"Turn-on" fluorescent sensor for glycerol based on hydrazine-bridged bis-tetraphenylimidazole.

Glycerol is an important biological molecule, but no facile and on-site fluorescence sensor for detecting glycerol has been reported up to now. In this work, the organic fluorescent sensor for glycerol was prepared based on hydrazine-bridged bis-tetraphenylimidazole (HBT), which exhibited an excellent "turn-on" blue fluorescence response in detecting glycerol for the first time. The good sensing selectivity for glycerol among all kinds of organic molecules and ions was confirmed with the low detection limitation (LOD=0.48 µM). The sensing mechanism was proposed as that the photo-induced electron transfer process between the lone pair electrons of the Schiff group and the tetraphenylimidazole moiety was interrupted by the multiple hydrogen-bond action between glycerol and HBT. The sensing ability of HBT for glycerol was successfully used for the detection of glycerol in test paper and real samples (glycerine enema and aloe vera gel), demonstrating the good potential for simple, rapid and in-situ detection of glycerol in daily life.

Insight into the bimetallic structure sensibility of catalytic nitrate reduction over Pd-Cu nanocrystals.

Catalytic reduction of nitrate over bimetallic catalysts has emerged as a technology for sustainable treatment of nitrate-containing groundwater. However, the structure of bimetallic has been much less investigated for catalyst optimization. Herein, two main types of Pd-Cu bimetallic nanocrystal structures, heterostructure and intermetallic, were prepared and characterized using high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The results show that two individual Pd and Cu nanocrystals with a mixed interface exist in the heterostructure nanocrystals, while Pd and Cu atoms are uniformly distributed across the intermetallic Pd-Cu nanocrystals. The catalytic nitrate reduction experiments were carried out in a semibatch reactor under constant hydrogen flow. The nitrate conversion rate of the heterostructure Pd-Cu nanocrystals supported on α-Al2O3, γ-Al2O3, SBA-15, and XC-72R exhibited 3.82-, 6.76-, 4.28-, 2.44-fold enhancements relative to the intermetallic nanocrystals, and the nitrogen and nitrite were the main products for the heterostructure and intermetallic Pd-Cu nanocrystals, respectively. This indicates that the catalytic nitrate reduction over Pd-Cu catalyst is sensitive to the bimetallic structures of the catalysts, and heterostructure bimetallic nanocrystals exhibit better catalytic performances on both the activity and selectivity, which may provide new insights into the design and optimization of catalysts to improve catalytic activity and selectivity for nitrate reduction in water.

Absorption mechanism of SO3 on various alkaline absorbents in the presence of SO2.

Sulfur trioxide (SO3) as a condensable particle matter has a significant influence on atmospheric visibility, which easily arouses formation of haze. It is imperative to control the SO3 emission from the industrial flue gas. Three commonly used basic absorbents, including Ca(OH)2, MgO and NaHCO3 were selected to explore the effects of temperature, SO2 concentration on the SO3 absorption, and the reaction mechanism of SO3 absorption was further illustrated. The suitable reaction temperature for various absorbents were proposed, Ca(OH)2 at the high temperatures above 500°C, MgO at the low temperatures below 320°C, and NaHCO3 at the temperature range of 320-500°C. The competitive absorption between SO2 and SO3 was found that the addition of SO2 reduced the SO3 absorption on Ca(OH)2 and NaHCO3, while had no effect on MgO. The order of the absorption selectivity of SO3 follows MgO, NaHCO3 and Ca(OH)2 under the given conditions in this work. The absorption process of SO3 on NaHCO3 follows the shrinking core model, thus the absorption reaction continues until NaHCO3 was exhausted with the utilization rate of nearly 100%. The absorption process of SO3 on Ca(OH)2 and MgO follows the grain model, and the dense product layer hinders the further absorption reaction, resulting in low utilization of about 50% for Ca(OH)2 and MgO. The research provides a favorable support for the selection of alkaline absorbent for SO3 removal in application.

2D copper-iron bimetallic metal-organic frameworks for reduction of nitrate with boosted efficiency and ammonia selectivity.

Electrocatalytic reduction of nitrate to ammonia has been considered a promising and sustainable pathway for pollutant treatment and ammonia has significant potential as a clean energy. Therefore, the method has received much attention. In this work, Cu/Fe 2D bimetallic metal-organic frameworks were synthesized by a facile method applied as cathode materials without high-temperature carbonization. Bimetallic centers (Cu, Fe) with enhanced intrinsic activity demonstrated higher removal efficiency. Meanwhile, the 2D nanosheet reduced the mass transfer barrier between the catalyst and nitrate and increased the reaction kinetics. Therefore, the catalysts with a 2D structure showed much better removal efficiency than other structures (3D MOFs and Bulk MOFs). Under optimal conditions, Cu/Fe-2D MOF exhibited high nitrate removal efficiency (87.8%) and ammonium selectivity (89.3%) simultaneously. The ammonium yielded up to significantly 907.2 µg/(hr·mgcat) (7793.8 µg/(hr·mgmetal)) with Faradaic efficiency of 62.8% at an initial 100 mg N/L. The catalyst was proved to have good stability and was recycled 15 times with excellent effect. DFT simulations confirm the reduced Gibbs free energy of Cu/Fe-2D MOF. This study demonstrates the promising application of Cu/Fe-2D MOF in nitrate reduction to ammonia and provides new insights for the design of efficient electrode materials.

11-Azaartemisinin derivatives bearing halogenated aromatic moieties: Potent anticancer agents with high tumor selectivity.

While artemisinin and its derivatives, including 11-azaartemisinin-based compounds, have shown promising anticancer activity, the integration of halogens into aromatic structures can amplify drug potency, metabolic stability, and selectivity. Herein, we present the synthesis of new novel 11-azaartemisinin derivatives bearing halogenated aromatic moieties connected via 1,2,3-triazole bridges and evaluate their anticancer activities against three human tumor cell lines: epidermoid carcinoma (KB), hepatocellular carcinoma (HepG2), and human lung adenocarcinoma (A549). Among the synthesized compounds, six of them (8c-h) displayed good to excellent antiproliferative activity in the low micromolar range across all three human cancer cell lines. In general, the m-bromide (8c) and m-iodide (8d) compounds exhibited superior anticancer activities compared to their o- and p-analogs, as well as the m-chloride and m-fluoride compounds. The most promising m-Br compound (8c) displayed 50 % inhibition of KB, HepG2, and A549 cell growth at concentrations of 7.7, 42.5, and 15.5 µM, respectively. Notably, the m-Br compound (8c) exhibited approximately 32-, 6-, and 16-fold lower activity in normal cells (Hek293) compared to KB, HepG2, and A549 tumor cells, respectively, indicating a significant tumor-selectivity.

Rationally designed BCR-ABL kinase inhibitors for improved leukemia treatment via covalent and pro-/dual-drug targeting strategies.

BACKGROUND: Chronic Myeloid Leukemia (CML) is a blood cancer that remains challenging to cure due to drug resistance and side effects from current BCR-ABL inhibitors. There is an urgent need for novel and more effective BCR-ABL targeting inhibitors and therapeutic strategies to combat this deadly disease. METHOD: We disclose an "OH-implant" strategy to improve a noncovalent BCR-ABL inhibitor, PPY-A, by adding a hydroxyl group to its scaffold. By taking advantage of this OH "hot spot", we designed a panel of irreversible covalent kinase inhibitors and hypoxia-responsive pro-/dual-drugs, and their biological activities were studied in vitro, in cellulo and in vivo. RESULT: The resulting compound B1 showed enhanced solubility and biological activity. B4 achieved sustained BCR-ABL inhibition by forming a stable covalent bond with ABL kinase. Hypoxia-responsive prodrug P1 and dual-drugs D1/D2/D3 demonstrated significant anti-tumor effects under hypoxic conditions. The in vivo studies using K562-xenografted mice showed that B1 displayed superior antitumor activity than PPY-A, while P1 and D3 offered better safety profiles alongside significant tumor control. CONCLUSION: We have successfully developed a chemical biology approach to convert a known noncovalent BCR-ABL inhibitor into more potent and safer inhibitors through covalent and pro-/dual-drug targeting strategies. Our "OH-implant" approach and the resulting drug design strategies have general applicability and hold promise for improvement the performance of various other reported drugs/drug candidates, thereby providing advanced medicines for disease treatment.

Graspable foods and tools elicit similar responses in visual cortex.

The extrastriatal visual cortex is known to exhibit distinct response profiles to complex stimuli of varying ecological importance (e.g. faces, scenes, and tools). Although food is primarily distinguished from other objects by its edibility, not its appearance, recent evidence suggests that there is also food selectivity in human visual cortex. Food is also associated with a common behavior, eating, and food consumption typically also involves the manipulation of food, often with hands. In this context, food items share many properties with tools: they are graspable objects that we manipulate in self-directed and stereotyped forms of action. Thus, food items may be preferentially represented in extrastriatal visual cortex in part because of these shared affordance properties, rather than because they reflect a wholly distinct kind of category. We conducted functional MRI and behavioral experiments to test this hypothesis. We found that graspable food items and tools were judged to be similar in their action-related properties and that the location, magnitude, and patterns of neural responses for images of graspable food items were similar in profile to the responses for tool stimuli. Our findings suggest that food selectivity may reflect the behavioral affordances of food items rather than a distinct form of category selectivity.

Update on JNK inhibitor patents: 2015 to present.

INTRODUCTION: c-Jun N-terminal kinase (JNK) regulates various biological processes through the phosphorylation cascade and is closely associated with numerous diseases, including inflammation, cardiovascular diseases, and neurological disorders. Therefore, JNKs have emerged as potential targets for disease treatment. AREAS COVERED: This review compiles the patents and literatures concerning JNK inhibitors through retrieving relevant information from the SciFinder, Google Patents databases, and PubMed from 2015 to the present. It summarizes the structure-activity relationship (SAR) and biological activity profiles of JNK inhibitors, offering valuable perspectives on their potential therapeutic applications. EXPERT OPINION: The JNK kinase serves as a novel target for the treatment of neurodegenerative disorders, pulmonary fibrosis, and other illnesses. A variety of small-molecule inhibitors targeting JNKs have demonstrated promising therapeutic potential in preclinical studies, which act upon JNK kinases via distinct mechanisms, encompassing traditional ATP competitive inhibition, covalent inhibition, and bidentate inhibition. Among them, several JNK inhibitors from PregLem SA, Celegene SA, and Xigen SA have accomplished the early stage of clinical trials, and their results will guide the development and indications of future JNK inhibitors.

Massively Enhanced Charge Selectivity, Ion Transport, and Osmotic Energy Conversion by Antiswelling Nanoconfined Hydrogels.

Developing a nanofluidic membrane with simultaneously enhanced ion selectivity and permeability for high-performance osmotic energy conversion has largely been unexplored. Here, we tackle this issue by the confinement of highly space-charged hydrogels within an orderedly aligned nanochannel array membrane. The nanoconfinement effect endows the hydrogel-based membrane with excellent antiswelling property. Furthermore, experimental and simulation results demonstrate that such a nanoconfined hydrogel membrane exhibits massively enhanced cation selectivity and ion transport properties. Consequently, an amazingly high power density up to ∼52.1 W/m2 with an unprecedented energy conversion efficiency of 37.5% can be reached by mixing simulated salt-lake water (5 M NaCl) and river water (0.01 M NaCl). Both efficiency indexes surpass those of most of the state-of-the-art nanofluidic membranes. This work offers insights into the design of highly ion-selective membranes to achieve ultrafast ion transport and high-performance osmotic energy harvesting.

Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1.

Human voltage-gated proton (hHv1) channels are crucial for regulating essential biological processes such as immune cell respiratory burst, sperm capacitation, and cancer cell migration. Despite the significant concentration difference between protons and other ions in physiological conditions, hHv1 demonstrates remarkable proton selectivity. Our calculations of single-proton, cation, and anion permeation free energy profiles quantitatively demonstrate that the proton selectivity of the wild-type channel originates from its strong proton affinity via the titration of the key residues D112 and D174, although the channel imposes similar kinetic blocking effects for protons compared to other ions. A two-proton knock-on model is proposed to mathematically explain the electrophysiological measurements of the pH-dependent proton conductance in the conductive state. Moreover, it is shown that the anion selectivity of the D112N mutant channel is tied to impaired proton transport and substantial anion leakage.

Chiral Pd(II) Nanofiber Promoting Electron Transfer of g-C3N4 for Efficient Photocatalytic Hydrogen Production.

The rapid transfer and separation of photogenerated electrons is very important for the improvement of photocatalytic efficiency. Here, chiral induced spin selectivity effect (CISS effect) was developed to accelerate electron transfer for efficient photocatalytic hydrogen production. A chiral and achiral racemic supramolecular Pd(II) complex nanofiber was fabricated via supramolecular self-assembly of chiral L-Py or its racemes with Pd(II) and used to modify carbon nitride (g-C3N4). The obtained chiral photocatalyst L-Py-Pd/g-C3N4-4 and achiral photocatalyst Rac-Pd/g-C3N4-4, show enhanced photocatalytic activities with hydrogen evolution rates of 2476 and 1339 µmol g-1 h-1, respectively, while that of pure g-C3N4 is 30.5 µmol g-1 h-1. Chiral photocatalyst has 85% higher activity than achiral one and is 82.5-fold of pure g-C3N4, due to better suppression of the recombination of photogenerated electron-hole pairs in the interface of g-C3N4 contact with chiral molecule. Spectral tests and photoelectrochemical tests proved that the chiral supramolecular Pd(II) complex can act both as an electron spin filter and hydrogen reduction catalytic center to enhance photocatalytic efficiency. This work offers a new route to facilitate electron transfer by the CISS effect for photocatalytic hydrogen evolution.

N-doped carbon nanospheres synthesized from a newly designed eco-friendly sustainable polymer for highly selective CO2 capture.

N-doped carbon nanospheres and porous carbon were produced by a hydrothermal template and the activation of hexamethylenetetramine (HMTA as a nitrogen source and activator) and ZnCl2 (only as an activator) from a poly(Ri-S-ε-CL-PDMS) multiblock/graft copolymer produced using a renewable resource and eco-friendly autoxidation. N-doped carbon nanospheres (PPiSiHMTA) exhibited excellent CO2 adsorption (2.73 mmol/g at 0 °C and 0.15 atm, 1.72 mmol/g at 25 °C and 0.15 atm) and CO2/N2 selectivity (344-512). Despite the higher BET surface area and pore volume, porous carbon (PPiSi) showed low CO2 adsorption (1.21 and 0.71 mmol/g, 0.15 atm) and CO2/N2 selectivity (57 and 112). PPiSiHMTA and PPiSi have low isosteric heats of adsorption (Qst, 18-33 kJ/mol) and stability in humid environments. In addition, PPiSiHMTA exhibited an excellent CO2 recycling performance. The experimental data on CO2 adsorption was evaluated using various isotherm models, including Freundlich, Langmuir, Sips, and Temkin. The results demonstrated a nearly perfect fit between the Freundlich isotherm and the experimental data, indicating the heterogeneous nature of the adsorbent surfaces. Our study is promising for industrial applications, offering excellent CO2 adsorption, CO2/N2 selectivity, moisture stability, and porous material fabrication strategies.

A Novel Sulfonated Polyimide Composite Membrane Containing a Sulfonated Porous Material for All-Vanadium Redox Flow Batteries.

To improve the battery efficiency and cycling stability of sulfonated polyimide (SPI), a polyphosphazene with built-in -SO3H moieties (PP-SO3H), which is a porous covalent organic framework (COF) material, is facilely synthesized by the polymeric combination of hexachlorocyclotriphosphazene (HCCP) and p-diaminobenzenesulfonic acid. Due to its tunable pore size and flexible molecular design, the COF material can address the trade-off between the conductivity and the ion permeability of ion exchange membranes well, thereby improving the ion selectivity of membranes. The experimental results show that the SPI/PP-SO3H composite membrane has an excellent conductivity (up to 114.8 mS cm-1); the ion selectivity of the SPI/2% PP-SO3H membrane is 11.69 × 104 S min cm-3, which is 2.18 times higher than that of the SPI base membrane. PP-SO3H also improves the SPI membrane's mechanical strength, and the effect of PP-SO3H on SPI intermolecular interactions is analyzed by surface electrostatic potential (ESP) theoretical calculations. The Coulombic efficiency (CE) of the SPI/2% PP-SO3H membrane is 98.92%, the energy efficiency (EE) is 84.1% at a current density of 100 mA cm-2, and the self-discharge time of the SPI/2% PP-SO3H membrane is 3.5 times compared with the SPI base membrane. To measure the cycling stability of the composite membrane, the SPI/2% PP-SO3H membrane is cycled in the VRFB for more than 400 cycles, which is more stable than that of the SPI base membrane. These results show that SPI/2% PP-SO3H composite membranes are viable for VRFB applications.

Cyano-determined mercury (II) ion selective fluorescence assay over polymeric carbon nitride.

Selective response is the key index to evaluate the performance of polymeric carbon nitride (PCN)-based heavy metal ion fluorescence sensors. Herein, to explore the role of cyano groups on selectivity, four kinds of PCN, including PCN-Cl, PCN-Ac, PCN-B and PCN-K were prepared by the molten salt method of sodium chloride and sodium acetate, the reduction method of sodium borohydride and the etching method of potassium hydroxide, respectively. These PCNs exhibited different surface cyano characteristics, but all of them had significant blue emission under ultraviolet excitation. It is proved that the assistant of sodium chloride or potassium hydroxide is an effective method to prepare PCNs with abundant surface cyano group. A series of fluorescence quenching experiments of metal ions showed that the cyano-rich degree of PCN is closely related to its selective response to mercury (II) ions. PCN-Cl and PCN-K emerged good selective quenching of mercury (II) ions, which may be related to the soft acid-soft base strong interaction between mercury (II) ions and cyano groups. Both PCN-Cl and PCN-K fluorescent probes for mercury (II) ions had a linear range of 5 âˆ¼ 50 µmol L-1, and PCN-Cl exhibited a lower detection limit of 0.38 µmol L-1. This work confirmed the selective fluorescence response of cyano-rich PCN to mercury (II) ions, proposed the mechanism of selective fluorescence quenching response of mercury (II) ions, and provided a new idea for the design of efficient and accurate PCN-based fluorescence probes.

Tissue-aware interpretation of genetic variants advances the etiology of rare diseases.

Pathogenic variants underlying Mendelian diseases often disrupt the normal physiology of a few tissues and organs. However, variant effect prediction tools that aim to identify pathogenic variants are typically oblivious to tissue contexts. Here we report a machine-learning framework, denoted "Tissue Risk Assessment of Causality by Expression for variants" (TRACEvar, https://netbio.bgu.ac.il/TRACEvar/ ), that offers two advancements. First, TRACEvar predicts pathogenic variants that disrupt the normal physiology of specific tissues. This was achieved by creating 14 tissue-specific models that were trained on over 14,000 variants and combined 84 attributes of genetic variants with 495 attributes derived from tissue omics. TRACEvar outperformed 10 well-established and tissue-oblivious variant effect prediction tools. Second, the resulting models are interpretable, thereby illuminating variants' mode of action. Application of TRACEvar to variants of 52 rare-disease patients highlighted pathogenicity mechanisms and relevant disease processes. Lastly, the interpretation of all tissue models revealed that top-ranking determinants of pathogenicity included attributes of disease-affected tissues, particularly cellular process activities. Collectively, these results show that tissue contexts and interpretable machine-learning models can greatly enhance the etiology of rare diseases.

Synthesis and photooxygenation of 3-(p-substituted phenyl)-3a,8a-dihydro-4H-cyclohepta[d]isoxazoles: facial selectivity.

Two 3-(p-substituted phenyl)-3a,8a-dihydro-4H-cyclohepta[d]isoxazoles were synthesized by 1,3-dipolar cycloaddition of the corresponding nitrile oxides with cycloheptatriene. Two endoperoxides were synthesized as facially selective and single products in high yields (93%-95%) from the reactions of isoxazole derivatives with singlet oxygen. The exact configurations of the endoperoxide with a methyl group in the phenyl ring and the diol synthesized from it were confirmed by X-ray analysis. To elucidate the mechanism, the formation energy of the endoperoxide was investigated by simulations using the software package Gaussian 09 and density functional theory calculations via the M06-2X/6-311+G(d,p) level method in dichloromethane. The results were consistent with experimental findings showing the formation of isoxazole products.

Multi-Stage Optimization of Pore Size and Shape in Pore-Space-Partitioned Metal-Organic Frameworks for Highly Selective and Sensitive Benzene Capture.

Compared to exploratory development of new structure types, pushing the limits of isoreticular synthesis on a high-performance MOF platform may have higher probability of achieving targeted properties. Multi-modular MOF platforms could offer even more opportunities by expanding the scope of isoreticular chemistry. However, navigating isoreticular chemistry towards best properties on a multi-modular platform is challenging due to multiple interconnected pathways. Here on the multi-modular pacs (partitioned acs) platform, we demonstrate accessibility to a new regime of pore geometry using two independently adjustable modules (framework-forming module 1 and pore-partitioning module 2). A series of new pacs materials have been made. Benzene/cyclohexane selectivity is tuned, progressively, from 4.5 to 15.6 to 195.4 and to 482.5 by pushing the boundary of the pacs platform towards the smallest modules known so far. The exceptional stability of these materials in retaining both porosity and single crystallinity enables single-crystal diffraction studies of different crystal forms (as-synthesized, activated, guest-loaded) that help reveal the mechanistic aspects of adsorption in pacs materials.

Highly selective ethanol vapour sensing materials for a new generation of gas sensors based on molecularly imprinted polymers.

A simple gas sensor consisting of a molecularly imprinted polymer-carbon nanotube composite cast onto a screen-printed electrode has been developed with extremely high selectivity for ethanol vapour over methanol vapour. Ethanol gas sensors typically display selectivity for ethanol over methanol in the range 2-4 times, while the mean ratio of ethanol to methanol response observed with the described device was 672. This selectivity was achieved under ambient conditions. Additionally, the molecularly imprinted polymer was produced using reagents previously applied in the development of a device selective for methanol, with only the template being changed. This demonstrates the versatility of molecular imprinting and provides a foundation for their greater integration into future gas sensors.

Ag modified ZnO nanoflower gas sensitive sensor for selective detection of n-butanol.

Ag modified ZnO nanoflowers were successfully prepared by sunlight induced solvent reduction method. The samples were characterized by XRD, FESEM, TEM and EDS, and the results confirmed the presence of Ag nanoparticles on the ZnO nanoflower. The gas sensing performance of the materials was studied at different operating temperatures and different n-butanol concentrations. The results showed that the Ag modified ZnO nanoflower sensor responded to 50 ppm n-butanol up to 147.17 at 280 °C, and the Ag modified ZnO nanoflower sensor exhibited excellent repeatability, stability and response recovery time. In addition, different target gases were employed for the selectivity study of the Ag modified ZnO nanoflower. It can be found that the Ag modified ZnO nanoflower had good selectivity for n-butanol. The improved response of the Ag modified ZnO nanoflower sensor was attributed to the catalytic effect of Ag nanoparticles. The results indicate that the Ag modified ZnO nanoflower will become a very promising sensing material for n-butanol gas detection. .

Ultra-High Metal-Ions Selectivity Induced by Intramolecular Cation-π Interaction for the One-Pot Synthesis of Precise Heterometallic Architecture.

Heterometallic supramolecules, known for their unique synergistic effects, have shown broad applications in photochemistry, host-guest chemistry, and catalysis. However, there are great challenges to precisely construct heterometallic supramolecules rather than statistical mixture, due to the limited metal-ions selectivity of coordination units. Especially, heterometallic architectures precisely encoding with different metal ions usually fail to obtain in one-pot method when only one type of coordinated motif exists due to its poor metal-ion selectivity. Herein, we proposed an effective intramolecular cation-π (ICπ) strategy and successfully constructed the heterometallic supramolecule Zn2Cu4L34 by one-pot self-assembly of tritopic terpyridyl ligand L3 with Zn(II) and Cu(II), following the clear self-assembly mechanism that only thermodynamic dimers ZnL12 and Cu2L22 were constructed with model ligands L1, L2, Zn(II) and Cu(II) with perfect self-sorting and ultra-high metal-selectivity feature. The successful construction of the heterometallic supramolecule Zn2Cu4L34, encoding the definite sequence of metal ions Zn(II) and Cu(II) in one-pot method, will offer a novel approach to precisely construct heterometallic architectures.