Favorable Selectivity Research Articles

Emerging therapeutics: The imidazo[1,2-b]pyridazine scaffold as a novel drug candidate for eumycetoma, a neglected tropical disease

Mycetoma is a neglected invasive infection endemic in tropical and subtropical regions, presenting as a chronic subcutaneous inflammatory mass that can spread to deeper structures, leading to deformities, disabilities, and potentially mortality. The current treatment of eumycetoma, the fungal form of mycetoma, involves antifungal agents, such as itraconazole, combined with surgical intervention. However, this approach has limited success, with low cure rates and a high risk of recurrence. This study addresses to the urgent need for more effective therapeutics by designing and synthesising 47 diversely pharmacomodulated imidazo [1,2-b]pyridazine derivatives using a simple synthetic pathway with good yields and purity. Of these, 17 showed promising in vitro activity against Madurella mycetomatis, the prime causative agent of eumycetoma, with IC50 ≤ 5 μM and demonstrated significantly lower cytotoxicity compared to standard treatments in NIH-3T3 fibroblasts. Notably, compound 14d exhibited an excellent activity with an IC50 of 0.9 μM, in the same order then itraconazole (IC50 = 1.1 μM), and achieved a favourable selectivity index of 16 compared to 0.8 for itraconazole. These promising results warrant further research to evaluate the clinical potential of these novel compounds as safer, more effective treatments for eumycetoma, thus addressing a profound gap in current therapeutic strategies.

High-efficiency polarization-selective two-dimensional diffraction gratings based on silver cuboid arrays

A two-dimensional (2D) diffraction grating based on silver cuboid arrays is demonstrated. With the structural optimization by three-dimensional (3D) finite-difference time-domain method, the proposed grating exhibits favorable polarization selectivity. At wavelength 1550 nm, high diffraction efficiency and polarization correlation can be realized in the case of two-port output ((0, ±1) or (±1, 0)) under TE polarization, as well as five-port output ((0, 0), (0, ±1) and (±1, 0)) under TM polarization. Under the two-port output state, the diffraction efficiency is nearly 48% with the extinction ratio of 16.44 dB and insertion loss of 0.20 dB. Under the five-port output status, the efficiency is larger than 19% for each diffraction order, meanwhile, the total efficiency and uniformity are 97% and 0.58%, respectively. The proposed grating with positive implications has good potentials in polarization multiplexing and polarization-correlated grating interferometry.

In silico enzyme screening identifies an SDR ketoreductase from Thermus caliditerrae as an attractive biocatalyst and promising candidate for protein engineering

Introduction: Biocatalysis, particularly through engineered enzymes, presents a cost-effective, efficient, and eco-friendly approach to compound synthesis. We sought to identify ketoreductases capable of synthesizing optically pure alcohols or ketones, essential chiral building blocks for active pharmaceutical ingredients.Methods: Using BioMatchMaker®, an in silico high-throughput platform that allows the identification of wild-type enzyme sequences for a desired chemical transformation, we identified a bacterial SDR ketoreductase from Thermus caliditerrae, Tcalid SDR, that demonstrates favorable reaction efficiency and desired enantiomeric excess.Results: Here we present two crystal structures of the Tcalid SDR in an apo-form at 1.9 Å and NADP-complexed form at 1.7 Å resolution (9FE6 and 9FEB, respectively). This enzyme forms a homotetramer with each subunit containing an N-terminal Rossmann-fold domain. We use computational analysis combined with site-directed mutagenesis and enzymatic characterization to define the substrate-binding pocket. Furthermore, the enzyme retained favorable reactivity and selectivity after incubation at elevated temperature.Conclusion: The enantioselectivity combined with the thermostability of Tcalid SDR makes this enzyme an attractive engineering starting point for biocatalysis applications.

Organosilane-assisted synthesis of EU-1 nanozeolite aggregates with improved activity in catalytic cracking of n-hexane

One-dimensional microporous zeolite, EU-1, exhibits more favorable selectivity of propylene in cracking of petroleum components. However, it faced the problem of low catalytic activity for the poor utilization of active sites. In this work, dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (TPOAC) was used to functionalize protozeolitic units and inhibit the excessive growth of crystals by the long hydrophobic alkyl chain. The introduction of TPOAC decreased the crystal sizes into nanoscale, enhanced the mesoporous volume of EU-1 zeolite, and exposed more external acid sites. Moreover, TPOAC could interact with Al species, and in this case, fewer Al atoms were incorporated into the zeolite framework, reducing the acid strength and amount. Intelligent gravitation analyzer test indicated that the zeolite prepared with the presence of 0.30 g TPOAC exhibited the largest accessible volumes in n-hexane adsorption, and the highest accessibility of acid sites, which synergistically promoted cracking of n-hexane for the production of light olefins.

Customizing pyridinic nitrogen coordination in Ni–N–C for electrocatalytic CO2 reduction towards CO

Nickel anchored N-doped carbon electrocatalysts (Ni–N–C) are rapidly developed for the electrochemical reduction reaction of carbon dioxide (CO2RR). However, the high-performanced Ni–N–C analogues design for CO2RR remains bewilderment, for the reason lacking of definite guidance for its structure-activity relationship. Herein, the correlation between the proportion of nitrogen species derived from various nitrogen sources and the CO2RR activity of Ni–N–C is investigated. The x-ray photoelectron spectroscopy (XPS) spectrum combined with the CO2RR performance results show that pyridinic-N content has a positive correlation with CO2RR activity. Moreover, density functional theory (DFT) demonstrates that pyridinic-N coordinated Ni–N4 sites offers optimized free energy and favorable selectivity towards CO2RR compared with pyrrolic-N. Accordingly, Ni–Na–C with highest pyridinic-N content (ammonia as nitrogen source) performs superior CO2RR activity, with the maximum carbon monoxide faradaic efficiency (FECO) of 99.8% at −0.88 V vs. RHE and the FECO surpassing 95% within potential ranging of −0.88 to −1.38 V vs. RHE. The building of this parameter for CO2RR activity of Ni–N–C give instructive forecast for low-cost and highly active CO2RR electrocatalysts.

A high-fidelity dual-channel fluorescence probe for benzoyl peroxide detection and toxicity early warning in food, zebrafish, and mice

Benzoyl peroxide (BPO), as a widely used organic peroxide, has attracted widespread attention from all sectors of society for its environmental hazards and potential risks to human health. Herein, we employed a Förster resonance energy transfer (FRET) strategy to construct a novel ratiometric fluorescent probe CY-DCI for BPO detection in food, zebrafish, and mice. Specifically, a hemicyanine fluorophore and a dicyanoisophorone fluorophore were connected with a piperazine group as donor and acceptor, respectively, and an olefinic unsaturated bond as the reaction site. CY-DCI has favorable selectivity and an excellent detection limit as low as 58.1 nM, and the recovery rates for real-sample detection ranged from 95.8 % to 104 %, with relative standard deviations (RSD) less than 2.58 %. To further improve its practicality, silica gel plates and test strips containing CY-DCI (0–50 μM) were developed for naked-eye detection of BPO with satisfactory results. Additionally, this novel probe was then applied for ratiometric imaging of living zebrafish and mice and showed high ratiometric imaging resolution in the green and red channels, thus demonstrating its practical application for BPO detection and toxicity early warning in food and biosystems.

Density Functional Theory Investigation on the Nitrogen Reduction Mechanism in Two-Dimensional Transition-Metal Boride with Ordered Metal Vacancies.

The creation of ordered collective vacancies in experiment proves challenging within a two-dimensional lattice, resulting in a limited understanding of their impact on catalyst performance. Motivated by the successful experimental synthesis of monolayer molybdenum borides with precisely ordered metal vacancies [Zhou et al. Science 2021, 373, 801-805] through dealloying, the nitrogen reduction reaction (NRR) in monolayer borides was systematically investigated to elucidate the influence of such ordered metal vacancies on catalytic reactions and the underlying mechanisms. The results reveal that the N-containing intermediates tend to dissociate, facilitating the NRR process with reduced UL. The emergence of ordered metal vacancies modulates the electronic properties of the catalyst and partially facilitates the decomposition of N-containing intermediates. However, the UL for NRR in Mo4/3B2 and W4/3B2 exhibits a significant increase. The compromised electrochemical performance is explained through the development of a simple electronic descriptor of the d-p band center (ΔdM-pB). Among these materials, Mo4/3Sc2/3B2 exhibits the most superior catalytic activity with a UL of -0.5 V and favorable NRR selectivity over the HER. Our results provide mechanistic insights into the role of ordered metal vacancies in transition-metal boride for the NRR and highlight a novel avenue toward the rational design of superior NRR catalysts.

Discovery and optimization of 3-(indolin-5-yloxy)pyridin-2-amine derivatives as potent necroptosis inhibitors.

Necroptosis is a form of regulated necrotic cell death and has been confirmed to play pivotal roles in the pathogenesis of multiple autoimmune diseases such as rheumatoid arthritis (RA) and psoriasis. The development of necroptosis inhibitors may offer a promising therapeutic strategy for the treatment of these autoimmune diseases. Herein, starting from the in-house hit compound 1, we systematically performed structural optimization to discover potent necroptosis inhibitors with good pharmacokinetic profiles. The resulting compound 33 was a potent necroptosis inhibitor for both human I2.1 cells (IC50 < 0.2 nM) and murine Hepa1-6 cells (IC50 < 5 nM). Further target identification revealed that compound 33 was an inhibitor of receptor interacting protein kinase 1 (RIPK1) with favorable selectivity. In addition, compound 33 also exhibited favorable pharmacokinetic profiles (T1/2 = 1.32 h, AUC = 1157 ng·h/mL) in Sprague-Dawley rats. Molecular docking and molecular dynamics simulations confirmed that compound 33 could bind to RIPK1 with high affinity. In silico ADMET analysis demonstrated that compound 33 possesses good drug-likeness profiles. Collectively, compound 33 is a promising candidate for antinecroptotic drug discovery.

Hydrothermal pre-anchoring and in-situ preparation of Prussian blue analogue-polymeric carbon nitride nanorods hybrid for robust and efficient cesium adsorption

Prussian blue analogues (PBAs) are recognized as effective and selective adsorbents for Cs+, however, they suffered from unsatisfactory post-separation performance and inevitable dissolution loss arising from the small size and inferior water instability. In this study, Zn-PBA nanoparticles were integrated onto polymeric carbon nitride (PCN) nanorods to form PBA-PCN hybrid via hydrothermal pre-anchoring and in-situ growth method. The robust and amino-rich PCN played dual roles in securely anchoring the Zn2+ precursor and attracting Cs+ to the surface. Benefiting from the effects of PCN and in-situ generated PBA, PBA-PCN exhibited boosting post-separation performance and water stability in acid and alkaline solutions, which was attractive in different application scenarios. Moreover, PBA-PCN has been demonstrated to be with high adsorption capacity of 376.41 mg/g and favorable selectivity even in the presence of excessive competitive ions. The experimental results and DFT calculations suggested the adsorption mechanism involving strong incorporation/ion exchange and weak electrostatic attraction. The remarkable adsorption performance along with the satisfactory post-separation performance and water stability made it a promising candidate in Cs+ removal and separation.

Efficient fluoride removal in hybrid capacitive deionization enabled by Ce-Zn-MOF-derived CeO2@C and birnessite electrodes

Fluorine pollution has become a public health issue of global concern. Capacitive deionization (CDI) presents the benefits of simple operation, high energy efficiency, and good sustainability. The development of high adsorption performance, economical and environmentally friendly defluorination electrodes is the key direction of capacitive deionization. Here, a spherical metal–organic framework (MOF) Ce/Zn-BTC was prepared by solvothermal method utilizing benzene-tricarboxylic (BTC) acid as solvent, and then it was transformed into CeO2@C composites through pyrolysis. The spherical structure of the original MOFs is preserved by CeO2@C, leading to significant enhancements in specific surface area (275.48 m2/g), pore volume (0.3359 cm3/g), and electrochemical performance. In this work, the anode material CeO2@C was employed for the first time, while birnessite-type MnO2 (δ-MnO2) was utilized as a cathode material for the fabrication of a hybrid CDI (HCDI) device for the treatment of fluorinated wastewater. The CeO2@C/δ-MnO2 cell shows excellent fluoride removal performance with a removal capacity of 22.03 mg/g for 50 mg/L fluoride solutions under a 1.2 V applied voltage, which is better than most carbon-based materials. Importantly, the CeO2@C/δ-MnO2 cell has favorable fluoride selectivity and regeneration performance (>75 %) even after undergoing ten cycles. Fluoride is mainly removed by intercalation into the carbon skeleton, coordination with Ce, and electrostatic interaction. This study shows that the CeO2@C/δ-MnO2 cell has excellent fluoride removal performance and practical application prospects.

Exploring the CO2 Electrocatalysis Potential of 2D Metal-Organic Transition Metal-Hexahydroxytriquinoline Frameworks: A DFT Investigation.

Metal-organic frameworks have demonstrated great capacity in catalytic CO2 reduction due to their versatile pore structures, diverse active sites, and functionalization capabilities. In this study, a novel electrocatalytic framework for CO2 reduction was designed and implemented using 2D coordination network-type transition metal-hexahydroxytricyclic quinazoline (TM-HHTQ) materials. Density functional theory calculations were carried out to examine the binding energies between the HHTQ substrate and 10 single TM atoms, ranging from Sc to Zn, which revealed a stable distribution of metal atoms on the HHTQ substrate. The majority of the catalysts exhibited high selectivity for CO2 reduction, except for the Mn-HHTQ catalysts, which only exhibited selectivity at pH values above 4.183. Specifically, Ti and Cr primarily produced HCOOH, with corresponding 0.606 V and 0.236 V overpotentials. Vanadium produced CH4 as the main product with an overpotential of 0.675 V, while Fe formed HCHO with an overpotential of 0.342 V. Therefore, V, Cr, Fe, and Ti exhibit promising potential as electrocatalysts for carbon dioxide reduction due to their favorable product selectivity and low overpotential. Cu mainly produces CH3OH as the primary product, with an overpotential of 0.96 V. Zn primarily produces CO with a relatively high overpotential of 1.046 V. In contrast, catalysts such as Sc, Mn, Ni, and Co, among others, produce multiple products simultaneously at the same rate-limiting step and potential threshold.

Unraveling Genetic Variability, Correlation and Path Analysis for Yield and Its Components in Barley (Hordeum vulgare L.)

The current study aimed to assess the genetic variability of yield and yield-related traits while examining the direct and indirect effects of trait interactions. Conducted at a research farm in Chaudhary Charan Singh University, Meerut, Uttar Pradesh, India, the experiment involved fourteen parents and their BC1F1 crosses, analyzed using a randomized block design (RBD). Significant differences were observed among the varieties for most traits, indicating a broad range of mean values and diversity. Both phenotypic and genotypic coefficients of variance (PCV and GCV) were generally low, with biological yield showing the highest values (26.57 for GCV and 40.48 for PCV). PCV values were slightly higher than GCV values. Traits such as seed per spike, biological yield, flag leaf breadth, days of heading, and days of maturity exhibited relatively high heritability. Notably, grain yield showed high heritability and genetic progress, making it a favourable selection indicator. Several traits, including days of anthesis, days of maturity, and spike length, demonstrated significant positive correlations with yield while also showing significant negative correlations with grain filling period and biological yield. Conversely, these traits showed highly non-significant positive correlations with harvest index, plant height, thousand seeds weight, and chlorophyll content and highly non-significant negative correlations with tiller number and seeds per spike.

Antibacterial and Osteogenic Doxycycline Imprinted Bioglass Microspheres to Combat Bone Infection.

Currently, postoperative infection is a significant challenge in bone and dental surgical procedures, demanding the exploration of innovative approaches due to the prevalence of antibiotic-resistant bacteria. This study aims to develop a strategy for controlled and smart antibiotic release while accelerating osteogenesis to expedite bone healing. In this regard, temperature-responsive doxycycline (DOX) imprinted bioglass microspheres (BGMs) were synthesized. Following the formation of chitosan-modified BGMs, poly N-isopropylacrylamide (pNIPAm) was used for surface imprinting of DOX. The temperature-responsive molecularly imprinted polymers (MIPs) exhibited pH and temperature dual-responsive adsorption and controlled-release properties for DOX. The temperature-responsive MIP was optimized by investigating the molar ratio of N,N'-methylene bis(acrylamide) (MBA, the cross-linker) to NIPAm. Our results demonstrated that the MIPs showed superior adsorption capacity (96.85 mg/g at 35 °C, pH = 7) than nonimprinted polymers (NIPs) and manifested a favorable selectivity toward DOX. The adsorption behavior of DOX on the MIPs fit well with the Langmuir model and the pseudo-second-order kinetic model. Drug release studies demonstrated a controlled release of DOX due to imprinted cavities, which were fitted with the Korsmeyer-Peppas kinetic model. DOX-imprinted BGMs also revealed comparable antibacterial effects against Staphylococcus aureus and Escherichia coli to the DOX (control). In addition, MIPs promoted viability and osteogenic differentiation of MG63 osteoblast-like cells. Overall, the findings demonstrate the significant potential of DOX-imprinted BGMs for use in bone defects. Nonetheless, further in vitro investigations and subsequent in vivo experiments are warranted to advance this research.

An Ultramicroporous Graphene-Based 3D Structure Derived from Cellulose-Based Biomass for High-Performance CO2 Capture.

The use of powered activated carbon is often limited by inconsistent particle sizes and porosities, leading to reduced adsorption efficiencies. In this study, we demonstrated a practical and environmentally friendly method for creating a 3D graphene nanostructure with highly uniform ultramicropores from wood-based biomass through a series of delignification, carbonization, and activation processes. In addition, we evaluated the capture characteristics of this structure for CO2, CH4, and N2 gases as well as its selectivity for binary-mixture gases. Based on textural and chemical analyses, the delignified monolith had a lamellar structure interconnected by cellulose-based fibers. Interestingly, applying the KOH vapor activation technique solely to the delignified samples led to the formation of a monolithic 3D network composed of interconnected graphene sheets with a high degree of crystallinity. Especially, the Act. 1000 sample exhibited a specific surface area of 1480 m2/g and a considerable pore volume of 0.581 cm3/g, featuring consistently uniform ultramicropores over 90% in the range of 3.5-11 Å. The monolithic graphene-based samples, predominantly composed of ultramicropores, demonstrated a notably heightened capture capacity of 6.934 mol/kg at 110 kPa for CO2, along with favorable selectivity within binary gas mixtures (CO2/N2, CO2/CH4, and CO2/CH4). Our findings suggest that this biomass-derived 3D structure has the potential to serve as a monolithic adsorbent in gas separation applications.

High-efficient depletion and separation of histidine-rich proteins via Cu2+-chelated porous polymer microspheres

Depletion and separation of histidine-rich proteins from complicated biosamples are crucial for various downstream applications in proteome research and clinical diagnosis. Herein, porous polymer microspheres coated with polyacrylic acid (SPSDVB-PAA) were fabricated through double emulsion interfacial polymerization technique and followed by immobilization of Cu2+ ions on the surface of SPSDVB-PAA. The as-prepared SPSDVB-PAA-Cu with uniform size and nanoscale pore structure enabled coordination interaction of Cu2+ with histidine residues in his-rich proteins, resulting in high-performance adsorption. As metal affinity adsorbent, the SPSDVB-PAA-Cu exhibited favorable selectivity for adsorbing hemoglobin (Hb) and human serum albumin (HSA) with the maximum adsorption capacities of 152.2 and 100.7 mg g−1. Furthermore, the polymer microspheres were used to isolate histidine-rich proteins from human whole blood and plasma, underscoring their effectiveness. The liquid chromatography tandem mass spectrometry (LC-MS/MS) results indicated that the content of 14 most abundant proteins in human plasma was depleted from 81.6 % to 30.7 % and low-abundance proteins were enriched from 18.4 % to 69.3 % after treatment with SPSDVB-PAA-Cu, illustrating potential application of SPSDVB-PAA-Cu in proteomic research.

Nanoparticle-based delivery of harmine: A comprehensive study on synthesis, characterization, anticancer activity, angiogenesis and toxicity Evaluation

The effective treatment of cancer presents numerous challenges, including drug resistance and the risk of detrimental effects on normal tissues. Harmine, a beta-carboline alkaloid, has demonstrated diverse biological properties. This study aimed to synthesize and characterize harmine encapsulated in polylactic-co-glycolic acid (PLGA) nanoparticles (Ha-PLGA-NPs) to investigate their potential as agents against cancer and angiogenesis. The synthesized Ha-PLGA-NPs were thoroughly characterized, exhibiting a connected rod-shaped crystal which some retaining the spherical shape of nanoparticles with an average size of 302.96 nm. Furthermore, the nanoparticles demonstrated a dispersion index of 0.23 and a surface charge of −16.51 mV. In vitro cytotoxicity assays conducted on the breast cancer cell line (MCF-7) revealed that Ha-PLGA-NPs possessed significant cytotoxic properties, with an observed IC50 value of 87.74 μg/mL. Notably, no substantial cytotoxicity was observed in human foreskin fibroblasts, indicating a favorable selectivity towards cancer cells. Evaluation of the anti-angiogenic activity of Ha-PLGA-NPs demonstrated a concentration-dependent inhibition of angiogenesis. Mechanistic investigations indicated that the observed inhibition was mediated through the regulation of key genes involved in angiogenesis, including caspase 3, caspase 9, VEGF, and VEGF-R. In vivo studies involving dietary administration of Ha-PLGA-NPs in mice revealed improvements in weight gain, feed intake, liver enzyme levels, and redox potential. These findings underscore the potential of Ha-PLGA-NPs as a promising therapeutic agent for cancer treatment. The observed effects are attributed to their ability to induce programmed cell death and inhibit angiogenesis, thus offering a multifaceted approach to combat cancer.

Machine learning-assisted high-throughput screening of MOFs for efficient adsorption and separation of CF4/N2

There is an imperative need for top-performing materials with extraordinary adsorption selectivity and working capacity, in order to achieve productive adsorption of CF4 in a CF4/N2 mixture. In this work, the High-Throughput Grand Canonical Monte Carlo (HT-GCMC) simulation method and the Machine Learning (ML) method were employed to predict and screen the adsorption performance of 10 143 computation-ready experimental metal-organic frameworks (CoRE-MOFs) for separating CF4/N2 mixed gas. Through computational simulation and ML prediction, 15 and 73 highly promising adsorbents were selected out of the 690 randomly sampled MOFs and the CoRE-MOFs database. The selection process was based on criteria that balanced favorable CF4 selectivity, working capacity, and regenerability: selectivity >60, working capacity >70 mg g−1 (0.8 mmol g−1) and regenerability >70%. The maximum observed capacity of the 15 top evaluated metal-organic frameworks (MOFs) was: 52.85 mg g−1 (0.6 mmol g−1) at 1 bar; and 204.90 mg g−1 (2.3 mmol g−1) at 10 bar. The maximum working capacity was 152.06 mg g−1 (1.7 mmol g−1) and the highest selectivity reached was 118.12 (YEGCUJ) and 101.80 (VEHLIE) at 1 bar and 10 bar, respectively. Notably, the most promising MOFs exhibited elevated Zn content relative to the overall MOF population and also possessed a significant nitrogen content. This result should serve as a compelling motivation to further investigate the utilisation of MOFs with a high Zn content (e. g. zeolitic imidazolate frameworks), for enhanced adsorption applications.

Synergized enzyme-ultrasound-assisted aqueous two-phase extraction and antioxidant activity validation of polysaccharides from tobacco waste

A powerful and innovative technique was developed to efficiently extract and refine polysaccharides from tobacco waste. This was achieved through a combination of enzyme and ultrasound-assisted extraction assisted aqueous two-phase extraction (EUAATPE). The formation of an aqueous two-phase system (ATPS) using various salts and ethanol was investigated. ATPS of 18.0 % (NH4)2SO4 (w/w) and 25.0 % ethanol (w/w) was chosen due to its favorable selection extraction ability and high recovery of 93.68 ± 0.40 %. By utilizing both single-factor experiments and response surface method (RSM), the key factors involved in the EUAATPE process were optimized. The optimal conditions were as follows: ultrasonic power 180 W, ultrasonic time 9 min, cellulase concentration 2.0 %, pectinase concentration 1.0 %, extraction temperature 50 °C, extraction time 1.5 h, and liquid-to-solid ratio 30:1 (g/g). Under the optimal conditions, the extraction yield of polysaccharides was 6.72 ± 0.11 (mg/g), and the purity of the polysaccharides from the bottom phase was 78.73 ± 3.17 %. EUAATPE resulted in a significant enhancement in the extraction yield and purity of polysaccharides from tobacco waste compared to traditional methods such as hot water extraction (HWE), ultrasound-assisted extraction (UAE) and enzyme-assisted extraction (EAE). Polysaccharides of tobacco waste obtained from various methods had analogous monosaccharide compositions, different molar ratio compositions and surface structure characteristics. Moreover, all polysaccharides exhibited a certain extent antioxidant activities and polysaccharides from the bottom phase (PBP) extracted by EUAATPE showed superior antioxidant activity. Hence, EUAATPE, being an innovative and eco-friendly extraction technique, presents a productive substitute for extracting and refining polysaccharides from discarded tobacco resources.

Density Functional Study of Electrocatalytic Carbon Dioxide Reduction in Fourth-Period Transition Metal-Tetrahydroxyquinone Organic Framework.

This study investigates the utilisation of organometallic network frameworks composed of fourth-period transition metals and tetrahydroxyquinone (THQ) in electrocatalytic CO2 reduction. Density functional theory (DFT) calculations were employed in analysing binding energies, as well as the stabilities of metal atoms within the THQ frameworks, for transition metal TM-THQs ranging from Y to Cd. The findings demonstrate how metal atoms could be effectively dispersed and held within the THQ frameworks due to sufficiently high binding energies. Most TM-THQ frameworks exhibited favourable selectivity towards CO2 reduction, except for Tc and Ru, which experienced competition from hydrogen evolution reaction (HER) and required solution environments with pH values greater than 5.716 and 8.819, respectively, to exhibit CO2RR selectivity. Notably, the primary product of Y, Ag, and Cd was HCOOH; Mo produced HCHO; Pd yielded CO; and Zr, Nb, Tc, Ru, and Rh predominantly generated CH4. Among the studied frameworks, Zr-THQ displayed values of 1.212 V and 1.043 V, corresponding to the highest limiting potential and overpotential, respectively, while other metal-organic frameworks displayed relatively low ranges of overpotentials from 0.179 V to 0.949 V. Consequently, it is predicted that the TM-THQ framework constructed using a fourth-period transition metal and tetrahydroxyquinone exhibits robust electrocatalytic reduction of CO2 catalytic activity.

The discovery of a novel pyrrolo[2,3-b]pyridine as a selective CDK8 inhibitor offers a new approach against psoriasis

Currently, the drugs used in clinical to treat psoriasis mainly broadly suppress cellular immunity. However, these drugs can only provide temporary and partial symptom relief, they do not cure the condition and may lead to recurrence or even serious toxic side effects. In this study, we describe the discovery of a novel potent CDK8 inhibitor as a treatment for psoriasis. Through structure-based design, compound 46 was identified as the most promising candidate, exhibiting a strong inhibitory effect on CDK8 (IC50 value of 57 nM) along with favourable inhibition against NF-κB. Additionally, it demonstrated a positive effect in an in vitro psoriasis model induced by TNF-α. Furthermore, this compound enhanced the thermal stability of CDK8 and exerted evident effects on the biological function of CDK8, and it had favourable selectivity across the CDK family and tyrosine kinase. This compound showed no obvious inhibitory effect on CYP450 enzyme. Further studies confirmed that compound 46 exhibited therapeutic effect on IMQ-induced psoriasis, alleviated the inflammatory response in mice, and enhanced the expression of Foxp3 and IL-10 in the dorsal skin in vivo. This discovery provides a new strategy for developing selective CDK8 inhibitors with anti-inflammatory activity for the treatment of psoriasis.