Crown-Ether-Based Artificial K+ Selective Ionic Filter.

In this study, we have successfully synthesized bis (cholesterol-dibenzo-18-crown-6-ether)-pillar[5]arene compound 1 through a click reaction, which could spontaneously insert into lipid bilayers to form ion channel due to the membrane anchor cholesterol group and show significant transport activity of K+ superior to Na+, with a permeability ratio of K+/Na+ equal to 4.58. Compound 1 two crown ether modules act as selective filters similar to natural K+ channel, which are determined to 1:2 binding stoichiometry to K+ by Job's plot and NMR titration. This structurally unambiguously unimolecule artificial channel provides ideas for constructing highly K+/Na+ selective molecular filters.

Switchable Site-Selective Benzanilide C(sp2)-H Bromination via Promoter Regulation.

Regioselective benzanilide bromination that generates either regioisomer from the same starting material is desirable. Herein, we develop switchable site-selective C(sp2)-H bromination by promoter regulation. This protocol leads to regiodivergent brominated benzanilide starting from the single substrate via selection of promoters. The protocol demonstrates excellent regioselectivity and good tolerance of functional groups with high yields. The utility effectiveness of this method has been well exemplified in the late-stage modification of biologically important molecules.

Redox-Regulated Synthetic Channels: Enabling Reversible Ion Transport by Modulating the Ion-Permeation Pathway.

Natural redox-regulated channel proteins often utilize disulfide bonds as redox sensors for adaptive regulation of channel conformations in response to diverse physiological environments. In this study, we developed novel synthetic ion channels capable of reversibly switching their ion-transport capabilities by incorporating multiple disulfide bonds into artificial systems. X-ray structural analysis and electrophysiological experiments demonstrated that these disulfide-bridged molecules possess well-defined tubular cavities and can be efficiently inserted into lipid bilayers to form artificial ion channels. More importantly, the disulfide bonds in these molecules serve as redox-tunable switches to regulate the formation and disruption of ion-permeation pathways, thereby achieving a transition in the transmembrane transport process between the ON and OFF states.

Unimolecular Chiral Stepping Inversion Machine.

Intelligent molecular machines that are driven by light, electricity, and temperature have attracted considerable interest in the fields of chemistry, materials, and biology. Herein, a unimolecular chiral stepping inversion molecular machine (SIMM) was constructed by a coupling reaction between dibromo pillar[5]arene and a tetrathiafulvalene (TTF) derivative (PT3 and PT5). Compared with the longer aliphatic linker PT5, PT3 with a shorter aliphatic linker shows chiral stepping inversion, achieving chiral inversion under a two-electron redox potential. Benefiting from the successive reversible two-electron redox potential of TTF, the self-exclusion and self-inclusion conformational transformations of SIMM can proceed in two steps under redox, leading to the chirality step inversion in the pillar[5]arene core. Electrochemical experiments and circular dichroism (CD) spectra show that the redox processes can cause SIMM CD signaling to reversibly switch. More importantly, as the oxidant Fe(ClO4)3 was increased from 0.1 to 1 equiv, the CD spectral signal of SIMM disappeared at 1 equiv, and further addition of Fe(ClO4)3 resulted in the CD signal reversed from positive to negative at 309 nm, indicating that the chirality was reversed after chemical oxidation and reached a negative maximum with the addition of 2 equiv Fe(ClO4)3; thus, redox-triggered chiral stepping inversion was achieved. Furthermore, the chiral inversion can be restored to its original state after the addition of 2 equiv of reducing agent, sodium ascorbate. This work demonstrates unimolecular chiral stepping inversion, providing a new perspective on stimulus-responsive chirality in molecular machines.

Isolation of lignocelluloses from the spent liquor of thermomechanical pulping process with fly ash and cationic polymer.

In this work, fly ash (FA) and polydiallyldimethylammonium chloride (PDADMAC) were utilized to treat the spent liquor (SL) of thermomechanical pulping (TMP) process in an effort to remove its lignocelluloses. The incorporation of PDADMAC into the system reduced the dosage of FA required for achieving acceptable lignocellulose removals. The maximum lignocellulose removals of 81%, 78%, 56%, 53% and 97% were achieved for lignin, hemicellulose, COD, BOD, and turbidity via treating SL with 100 g/L of FA at 25 °C for 60 min and subsequently treating with 100 mg/L of PDADMAC at 25 °C for 30 min, respectively. Comparing the two-step processes, FA pretreatment with PDADMAC post treatment was more effective than the two step process of PDADMAC pretreatment and FA post treatment. In this case, the FA pretreatment generated metal-organic complexes, and the addition of PDADMAC facilitated the formation of large flocs that could be separated from the system readily. A one stage process of combined PDADMAC and FA was less effective than the two-stage process of FA and PDADMAC treatments in removing lignocelluloses from SL.

Artificial K+ Channels Formed by Pillararene-Cyclodextrin Hybrid Molecules: Tuning Cation Selectivity and Generating Membrane Potential.

A class of artificial K+ channels formed by pillararene-cyclodextrin hybrid molecules have been designed and synthesized. These channels efficiently inserted into lipid bilayers and displayed high selectivity for K+ over Na+ in fluorescence and electrophysiological experiments. The cation transport selectivity of the artificial channels is tunable by varying the length of the linkers between pillararene and cyclodexrin. The shortest channel showed specific transmembrane transport preference for K+ over all alkali metal ions (selective sequence: K+ > Cs+ > Rb+ > Na+ > Li+ ), and is rarely observed for artificial K+ channels. The high selectivity of this artificial channel for K+ over Na+ ensures specific transmembrane translocation of K+ , and generated stable membrane potential across lipid bilayers.

[Application of single nucleotide polymorphism microarray and fluorescence in situ hybridization analysis for the prenatal diagnosis of a case with Pallister-Killian syndrome].

OBJECTIVE: To explore the clinical and genetic characteristics of a case with Pallister-Killian syndrome (PKS). METHODS: Chromosomal karyotype of umbilical cord blood sample derived from a 36-year-old pregnant woman was analyzed by G-banding analysis. After birth, the child was further analyzed with single nucleotide polymorphism microarray (SNP array) and fluorescence in situ hybridization (FISH) using 12pter/12qter probes. RESULTS: G-banding analysis showed that the fetus has a karyotype of 46,XY [77]/47,XY,+mar [23]. After birth, Affymetrix CytoScan 750K array analysis showed a segmental tetrasomy of arr [hg19] 12p13.33p11.1(173 786 - 34 835 641)×4 and a 34.6 Mb repeat at 12p13.33p11.1 with in the neonate. FISH analysis confirmed that 39% of cells harbored the 12p tetrasomy. CONCLUSION: Combined clinical examination, G-banded chromosomal karyotyping, FISH and microarray analysis can delineate the origin and fragments of small supernumerary marker chromosomes and diagnose PKS with precision.

Flocculation of thermomechanical pulping spent liquor with polydiallyldimethylammonium chloride.

Currently, the dissolved lignocelluloses in the spent liquor (SL) of a thermomechanical pulping process are treated in wastewater treatment systems and thus they are wasted. In this work, polydiallyldimethylammonium chloride (PDADMAC), with different molecular weights, was used for flocculating lignocelluloses of SL and thus isolating them from SL. Results showed that the maximum removals were 38% via treating SL with 100 mg/L of PDADMAC (with 1045 kg/mol molecular weight) at 25 °C for 30 min. The focused beam reflectance measurement of the flocculation process revealed that the chord length of the flocs with the maximum square weighted counts was increased from 70 to 100 µm and also their maximum square weighted counts was increased from 5 to 25 µm2/s. The flocs contained 60.71-74.41 wt% PDADMAC, the balance of lignocelluloses and the heating value of 24-25 MJ/kg. The high molecular PDADMAC generated flocs with more organics and a higher heating value.

Recent Advances in Artificial Anion Channels and Their Selectivity.

Nature performs critical physiological functions using a series of structurally and functionally diverse membrane proteins embedded in cell membranes, in which native ion protein channels modify the electrical potential inside and outside the cell membrane through charged ion movements. Consequently, the cell responds to external stimuli, playing an essential role in various life activities, such as nerve excitation conduction, neurotransmitter release, muscle movement, and control of cell differentiation. Supramolecular artificial channels, which mimic native protein channels in structure and function, adopt unimolecular or self-assembled structures, such as crown ethers, cyclodextrins, cucurbiturils, column arenes, cyclic peptide nanotubes, and metal-organic artificial channels, in channel construction strategies. Owing to the various driving forces involved, artificial synthetic ion channels can be divided into artificial cation and anion channels in terms of ion selectivity. Cation selectivity usually originates from ion coordination, whereas anion selectivity is related to hydrogen bonding, ion pairing, and anion-dipole interactions. Several studies have been conducted on artificial cation channels, and several reviews have summarized them in detail; however, the research on anions is still in the initial stages, and related reviews have rarely been reported. Hence, this article primarily focuses on the recent research on anion channels.

Significantly enhanced uranium extraction by intelligent light-driven nanorobot catchers with precise controllable moving trajectory.

Uranium, as the most essential resource for nuclear power production, provides 13% of global electricity demand, has attracted considerable attention. However, it is still a great challenge for uranium extraction from natural water like salt lakes as the background of high salinity and low concentration (3.3 ∼ 330 ppb). Meanwhile, current uranium extraction strategies are generally focus on extraction capacity or selectivity but neglect to enhance extraction rate. In this work, we designed a novel kind of NIR-driven intelligent nanorobots catchers (MSSA-AO) with amidoxime as claws for uranium capture, which showed almost 100% extraction rate and an ultrafast extraction rate. Importantly, high extraction capacity (221.5 mg g-1) and selectivity were taken into consideration as well as good regeneration performance. Furthermore, amidoxime NRCs boosted in extraction amount about 16.7% during the first 5 min with self-driving performance. Overall, this work suggests a new strategy for ultrafast extraction of uranium from natural water with low abundance selectively by self-propelled NRCs, showing great possibility in outdoor application and promising for meeting huge energy needs globally.

Two-Layer Asynchronous Control for a Class of Nonlinear Jump Systems: An Interval Segmentation Approach.

This article proposes the two-layer asynchronous control scheme for a class of networked nonlinear jump systems. For the constructed system in a network environment, the data transmission may suffer from many restrictions, such as incomplete acceptable mode information and transition information, nonlinearity of system and inadequate bandwidth resources, etc. Then, the two-layer asynchronous controller is developed to stabilize the plant constructed by Takagi-Sugeno (T-S) fuzzy method and semi-Markov theory (SMT). Herein, the hidden semi-Markov process with time-varying emission probability is introduced to establish the relation between the system modes and the controller modes, in which the interval segmentation method is presented to deal with this time-varying probability. Compared with some published results, this method can make full use of the transition rate information, which may lead to the reduction of conservatism in the proposed asynchronous control design. At the same time, the limited bandwidth problem in the communication channel is addressed by introducing the bilateral quantization strategy, and the new sufficient conditions are derived on the stochastic stability of the nonlinear jump system with/without incomplete transition and sojourn-time information. Finally, the numerical simulation examples about DC motor illustrate the effectiveness and the feasibility of the proposed approach.

A unimolecular artificial cation channel based on cascaded hydrated acid groups.

A cation channel possessing cascaded hydrated acid groups has been successfully constructed using pillar[5]arene integrated with dual cyclodextrins. As a proof-of-concept, the secondary side of cyclodextrin substituted by 24 -CO2H groups presents high coordination sites, which helps hydrated cations to quickly dehydrate and accelerates efficient cation transport (Rb+ > Cs+ > K+ > Na+ > Li+). Notably, benefitted by the protonation and deprotonation of -CO2H groups, ion permeation activity of the channel molecules under acidic condition (pH = 6.0) is 2.8 times higher than that under alkaline conditions (pH = 8.0), exhibiting pH-modulated property and promising potential in building intelligent artificial ion channels with customized features.

Discovery of first-in-class PROTACs targeting maternal embryonic leucine zipper kinase (MELK) for the treatment of Burkitt lymphoma.

Maternal embryonic leucine zipper kinase (MELK) is a novel target for the treatment of various kinds of B-cell malignancies. However, the toxicity of inhibitors of MELK has led to clinical failures in cancer treatments. Moreover, inactivation of MELK catalytic domain is insufficient for achieving cancer cell apoptosis. To further confirm the role of MELK in Burkitt lymphoma treatment, we describe herein a structure-guided design of PROTACs targeting MELK. Through design, computer-assisted optimization and SAR studies, we developed the first-in-class MELK-targeting PROTAC MGP-39, which promoted a rapid and potent degradation of MELK in RAMOS cells. Additionally, the newly designed MELK degrader induced significant cell cycle arrest and apoptosis in cancer cells. Notably, compared to MELK inhibitors, MGP-39 has better anti-cancer activity and lower toxicity, indicating the practical role of PROTACs in avoiding the side effects of traditional inhibitors. More importantly, our results show that the use of a PROTAC can be adopted as a general and effective strategy for targeted cancer therapy.

Synthetic cation channel: reconstructing the ion permeation pathway of TRPA1 in an artificial system.

A novel artificial cation channel was developed by rebuilding the ion permeation pathway of the natural channel protein (TRPA1) in a synthetic system. This tubular molecule can effectively embed into lipid bilayers and form transmembrane channels, thereby mediating cation transport. Furthermore, due to its carboxyl-modified ion permeation pathway, the transport activity of this artificial channel can be modulated by the pH of the buffer solution.

From Lignin to Value-Added Pharmaceutical Intermediates Based on a Benzylic Oxidation Method with O2.

We present a catalytic strategy for converting lignin into various pharmaceutical intermediates based on a highly selective lignin depolymerization method and a green benzylic oxidation method employing O2. Selective depolymerization of lignin first afforded 4-ethylphenol, which then efficiently generates several pharmaceutical intermediates with a simple 5-step process, resulting in substantial economic benefits. The study provides an innovative solution for the efficient utilization of lignin and the green acquisition of pharmaceutical intermediates.

Interface-Strengthened Ru-Based Electrocatalyst for High-Efficiency Proton Exchange Membrane Water Electrolysis at Industrial-Level Current Density.

Developing an OER electrocatalyst that balances high performance with low cost is crucial for widely adopting PEM water electrolyzers. Ru-based catalysts are gaining attention for their cost-effectiveness and high activity, positioning them as promising alternatives to Ir-based catalysts. However, Ru-based catalysts can be prone to oxidation at high potentials, compromising their durability. In this study, we utilize a simple synthesis method to synthesize a SnO2, Nb2O5, and RuO2 composite catalyst (SnO2/Nb2O5@RuO2) with multiple interfaces and abundant oxygen vacancies. The large surface area and numerous active sites of the SnO2/Nb2O5@RuO2 catalyst lead to outstanding acidic oxygen evolution reaction (OER) performance, achieving current densities of 10, 50, and 200 mA cm-2 at ultralow overpotentials of 287, 359, and 534 mV, respectively, significantly surpassing commercial IrO2. Moreover, incorporating Nb2O5 into the SnO2/Nb2O5@RuO2 alters the electronic structure at the interfaces and generates a high density of oxygen vacancies, markedly enhancing durability. Consequently, the membrane electrode composed of SnO2/Nb2O5@RuO2 and commercial Pt/C demonstrated stable operation in the PEM cell for 25 days at an industrial current density of 1 A cm-2. This research presents a convenient approach for developing a highly efficient and durable Ru-based electrocatalyst, underscoring its potential for proton exchange membrane water electrolysis.

Iterative Learning Control of Constrained Systems With Varying Trial Lengths Under Alignment Condition.

This brief is concerned with iterative learning control (ILC) of constrained multi-input multi-output (MIMO) nonlinear systems under the state alignment condition with varying trial lengths. A modified reference trajectory is constructed to meet the alignment condition by adjusting the reference trajectory to be spatially closed. Resorting to the barrier composite energy function (BCEF) approach, an adaptive ILC scheme is built to guarantee the bounded convergence of the resultant closed-loop system. Illustrative examples are presented to verify the validity of the proposed iteration scheme.

Bioinspired construction of magnetic nano stirring rods with radially aligned dual mesopores and intrinsic rapid adsorption of palladium.

Quick and precise recovery of palladium (Pd) from electronic waste remains a serious task, owing to the strong acid and complexity of chemical compounds in leachate. Here, bioinspired construction of magnetic nano stirring rod with radially aligned dual mesopores and abundant 8-aminoquinoline (MNSR-DM-AQ) is proposed for selective and rapid extraction of Pd(II) from highly acidic sample solutions. Benefit from the unique dual mesoporous (12.4 nm and 3.6 nm) and the stirring motion under an external magnetic field, MNSR-DM-AQ possesses enhanced adsorption capacity and kinetics, achieving 11.62 mg g-1 (97.2 % of the maximum adsorption capacity) in 15 min. Distribution coefficient (KD = 299.0 mL g-1), separation factor (α above 25.54) and concentration factor (CF = 230.2 mL g-1) reveal the excellent selectivity of MNSR-DM-AQ towards Pd(II) when comparing with the coexisting ions (Ca(II), Co(II), Cu(II), Fe(II), Mg(II), Ni(II), Pb(II), Zn(II)). The adsorption mechanisms of MNSR-DM-AQ are ion exchange and chelation due to a strong affinity between Pd(II) and N. Meanwhile, 96.82 % of the captured Pd(II) can be easily eluted within 15 min, and the adsorption capacity remains stable after five adsorption-desorption cycles. It is worthwhile to mention that MNSR-DM-AQ exhibits a high adsorption capacity of 8.39 mg g-1 from leachate of abandoned high-voltage patch capacitor, which is greatly desired in Pd(II) extraction from electronic waste.

Design, synthesis, and evaluation of BTK-targeting PROTACs with optimized bioavailability in vitro and in vivo.

Ibrutinib is a first-line drug for the treatment of B-cell malignancies. BTKC481S mutation has led to drug resistance during clinical application. Herein, a novel BTK-targeting PROTAC molecule with better solubility and bioavailability was developed. Compound 15-271 has better solubility than ibrutinib and some reported BTK PROTACs. 15-271 has better liver microsomal stability than its analogues in multiple species. More importantly, 15-271 has a longer half-life and better bioavailability in vivo. The development strategy of compound 15-271 can be a general procedure for the optimization of other PROTACs.

Synthesis of Polycarboxylate Viscosity Reducer and the Effect of Different Chain Lengths of Polyether on Viscosity Reduction of Heavy Oil.

Since there are not many studies on the application of polymeric surfactants in viscosity reduction emulsification of heavy oil, a series of polyether carboxylic acid-sulfonate polymeric surfactants were synthesized. The viscosity reduction performance and the effect of different chain lengths on the viscosity reduction effect were also investigated. The viscosity reduction, emulsification, wetting, and foaming performance tests showed that the viscosity reduction performance of this series of polymeric surfactants was excellent, with the viscosity reduction rate exceeding 95%, and the viscosity was reduced to 97 mPa·s by the polymeric surfactant with a molecular weight of 600 polyethers. It was also concluded that among the three surfactants with different side chains, the polymeric surfactant with a polyether molecular weight of 600, which is the medium side-chain length, had the best viscosity reduction performance. The study showed that the polyether carboxylic acid-sulfonate polymer surfactant had a promising application in the viscosity reduction of heavy oil.