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The toxic metal ions leaching and metal nanoparticles agglomeration were the critical issues for metal-based carbon materials during the peroxymonosulfate (PMS) activation processes. Herein, a facile strategy was first proposed that zero-dimensional Fe/Fe3C nanoparticles were embedded in one-dimensional N-doped carbon nanofiber (Fe/Fe3C@NCNF) to solve the above challenges. The as-obtained Fe/Fe3C@NCNF-800 possessed a low Ea value (11.7 kJ/mol) and exhibited high activity for activating PMS to degrade tetracycline (TC) in a wide range of pH 3-11. As expected, the iron ions leaching concentration of Fe/Fe3C@NCNF-800 was very low (0.082 mg/L). Meanwhile, the Fe/Fe3C@NCNF-800 was easily recovered from the reaction solution due to its magnetic properties. Both superoxide radicals (O2∙−) and non-radical of singlet oxygen (1O2) were the primary reactive oxygen species (ROS) in the Fe/Fe3C@NCNF-800/PMS system via quenching tests and electron spin resonance spectroscopy (ESR). The catalytic mechanism suggested that the Fe/Fe3C and graphitic N were the main active sites in the Fe/Fe3C@NCNF-800 for PMS activation. This work provided a facile method for the preparation of Fe-based carbon materials with high catalytic ability, low metal leaching and easy recycling, showing a broad prospect for environmental applications.

Catalysts often undergo changes during the process of catalytic reactions, which makes the whole catalytic reaction system complicated and brings about much difficulty for the exploration of catalytic mechanism. Herein, we report that an octahedral metal organic cage (MOC) with stress was directionally transformed into two-dimensional nanoarrays maintaining the structure of precursor and new soluble low-nuclear complexes during the electrocatalytic oxygen evolution reaction (OER). The in-situ generated miscible electrocatalyst exhibits an overpotential as low as 197 mV at 10 mA cm−2, with a high electrochemical stability up to 5 hours. Notably, the miscible catalyst can be used as bifunctional electrocatalyst for OER and hydrogen evolution reaction (HER) and exhibits an ultra-low overpotential of 293 mV, even achieve overall water splitting under the voltage provided by a 1.5 V AA battery. As revealed by density functional theory simulations, the position of SO42− in MOC heterogeneous catalyst is regulated by the soluble low-nuclear complexes to reduce the activation energy of the reaction, leading to an optimization of the OER activity for the reaction system. This work provides a new strategy for the rational design of high-efficiency electrocatalytic system.

Salmonella is a foodborne pathogen that has contributed to numerous food safety accidents worldwide, making it necessary to detect contamination at an early stage. A pair of specific primers based on the invA gene of Salmonella was designed for PCR. Target double-stranded DNA (dsDNA) from PCR was purified and denatured at high temperature to obtain target single-stranded DNA (ssDNA). Two carboxyfluorescein-labeled hairpin probes (H1-FAM and H2-FAM) were designed with complementary portions to the ssDNA sequence so that binding could trigger H1-FAM and H2-FAM hybridization chain reaction (HCR) to produce a long dsDNA complex. In this study, graphene oxide (GO) was used in the development of a homogeneous fluorescence detection platform for Salmonella. Using this HCR-GO assay platform, Salmonella detection was completed in 3.5 h. Salmonella was reliably and specifically detected with a limit of detection (LOD) of 4.2 × 101 cfu/mL in pure culture. Moreover, this new HCR-GO assay platform was successfully applied to the detection of Salmonella in artificially contaminated milk with a LOD of 4.2 × 102 cfu/mL.

This study revealed activation mechanisms of apatite by polyacrylamide (PAM) during flotation of rare earth minerals in Bayan Obo Ore. This activation leads to high phosphorus content in rare earth concentrate. Ultraviolet (UV) absorption measurements show that adsorption of PAM on the surfaces of apatite and rare earths follows a pseudo-second-order reaction kinetic model. The isothermal adsorption process follows the Freundlich adsorption model, indicating that the adsorption of PAM on apatite is a multi-layer, non-uniform process, that is, physical and chemical adsorption occurs simultaneously. The measured zeta potential shows that under weakly alkaline conditions, amide groups with a negative charge are adsorbed on the surface of apatite, increasing the electronegativity, so that the potential is shifted negatively; however, the negative shift of the potential on the surface of rare earths is insignificant. Fourier transform infrared (FT-IR) test and X-ray photoelectron spectroscopy (XPS) results imply that PAM is chemically adsorbed on the surface of apatite, while 506E undergoes stronger chemical adsorption than PAM on the surface of rare earth minerals. It is found that multi-layer, non-uniform adsorption of PAM combining physical and chemical adsorption occurs on the surface of apatite and the process is dominated by physical adsorption: the adsorption of PAM on surfaces of apatite is stronger than that on the surface of rare earth minerals. Such adsorption activates the apatite, causing it to float during the flotation of rare earths, which is the reason for the high phosphorus content in the rare earth concentrate.

Herein, we subtly engineered a pH and membrane receptor dual-activatable aptamer therapeutic for bispecific tumor cell imaging and in situ drug release by utilizing a hairpin-contained i-motif as the acid-responsive element to be complementary with a tumor-targeted aptamer, named as an aptamer "molecule-doctor" (pH-Apt-MD). Specifically, the pH-Apt-MD consisted of two DNA strands, where the Apt-sgc8c was labeled with AF488 and Cy3 at its 5'- and 3'-end, respectively. The I-strand, a hairpin-contained i-motif, was complementary to the Apt-sgc8c strand partially, labeled with a BHQ2 in the middle, thus generating Cy3 with quenched fluorescence and only AF488-emitted fluorescence. The double-helix region of pH-Apt-MD was designed rich in GC bases, providing sites for doxorubicin (Dox) intercalation. Once target cells were encountered, the pH-Apt-MD disassembled due to the specific recognition of the aptamer and conformation change of the i-motif, with activated fluorescence resonance energy transfer (FRET) signals between AF488 and Cy3, accompanied by Dox release in situ. Benefiting from the design of the hairpin-contained i-motif, the pH-Apt-MD presented a narrow pH response range (pH 6.0-6.8) with a transition midpoint (pHT) of 6.50 ± 0.04. Furthermore, living cell studies revealed that the stimuli-responsive FRET signal activation of pH-Apt-MD was successfully achieved on the HCT116 cell surface with ultralow background and enhanced imaging contrast. Then, the cytotoxicity experiments proved that accurate drug release and cell killing were realized to target cells in an acidic microenvironment. As a facile double stimuli-responsive strategy, the pH-Apt-MD may hold great promise for application in precise diagnosis and therapy of cancer cells.

The photostability and dispersity under aggregation states always become an obstacle for the development of small-molecular organic dye (SMOD) composites. Herein, a novel supramolecular assembly strategy with a two-step assembly method is implemented to encapsulate SMODs for improving their photostability and acquiring uniformly dispersed nanoaggregates in aqueous solution. By the novel assembly strategy, photodegradation rates of the anthraquinone-type dyes can decrease significantly, and the stability of dispersed nanoassembly bodies can be improved in solution. Based on the two-step supramolecular assembly strategy, a new kind of aqueous processing composite system can be developed for preparing multiband laser-responsive devices and in situ healing of optical composite films. This two-step supramolecular assembly strategy can provide a new template and reference for improving the defects of SMODs and fabricating high-performance optical devices.

In situ stimuli-responsive molecular devices have gained much attention in biomedical areas due to their characteristics of increased image contrast and drug accumulation. Herein, we present a hand-in-hand in situ tile assembly for improved visualization of TK1 mRNA and killing of cancer cells. A pH-responsive and aptamer-functionalized tile motif (pH-Apt-TM) was first formed by four single-strand DNA, possessing pH-responsiveness and intracellular TK1 mRNA recognition capacity. When encountering target cells, the pH-Apt-TM could recognize target receptors on the cell surface through the aptamer domain. Meanwhile, the extracellular acidic pH gathered the pH-Apt-TM into a multifunctional hand-in-hand DNA tile assembly (HDTA) on the cells' surface. Compared to the pH-Apt-TM, studies revealed that the HDTA exhibited enhanced recognition, efficient cellular uptake, and improved visualization of TK1 mRNA, accompanied by gene silencing. Moreover, using Dox as a chemotherapeutic model, specific drug delivery and enhanced cell killing were achieved with target cells.

For intracellular molecular detection, the appropriate probes should include the abilities to enter target cells noninvasively, target specific sites, and then respond to the analytes reliably. Herein, a ratiometric fluorescent DNA nanostructure (RFDN) was designed for mitochondrial adenosine triphosphate (ATP) imaging in living cells. The DNA nanostructure was constructed by continuous hybridization of two hairpin DNA strands (HS1-Cy3 and HS2-Cy5) under the initiation of the trigger. HS1-Cy3 and HS2-Cy5 contained split aptamer fragments of ATP and are labeled with a fluorescent donor (Cy3) and acceptor (Cy5), respectively. The RFDN integrated multiple split aptamer fragments and increased the local concentration of sensing probes. The binding of ATP to aptamer fragments on the RFDN shortened the distance between Cy3 and Cy5, resulting in obvious ratiometric signals (fluorescence resonance energy transfer). The RFDN showed good biocompatibility and can be internalized into cells in a caveolin-dependent endocytosis pathway. The co-localization imaging results indicated that the DNA nanostructure could target the mitochondria via Cy3 and Cy5. Moreover, the confocal imaging results showed that the intracellular ATP changes stimulated by drugs in living cells could be indicated by the RFDN. In this way, the RFDN is expected to be a simple, flexible, and general platform for chemo/biosensing in living cells.

An all-inorganic CsPbI3 perovskite has exhibited some special excellent properties particularly high thermal stability and potential for tandem solar cells, yet its poor humidity stability and grai...

Siloxane rubber shows attractive properties of high stability, elasticity and transparency. Besides, the regulation of its properties renders it widely used in many application fields. However, most of the reported performance improvement methods of siloxane rubber focus on the change of chemical composition of siloxane rubber, including the design of molecular chain and the introduction of other compounds, etc. Such a strategy is still faced with many limitations in practical application. In this work, on the premise of not changing the chemical composition of siloxane rubber, we propose a facile solvothermal polymerization process to change the structure of cross-linking networks, so as to obtain the siloxane rubber with controllable mechanical properties. Compared to the normal curing method, we realized polydimethylsiloxane elastomer (PDMS) with maximum elongation of more than 3,000% (> 10 times of normally cured one) and tensile modulus lower than 0.15 MPa (< 1/10 of normally cured one). In addition to superior stretchability, it gains extra high softness, stickiness and sensitive response to organic solvents. Based on our solvothermal cured PDMS, its applications in oil collection and organic solvent sensor have been demonstrated. It is expected that this method can be readily utilized widely and shows great application potentials.

Phenolic resin modified by common physical methods cannot be applied directly in the military and aerospace fields due to its brittleness, poor heat resistance, and poor friction and wear resistance. Here, a strategy to significantly reinforce these properties was proposed by constructing self-assembled hybrid particles of graphite oxide (GO) and zirconia (ZrO2) nanoparticles to modify phenolic resin. The bending and impact test results showed that the bending strength, bending modulus, and impact strength maximumly increased by 73.6%, 52.3%, and 115.3%, respectively. The thermogravimetric analysis showed that the residual carbon rate increased by 19.7%, and the temperature Td, max at the fastest thermal decomposition rate increased by 18 °C. The friction and wear tests showed that the friction coefficient and wear rate reduced by 27.7% and 64.8%, respectively. The modified phenolic resin has met the applicable standards in military and aerospace fields. This strategy is also applicable to the performance reinforcement of other polymers. Strategy to significantly achieve multifunctional collaborative enhancement for phenolic resin by constructing self-assembled hybrid particles of graphite oxide as nano-fillers

Summary Efficient strategies to assemble enantioenriched pyridine derivatives are highly important, given their significance in both synthetic and medicinal chemistry. Here, we report an enantioselective nickel-catalyzed intermolecular [2 + 2 + 2] cycloaddition of alkyne-tethered malononitriles with alkynes for the synthesis of densely substituted pyridines. The α-all-carbon quaternary center adjacent to pyridine is introduced by desymmetrizing the two cyano groups of disubstituted malononitriles. Notably, terminal alkynes are also tolerated with good regioselectivity to afford tetrasubstituted pyridines. Zinc halide is essential to enable the occurrence of the transformation by promoting the hetero-cyclometallation step. The reaction uses bio-renewable 2-MeTHF as the solvent and features mild reaction conditions, good functional group compatibilities, and enantioselectivities. This study offers a straightforward approach to the valuable enantioenriched heteroarenes from feedstock chemicals by forming three bonds and one quaternary stereocenter simultaneously in a single reaction step.

Recently the phase 3 BEACON trial showed that the combination of encorafenib, cetuximab, and binimetinib versus cetuximab and irinotecan/FOLFIRI improved overall survival in pre-treated patients with metastatic colorectal cancer (mCRC) with BRAF V600E mutation. However, whether the benefits of these therapies justify their high costs has not been estimated in the USA. The purpose of this study was to evaluate the cost-effectiveness of BEC (binimetinib, encorafenib, and cetuximab), EC (encorafenib and cetuximab), and CI/CF (cetuximab with irinotecan or FOLFIRI) in patients with BRAF V600E-mutated mCRC after first- and second-line therapy. A Markov model was constructed to determine the costs and effects of BEC, EC, and CI/CF on the basis of BEACON trial outcomes data. Health outcomes were measured in life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses characterized parameters influencing cost-effectiveness. Subgroup analyses were conducted as well. The QALYs gained in BEC, EC, and CI/CF were 0.62, 0.54, and 0.40, respectively. BEC resulted in ICERs of $883,895.73/QALY and $1,646,846.14/QALY versus CI/CF and EC, respectively. Compared with CI/CF, the ICER was $435,449.88/QALY in EC. The most sensitive parameters in the comparison among the three arms were the utilities of progressive disease and progression-free survival. Probabilistic sensitivity analyses showed that the probability of BEC and EC being cost-effective was 0%. In subgroup analyses, the ICER remained above the willingness-to-pay threshold of $150,000 per QALY. BEC and EC were not cost-effective regimens for patients with pre-treated mCRC with BRAF V600E mutation.

Three nickel(II) complexes (C1–C3) bearing diamine-bridged 4-hydroxysalicylaldehyde ligands (L1–L3) were successfully synthesized, and all the compounds were characterized by physicochemical and spectroscopic methods. The influence of the oligomerization parameters on the catalytic properties of complex C2 was systematically investigated. The results showed that oligomerization parameters played an important role in the catalytic properties and the catalytic activity was 19.90 × 104 g/(mol·Ni·h) and the selectivity of C8+ olefins was 60.25% when the precatalyst dosage was 5 μmol, the Al/Ni molar ratio was 500, the temperature was 25 °C, the reaction time was 30 min and the pressure of ethylene was 0.7 MPa. Complexes C1–C3 with different lengths of the bridged group were evaluated for ethylene oligomerization, and the results showed that the length of the alkyl chain in the ligand had little influence on the catalytic properties. Complex C4 based on ethanediamine-bridged salicylaldimine and C5 based on the hyperbranched salicylaldimine in our previous work were also investigated to study the influence of the ligand structure on the catalytic properties. The catalytic activity [31.80 × 104 g/(mol·Ni·h)] and the content of the low-carbon oligomers (70.16%) for complex C4 were higher than complex C2 with hydroxyl substituent in benzene ring. The catalytic activity and the content of the low carbon oligomers for complex C5 were far higher than other four complexes.

Background: The antagonistic relationship between adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling play a vital role in cancer development. The anti-cancer effects of berberine have been reported as a main component of the traditional Chinese medicine Rhizoma coptidis, although the roles of these signaling pathways in these effects have not been systematically reviewed. Methods: We searched the PubMed database for studies with keywords including [“berberine”] and [“tumor” or “cancer”] and [“AMPK”] or [“AKT”] published between January 2010 and July 2020, to elucidate the roles of the AMPK and PI3K/AKT pathways and their upstream and downstream targets in the anti-cancer effects of berberine. Results: The anti-cancer effects of berberine include inhibition of cancer cell proliferation, promotion of apoptosis and autophagy in cancer cells, and prevention of metastasis and angiogenesis. The mechanism of these effects involves multiple cell kinases and signaling pathways, including activation of AMPK and forkhead box transcription factor O3a (FOXO3a), accumulation of reactive oxygen species (ROS), and inhibition of the activity of PI3K/AKT, rapamycin (mTOR) and nuclear factor-κB (NF-κB). Most of these mechanisms converge on regulation of the balance of AMPK and PI3K/AKT signaling by berberine. Conclusion: This evidence supports the possibility that berberine is a promising anti-cancer natural product, with pharmaceutical potential in inhibiting cancer growth, metastasis and angiogenesis via multiple pathways, particularly by regulating the balance of AMPK and PI3K/AKT signaling. However, systematic preclinical studies are still required to provide scientific evidence for further clinical studies.

DNA amplification is one of the most valuable tools for the clinical diagnosis of nucleic acid-related diseases, but current techniques for DNA amplification are based on intermolecular polymerization reactions, resulting in the risk of errors in the intermolecular reaction pattern. In this article, we introduce the concept of intramolecular polymerization and isomerization cyclic amplification (PICA), which extends a short DNA strand to a long strand containing periodic repeats of a sequence through cyclic alternating polymerization and isomerization. To the best of our knowledge, this is the first time that a real ssDNA self-extension method without any additional auxiliary oligonucleotides has been reported. By interfacing PICA with external molecular elements, it can be programmed to respond to different targets. Herein, we designed two distinct types of amplified nucleic acid detection platforms that can be implemented with PICA, including cyclic reverse transcription (CRT) and cyclic replication (CR). We experimentally demonstrate the mechanisms of CRT-PICA and CR-PICA using mammalian miRNA and virus DNA. The results showed that this proposed detection platform has excellent sensitivity, selectivity, and reliability. The detection level could reach the aM level, that is, several copies of target molecules can be detected if a small volume is taken into account., DNA amplification is one of the most valuable tools for the clinical diagnosis of nucleic acid-related diseases, but current techniques for DNA amplification are based on intermolecular polymerization reactions, resulting in the risk of errors in the intermolecular reaction pattern.

Inflammatory cytokines produced by muscularis macrophages largely contribute to the pathological signs of postoperative ileus (POI). Electroacupuncture (EA) can suppress inflammation, mainly or partly via activation of vagal efferent. The goal of this study was to investigate the mechanisms by which EA stimulation at an hindlimb region ameliorates inflammation in POI. Methods: Intestinal motility and inflammation were examined after 24 h after intestinal manipulation (IM)-induced POI in mice. Local immune response in the intestinal muscularis, expression of macrophages, α7 nicotinic acetylcholine receptor (α7nAChR), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined by flow cytometry, Western Blot, qPCR and immunofluorescence. The effects of α7nAChR antagonists (methyllycaconitine and α-bungarotoxin) and JAK2/STAT3 inhibitors (AG490 and WP1066) were also administered in a subset of mice prior to EA. In the parasympathetic pathways, intestinal motility and inflammation were determined after cervical vagotomy and sub-diaphragmatic vagotomy. The expression of gamma absorptiometry aminobutyric acid (GABAA) receptor in dorsal motor nucleus of vagal (DMV) cholinergic neurons was assessed by immunofluorescence and the response to DMV microinjection of bicuculine (antagonist of GABAA receptor) or muscimol (agonist of GABAA receptor) were assessed. Results: EA suppressed intestinal inflammation and promoted gastrointestinal motility. Mechanistically, EA activated the α7nAChR-mediated JAK2/STAT3 signaling pathway in macrophages which reduced the production of inflammatory cytokines. Furthermore, we also demonstrated that hindlimb region stimulation drove vagal efferent output by inhibiting the expression of GABAA receptor in DMV to ameliorate inflammation. Conclusions: The present study revealed that EA of hindlimb regions inhibited the expression of GABAA receptor in DMV neurons, whose excited vagal nerve, in turn suppressed IM-induced inflammation via activation of α7nAChR-mediated JAK2/STAT3 signaling pathway.

Manganese-based nano materials used to enhance nano-contrasts in magnetic resonance imaging have low toxicity but suffer from a weak contrast imaging effect due to their low longitudinal relaxivity (r1). Moreover, the nanoparticle contrasts of manganese salt probably release manganese ions into the patient body during and after imaging process, causing potential toxicity problems. Thus, we took advantage of rod-shaped cellulose nanocrystals (CNCs) functionalized by diethylenetriamine pentaacetic dianhydride (coded as DCNCs) to anchor Mn2+ and improve its r1 for biocompatibility, highly chemical activity, and high specific area. Theoretical analysis indicated that the r1 could increase with the anchoring rate of Mn2+ on rod-shaped particles, and the large number of hydroxyl groups on CNCs made them able to carry as much as 5.9 mmol·g−1 of Mn2+. Then, we found the r1 increased linearly as the anchoring degree increased, up to 57.71 mM−1·s−1. The obtained DCNCs anchoring Mn2+ (Mn2+@DCNCs) nano-contrast showed low toxicity on RAW 264.7 and HUVEC, where the viability of the two cells was higher than 80%. Therefore, such a high r1 Mn2+-based material presents great advantage of commercial manganese and gadolinium contrasts, making the Mn2+@DCNCs of potential on diagnosing tumors and drug release.

Graphical abstract A series of water-soluble fullerene derivatives are synthesized to produce antitumor effects on three types of lung cancer cells. The fullerene compounds with sulfur-containing aromatic rings showed the most effective inhibition on cell proliferation among all fullerene compounds. The quantitative structure–activity relationship (QSAR) models illustrate that thiophene moiety in the fullerene cage has positive correlation with the antitumor effect of the fullerene derivatives., Water-soluble fullerene derivatives are actively investigated as potential drugs for cancer treatment due to their favorable membranotropic properties. Herein, cytotoxic effects of twenty fullerene derivatives with different solubilizing addends were evaluated in three different types of non-small-cell lung carcinoma (NSCLC). The potential structural descriptors of the solubilizing addends related to the inhibitory activities on each type of lung cancer cell were investigated by the quantitative structure–activity relationship (QSAR) approach. The determination coefficient r2 for the recommended QSAR model were 0.9325, 0.8404, and 0.9011 for A549, H460, and H1299 cell lines, respectively. The results revealed that the chemical features of the fullerene-based compounds including aromatic bonds, sulfur-containing aromatic rings, and oxygen atoms are favored properties and promote the inhibitory effects on H460 and H1299 cells. Particularly, thiophene moiety is the key functional group, which was positively correlated with strong inhibitory effects on the three types of lung cancer cells. The useful information obtained from our regression models may lead to the design of more efficient inhibitors of the three types of NSCLC.

On account of the utility of poly(methyl methacrylate) (PMMA) as a glass substitute, toughening of PMMA has attracted significant attention. Brittle failure can often be avoided by incorporating a small fraction of filler particles. Core-shell composite particles composed of a rubbery core and a glassy shell have recently attracted interest as a toughening agent for brittle polymers. Here, core/shell organic-inorganic hybrid polymer nanoparticles (Si-ASA HPNs) with a silicone-modified butyl acrylate copolymer (PBA) core and a styrene-acrylonitrile copolymer (SAN) shell were used to toughen PMMA. Silicone plays dual roles as a compatibilizer and a chain extender, and it not only improves interfacial adhesion between the PBA particles and SAN copolymer, but it also increases chain entanglement of poly(acrylonitrile-styrene-acrylate) (ASA). The mechanical properties of the PMMA/ASA alloys strongly depend on the Si content, and the impact strength and elongation at break greatly improve when silicone-modified ASA is added. However, this is accompanied by loss of rigidity. Specifically, the PMMA/ASA-2 composite exhibits a good balance between toughness and rigidity, indicating that ASA-2 with 5 wt% KH570 is the most suitable impact modifier. This research provides a facile and practical method to overcome the shortcomings of ASA and promote its application in a wider range of fields.

The stability of the intestinal microenvironment is the basis for maintaining the normal physiological activities of the intestine. On the contrary, disordered dynamic processes lead to chronic inflammation and disease pathology. Pinus massoniana pollen polysaccharide (PPPS), isolated from Taishan Pinus massoniana pollen, has been reported with extensive biological activities, including immune regulation. However, the role of PPPS in the intestinal microenvironment and intestinal diseases is still unknown. In this work, we initiated our investigation by using 16S rRNA high-throughput sequencing technology to assess the effect of PPPS on gut microbiota in mice. The result showed that PPPS regulated the composition of gut microbiota in mice and increased the proportion of probiotics. Subsequently, we established immunosuppressive mice using cyclophosphamide (CTX) and found that PPPS regulated the immunosuppressive state of lymphocytes in Peyer's patches (PPs). Moreover, PPPS also regulated systemic immunity by acting on intestinal PPs. PPPS alleviated lipopolysaccharide (LPS) -induced Caco2 cell damage, indicating that PPPS has the ability to reduce the damage and effectively improve the barrier dysfunction in Caco2 cells. In addition, PPPS alleviated colonic injury and relieved colitis symptoms in dextran sodium sulfate (DSS)-induced colitis mice. Overall, our findings indicate that PPPS shows a practical regulatory effect in the intestinal microenvironment, which provides an essential theoretical basis for us to develop the potential application value of PPPS further.

Cu/Ni-based metal-organic frameworks (CuNi@BTC) were prepared with benzene-1,3,5-tricarboxylate (H3BTC) as the organic ligand via the solvothermal method, and were then calcinated under N2 atmosphere to form C-coated CuNi catalysts (CuNi@C). TEM showed that carbon material on the surface of CuNi@C was a graphene-like structure. Then transfer hydrogenation of furfural catalyzed by CuNi@C was tested with alcohols as the hydrogen donor to optimize the Cu : Ni ratio, metal : organic ligand ratio, solvothermal synthesis, and calcination conditions. It was found that strong synergistic effect between Cu and Ni in the CuNi@C significantly enhanced the furfural transfer hydrogenation activity and raised the furfural selectivity. The reaction conditions of furfural transfer hydrogenation such as catalyst dosage, hydrogen donor, reaction temperature, and reaction time were studied. The catalytic mechanism for CTH of FF over CuNi@C catalyst was discussed.

Certain miRNAs, called oncomiRs, play a causal role in the onset and maintenance of cancer when overexpressed, thus, representing a potential new class of targets for therapeutic intervention. RNA-cleaving DNAzymes, mainly aimed at mRNA, have shown potential as therapeutic agents for various diseases. However, it's rarely reported that a DNAzyme was used for intracellular miRNA cleavage to suppress cell growth. Herein, we have developed a MnO2 nanosheet-mediated photo-controlled DNAzyme (NPD) for intracellular miRNA cleavage to suppress cell growth. MnO2 nanosheets adsorb photocaged DNAzymes, protect them from enzymatic digestion, and efficiently deliver them into cells. In the presence of intracellular glutathione (GSH), MnO2 nanosheets are reduced to Mn2+ ions, which serve as cofactors of the 8-17 DNAzyme for miRNA cleavage. Once the DNAzyme is activated by light, it can cyclically cleave endogenous miR-21 inside cells, which would suppress cancer cell migration and invasion, and finally induce cancer cell apoptosis.

Endogenous miRNA expression patterns are extremely cell-type-specific, thereby offering high prediction accuracy for different cell identities. Here, a DNA-tetrahedron-based "AND" logic gate is utilized as a molecular device that recognizes dual-miRNA inputs through strand hybridization to activate a computation cascade that produces controlled singlet oxygen in live cells, resulting in the death of the target cell.

We describe the lower critical solution temperature (LCST)-type phase behavior of poly(butyl acrylate) (PBA) dissolved in hydrophobic 1-alkyl-3-methylimidazolium bis{(trifluoromethyl) sulfonyl}amide ionic liquids (ILs). The temperature-composition phase diagrams of these PBA/ILs systems are strongly asymmetric with the critical composition shifted to low concentrations of PBA. As the molecular weight increases from 5.0×103 to 2.0×104, the critical temperature decreases by about 67 °C, and the critical composition shifts to a lower concentration. Furthermore, the LCST of PBA/ILs system increases as increasing the alkyl side chain length in the imidazolium cation. Using IL blends as solvents, the LCST of PBA can be tuned almost linearly over a wide range by varying the mixing ratio of two ionic liquids without modifying the chemical structure of the polymers.

Mimosa, a peculiar plant, can close immediately in response to external stimuli. Inspired by the stimuli-responsive behavior of mimosa, we designed a Y-shaped DNA nanosensor (regarded as DNA nanomimosa, DNM) for target tumor extracellular pH (pHe) sensing. The DNM consisted of four single-strand DNA strands, where A-strand contained an aptamer fragment and labeled with Cy5 at the 5'-end, I-strand contained an i-motif fragment, and the 3'-ends of L-strand and B-strand were labeled with Rox and BHQ2, respectively. Initially, the DNM was in an "open" state, Cy5 was separated from Rox and performed fluorescence resonance energy transfer (FRET) with neighboring BHQ2, and only Rox emitted fluorescence. When the DNM was anchored onto the cell surface through the aptamer fragment, the i-motif fragment tended to form a quadruple-helix structure due to low pH stimuli, releasing B-strand and bringing the DNM into a "close" state like stimulated mimosa. At this time, Cy5 was separated from BHQ2 but close to Rox, which led to the FRET signal generation between Rox and Cy5. The FRET ratio (Cy5/Rox) could be used as a signal for pHe sensing. Using the aptamer as an anchoring element, the DNM exhibited high cell-membrane-anchoring efficiency and excellent specificity. Additionally, relying on the pH-sensitive i-motif and twice FRET signaling mechanism, the DNM possessed a narrow pH response range (0.50 units) and performed imaging of pHe with high resolution. With these advantages, the DNM is expected to be a useful tool for the investigation of the tumor extracellular pH-related physiological processes.

Both E‐ and Z‐isomers of lycopene are encountered in nature. Although they were separated on C30‐HPLC by the mobile phase consisting of CH3CN‐MeOH (A) and MTBE (B), the quantification of Z‐isomers cannot be archived at present because either their commercially available reference samples are currently lacking, or they are unstable. In this study, both the specific and molar absorption coefficients of 5, 9, and 13 Z‐isomers in the mobile phase were determined on the analytical C30‐HPLC‐PDA‐ELSD, and further verified on the preparative C30‐HPLC‐PDA. The specific and molar absorption coefficients of 5, 9, and 13 Z‐isomers were finally verified to be A1cm1% = 3,422 and ε mol = 183,717, A1cm1% = 2,183 and ε mol = 117,199, and A1cm1% = 1,119 and ε mol = 60,076, respectively, in the mobile phase. With these determined coefficients, the quantifications of 5, 9, and 13 Z‐isomers were able to be archived on C30‐HPLC‐PDA with the mobile phase applied in this investigation., This is the first study reporting the values of 5, 9, and 13 Z‐isomers of lycopene. It revealed that the absorption coefficient of lycopene isomer corresponded to the location of geometrical isomerization in the molecule. The specific and molar absorption coefficients of 5, 9, and 13Z‐isomers determined in this study have great potential to be applied in the Z‐isomer quantification in the fields of life sciences, food quality control, animal and human metabolism research, and pharmacology.

With the rapid development of isothermal amplification technology, DNA molecular diagnosis has become an important reference for clinical treatment. In this work, we have designed a DNA molecular diagnostic technology with LAMP-like sensitivity for nucleic acid analysis and detection based on only one pair of hairpin primers. This DNA molecular diagnostic technology consists of Bst DNA polymerase and one pair of hairpin primers, which are designed easily by adding a stem-loop structure to a target binding domain. When the target is present, the polymerization reaction between the hairpin primers and the target generates a specific dumbbell DNA similar to LAMP, which triggers cyclic amplification reactions to extend a series of long dsDNA products with repeated sequences by inserting fluorescent dye Eva Green observed the increase in fluorescence signal. In our method, using the hairpin primers-mediated isothermal polymerization amplification, we can specifically monitor 3-5 copies of the target nucleic acid in the system without labeling and temperature cycling in the reaction. In addition, serum samples from 13 patients with suspected schistosomiasis were targeted; we further demonstrated the ability of the technology to detect complex clinic samples, and its potentially inestimable applicability in clinic early molecular diagnostic research.

Two-dimensional (2D) semiconductors are attractive for electronic devices with atomically thin channels. However, controlling the electronic properties of the 2D materials by incorporating impurity dopants is inherently difficult due to the limited physical space in the atomically thin lattices. Here we show that a solid-state ionic doping approach can be used to tailor the carrier type in 2D semiconductors and create programmable devices. Our strategy exploits a superionic phase transition in silver iodide to induce switchable ionic doping. We create few-layer tungsten diselenide (WSe2) devices that can be reversibly transformed into transistors with reconfigurable carrier types and into diodes with switchable polarities by controllably poling the van der Waals integrated silver iodide above the superionic phase transition temperature. We also construct complementary logic gates by integrating and programming identical transistors, and show that the programmed functions can be erased by an external trigger (temperature or ultraviolet irradiation) to create the temporary and delible electronics that are desirable for electronic security. The superionic phase transition in silver iodide can be used to tailor the carrier type in two-dimensional tungsten diselenide and create programmable transistors, diodes and logic gates, the functions of which can be erased by external triggers such as ultraviolet irradiation.

Triple-negative breast cancer (TNBC) is heterogeneous disease with a poor prognosis. It is therefore important to explore novel therapeutic agents to improve the clinical efficacy for TNBC. The inosine 5'-monophosphate dehydrogenase 2 (IMPDH2) is a rate-limiting enzyme in the de novo synthesis of guanine nucleotides. It is always overexpressed in many types of tumors, including TNBC and regarded as a potential target for cancer therapy. Through screening a library of natural products, we identified shikonin, a natural bioactive component of Lithospermum erythrorhizon, is a novel and selective IMPDH2 inhibitor. Enzymatic analysis using Lineweaver-Burk plot indicates that shikonin is a competitive inhibitor of IMPDH2. The interaction between shikonin and IMDPH2 was further investigated by thermal shift assay, fluorescence quenching, and molecular docking simulation. Shikonin treatment effectively inhibits the growth of human TNBC cell line MDA-MB-231, and murine TNBC cell line, 4T1 in a dose-dependent manner, which is impaired by exogenous supplementation of guanosine, a salvage pathway of purine nucleotides. Most importantly, IMPDH2 knockdown significantly reduced cell proliferation and conferred resistance to shikonin in TNBC. Collectively, our findings showed the natural product shikonin as a selective inhibitor of IMPDH2 with anti-TNBC activity, impelling its further study in clinical trials.

Printable elastic conductors promote the wide application of consumable electronic textiles (e-textiles) for pervasive healthcare monitoring and wearable computation. To assure a clean appearance, the e-textiles require a washing process to clean up the dirt after daily use. Thus, it is crucial to develop low-cost printable elastic conductors with strong adhesion to the textiles. Here, we report a composite elastic conductor based on Ag nanowires (NWs) and polyurethane elastomer. The composite could be dispersed into ink and easily printed onto textiles. One-step print could form robust conductive coatings without sealing on the textiles. Interestingly, the regional concentration of Ag NWs within the polyurethane matrix was observed during phase inversion, endowing the elastic conductor with a low percolation threshold of 0.12 vol.% and high conductivity of 3,668 S·cm−1. Thanks to the high adhesion of the elastic conductors, the resulted e-textiles could withstand repeated stretching, folding, and machine washing (20 times) without obvious performance decay, which reveals its potential application in consumable e-textiles.

The side reaction between the active material and liquid-electrolyte cause structural damage and particle pulverization is one of the important factors leading to the capacity decay of LiNi0.80Co0.15Al0.05O2 (NCA) materials in Li ion batteries (LIBs). Surface modification is an effective strategy for NCA cathodes, which could alleviate the degradation associated with surface processes. Herein, a surface structure rearrangement of NCA cathode secondary particles was reported by in-situ forming a solid electrolyte LiBO2. The LiBO2 is beneficial for alleviating the stress during charge/discharge process, thereby slowing down the rate of cracks formation in the secondary particles, which facilitates the Li+ de-intercalation as well as prevents penetration of the liquid-electrolyte into the interior of the particles. As a result, the surface structure rearrangement NCA (RS-NCA) delivers a high discharge capacity of 202.5 mAh g−1 at 0.1 C, and exhibits excellent cycle stability with discharge capacity retaining 148 mAh g−1 after 200 cycles at 2 C. This surface structure rearrangement approach provides a new viewpoint in designing high-performance high-voltage LIBs.

BACKGROUND Loss and/or dysfunction of interstitial Cajal-like cells (ICLCs) in the gallbladder may promote cholesterol gallstone formation by decreasing gallbladder motility. AIM To study the effect of cholesterol on the proliferation and apoptosis of ICLCs from guinea pig gallbladders. METHODS Guinea pig gallbladder ICLCs were isolated and cultured in vitro. The cells were exposed to cholesterol solutions at different concentrations (0, 25, 50, and 100 mg/L) for 24 h. Then, cell proliferation was detected by the CCK-8 method and the apoptosis rate was detected by flow cytometry. Further, the expression of the c-Kit protein was detected by Western blot and the expression level of c-Kit mRNA in the cells was detected by real-time quantitative PCR. RESULTS After ICLCs were cultured with cholesterol at concentrations of 25, 50, and 100 mg/L, the proliferation rates decreased significantly (P < 0.05), whereas the apoptosis rates increased significantly (P < 0.05). Moreover, the expression of c-Kit protein and mRNA decreased significantly (P < 0.05). CONCLUSION High cholesterol concentrations can inhibit the proliferation of ICLCs and promote apoptosis. This decrease in the ICLC proliferation rate might be caused by the inhibition of the stem cell factor/c-Kit signaling pathway.

Galacto-oligosaccharides (GOS), which can be produced by enzymatic transgalactosylation of lactose with β-galactosidases, have attracted much attention in recent years because of their prebiotic functions and wide uses in infant formula, infant foods, livestock feed, and pet food industries. In this study, a novel β-galactosidase-producing Klebsiella oxytoca ZJUH1705, identified by its 16S rRNA sequence (GenBank accession no. MH981243), was isolated. Two β-galactosidase genes, bga 1 encoding a 2058-bp fragment (GenBank accession no. MH986613) and bga 2 encoding a 3108-bp fragment (GenBank accession no. MN182756), were cloned from K. oxytoca ZJUH1705 and expressed in E. coli. The purified β-gal 1 and β-gal 2 had the specific activity of 217.56 U mg−1 and 57.9 U mg−1, respectively, at the optimal pH of 7.0. The reaction kinetic parameters Km, Vmax, and Kcat with oNPG as the substrate at 40 °C were 5.62 mM, 167.1 μmol mg−1 min−1, and 218.1 s−1, respectively, for β-gal 1 and 3.91 mM, 14.6 μmol mg−1 min−1, and 28.9 s−1, respectively, for β-gal 2. Although β-gal 1 had a higher enzyme activity for lactose hydrolysis, only β-gal 2 had a high transgalactosylation capacity. Using β-gal 2 with the addition ratio of ~ 2.5 U g−1 lactose, a high GOS yield of 45.5 ± 2.3% (w/w−1) was obtained from lactose (40% w/w−1 or 480 g L−1) in a phosphate buffer (100 mM, pH 7.0) at 40 °C in 48 h. Thus, the β-gal 2 from K. oxytoca ZJUH1705 would be a promising biocatalyst for GOS production from lactose.

Background Bloodstream infection (BSI) caused by carbapenem-resistant Enterobacteriaceae are potentially life-threatening related to poorer outcomes. Colistin is considered one of the last-resort treatments against human infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Therefore, emergence of strains from the blood that co-harboring mcr and carbapenem resistance genes were considered as a serious problem. Purpose In this study, two mcr-9-harboring MDR Enterobacter cloacae isolates BSI034 and BSI072 recovered from BSI patients were identified, one of which co-harbored mcr-9 and bla NDM-1. The genetic characteristics of the MDR plasmid needed to be clarified. Methods S1-PFGE and Southern blotting were conducted to determine the location of mcr-9. Whole-genome sequencing was performed to obtain the complete genome and plasmid sequences. The resistome and virulence genes of the strains, accompanied by the genetic characteristics of mcr-9- and bla NDM-1-harboring plasmids, were analyzed. Results Whole-genome sequencing showed that BSI034 harbored mcr-9-carrying IncHI2-type pBSI034-MCR9 and bla NDM-1-carrying IncX3-type pBSI034-NDM1. The 278,517 bp pBSI034-MCR9 carried mcr-9 along with the other 19 resistance genes. mcr-9 was flanked by IS903B (1057 bp) and IS26 (820 bp) in the same orientation. In addition to resistance genes, strain BSI034 also carried a chromosome-located Yersinia high-pathogenicity island, which harbored genes of yersiniabactin biosynthesis operon ybtSXQPAUTE, irp1/2, and fyuA. Conclusion We described the complete genome and mcr-9/bla NDM-1-co-harboring plasmid of E. cloacae from a BSI patient. Notable differences were observed within mosaic modules between pBSI034-MCR9 and other mcr-9-harboring plasmids due to extensive recombination via horizontal gene transfer.

The organocatalytic coupling of oxetanes and carbon dioxide (CO2) offers a sustainable route to poly(trimethylene carbonate)s and/or functional six-membered cyclic carbonate monomers. This transfor...

Three-dimensional (3D) graphene networks are performance boosters for functional nanostructures in energy-related fields. Although tremendous intriguing nanostructures-decorated 3D graphene network...

A hybrid flame retardant, of excellent stability in aqueous media, was designed to develop flame-retarded polyethyleneimine (PEI) foam. In this case, iron phosphonate (FeP) with carboxyl group and hydroxyl group was first designed and synthesized. The carboxyl group could be hydrogen bonded with the water-soluble ammonium polyphosphate (APP) in aqueous media, and then dispersed as nano-sized particles. Subsequently, the well-dispersed nano-hybrid of FeP and APP (FeP/APP) was blended with hydrophilic PEI to prepare a kind of composite foam through a freeze-drying process. For FeP/APP, the transition metal iron showed excellent catalytic carbonization performances. Meanwhile, APP could also catalyze the degradation of polymers to form a protective char layer. The thermogravimetric analysis coupled with Fourier transform infrared analysis (TG-FTIR) test disclosed that the improvement of flame retardancy for PEI-based foams was ascribed to the synergistic effect of FeP and APP in the condensed phase. The composite foam containing 30 wt% FeP/APP could self-extinguish and reach V-1 rating in UL-94 test. When the loading level of 45% FeP/APP reached 45%, the composite foam could elevate up to V-0 rating, and the peak of heat release rate and total heat release were reduced by 71.8% and 74.2%, respectively, compared to a neat PEI foam. It is worth noting that our work presents a promising way for preparation of stable aqueous flame retardant, and is expected to enhance the fire safety of aqueous foams, coatings, cotton textiles, and other flammable materials.

An efficient adsorbent for the treatment of Cr(VI) was simply fabricated by combining graphene oxide with MoS2 nanosheets via in situ hydrothermal process with CTAB as the surfactant. The experimental results indicated that the agglomeration of the MoS2 nanosheets are reduced and uniformly grown on the graphene sheet during the in situ hydrothermal process, and the introduction of graphene oxide provided higher specific surface area and abundant oxygenic groups. Based on this, the removal efficiency of Cr(VI) onto MoS2/rGO was 75.9% at pH 2.0, which was higher than that of bulk MoS2 (61.0%). On account of Sips adsorption isotherm model, the highest uptake capacity of MoS2/rGO toward Cr(VI) reached 80.8 mg g−1. The adsorption kinetic consequences showed that the chemisorption process was the control step, and the removal mechanism for Cr(VI) is redox and adsorption; in this way, the adsorbed Cr(VI) was partially reduced to Cr(III). Furthermore, this as-prepared adsorbent also presented satisfying reusability for removal of Cr(VI) and can be used for the selective removal of Cr(VI) in the presence of NO3−. In short, it may provide a potential route to enhance the adsorption property of MoS2 toward heavy metals through incorporating with GO, which would expand the applications of MoS2 in the field of treatment of the heavy metal wastewater.

Super elongation complex (SEC) is a positive regulator of RNA polymerase II, which is required for HIV-1 proviral transcription. AFF1/4 is the scaffold protein that recruits other components of SEC and forms dimer depending on its THD domain (TPRL with Handle Region Dimerization Domain). Here we report the crystal structure of the human AFF4-THD at the resolution of 2.4 Å. The α4, α5, and α6 of one AFF4-THD mediate the formation of a dimer and pack tightly against the equivalent part of the second molecule in the dimer of AFF-THD. Mutagenesis analysis revealed that single mutations of either Phe1014 or Tyr1096 of AFF4 to alanine impair the formation of the AFF4 dimer. In addition, transactivation assay also indicated that Phe1014 and Tyr1096 of AFF4 are critical to the transactivation activity of AFF4. Interestingly, the corresponding residues Phe1063 and Tyr1145 in AFF1 have an effect on the transactivation of HIV-1 provirus. However, such mutations of AFF1/4 have no effect on the interaction of AFF1/4 with other subunits of the SEC. Together, our data demonstrated that the dimerization of AFF1/4 is essential to transactivation of HIV-1 provirus.

BACKGROUND/AIM Contrast-induced AKI (CI-AKI) is an important clinical complication of intravascular use of iodinated contrast agents. The aim of the present study was to investigate the renoprotective effect of Apela on contrast-induced acute kidney injury. MATERIALS AND METHODS Blood samples from patients exposed to iodinated contrast agent were collected to assay for Apela and creatinine levels. The effects of ELA32 (Apela 32) on iodixanol-induced apoptosis, inflammation response, mitochondrial ROS production and DNA damage were examined in NRK-52E renal tubular epithelial cells. RESULTS Plasma Apela levels were decreased in patients exposed to the contrast agent. Iodixanol-induced apoptosis was reduced in ELA32 treated NRK-52E cells (p

The utilization of carbon dioxide as a comonomer to produce polycarbonates has attracted a great deal of attention from both industrial and academic communities because it promises to replace petroleum-derived plastics and supports a sustainable environment. Significant progress in the copolymerization of cyclic ethers (e.g., epoxide, oxetane) and carbon dioxide has been made in recent decades, owing to the rapid development of catalysts. In this Review, the focus is to summarize and discuss recent advances in the development of homogeneous catalysts, including metal- and organo-based complexes, as well as the preparation of carbon dioxide-based block copolymer and functional polycarbonates.

A self-assembled DNA nanostructure based on a DNA nanocreeper and multiplexed fluorescence supersandwich was designed for the sensitive and specific detection of tumour cells. This nanostructure could improve the binding affinity of current aptamers and trigger signal amplification, which provide potential for the discrimination of low abundant target cells in liquid biopsy.

In this study, to investigate the influence of support crystalline phase structure on the dispersion behaviors of the supported metal oxides, tetragonal rutile RuO2 supported on both tetragonal anatase a-TiO2 and tetragonal rutile r-TiO2 supports with different loadings have been prepared, characterized and probed by CO oxidation. It has been discovered that the monolayer dispersion capacity of RuO2 on r-TiO2 support is 0.84 mmol per 100 m2 surface, which is much higher than 0.15 mmol per 100 m2 surface on a-TiO2 support. Due to the close matching of the crystalline phase and lattice parameters between RuO2 and r-TiO2, Ru O Ti interfacial bonds can be effectively formed, thus facilitating the RuO2 dispersion and resulting in a high monolayer dispersion capacity. On the contrary, the big difference of the crystalline phase and lattice parameters between RuO2 and a-TiO2 support impedes the formation of Ru O Ti interfacial bonds and RuO2 dispersion, resulting in a low monolayer dispersion capacity. As a result, RuO2 has a much stronger interaction with r-TiO2 than with a-TiO2 support, which can generate more abundant mobile oxygen sites. Therefore, in comparison with RuO2/a-TiO2, the intrinsic activity of RuO2/r-TiO2 for CO oxidation is remarkably enhanced. On the basis of the results, it is rational to propose that a like-disperses-like phenomenon is present in the supported metal oxide systems.

Phosphorus-modified Zr-metal organic framework (P/Zr-MOF) catalysts were synthesized by a (NH4)2HPO4 pyrolysis approach starting from Zr-MOFs. The furfural catalytic transfer hydrogenation performance of P/Zr-MOFs was studied with i-propanol as a hydrogen donor. Experimental results show that the furfural conversion of P/Zr-MOFs rose from 59.1% to 96.1% compared with that of Zr-MOFs. In P/Zr-MOFs compared with Zr-MOFs, a part of O–Zr–O in the MOFs was phosphated to form O–Zr–P and P–Zr–P, in which Zr–P possessed stronger Lewis acidity and basicity than Zr–O, which is favorable for hexatomic ring-catalytic reactions. Hence, P/Zr-MOFs exhibited higher Meerwein–Ponndorf–Verley reactivity. Based on this result, a plausible mechanism of catalytic modification was proposed.

DNA lesions such as metholcytosine(mC), 8-OXO-guanine (OG), inosine (I), etc. could cause genetic diseases. Identification of the varieties of lesion bases are usually beyond the capability of conventional DNA sequencing which is mainly designed to discriminate four bases only. Therefore, lesion detection remains a challenge due to massive varieties and less distinguishable readouts for structural variations at the molecular level. Moreover, standard amplification and labeling hardly work in DNA lesion detection. Herein, we designed a single molecule interface from the mutant aerolysin (K238Q), whose sensing region shows high compatibility to capture and then directly convert a minor lesion into distinguishable electrochemical readouts. Compared with previous single molecule sensing interfaces, the temporal resolution of the K238Q aerolysin nanopore is enhanced by two orders, which has the best sensing performance in all reported aerolysin nanopores. In this work, the novel K238Q could discriminate directly at least three types of lesions (mC, OG, I) without labeling and quantify modification sites under the mixed heterocomposition conditions of the oligonucleotide. Such a nanopore electrochemistry approach could be further applied to diagnose genetic diseases at high sensitivity., Herein, we designed a single molecule interface from the mutant aerolysin (K238Q), whose sensing region shows high compatibility to capture and then directly convert a minor DnA lesion into distinguishable electrochemical readouts.