Acid precipitation-hydrothermal synthesis of needle-like hydroxyapatite for protein adsorption from waste phosphogypsum.

In order to promote the high-value utilization of waste phosphogypsum (PG), hydroxyapatite was directly synthesized from PG by acid precipitation-hydrothermal method (PGHAP), which was used for the adsorption of bovine serum albumin (BSA) and lysozyme (LYS). The synthesized PGHAP was characterized by XRD, SEM, FTIR and BET, and the effects of various factors on protein adsorption capacity were studied. The results showed that PGHAP exhibits a clear needle-like morphology, high crystallinity, and an average size of about 200 nm. The pH had the greatest effect on the adsorption of protein, and the highest adsorption capacity was obtained at pH 4.0. In addition, the adsorption mechanism of protein on PGHAP was explored by adsorption kinetics and adsorption isotherm. The adsorption of protein on PGHAP conforms to the Intra-particle diffusion model kinetic model, the maximum adsorption capacity of protein on PGHAP can reach 31 mg/g, which is comparable to other adsorbents in this field. In addition, the adsorption behaviour of PGHAP on protein is more appropriately described by Langmuir isotherm model, which indicates that the binding site with uniform energy on the surface of PGHAP realizes the monolayer adsorption of protein. The main adsorption mechanisms are ion exchange, co-precipitation, complexation reaction and so on. Therefore, the needle-like PGHAP synthesized from waste PG is a protein adsorbent with industrial application potential.

Harnessing 4f Electron Itinerancy for Integrated Dual-Band Redox Systems Boosts Lithium-Oxygen Batteries Electrocatalysis.

In-depth comprehension and manipulation of band occupation at metal centers are crucial for facilitating effective adsorption and electron transfer in lithium-oxygen battery (LOB) reactions. Rare earth elements play a unique role in band hybridization due to their deep orbitals and strong localization of 4f electrons. Herein, we anchor single Ce atoms onto CoO, constructing a highly active and stable catalyst with d-f a dual-band redox center. It is discovered that the itinerant behavior of 4f electrons introduces an enhanced spin-orbit coupling effect, which facilitates ideal σ/π bonding and flexible adsorption between the Ce/Co active sites and *O. Simultaneously, the injection of localized Ce 4f electrons strengthens the orbital bonding capacity of Co-O, effectively inhibits the dissolution of Co sites and improves the structural stability of the cathode material. Bracingly, the Ce1/CoO-based LOB exhibits an ultra-low charge-discharge polarization (0.46 V) and stable cyclic performance (1088 hours). This work breaks through the traditional limitations in catalyst activity and stability, providing new strategies and theoretical insights for developing high-performance LOBs powered by rare-earth elements.

Interleukin-12 sustained release system promotes hematopoietic recovery after radiation injury.

The continuous production of mature blood cell lineages is maintained by hematopoietic stem cells but they are highly susceptible to damage by ionizing radiation (IR) that induces death. Thus, devising therapeutic strategies that can mitigate hematopoietic toxicity caused by IR would benefit acute radiation syndrome (ARS) victims and patients receiving radiotherapy. Herein, we describe the preparation of an injectable hydrogel formulation based on Arg-Gly-Asp-alginate (RGD-Alg) and Laponite using a simple mixing method that ensured a slow and sustained release of interleukin-12 (IL-12) (RGD-Alg/Laponite@IL-12). The local administration of RGD-Alg/Laponite@IL-12 increased survival rates and promoted the hematopoietic recovery of mice who had received sublethal-dose irradiation. Local intra-bone marrow (intra-BM) injection of RGD-Alg/Laponite@IL-12 hydrogel effectively stimulated IL12 receptor-phosphoinositide 3-kinase/protein kinase B (IL-12R-PI3K/AKT) signaling axis, which promoted proliferation and hematopoietic growth factors secretion of BM mesenchymal stem/stromal cells. This signaling axis facilitates the repair of the hematopoietic microenvironment and plays a pivotal role in hematopoietic reconstitution. In conclusion, we describe a biomaterial-sustained release of IL-12 for the treatment of irradiated hematopoietic injury and provide a new therapeutic strategy for hematopoietic ARS.

Promoting CO2 Electroreduction to Hydrocarbon Products via Sulfur-Enhanced Proton Feeding in Atomically Precise Thiolate-Protected Cu Clusters.

Thiolate-protected Cu clusters with well-defined structures and stable low-coordinated Cu+ species exhibit remarkable potential for the CO2RR and are ideal model catalysts for establishing structure-electrocatalytic property relationships at the atomic level. However, extant Cu clusters employed in the CO2RR predominantly yield 2e- products. Herein, two model Cu4(MMI)4 and Cu8(MMI)4(tBuS)4 clusters (MMI = 2-mercapto-1-methylimidazole) are prepared to investigate the synergistic effect of Cu+ and adjacent S sites on the CO2RR. Cu4(MMI)4 can reduce CO2 to deep-reduced products with a 91.0% Faradaic efficiency (including 53.7% for CH4) while maintaining remarkable stability. Conversely, Cu8(MMI)4(tBuS)4 shows a remarkable preference for C2+ products, achieving a maximum FE of 58.5% with a C2+ current density of 152.1 mA∙cm-2. In situ XAS and ex situ XPS spectra reveal the preservation of Cu+ species in Cu clusters during CO2RR, extensively enhancing the adsorption capacity of *CO intermediates. Moreover, kinetic analysis and theoretical calculations confirm that S sites facilitate H2O dissociation into *H species, which directly participate in the protonation process on adjacent Cu sites for the protonation of *CO to *CHO. This study highlights the important role of Cu-S dual sites in Cu clusters and provides mechanistic insights into the CO2RR pathway at the atomic level.

High-Sensitivity Differential Sensor for Characterizing Complex Permittivity of Liquids Based on LC Resonators.

This paper proposes a high-sensitivity microstrip differential sensor for measuring the complex permittivity of liquids. The prototype of the differential sensor was formed by cascading two LC resonators on a microstrip transmission line based on stepped impedance. A strong electric field was found to be distributed in the circular patch of the LC resonator; therefore, a cylindrical micropore was set in the center of the circular LC resonator to measure the dielectric sample, which maximized the disturbance of the dielectric sample on the sensor. By optimizing the size of the circular LC resonator, a high-sensitivity sensor circuit was designed and manufactured. The complex permittivity of the test sample was calculated by measuring the transmission coefficient of different molar concentrations of ethanol-water solutions. The experimental results show that the designed differential sensor can accurately measure the complex permittivity of liquid materials with an average sensitivity of 0.76%.

Tumor microenvironment activation amplify oxidative stress promoting tumor energy remodeling for mild photothermal therapy and cuproptosis.

Tumor metabolic reprogramming requires high levels of adenosine triphosphate (ATP) to maintain treatment resistance, which poses major challenges to chemotherapy and photothermal therapy. Especially, high levels of ATP promote copper ion efflux for limiting the curative effect of cuproptosis. Here, an H2S-responsive mesoporous Cu2Cl(OH)3-loading chemotherapeutic cisplatin (CDDP) was synthesized, and the final nanoparticle, CDDP@Cu2Cl(OH)3-CDs (CDCuCDs), was encapsulated by electrostatic action with carbon dots (CDs). CDCuCDs reacted with overproduction H2S in colon tumor to produce photothermic copper sulfide for photothermal therapy. CDDP was released by lysis to achieve chemotherapeutic effects. Importantly, CDDP elevated H2O2 levels in cells through a cascade reaction and continuously transforms H2O2 into highly cytotoxic •OH through chemodynamic therapy between H2O2 and Cu+, which enables nanoparticles to generate •OH and improve the chemotherapeutic efficacy. Highly toxic •OH disrupts mitochondrial homeostasis, prohibiting it from performing normal energy-supplying functions. Down-regulated ATP inhibits heat shock protein expression, which promotes the therapeutic effect of mild photothermal therapy and reduces the efflux of intracellular copper ions, thus improving the therapeutic effect of cuproptosis. Our research provides a potential therapeutic strategy using overproduction H2S responses in tumors, allowing tumor microenvironment-activated •OH nanogenerators to promote tumor energy remodeling for cancer treatment.

Enantioselective Synthesis of Oxazocines via MQ-Phos Enabled Palladium-Catalyzed Asymmetric Formal [4+4]-Cycloadditions.

Oxazocines are key structural intermediates in the synthesis of natural products and pharmaceutical molecules. However, the synthesis of oxazocines especially in a highly enantioselective manner, is a long-standing formidable challenge due to unfavorable energetics involved in cyclization. Herein, a series of new PNP-Ligand P-chiral stereocenter is first designed and synthesized, called MQ-Phos, and successfully applied it in the Pd-catalyzed enantioselective higher-order formal [4+4]-cycloaddition of α, ß-unsaturated imines with 2-(hydroxymethyl)-1-arylallyl carbonates. The reaction features mild conditions, excellent regio- and enantiocontrol and a broad substrate scope (54 examples). Various medium-sized rings can be afforded in moderate to excellent yields (up to 92%) and excellent enantioselectivity (up to 99% ee). The newly developed MQ-Phos is critical for synthesis of the medium-sized ring in excellent catalytic reactivity and enantioselectivity.

Synthesis and bioactivity evaluation of mirror isomer salidroside derivatives as potent antioxidant and anti-inflammatory agents.

A series of derivatives of salidroside with mirror isomer glucose and different phenyl moieties were synthesized by Schmidt glycosylation in satisfactory yields, and their antioxidant and anti-inflammatory activities were evaluated by using LPS-induced RAW264.7 cells. One of the synthesized derivatives ʟ-Sal-4, bearing ʟ-glycosyl and -OMe modification at the phenyl ring, exhibited high activity in inhibiting the production of pro-inflammatory cytokines and oxidative stress biomarker MDA as well as in enhancing the activity of SOD enzyme, compared with the natural product and its corresponding ᴅ-enantiomer. Further proteomic analysis suggested that ʟ-Sal-4 exerted its anti-inflammatory activity through metabolic reprogramming. The in vitro activity showed that ʟ-Sal-4 is a potent antioxidant and anti-inflammatory agent. Our finding indicated that the ʟ-glucose-derived salidroside might be a promising lead compound in the development of salidroside derivatives as therapeutic agents.

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines.

BACKGROUND: Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26. However, the positive regulators of ANKRD26 are still unknown. AIM: To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription. METHODS: Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26. Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26. Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients. RESULTS: In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26. Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26. Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26. In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients. CONCLUSION: We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.

GCN5 mediates DNA-PKcs crotonylation for DNA double-strand break repair and determining cancer radiosensitivity.

BACKGROUND: DNA double-strand break (DSB) induction and repair are important events for determining cell survival and the outcome of cancer radiotherapy. The DNA-dependent protein kinase (DNA-PK) complex functions at the apex of DSBs repair, and its assembly and activity are strictly regulated by post-translation modifications (PTMs)-associated interactions. However, the PTMs of the catalytic subunit DNA-PKcs and how they affect DNA-PKcs's functions are not fully understood. METHODS: Mass spectrometry analyses were performed to identify the crotonylation sites of DNA-PKcs in response to γ-ray irradiation. Co-immunoprecipitation (Co-IP), western blotting, in vitro crotonylation assays, laser microirradiation assays, in vitro DNA binding assays, in vitro DNA-PK assembly assays and IF assays were employed to confirm the crotonylation, identify the crotonylase and decrotonylase, and elucidate how crotonylation regulates the activity and function of DNA-PKcs. Subcutaneous xenografts of human HeLa GCN5 WT or HeLa GCN5 siRNA cells in BALB/c nude mice were generated and utilized to assess tumor proliferation in vivo after radiotherapy. RESULTS: Here, we reveal that K525 is an important site of DNA-PKcs for crotonylation, and whose level is sharply increased by irradiation. The histone acetyltransferase GCN5 functions as the crotonylase for K525-Kcr, while HDAC3 serves as its dedicated decrotonylase. K525 crotonylation enhances DNA binding activity of DNA-PKcs, and facilitates assembly of the DNA-PK complex. Furthermore, GCN5-mediated K525 crotonylation is indispensable for DNA-PKcs autophosphorylation and the repair of double-strand breaks in the NHEJ pathway. GCN5 suppression significantly sensitizes xenograft tumors of mice to radiotherapy. CONCLUSIONS: Our study defines K525 crotonylation of DNA-PKcs is important for the DNA-PK complex assembly and DSBs repair activity via NHEJ pathway. Targeting GCN5-mediated K525 Kcr of DNA-PKcs may be a promising therapeutic strategy for improving the outcome of cancer radiotherapy.

H2S-driven chemotherapy and mild photothermal therapy induced mitochondrial reprogramming to promote cuproptosis.

The elevated level of hydrogen sulfide (H2S) in colon cancer hinders complete cure with a single therapy. However, excessive H2S also offers a treatment target. A multifunctional cascade bioreactor based on the H2S-responsive mesoporous Cu2Cl(OH)3-loaded hypoxic prodrug tirapazamine (TPZ), in which the outer layer was coated with hyaluronic acid (HA) to form TPZ@Cu2Cl(OH)3-HA (TCuH) nanoparticles (NPs), demonstrated a synergistic antitumor effect through combining the H2S-driven cuproptosis and mild photothermal therapy. The HA coating endowed the NPs with targeting delivery to enhance drug accumulation in the tumor tissue. The presence of both the high level of H2S and the near-infrared II (NIR II) irradiation achieved the in situ generation of photothermic agent copper sulfide (Cu9S8) from the TCuH, followed with the release of TPZ. The depletion of H2S stimulated consumption of oxygen, resulting in hypoxic state and mitochondrial reprogramming. The hypoxic state activated prodrug TPZ to activated TPZ (TPZ-ed) for chemotherapy in turn. Furthermore, the exacerbated hypoxia inhibited the synthesis of adenosine triphosphate, decreasing expression of heat shock proteins and subsequently improving the photothermal therapy. The enriched Cu2+ induced not only cuproptosis by promoting lipoacylated dihydrolipoamide S-acetyltransferase (DLAT) heteromerization but also performed chemodynamic therapy though catalyzing H2O2 to produce highly toxic hydroxyl radicals ·OH. Therefore, the nanoparticles TCuH offer a versatile platform to exert copper-related synergistic antitumor therapy.

Blocking OLFM4/galectin-3 axis in placental polymorphonuclear myeloid-derived suppressor cells triggers intestinal inflammation in newborns.

Fetal growth restriction (FGR) is a major cause of premature and low-weight births, which increases the risk of necrotizing enterocolitis (NEC); however, the association remains unclear. We report a close correlation between placental polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and NEC. Newborns with previous FGR exhibited intestinal inflammation and more severe NEC symptoms than healthy newborns. Placental PMN-MDSCs are vital regulators of fetal development and neonatal gut inflammation. Placental single-cell transcriptomics revealed that PMN-MDSCs populations and olfactomedin-4 gene (Olfm4) expression levels were significantly increased in PMN-MDSCs in later pregnancy compared to those in early pregnancy and non-pregnant females. Female mice lacking Olfm4 in myeloid cells mated with wild-type males showed FGR during pregnancy, with a decreased placental PMN-MDSCs population and expression of growth-promoting factors (GPFs) from placental PMN-MDSCs. Galectin-3 (Gal-3) stimulated the OLFM4-mediated secretion of GPFs by placental PMN-MDSCs. Moreover, GPF regulation via OLFM4 in placental PMN-MDSCs was mediated via hypoxia inducible factor-1α (HIF-1α). Notably, the offspring of mothers lacking Olfm4 exhibited intestinal inflammation and were susceptible to NEC. Additionally, OLFM4 expression decreased in placental PMN-MDSCs from pregnancies with FGR and was negatively correlated with neonatal morbidity. These results revealed that placental PMN-MDSCs contributed to fetal development and ameliorate newborn intestinal inflammation.

Iodosylbenzene-Promoted Glycosylation with Selenoglycosides: Application in One-Pot Glycosylation.

A novel method for the glycosylation of selenoglycosides activated by iodosylbenzene was developed. The glycosylation reaction conditions were mild, fast, and efficient, with a high tolerance to diverse protecting groups and a wide substrate scope, which is advantageous for synthesizing complex glycosides. In addition, selenoglycosides were shown to be orthogonal to thioglycosides under the promotion of iodosylbenzene. Notably, a high yield of the poorly reactive glucuronidation reaction product was obtained by acetyl-protected selenoglycoside. Finally, the orthogonal one-pot synthesis of ß-(1→6) oligoglucans demonstrated the usefulness of this method in oligosaccharide synthesis.

Active Micro-Nano-Collaborative Bioelectronic Device for Advanced Electrophysiological Recording.

The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience. In recent years, active micro/nano-bioelectronic devices have undergone significant advancements, thereby facilitating the study of electrophysiology. The distinctive configuration and exceptional functionality of these active micro-nano-collaborative bioelectronic devices offer the potential for the recording of high-fidelity action potential signals on a large scale. In this paper, we review three-dimensional active nano-transistors and planar active micro-transistors in terms of their applications in electro-excitable cells, focusing on the evaluation of the effects of active micro/nano-bioelectronic devices on electrophysiological signals. Looking forward to the possibilities, challenges, and wide prospects of active micro-nano-devices, we expect to advance their progress to satisfy the demands of theoretical investigations and medical implementations within the domains of cardiology and neuroscience research.

Plasma and urine proteomics and gut microbiota analysis reveal potential factors affecting COVID-19 vaccination response.

The efficacy of COVID-19 vaccination relies on the induction of neutralizing antibodies, which can vary among vaccine recipients. In this study, we investigated the potential factors affecting the neutralizing antibody response by combining plasma and urine proteomics and gut microbiota analysis. We found that activation of the LXR/FXR pathway in plasma was associated with the production of ACE2-RBD-inhibiting antibodies, while urine proteins related to complement system, acute phase response signaling, LXR/FXR, and STAT3 pathways were correlated with neutralizing antibody production. Moreover, we observed a correlation between the gut microbiota and plasma and urine proteins, as well as the vaccination response. Based on the above data, we built a predictive model for vaccination response (AUC = 0.85). Our study provides insights into characteristic plasma and urine proteins and gut microbiota associated with the ACE2-RBD-inhibiting antibodies, which could benefit our understanding of the host response to COVID-19 vaccination.

Association of Placental Tissue Metabolite Levels with Gestational Diabetes Mellitus: a Metabolomics Study.

The purpose of the study is to investigate the metabolic characteristics of placental tissue in patients diagnosed with gestational diabetes mellitus (GDM). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was employed to qualitatively and quantitatively analyze the metabolites in placental tissues obtained from 25 healthy pregnant women and 25 pregnant women diagnosed with GDM. Multilevel statistical methods are applied to process intricate metabolomics data. Meanwhile, we applied machine learning techniques to identify biomarkers that could potentially predict the risk of long-term complications in patients with GDM as well as their offspring. We identified 1902 annotated metabolites, out of which 212 metabolites exhibited significant differences in GDM placentas. In addition, the study identifies a set of risk biomarkers that effectively predict the likelihood of long-term complications in both pregnant women with GDM and their offspring. The accuracy of this panel was measured by the area under the receiver operating characteristic curve (ROC), which was found to be 0.992 and 0.960 in the training and validation sets, respectively. This study enhances our understanding of GDM pathogenesis through metabolomics. Furthermore, the panel of risk markers identified could prove to be a valuable tool in predicting potential long-term complications for both GDM patients and their offspring.

Strong Interfacial Chemical Bonding in Regulating Electron Transfer and Stabilizing Catalytic Sites in a Metal-Semiconductor Schottky Junction for Enhanced Photocatalysis.

The weak electronic interaction at metal-photocatalyst heterointerfaces often compromises solar-to-fuel performance. Here, a trifunctional Schottky junction, involving chemically stabilized ultrafine platinum nanoparticles (Pt NPs, ≈3 nm in diameter) on graphitic carbon nitride nanosheets (CNs) is proposed. The Pt-CN electronic interaction induces a 1.5% lattice compressive strain in Pt NPs and maintains their ultrafine size, effectively preventing their aggregation during photocatalytic reactions. Density functional theory calculations further demonstrate a significant reduction in the Schottky barrier at the chemically bonded CN-Pt heterointerface, facilitating efficient interfacial electron transfer, as supported by femtosecond transient absorption spectra (fs-TAS) measurements. The combined effects of lattice strain, stabilized Pt NPs, and efficient interfacial charge transport collaboratively enhance the photocatalytic performance, leading to over an 11-fold enhancement in visible light H2 production (8.52 mmol g-1 h-1) compared to the CN nanosheets with the in situ photo-deposited Pt NPs (0.76 mmol g-1 h-1). This study highlights the effectiveness of strong metal-semiconductor electronic interactions and underscores the potential for developing high-efficiency photocatalysts.

Stereocontrolled Synthesis of α-3-Deoxy-d-manno-oct-2-ulosonic Acid (α-Kdo) Glycosides Using C3-p-Tolylthio-Substituted Kdo Donors: Access to Highly Branched Kdo Oligosaccharides.

3-Deoxy-d-manno-oct-2-ulosonic acid (Kdo) is an eight-carbon monosaccharide found widely in bacterial lipopolysaccharides (LPSs) and capsule polysaccharides (CPSs). We developed an indirect method for the stereoselective synthesis of α-Kdo glycosides with a C3-p-tolylthio-substituted Kdo phosphite donor. The presence of the p-tolylthio group enhanced the reactivity, suppressed the formation of elimination by-products (2,3-enes), and provided complete α-stereocontrol. A variety of Kdo α-glycosides were synthesized by our method in excellent yields (up to 98 %). After glycosylation, the p-tolylthio group can be efficiently removed by free-radical reduction. Subsequently, the orthogonality of the phosphite donor and thioglycoside donor was demonstrated by the one-pot synthesis of a trisaccharide in Helicobacter pylori and Neisseria meningitidis LPS. Moreover, an efficient total synthesis route to the challenging 4,5-branched Kdo trisaccharide in LPSs from several A. baumannii strains was highlighted. To demonstrate the high reactivity of our approach further, the highly crowded 4,5,7,8-branched Kdo pentasaccharide was synthesized as a model molecule for the first time. Additionally, the reaction mechanism was investigated by DFT calculations.

Design and synthesis of doublecortin-like kinase 1 inhibitors and their bioactivity evaluation.

Doublecortin-like kinase 1 (DCLK) is a microtubule-associated serine/threonine kinase that is upregulated in a wide range of cancers and is believed to be related to tumour growth and development. Upregulated DCLK1 has been used to identify patients at high risk of cancer progression and tumours with chemotherapy-resistance. Moreover, DCLK1 has been identified as a cancer stem cell (CSC) biomarker in various cancers, which has received considerable attention recently. Herein, a series of DCLK1 inhibitors were prepared based on the previously reported XMD8-92 structure. Among all the synthesised compounds, D1, D2, D6, D7, D8, D12, D14, and D15 showed higher DCLK1 inhibitory activities (IC50 40-74 nM) than XMD8-92 (IC50 161 nM). Compounds D1 and D2 were selective DCLK1 inhibitors as they showed a rather weak inhibitory effect on LRRK2. The antiproliferative activities of these compounds were also preliminarily evaluated. The structure-activity relationship revealed by our compounds provides useful guidance for the further development of DCLK1 inhibitors.

Enhanced Direct Exchange Interaction and Hybridization by Single-Atom Linkers for High Curie Temperature and Superior Visible-Light Harvesting in Cr3(CN3)2.

Designing two-dimensional (2D) ferromagnetic (FM) semiconductors with elevated Curie temperature, high carrier mobility, and strong light harvesting is challenging but crucial to the development of spintronics with multifunctionalities. Herein, we show first-principles computation evidence of the 2D metal-organic framework Kagome ferromagnet Cr3(CN3)2. Monolayer Cr3(CN3)2 is predicted to be an FM semiconductor with a record-high Curie temperature of 943 K owing to the use of a single-atom linker (N), which results in strong direct d-p exchange interaction and hybridization between dyz/xz and pz of Cr and N, as well as excellent matching characteristics in energy and symmetry. The single-atom linker structural feature also leads to notable band dispersion and a relatively high carrier mobility of 420 cm2 V-1 s-1. Moreover, under the in-plane strain, 2D Cr3(CN3)2 can be tuned to possess a strong visible-light-harvesting functionality. These novel properties render monolayer Cr3(CN3)2 a distinct 2D ferromagnet with high potential for the development of multifunctional spintronics.