Visible Light-Gating Responsive Nanochannel for Controlled Release of the Fungicide.

Fungicides have been widely used to protect crops from the disease of pythium aphanidermatum (PA). However, excessive use of synthetic fungicides can lead to fungal pathogens developing microbicide resistance. Recently, biomimetic nano-delivery systems have been used for controlled release, reducing the overuse of fungicides, and thereby protecting the environment. In this paper, inspired by chloroplast membranes, visible light biomimetic channels are constructed by using retinal, the main component of green pigment on chloroplasts in plants, which can achieve the precise controlled release of the model fungicide methylene blue (MB). The experimental results show that the biomimetic channels have good circularity after and before light conditions. In addition, it is also found that the release of MB in visible light by the retinal-modified channels is 8.78 µmol·m-2·h-1, which is four times higher than that in the before light conditions. Furthermore, MB, a bactericide drug model released under visible light, can effectively inhibit the growth of PA, reaching a 97% inhibition effect. The biomimetic nanochannels can realize the controlled release of the fungicide MB, which provides a new way for the treatment of PA on the leaves surface of cucumber, further expanding the application field of biomimetic nanomembrane carrier materials.

A Visible-Light Regulated ATP Transport in Retinal-Modified Pillar[6]arene Layer-by-Layer Self-Assembled Sub-Nanochannel.

Natural light-responsive rhodopsins play a critical role in visual conversion, signal transduction, energy transmission, etc., which has aroused extensive interest in the past decade. Inspired by these gorgeous works of living beings, scientists have constructed various biomimetic light-responsive nanochannels to mimic the behaviors of rhodopsins. However, it is still challenging to build stimuli-responsive sub-nanochannels only regulated by visible light as the rhodopsins are always at the sub-nanometer level and regulated by visible light. Pillar[6]arenes have an open cavity of 6.7 Å, which can selectively recognize small organic molecules. They can be connected to ions of ammonium or carboxylate groups on the rims. Therefore, we designed and synthesized the amino and carboxyl-derived side chains of pillar[6]arenes with opposite charges. The sub-nanochannels were constructed through the electrostatic interaction of layer-by-layer self-assembled amino and carboxyl-derived pillar[6]arenes. Then, the natural chromophore of the retinal with visible light-responsive performance was modified on the upper edge of the sub-nanochannel to realize the visible light switched on and off. Finally, we successfully constructed a visible light-responsive sub-nanochannel, providing a novel method for regulating the selective transport of energy-donating molecules of ATP.

Selectively Transport and Removal of Fluoride Ion by Pillar[5]Arene Polymer-Filled Nanochannel Membrane.

Excess fluoride ions in groundwater accumulate through the roots of crops, affecting photosynthesis and inhibiting their growth. Long-term bioaccumulation also threatens human health because it is poorly degradable and toxic. Currently, one of the biggest challenges is developing a unique material that can efficiently remove fluoride ions from the environment. The excellent properties of functionalized pillar[5]arene polymer-filled nanochannel membranes were explored to address this challenge. Constructing a multistage porous nanochannel membrane, consisting of microscale etched nanochannels and nanoscale pillar[5]arene cross-linked polymer voids. A fluoride removal rate of 0.0088 mmol ⋅ L-1 ⋅ min-1 was achieved. Notably, this rate surpassed the rates observed with other control ions by a factor of 6 to 8.8. Our research provides a new direction for developing water fluoride ion removal materials.

Molecular insights into the defense of Dioscorea opposita cv. 'Tiegun' callus against pathogenic and endophytic fungal infection through transcriptome analysis.

Dioscorea opposita cv. 'Tiegun' is an economically important crop with high nutritional and medicinal value. Plants can activate complex and diverse defense mechanisms after infection by pathogenic fungi. Moreover, endophytic fungi can also trigger the plant immune system to resist pathogen invasion. However, the study of the effects of endophytic fungi on plant infection lags far behind that of pathogenic fungi, and the underlying mechanism is not fully understood. Here, the black spot pathogen Alternaria alternata and the endophytic fungus Penicillium halotolerans of 'Tiegun' were identified and used to infect calli. The results showed that A. alternata could cause more severe membrane lipid peroxidation, while P. halotolerans could rapidly increase the activity of the plant antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT); thus, the degree of damage caused by P. halotolerans to the callus was weaker than that caused by A. alternata. RNA-seq analysis revealed that various plant defense pathways, such as phenylpropanoid biosynthesis, flavonoid biosynthesis, plant hormone signal transduction, and the MAPK signaling pathway, play important roles in triggering the plant immune response during fungal infection. Furthermore, the tryptophan metabolism, betalain biosynthesis, fatty acid degradation, flavonoid biosynthesis, tyrosine metabolism and isoquinoline alkaloid biosynthesis pathways may accelerate the infection of pathogenic fungi, and the ribosome biogenesis pathway in eukaryotes may retard the damage caused by endophytic fungi. This study lays a foundation for exploring the infection mechanism of yam pathogens and endophytic fungi and provides insight for effective fungal disease control in agriculture.

Chiral Transport in Nanochannel Based Artificial Drug Transporters.

The precise regulation of chiral drug transmembrane transport can be achieved through drug transporters in living organisms. However, implementing this process in vitro is still a formidable challenge due to the complexity of the biological systems that control drug enantiomeric transport. Herein, a facile and feasible strategy is employed to construct chiral L-tyrosine-modified nanochannels (L-Tyr nanochannels) based on polyethylene terephthalate film, which could enhance the chiral recognition of propranolol isomers (R-/S-PPL) for transmembrane transport. Moreover, conventional fluorescence spectroscopy, patch-clamp technology, laser scanning confocal microscopy, and picoammeter technology are employed to evaluate the performance of nanochannels. The results show that the L-Tyr nanochannel have better chiral selectivity for R-/S-PPL compared with the L-tryptophan (L-Trp) channel, and the chiral selectivity coefficient is improved by about 4.21-fold. Finally, a detailed theoretical analysis of the chirality selectivity mechanism is carried out. The findings would not only enrich the basic theory research related to chiral drug transmembrane transport, but also provide a new idea for constructing artificial channels to separate chiral drugs.

Electricity-Wettability Controlled Fast Transmission of Dopamine in Nanochannels.

Achieving fast transmembrane transmission of molecules in organisms is a challenging problem. Inspired by the transport of Dopmine (DA) in organisms, the DA transporter (DAT) binds to DA in a way that has a ring recognition (the recognition group is the tryptophan group). Herein, D-Tryptophan-pillar[5]arene (D-Trp-P5) functionalized conical nanochannel is constructed to achieve fast transmission of DA. The D-Trp-P5 functionalized nanochannel enables specific wettability recognition of DA molecules and has great cycle stability. With the controlling of voltage to wettability, the transport flux of DA is up to 499.73 nmol cm-2 h-1 at -6 V, 16.88 times higher than that under positive voltages. In response to these results, a high-throughput DA transport device based on controlled electricity-wettability is provided.

Metformin Ameliorates Postoperative Cognitive Dysfunction through Regulation of the AMPK/SIRT1 Pathway.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. The purpose of this study was to investigate the mechanism through which metformin improves postoperative cognitive function. METHODS: In the in vivo experiment, 18-month-old Sprague-Dawley (SD) rats were randomly divided into four groups (n = 12 in each group): the control, metformin, operation, and operation plus metformin groups. The animals were pretreated with metformin by gavage once daily for two weeks. The Morris water maze (MWM) was used to measure cognitive ability. In the in vitro experiment, BV2 cells were divided into five groups: the control, metformin, lipopolysaccharide (LPS), LPS plus metformin, and LPS plus metformin plus compound C groups. We stimulated microglia with LPS (500 ng/mL). Immunofluorescence and Western blotting were used to assess ROS (reactive oxygen species) levels, autophagy-associated protein levels and adenosine monophosphate-activated protein kinase (AMPK)/regulator factor 2-related enzyme 1 (SIRT1) signaling pathway activity in the rat cortex and microglial cells. RESULTS: In the MWM test, the metformin-pretreated rats spent a higher proportion of time in the target quadrant. Immunofluorescence showed that the fluorescence intensity of LC3 in the cortex was increased in rats pretreated with metformin. Western blotting indicated that metformin upregulated the expression of autophagy-related and AMPK/SIRT1 signaling pathway-related proteins in the cortex after surgery. By activating the AMPK/SIRT1 signaling pathway in vitro, metformin reduced microglial activation and oxidative stress and promoted autophagy. CONCLUSIONS: Through the AMPK/SIRT1 pathway, metformin can boost autophagy and reduce oxidative stress in cortical microglia in older rats, in turn improving postoperative cognitive function.

Highly Chiral Selective Resolution in Pillar[6]arenes Functionalized Microchannel Membranes.

High flux microchannel membranes have the potential for large scale separations. However, it is prevented by poor enantioselectivity. Therefore, the development of a high-enantioselective microchannel membrane is of great importance for large scale chiral separations. In this work, chiral gold nanoparticles are incorporated into the microchannel membrane to astringe the large pores and improve the enantioselectivity. Here, the gold nanoparticles are functionalized by l-phenylalanine-derived pil-lararenes (l-Phe-P6@AuNPs) as the chiral receptor of R-phenylglycinol (R-PGC) over its enantiomer. This chiral Au NPs coated microchannel membrane (l-Phe-P6@AuNPs microchannel) shows a selectivity of 5.40 for R-PGC and a flux of 140.35 nmol·cm-2·h-1, where the enantioselectivity is improved, ensuring its flux. Compared with the enantioselectivity and flux of nanochannel membranes reported in literatures, the l-Phe-P6@AuNPs microchannel has the advantage for enantioselectivity and flux for chiral separation.

Triazol-Methanaminium-Pillar[5]arene-Functionalized Single Nanochannel for Quantitative Analysis of Pyrophosphate in Water.

Inorganic pyrophosphate (PPi) is an important biological functional anion and plays crucial roles in life science, environmental science, medicine, and chemical process. Quantification of PPi in water has far-reaching significance for life exploration, disease diagnosis, and water pollution control. The label-free quantitative detection of PPi anions with a nanofluidic sensing device based on a conical single nanochannel is demonstrated. The channel surface is functionalized with a synthetic PPi receptor, triazol-methanaminium-functionalized pillar[5]arene (TAMAP5), using carbodiimide coupling chemistry. Due to the specific binding between TAMAP5 and PPi, the functionalized nanochannel can discriminate PPi from other inorganic anions with high selectivity through ionic current recording, even in the presence of various interfering anions. The current response exhibits a linear correlation with PPi concentration in the range from 1 × 10-7 to 1 × 10-4 M with a limit of detection of 6.8 × 10-7 M. A spike-and-recovery analysis of PPi in East Lake water samples indicates that the proposed nanofluidic sensor has the ability to quantitate micromolar concentrations of PPi in environmental water samples.

Guest-Induced Planar-Chiral Pillar[5]arene Surface for Selectively Adsorbing Protein Based on Host-Guest Chemistry.

In living systems, the adsorption of a protein on biointerfaces is a universal phenomenon, such as the specific binding of an antibody and antigen, which plays an important role in body growth and life maintenance. The exploration of a protein-selective adsorption on the biointerface is of great significance for understanding the life process and treatment in vitro. Herein, on the basis of biomimetic strategies, we fabricated a planar-chiral NH2-pillar[5]arene modified silicon surface (pR-/pS-NP5 surfaces) for a highly enantioselective adsorption of protein by taking advantage of the guest-induced planar chirality of pillar[5]arenes. Results from practical experiments and theoretical calculations show that the pR-NP5 surface possesses a high adsorption capacity and chiral selectivity for bovine serum albumin (BSA). Moreover, it was identified that the guest-induced chiral effect the generation and amplification of planar chirality, which was much beneficial for enhancing the interaction between planar-chiral pillar[5]arene host and BSA. The binding capacity of pR-NP5 and BSA is stronger than that of pS-NP5, thus promoting the chiral selective adsorption of BSA. This work affords a deeper understanding of the chiral influence of protein adsorption on biointerfaces and meanwhile provides a new perspective for chiral-sensing applications.

Highly enantioselective recognition of S-ibuprofen by a host-guest induced chiral nanochannel.

Chirality is an important property, especially for chiral drug enantiomers with huge differences in pharmacology and toxicity. Chiral recognition of drug enantiomers is the first step to understanding the physiological phenomenon and ensuring medical safety. To efficiently identify and isolate these chiral drugs, we prepared a nanochannel. Here, a chiral sensor was fabricated by introducing the host-guest system of pillar[5]arene (WAP5) and phenethylamine into solid-state nanochannels. The chiral guest R-phenethylamine (R-PEA) induced the chirality of the host-guest system and amplified the chiral selectivity for ibuprofen enantiomers in the host-guest-based nanochannels, which was significantly greater than that in the aqueous phase or the R-PEA modified nanochannels. This study provides a strategy to fabricate highly enantioselective nanosensors for chiral drugs.

Rhomboidal Pt(II) metallacycle-based NIR-II theranostic nanoprobe for tumor diagnosis and image-guided therapy.

Fluorescent theranostics probes at the second near-IR region (NIR-II; 1.0-1.7 µm) are in high demand for precise theranostics that minimize autofluorescence, reduce photon scattering, and improve the penetration depth. Herein, we designed and synthesized an NIR-II theranostic nanoprobe 1 that incorporates a Pt(II) metallacycle 2 and an organic molecular dye 3 into DSPE-mPEG5000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]). This design endows 1 with good photostability and passive targeting ability. Our studies show that 1 accurately diagnoses cancer with high resolution and selectively delivers the Pt(II) metallacycle to tumor regions via an enhanced permeability and retention effect. In vivo studies reveal that 1 efficiently inhibits the growth of tumor with minimal side effects. At the same time, improved fluorescent imaging quality and signal-to-noise ratios are shown due to the long emission wavelengths. These studies demonstrate that 1 is a potential theranostic platform for tumor diagnosis and treatment in the NIR-II region.

A Funnel-Shaped Chloride Nanochannel Inspired By ClC Protein.

Chloride transport participates in a great variety of physiological activities, such as regulating electrical excitability and maintaining acid-base equilibrium. However, the high flux is the prerequisite to ensure the realization of the above functions. Actually, the high flux of ion transport is significant, not only for living things but also for practical applications. Herein, inspired by chloride channel (ClC) protein, a novel NH2-pillar[5]arene functionalized funnel-shaped nanochannel was designed and constructed. The introduction of functional molecules changed surface charge property and endowed the nanochannel with Cl- selectivity, which facilitated Cl- transport. Moreover, by adjusting the asymmetric degree of the nanochannel, the Cl- transport flux can be improved greatly. The successful construction of an artificial ion channel with high flux will be much useful for practical applications like microfluidic devices, sensors, and ion separation.

Chiral Covalent Organic Framework Packed Nanochannel Membrane for Enantioseparation.

A nanochannel membrane has the prospect of large-scale separation. However, selectivity in enantioseparation is a challenge, due to the size difference between nanochannels and enantiomers. Here, we compartmented nanochannels by the in situ synthesis of a L-tyrosine functionalized covalent organic framework (L-Tyr-COF). The L-Tyr-COF decreased the pore size of channels to match with naproxen enantiomers (S/R-NPX) and improved the enantioselective gating. In contrast to the surface-functionalized nanochannels (L-Tyr channel), the L-Tyr-COF packed nanochannels (L-Tyr-COF channel) exhibited high enantioselectivity for S-NPX and realized the enantioseparation with the enantiomer excess value up to 94.2 %. The separation flux through the highly porous L-Tyr-COF channel was 1.33 mmol m-2 h-1 . This study provided a size-matching strategy and the chiral covalent organic framework packed nanochannel membrane to realize enantioseparation with high selectivity and flux.

Nanopore-Based Electrodes for Quinotrione Detection: Host-Guest-Induced Electrochemical Signal Switching.

Nanopore-based detection techniques, with a wide range of transport properties, exhibit impressive selectivity and sensitivity for analytes. To expand the application of nanoporous sensors, real-time and fast detection of targets, all within a portable device, is highly desired for nanopore-based sensors. In addition, to improve the accuracy of the output signal, more appropriate readout methods also need to be explored. In this manuscript, we describe a nanopore-based electrode, regarded as NAC-P6-PC@AuE, prepared by coupling a pillararene-based nanoporous membrane with an electrochemical impedance measurement method. The fabricated device is demonstrated by exposing pillararene-based receptors to trace amounts of pesticide molecules. NAC-P6-PC@AuE devices exhibit distinguished selectivity to quinotrione, as well as the ability to quantify quinotrione with a limit of quantitation (LOQ) of 10 nM. The mechanism that allows sensing was verified using finite-element simulations and may be explained as host-guest-induced surface charge shielding, which influences the electrochemical response of probe molecules. The applications of this nanopore-based electrode may be extended toward other target molecules by decorating the nanopore surfaces with specifically chosen receptors.

Highly Efficient Ionic Gating of Solid-State Nanosensors by the Reversible Interaction between Pillar[6]arene-AuNPs and Azobenzene.

By mimicking nature, various artificial nanofluidic platforms have been widely applied in a range of scientific fields. However, their low performance in terms of gating efficiency (<25) still hinders their practical applications. Herein, we present a highly efficient ionic gating nanosensor by fusing the merits of host-guest chemistry and Au nanoparticles (AuNPs). Based on this strategy, the pillar[6]arene (WP6)-functionalized AuNPs facilely regulated an azobenzene (AZO)-modified nanosensor with an excellent ion rectification ratio (∼22.2) and gating efficiency (∼89.5). More importantly, this gating nanosensor system also demonstrated promising stability and recyclability under conditions of alternative irradiation of visible and ultraviolet light. These excellent results would significantly help in expanding the utilization of artificial nanosensors for controllable drug delivery and biosensors.

Efficient Chiral Nanosenor Based on Tip-Modified Nanochannels.

Enantiomers of various drug molecules have a specific effect on living organisms. Accordingly, developing a sample method for the efficient and rapid recognition of chiral drug enantiomers is of great industrial value and physiological significance. Here, inspired by the structure of ion channels in living organisms, we developed a chiral nanosensor based on an artificial tip-modified nanochannel system that allows efficient selective recognition of chiral drugs. In this system, l-alanine-pillar[5]arenes as selective receptors were introduced on the tip side of conical nanochannels to form an enantioselective "gate". The selective coefficient of our system toward R-propranolol is 4.96, which is higher than the traditional fully modified nanochannels in this work.

Association between epidural analgesia and indications for intrapartum caesarean delivery in group 1 of the 10-group classification system at a tertiary maternity hospital, Shanghai, China: a retrospective cohort study.

BACKGROUND: In this study, we aimed to determine whether epidural analgesia affects the indications for intrapartum caesarean delivery, such as foetal distress, dystocia, or maternal request, in nulliparous term women with spontaneous labour (Group 1 in the 10-Group Classification System). METHODS: We conducted a retrospective cohort study and collected data from the electronic medical records of deliveries performed in our institution between 1 January 2017 and 30 June 2017. Women conforming to the criterion of Group 1 according to the 10-Group Classification System were enrolled. We compared labour outcomes between women with and without epidural analgesia and analysed the association between epidural analgesia and indications for caesarean by using multivariate logistic regression analysis. RESULTS: A total of 3212 women met the inclusion criteria, and 2876 were enrolled in the final analyses. Women who received epidural analgesia had a significantly lower intrapartum caesarean delivery rate (16.0% vs. 26.7%, P < 0.001), higher rates of amniotomy (53.4% vs. 42.3%, P < 0.001) and oxytocin augmentation (79.5% vs. 67.0%, P < 0.001), and a higher incidence of intrapartum fever (≥38 °C) (23.3% vs. 8.5%, P < 0.001) than those who did not receive epidural analgesia. There were no significant differences between the groups for most indications, except a lower probability of maternal request for caesarean delivery (3.9% vs. 10.5%, P < 0.001) observed in women who received epidural analgesia than in those who did not. Epidural analgesia was revealed to be associated with a decreased risk of maternal request for caesarean delivery (adjusted odds ratio [aOR], 0.30; 95% confidence interval [CI], 0.22-0.42; P < 0.001); however, oxytocin augmentation was related to an increased risk of maternal request (aOR, 2.34; 95%CI, 1.47-3.75; P < 0.001). Regarding the reasons for the maternal request for caesarean delivery, significantly fewer women complained of pain (0.5% vs. 4.6%, P < 0.001) or had no labour progress (1.3% vs. 3.6%, P < 0.001) among those who received analgesia. CONCLUSIONS: Among the women in Group 1, epidural analgesia was associated with a lower intrapartum caesarean delivery rate, which may be explained by a reduction in the risk of maternal request for an intrapartum caesarean delivery.

A Visible-Light-Regulated Chloride Transport Channel Inspired by Rhodopsin.

Inspired by the light-regulating capabilities of naturally occurring rhodopsin, we have constructed a visible-light-regulated Cl- -transport membrane channel based on a supramolecular host-guest interaction. A natural retinal chromophore, capable of a visible-light response, is used as the guest and grafted into the artificial channel. Upon introduction of an ethyl-urea-derived pillar[6]arene (Urea-P6) host, threading or de-threading of the retinal and selective bonding of Cl- can be utilized to regulate ion transport. Based on the visible-light responsiveness of the host-guest interaction, Cl- transport can be regulated by visible light between ON and OFF states. Visible-light-regulated Cl- transport as a chemical model permits to understand comparable biological ion-selective transport behaviors. Furthermore, this result also supplies a smart visible-light-responsive Cl- transporter, which may have applications in natural photoelectric conversion and photo-controlled delivery systems.

Construction of A High-Flux Protein Transport Channel Inspired by the Nuclear Pore Complex.

Inspired by the nuclear pore complex (NPC), herein we have established a biomimetic high-flux protein delivery system via the ingenious introduction of pillar[5]arene-based host-guest system into one side of artificial hour-glass shaped nanochannel. With a transport flux of 660 lysozymes per minute, the system provides efficient high-flux protein transport at a rate which is significantly higher than that of an unmodified nanochannel and conventional bilateral symmetrical modified nanochannels. In view of these promising results, the use of artificial nanochannel to improve protein transport not only presents a new potential chemical model for biological research and better understanding of protein transport behavior in the living systems, but also provides a high-flux protein transporter device, which may have applications in the design of protein drug release systems, protein separation systems and microfluidics in the near future.