) was observed. The measured rate constant suggests that the coordination of a single ion with an amino acid follows hard–soft-acid–base theory, which has never been systematically validated in the case of a single molecule. By adjusting the measurement pH from 6.8 to 8.0, the duration of a single ion binding event could be modified with a ∼46-fold time extension. The phenomena reported suggest MspA to be a superior engineering template for probing a variety of extremely small analytes, such as monatomic and polyatomic ions, small molecules or chemical intermediates, and the principle of hard–soft-acid–base interaction may be instructive in the pore design., The principle of hard–soft-acid–base (HSAB) theory was first validated in single molecule by measurements with engineered Mycobacterium smegmatis porin A (MspA) nanopore reactors.

Acknowledging its unique conical lumen structure, Mycobacterium smegmatis porin A (MspA) was the first type of nanopore that has successfully sequenced DNA. Recent developments of nanopore single molecule chemistry have also suggested MspA to be an optimum single molecule reactor. However, further investigations with this approach require heavy mutagenesis which is labor intensive and requires high end instruments for purifications. We here demonstrate an efficient and economic protocol which performs rapid and multiplex preparation of a variety of MspA mutants. The prepared MspA mutants were demonstrated in operations such as nanopore insertion, sequencing, optical single channel recording (oSCR), nanopore single molecule chemistry and nanopore rectification. The performance is no different from that of pores however prepared by other means. The time of all human operations and the cost for a single batch of preparation have been minimized to 40 min and 0.4$, respectively. This method is extremely useful in the screening of new MspA mutants, which has an urgent requirement in further investigations of new MspA nanoreactors. Its low cost and simplicity also enable efficient preparations of MspA nanopores for both industrial manufacturing and academic research., A rapid and multiplex approach to prepare engineered Mycobacterium smegmatis porin A (MspA) nanopores for single molecule sensing and sequencing.

Highlights The formation of manganese oxide induces self-assembly of block copolymers to form polymeric vesicles.The polymeric vesicles possessed strong stability and high drug loading capacity.The drug-loaded polymeric vesicles have been demonstrated, especially in in vivo studies, to exhibit a higher efficacy of tumor suppression without known cardiotoxicity. Abstract Molecular self-assembly is crucially fundamental to nature. However, the aqueous self-assembly of polymers is still a challenge. To achieve self-assembly of block copolymers [(polyacrylic acid–block–polyethylene glycol–block–polyacrylic acid (PAA68–b–PEG86–b–PAA68)] in an aqueous phase, manganese oxide (MnO2) is first generated to drive phase separation of the PAA block to form the PAA68–b–PEG86–b–PAA68/MnO2 polymeric assembly that exhibits a stable structure in a physiological medium. The polymeric assembly exhibits vesicular morphology with a diameter of approximately 30 nm and high doxorubicin (DOX) loading capacity of approximately 94%. The transformation from MnO2 to Mn2+ caused by endogenous glutathione (GSH) facilitates the disassembly of PAA68–b–PEG86–b–PAA68/MnO2 to enable its drug delivery at the tumor sites. The toxicity of DOX-loaded PAA68–b–PEG86–b–PAA68/MnO2 to tumor cells has been verified in vitro and in vivo. Notably, drug-loaded polymeric vesicles have been demonstrated, especially in in vivo studies, to overcome the cardiotoxicity of DOX. We expect this work to encourage the potential application of polymer self-assembly. Electronic supplementary material The online version of this article (10.1007/s40820-020-00447-9) contains supplementary material, which is available to authorized users.

The first demonstration of direct sequencing of 2′-deoxy-2′-fluoroarabinonucleic acid (FANA) using Nanopore-Induced Phase-Shift Sequencing (NIPSS)., 2′-deoxy-2′-fluoroarabinonucleic acid (FANA), which is one type of xeno-nucleic acid (XNA), has been intensively studied in molecular medicine and synthetic biology because of its superior gene-silencing and catalytic activities. Although urgently required, FANA cannot be directly sequenced by any existing platform. Nanopore sequencing, which identifies a single molecule analyte directly from its physical and chemical properties, shows promise for direct XNA sequencing. As a proof of concept, different FANA homopolymers show well-distinguished pore blockage signals in a Mycobacterium smegmatis porin A (MspA) nanopore. By ligating FANA with a DNA drive-strand, direct FANA sequencing has been demonstrated using phi29 DNA polymerase by Nanopore-Induced Phase Shift Sequencing (NIPSS). When bound with an FANA template, the phi29 DNA polymerase shows unexpected reverse transcriptase activity when monitored in a single molecule assay. Following further investigations into the ensemble, phi29 DNA polymerase is shown to be a previously unknown reverse transcriptase for FANA that operates at room temperature, and is potentially ideal for nanopore sequencing. These results represent the first direct sequencing of a sugar-modified XNA and suggest that phi29 DNA polymerase could act as a promising enzyme for sustained sequencing of a wide variety of XNAs.

Functionality of polymers is crucially fundamental to polymers. However, the application of polymers faces great challenges due to the insufficient function of hydrophobic chain, especially in drug delivery. One novel approach to solve this dilemma involves the use of medicated hydrophobic chains. Herein, the polymer-doxorubicin conjugates are synthesized from hydrophilic copolymer and hydrophobic chain composed of doxorubicin (DOX). DOX, a common hydrophobic anticancer drug, is used to serve as a hydrophobic pendant for inducing self-assembly of polymer-doxorubicin conjugates. The self-assembly of polymer-drug conjugates is employed to encapsulate the unreacted drug for the first time and form drug-loaded polyprodrug micelles that possess a low critical micelle concentration (CMC), which improves the use efficiency of expensive drug. The detachment of DOX moieties from polymer-doxorubicin conjugates caused by amidase facilitates the disintegration of DOX-loaded polyprodrug micelles to trigger the enhanced release of DOX in a slightly acidic medium. It is demonstrated that the DOX-loaded polyprodrug micelles have a higher suppression against cancer cells in in vitro investigations. This work thus proposes a strategy to modify the poor functionality of polymer-based nanostructures, through designing the medicated hydrophobic chains. This strategy facilitates the potential application of polymer-drug conjugates and provides profound insights into the effect of medicated polymer on drug delivery system.

Biological nanopores are capable of resolving small analytes down to a monoatomic ion. In this research, tetrachloroaurate(III), a polyatomic ion, is discovered to bind to the methionine residue (M113) of a wild-type α-hemolysin by reversible Au(III)-thioether coordination. However, the cylindrical pore geometry of α-hemolysin generates shallow ionic binding events (~5–6 pA) and may have introduced other undesired interactions. Inspired by nanopore sequencing, a Mycobacterium smegmatis porin A (MspA) nanopore, which possesses a conical pore geometry, is mutated to bind tetrachloroaurate(III). Subsequently, further amplified blockage events (up to ~55 pA) are observed, which report the largest single ion binding event from a nanopore measurement. By taking the embedded Au(III) as an atomic bridge, the MspA nanopore is enabled to discriminate between different biothiols from single molecule readouts. These phenomena suggest that MspA is advantageous for single molecule chemistry investigations and has applications as a hybrid biological nanopore with atomic adaptors., Engineered biological nanopores enable observation of single molecule chemistry events; however a cylindrical pore geometry can have undesired effects. The authors report a conical biological pore which was embedded with tetrachloroaurate(III) to allow for discrimination between different biothiols.

Objective To explore the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in vivo and in vitro and its mechanism. Methods 60 rats were underwent surgery to construct rat models of IVDD and divided in the sham group, model group and gradient G-Rg1 groups (10 mg/kg/d, 20 mg/kg/d and 40 mg/kg/d).The change of histology was observed by HE staining, the water content and the expression of β-catenin in IVD were detected. Rat nucleus pulposus cells(NPCs) were isolated from IVDD rats and divided in D-NPCs group, and gradient G-Rg1 groups(20 μg/ml, 50 μg/ml and 100 μg/ml).The cell proliferation activity, cell apoptosis rate,the expression of proteins related to ECM and Wnt/β-catenin were detected respectively, Finally the agonist of Wnt/β-catenin pathway LiCl was used for reversed experiments. Results In vivo, G-Rg1 treatment could improve the structural disorganization, low water content, NPCs number and aggrecan and collagenⅡ expression in IVD and down-regulate the expression of β-catenin. In vitro NPCs, G-Rg1 treatment could improve the low cell proliferation, high apoptosis rate and low expression of aggrecan and collagenⅡ in degenerative NPCs in a dose-dependent manner.G-Rg1 treatment could down-regulate the expression of proteins related to β-catenin signal and LiCl could reverse the increase of cell proliferation and ECM synthesis, decrease of apoptosis of degenerative NPCs induced by G-Rg1. Conclusion G-Rg1 could promote ECM synthesis of degenerative NPCs and inhibiting its apoptosis, improve the IVDD via inhibiting the Wnt/β-catenin pathway.

Photo-responsive materials with tunable properties by multiple stimuli have been widely used as molecular machines, molecular logic gates, optical data storages, etc. In this work, we report a rhodamine B-based photo-responsive system, whose properties could be facilely modulated by metal ions (Zn(II), Ni(II) and Hg(II)). These metal ions endow the complexes (L-Zn, L-Ni and L-Hg) with similar photochromic property but distinctly different photo-induced fluorescence change. Upon UV light irradiation, the spirolactam ring in rhodamine B moiety turned from a close form to an open form, along with enlarged conjugated structure with intense absorbance. Interestingly, fluorescence “turn off”, “no change” and “turn on” responses were induced by Zn(II), Ni(II) and Hg(II) respectively upon UV light irradiation. Taking advantage of the prominently different characteristics caused by metal ions, different logic gates were designed by simply varying the inputs of metal ions and UV light. This work provided a new strategy for developing multifunctional photo-responsive materials, which were further beneficial for constructing photo-controlled logic gates with tunable performance.

Based on asymmetric lithium salt of 1-(4-pyridinylmethyl)-1H-1,2,4-triazole-3-carboxylic acid ligand (pmtcLi), five Pb(II)-containing polymers [Pb(pmtc)(OAc)]n (1), [Pb(pmtc)(Cl)]n (2), [Pb(pmtc)(Br)]n (3), [Pb(pmtc)(I)]n (4) and {[Pb(pmtc)2(H2O)3]·H2O}n (5) have been hydrothermally synthesized and structurally characterized. 1–4 display 2D networks, in which 1 and 2 present (4.82) topology, whereas 3 and 4 show (44.62) topology, respectively. 5 is a 1D chain structure. The counter anions have an important influence on their structures and photoluminescent properties. Through calculations of the frontier molecular orbital (FMOs) of 1–5, their photoluminescence should be attributed to the n → π* transition.

The endoplasmic reticulum is the largest organelle in the cell. Studies have shown that the concentration of HClO is related to many diseases. A new type of probe R1 has positioned to the endoplasmic reticulum. The probe shows good positioning effect, excellent selectivity and high sensitivity, excellent anti-interference, and can quickly reach the response platform. The obvious color change can be used for naked eye observation. Due to its low cytotoxicity, probe R1 was successfully used for EC1 cells imaging under a laser scanning confocal microscope.

O; 6; -carboxymethylguanine (O; 6; -CMG) is a highly mutagenic alkylation product of DNA, triggering transition mutations relevant to gastrointestinal cancer. However, precise localization of a single O; 6; -CMG with conventional sequencing platforms is challenging. Here nanopore sequencing (NPS), which directly senses single DNA bases according to their physiochemical properties, was employed to detect O; 6; -CMG. A unique O; 6; -CMG signal was observed during NPS and a single-event call accuracy of >95 % was achieved. Moreover, O; 6; -CMG was found to be a replication obstacle for Phi29 DNA polymerase (Phi29 DNAP), suggesting this lesion could cause DNA sequencing biases in next generation sequencing (NGS) approaches.

A spiro bisphosphine oxide (SpinPO) was found to be an efficient chiral Lewis base catalyst in asymmetric reductive aldol reaction of enones and aldehydes in the presence of trichlorosilane as the reductant, affording a variety of β-hydroxyketones in good yields with moderate to high levels of diastereo- and enantioselectivities.

An efficient and convenient transition-metal-free strategy for the synthesis of 3-alkyl quinolinones via the radical cross-dehydrogenative coupling reaction of quinolinones with ethers was developed with moderate to good yields. This strategy using a straightforward route exhibited broad substrate scope, good functional group tolerance, and high atom economy, to afford various important quinolinone derivatives, which are privileged structures possessing a rich diversity of biological properties.

Symmetry swap: A C2 -chiral spiro diphosphine oxide (SpinPO) has been found to be highly efficient and enantioselective in the catalysis of double-aldol reactions of ketones and aldehydes to give the corresponding optically active double-aldol products, which can be readily transformed into optically active C3 - and pseudo-C3 -symmetric molecules.

In this work, a synchronized polarization induced electrospray ionization (SPI-ESI) method is developed and applied for the analysis of single-cell samples. In SPI-ESI, periodic alternating current square wave voltage (AC-SWV) is applied to induce the bipolar spray and both positive-ion and negative-ion mass spectra are obtained through one measurement by synchronizing the mode of mass analyzer with the bipolar spray process. Compared with conventional nanoelectrospray ionization (nESI, flow rate1000 nL/min), ultralow spray flow rate (pico-electrospray ionization, pESI, flow rate1000 pL/min) is achieved in SPI-ESI without loss of its sensitivity. The decrease of flow rate prolongs the MS signal duration from single-cell samples to acquire ms(2) data for components determination. To our knowledge, this is the first time to successfully achieve comprehensive analysis of single-cell samples by combining both positive-ion and negative-ion mass spectra. Ultimately, 86 components are profiled from single Allium cepa cells and 94 components are profiled from single PC-12 cells.

Due to the promotion of the surface area and the dispersion of active components upon supporting mixed metal oxides on the porous material active carbon, the copper-manganese oxide on carbon system has been proven to be much more efficient than the co-precipitation prepared Cu-Mn oxide in mediating the 2,2,6,6-tetramethylpiperidyl-1-oxyl (TEMPO)-catalyzed aerobic oxidation of alcohols. Even at 30 °C and with a 0.1 mol% load of TEMPO, the oxidations proceeded smoothly. Upon catalysis with the Cu-Mn oxide/C (10 wt%) and TEMPO (0.5–5 mol%), various alcohols were oxidized selectively to the corresponding aldehydes or ketones with molecular oxygen at 80 °C. Such a stable, recyclable heterogeneous cocatalyst permits alcohols to be oxidized under neutral and mild conditions.

Symmetry swap: A C2 -chiral spiro diphosphine oxide (SpinPO) has been found to be highly efficient and enantioselective in the catalysis of double-aldol reactions of ketones and aldehydes to give the corresponding optically active double-aldol products, which can be readily transformed into optically active C3 - and pseudo-C3 -symmetric molecules.