The protein phosphatase PC1 dephosphorylates and deactivates CatC to negatively regulate H2O2 homeostasis and salt tolerance in rice.

Catalase (CAT) is often phosphorylated and activated by protein kinases to maintain hydrogen peroxide (H2O2) homeostasis and protect cells against stresses, but whether and how CAT is switched off by protein phosphatases remains inconclusive. Here, we identified a manganese (Mn2+)-dependent protein phosphatase, which we named PHOSPHATASE OF CATALASE 1 (PC1), from rice (Oryza sativa L.) that negatively regulates salt and oxidative stress tolerance. PC1 specifically dephosphorylates CatC at Ser-9 to inhibit its tetramerization and thus activity in the peroxisome. PC1 overexpressing lines exhibited hypersensitivity to salt and oxidative stresses with a lower phospho-serine level of CATs. Phosphatase activity and seminal root growth assays indicated that PC1 promotes growth and plays a vital role during the transition from salt stress to normal growth conditions. Our findings demonstrate that PC1 acts as a molecular switch to dephosphorylate and deactivate CatC and negatively regulate H2O2 homeostasis and salt tolerance in rice. Moreover, knockout of PC1 not only improved H2O2-scavenging capacity and salt tolerance but also limited rice grain yield loss under salt stress conditions. Together, these results shed light on the mechanisms that switch off CAT and provide a strategy for breeding highly salt-tolerant rice.

3 nm-wide Cyanometallate Fe-Co Tape Exhibiting Single-Chain Magnet Behavior.

Treatment of Co(OTf)2·6H2O, Li[(pzTp)FeIII(CN)3], and H3PMo12O40·nH2O in protic solvents afforded two structurally related Fe-Co cyanometallate complexes: [{(pzTp)Fe(CN)3}3Co3(MeOH)10][PMo12O40]·H2O·11MeOH (1, pzTp- = tetra(pyrazolyl)borate) and {[(pzTp)Fe(CN)3]4Co3(MeOH)5(H2O)3}n[HPMo12O40]n·3 nMeOH·6.5nH2O (2). Complex 1 consists of a cyanide-bridged hexanuclear [Fe3Co3] cage, characterized by the fused conjunction of two mutually perpendicular trigonal bipyramids (TBPs, [Fe2Co3] and [Co2Fe3]), while complex 2 showcases an intricate cyanide-bridged Fe-Co tape comprising a central chain backbone of vertex-sharing [Fe2Co3] TBPs alongside peripheral [Fe2Co2] squares. Complex 2 is among the widest one-dimensional coordination assemblies characterized by the single-crystal X-ray diffraction technique. Magnetic studies revealed that complex 2 behaved as a single chain magnet with an effective energy barrier (Ueff/kB) of 46.8 K. Our findings highlight the possibilities in the development of cyanometallate-POM hybrid materials with captivating magnetic properties.

Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway.

AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.

Non-invasive molecular imaging for precision diagnosis of metastatic lymph nodes: opportunities from preclinical to clinical applications.

Lymph node metastasis is an indicator of the invasiveness and aggressiveness of cancer. It is a vital prognostic factor in clinical staging of the disease and therapeutic decision-making. Patients with positive metastatic lymph nodes are likely to develop recurrent disease, distant metastasis, and succumb to death in the coming few years. Lymph node dissection and histological analysis are needed to detect whether regional lymph nodes have been infiltrated by cancer cells and determine the likely outcome of treatment and the patient's chances of survival. However, these procedures are invasive, and tissue biopsies are prone to sampling error. In recent years, advanced molecular imaging with novel imaging probes has provided new technologies that are contributing to comprehensive management of cancer, including non-invasive investigation of lymphatic drainage from tumors, identifying metastatic lymph nodes, and guiding surgeons to operate efficiently in patients with complex lesions. In this review, first, we outline the current status of different molecular imaging modalities applied for lymph node metastasis management. Second, we summarize the multi-functional imaging probes applied with the different imaging modalities as well as applications of cancer lymph node metastasis from preclinical studies to clinical translations. Third, we describe the limitations that must be considered in the field of molecular imaging for improved detection of lymph node metastasis. Finally, we propose future directions for molecular imaging technology that will allow more personalized treatment plans for patients with lymph node metastasis.

Cyanide-Bridged Rope-like Chains Based on Trigonal-Bipyramidal [Fe2Cu3] Subunits.

Extending a selected cyanometalate block into a higher dimensional framework continues to present intriguing challenges in the fields of chemistry and material science. Here, we prepared two rope-like chain compounds of {[(Tp*Me)Fe(CN)3]2Cu2X2(L)}·sol (1, X = Cl, L = (MeCN)0.5(H2O/MeOH)0.5, sol = 2MeCN·1.5H2O; 2, X = Br, L = MeOH, sol = 2MeCN·0.75H2O; Tp*Me = tris(3, 4, 5-trimethylpyrazole)borate) in which the cyanide-bridged trigonal-bipyramidal [Fe2Cu3] subunits were linked with the adjacent ones via two vertex Cu(II) centers, providing a new cyanometallate chain archetype. Direct current magnetic study revealed the presence of ferromagnetic couplings between Fe(III) and Cu(II) ions and uniaxial anisotropy due to a favorable alignment of the anisotropic tricyanoiron(III) units. Moreover, compound 1 exhibits single-chain magnet behavior with an appreciable energy barrier of 72 K, while 2 behaves as a metamagnet, likely caused by the subtle changes in the interchain interactions.

Fibronectin-targeting and metalloproteinase-activatable smart imaging probe for fluorescence imaging and image-guided surgery of breast cancer.

Residual lesions in the tumor bed have been a challenge for conventional white-light breast-conserving surgery. Meanwhile, lung micro-metastasis also requires improved detection methods. Intraoperative accurate identification and elimination of microscopic cancer can improve surgery prognosis. In this study, a smart fibronectin-targeting and metalloproteinase-activatable imaging probe CREKA-GK8-QC is developed. CREKA-GK8-QC possesses an average diameter of 21.7 ± 2.5 nm, excellent MMP-9 protein responsiveness and no obvious cytotoxicity. In vivo experiments demonstrate that NIR-I fluorescence imaging of CREKA-GK8-QC precisely detects orthotopic breast cancer and micro-metastatic lesions (nearly 1 mm) of lungs with excellent imaging contrast ratio and spatial resolution. More notably, fluorescence image-guided surgery facilitates complete resection and avoids residual lesions in the tumor bed, improving survival outcomes. We envision that our newly developed imaging probe shows superior capacity for specific and sensitive targeted imaging, as well as providing guidance for accurate surgical resection of breast cancer.

Manipulating Electron-Transfer Events in [Fe4 Co4 ] Cubes via a Mixed-Ligand Approach: The Impact of Elastic Frustration.

The engineering of intermolecular interaction is challenging but critical for magnetically switchable molecules. Here, we prepared two cyanide-bridged [Fe4 Co4 ] cube complexes via the alkynyl- and alcohol-functionalized trispyrazoyl capping ligands. The alkynyl-functionalized complex 1 exhibited a thermally-induced incomplete metal-to-metal electron transfer (MMET) behaviour at around 220 K, while the mixed alkynyl/alcohol-functionalized cube of 2 showed a complete and abrupt MMET behaviour at 232 K. Remarkably, both compounds showed a long-lived photo-induced metastable state up to 200 K. The crystallographic study demonstrated that the incomplete transition of 1 was likely due to the possible elastic frustration originating from the competition between the anion-propagated elastic interactions and inter-cluster alkynyl-alkynyl & CH-alkynyl interactions, whereas the latter are eliminated in 2 as a result of the partial substitution by the alcohol-functionalized ligand. Additionally, the introduction of chemically distinguishable cobalt centers within the cube unit of 2 did not lead to a two-step but a one-step transition, possibly because of the strong ferroelastic intramolecular interaction through the cyanide bridges.

Polyoxometalate-Assisted Assembly of Pearl-Chain-Like Cyanide-Bridged Single-Chain Magnets.

The introduction of Keggin-type POMs of [PMo12O40]3- or [SiW12O40]4- as counteranions into the FeIII-MII cyanometalate system afforded three chain complexes: [(Tp*)Fe(CN)3Ni(DMF)4]2{[(Tp*)Fe(CN)3Ni(DMF)3(H2O)]2Ni(DMF)4}[PMo12O40]2·14DMF (1, Tp*= hydridotris(3,5-dimethylpyrazol-1-yl)borate) and {[(Tp*)Fe(CN)3M(DMF)3(H2O)]2M(DMF)4}[SiW12O40]·3DMF (2, M = NiII; 3, M = CoII). Complex 1 contains both discrete cationic [Fe2Ni2]2+ squares and less-studied {Fe2Ni3}n pearl chains, namely 3,2-chains, while 2 and 3 consist of pure 3,2-chains due to the replacement of [PMo12O40]3- with [SiW12O40]4- bearing one more negative charge. Magnetic studies revealed that all of the complexes exhibit single-chain-magnet (SCM) behaviors with the effective thermal barriers of Δτ1/kB = 61.6 K (infinite regime) and Δτ2/kB = 36.5 K (finite regime) for 1, Δτ/kB = 46.9 K for 2 (finite), and Δτ/kB = 30.6 K for 3 (finite). The POM moieties may play a pivotal role for the realization of this promising archetype of favoring SCM property: (1) the highly negatively charged POMs may facilitate the formation of the uncommon highly positive "pearl chain"; (2) the nanosized POMs necessarily led to the good isolation of the chains in the title complexes, and (3) the employment of POMs with different charges may regulate the resultant complexes in both structure and magnetism.

Series of Benzoquinone-Bridged Dicobalt(II) Single-Molecule Magnets.

Mononuclear complexes within a particular coordination geometry have been well recognized for high-performance single-molecule magnets (SMMs), while the incorporation of such well-defined geometric ions into multinuclear complexes remains less explored. Using the rigid 2-(di(1H-pyrazol-1-yl)methyl)-6-(1H-pyrazol-1-yl)pyridine (PyPz3) ligand, here, we prepared a series of benzoquinone-bridged dicobalt(II) SMMs [{(PyPz3)Co}2(L)][PF6]2, (1, L = 2,5-dioxo-1,4-benzoquinone (dhbq2-); 2, L = chloranilate (CA2-); and 3, L = bromanilate (BA2-)), in which each Co(II) center adopts a distorted trigonal prismatic (TPR) geometry and the distortion increases with the sizes of 3,6-substituent groups (H (1) < Cl (2) < Br (3)). Accordingly, the magnetic study revealed that the axial anisotropy parameter (D) of the Co ions decreased from -78.5 to -56.5 cm-1 in 1-3, while the rhombic one (E) increased significantly. As a result, 1 exhibited slow relaxation of magnetization under a zero dc field, while both 2 and 3 showed only the field-induced SMM behaviors, likely due to the increased rhombic anisotropy that leads to the serious quantum tunneling of the magnetization. Our study demonstrated that the relaxation dynamics and performances of a multinuclear complex are strongly dependent on the coordination geometry of the local metal ions, which may be engineered by modifying the substituent groups.

[AuI(CN)2]-Armed [FeIII2FeII2] Square Complex Showing Unusual Spin-Crossover Behavior Due to a Symmetry-Breaking Phase Transition.

The incorporation of two different cyanide building blocks of [(TpR)FeIII(CN)3]- and [AuI(CN)2]- into one molecule afforded a novel hexanuclear [FeIII2FeII2AuI2] complex (1·2Et2O), in which the cyanide-bridged [FeIII2FeII2] square was further grafted by two [AuI(CN)2]- fragments as long arms in syn orientations. Complex 1·2Et2O undergoes a gradual spin crossover (SCO) ffrom low-spin (LS) to high-spin (HS) state for the Fe(II) centers upon desolvation. Remarkably, its desolvated phase (1) exhibits a reversible but atypical two-step (sharp-gradual) SCO behavior with considerable hysteresis (21 K). Variable-temperature single-crystal X-ray structural studies reveal that the hysteretic spin transition takes place synchronously with the concerted displacive motions of the molecules, representing another rare example including multistep and hysteretic spin transitions due to the synergetic SCO and structural phase transition.

Repair mechanism of radiation-induced salivary gland injury by hypoxia-pretreated human urine-derived stem cell exosomes.

OBJECTIVE: To explore the protective effect of human urine-derived stem cell exosomes (hUSC-Exos) on radiation-induced salivary gland (SG) injuries in Sprague Dawley rats. METHODS: Fresh adult urine was collected, and primary hUSCs were isolated and identified. The hUSCs were hypoxia-pretreated with 1% oxygen for 24 h and then transferred to a normoxic culture environment for 24 h. The hUSC-Exos were collected and identified for exosomes. A radiation-induced injury model was established in the rats, and exosomes were introduced by local injection in the SG and tail vein. The submandibular gland was excised for morphological observation 1 week later. Immunohistochemical detection of the glandular tissue was conducted by α-smooth muscle actin (a-SMA), stem cell growth factor receptor (c-Kit) staining, and periodic acid-Schiff staining. Qualitative polymerase chain reaction and western blot analysis were adopted to detect the gene and protein expression of Wnt3a, GSK3ß, and Axin. RESULTS: In both the normoxic and hypoxic hUSC-Exo groups, microvesicular structures with bilayer membranes of approximately 80 nm in diameter were detected, and the expressions of CD9 and CD63 were detected by nanoflow cytometry. Compared with the control group, in the radiation-induced injury model group, the expression of a-SMA was significantly higher, the expression of c-Kit was significantly lower, and the expressions of Wnt3a, GSK3ß, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). Compared with the model group, in the normoxic and hypoxic hUSC-Exo groups, the expression of a-SMA was significantly decreased, the expression of c-Kit was significantly increased, and the expressions of Wnt3a, GSK3ß, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). CONCLUSION: Hypoxia-pretreated hUSC-Exos could repair radiation-induced SG injuries by activating the Wnt3a/GSK3ß pathway to suppress the expressions of a-SMA and c-Kit.

[Construction strategies and prospect of the Global Medicinal Plant Stem Cell Bank].

Medicinal plant stem cells are separated from the meristem and vascular cambium of medicinal plants, which can produce active components for preventing and treating diseases and improving body physical functions under certain conditions. Medicinal plant stem cells come from a broad category of medicinal plants, including ethnic medicinal plants, folk medicinal plants, original plants of health products, vegetables, fruits, and other potential medicinal plants. At present, the techniques for the isolation, identification, preservation and culture of medicinal plant stem cells have become increasingly mature, and the mechanism of stem cell differentiation, growth and regulation of secondary metabolites has been studied in depth. Medicinal plant stem cells have a broad application prospect in medicine, health food, food and medical beauty products. As a strategic resource, the construction of the "Global Medicinal Plant Stem Cell Bank" was first proposed to preserve various kinds of medicinal plant resources in the world, and it will go global relying on the internationalization strategy of traditional Chinese medicine. The bank should follow safety, environmental protection, advanced and practical design principles. The main construction contents include the original plant bank, stem cell bank, component resource bank, gene bank, database and resource sharing system, with genetic and data resources incorporated into the scope of protection and utilization. The bank will establish a new strategy for medicinal plant resources protection and regeneration, and provide a new resource for natural products drug discovery and a technology sharing platform for various medicinal plant stem cells. As a resource treasury, a source of innovative technologies and a center of cooperation, it will become the core driving force of the global medicinal plant stem cell industry.

Host-Guest Molecular Interaction Enabled Separation of Large-Diameter Semiconducting Single-Walled Carbon Nanotubes.

Semiconducting single-walled carbon nanotubes (s-SWCNTs) with a diameter of around 1.0-1.5 nm, which present bandgaps comparable to silicon, are highly desired for electronic applications. Therefore, the preparation of s-SWCNTs of such diameters has been attracting great attention. The inner surface of SWCNTs has a suitable curvature and large contacting area, which is attractive in host-guest chemistry triggered by electron transfer. Here we reported a strategy of host-guest molecular interaction between SWCNTs and inner clusters with designed size, thus selectively separating s-SWCNTs of expected diameters. When polyoxometalate clusters of ∼1 nm in size were filled in the inner cavities of SWCNTs, s-SWCNTs with diameters concentrated at ∼1.3-1.4 nm were selectively extracted with the purity of ∼98% by a commercially available polyfluorene derivative. The field-effect transistors built from the sorted s-SWCNTs showed a typical behavior of semiconductors. The sorting mechanisms associated with size-dependent electron transfer from nanotubes to inner polyoxometalate were revealed by the spectroscopic and in situ electron microscopic evidence as well as the theoretical calculation. The polyoxometalates with designable size and redox property enable the flexible regulation of interaction between the nanotubes and the clusters, thus tuning the diameter of sorted s-SWCNTs. The present sorting strategy is simple and should be generally feasible in other SWCNT sorting techniques, bringing both great easiness in dispersant design and improved selectivity.

Transcriptome sequencing analysis of sorghum callus with various regeneration capacities.

MAIN CONCLUSION: The possible molecular mechanisms regulating sorghum callus regeneration were revealed by RNA-sequencing. Plant callus regeneration has been widely applied in agricultural improvement. Recently, callus regeneration has been successfully applied in the genetic transformation of sorghum by using immature sorghum embryos as explants. However, the mechanism underlying callus regeneration in sorghum is still largely unknown. Here, we describe three types of callus (Callus I-III) with different redifferentiation abilities undergoing distinct induction from immature embryos of the Hiro-1 variety. Compared with nonembryonic Callus III, Callus I produced only some identifiable roots, and embryonic Callus II was sufficient to regenerate whole plants. Genome-wide transcriptome profiles were generated to reveal the underlying mechanisms. The numbers of differentially expressed genes for the three types of callus varied from 5906 to 8029. In accordance with the diverse regeneration abilities observed for different types of callus and leaf tissues, the principal component analysis revealed that the gene expression patterns of Callus I and Callus II were different from those of Callus III and leaves regenerated from Callus II. Notably, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses, pharmacological treatment, and substance content determinations revealed that plant ribosomes, lignin metabolic processes, and metabolism of starch and sucrose were significantly enriched, suggesting that these factors are associated with callus regeneration. These results helped elucidate the molecular regulation of three types of callus with different regeneration abilities in sorghum.

The Receptor-Like Cytoplasmic Kinase STRK1 Phosphorylates and Activates CatC, Thereby Regulating H2O2 Homeostasis and Improving Salt Tolerance in Rice.

Salt stress can significantly affect plant growth and agricultural productivity. Receptor-like kinases (RLKs) are believed to play essential roles in plant growth, development, and responses to abiotic stresses. Here, we identify a receptor-like cytoplasmic kinase, salt tolerance receptor-like cytoplasmic kinase 1 (STRK1), from rice (Oryza sativa) that positively regulates salt and oxidative stress tolerance. Our results show that STRK1 anchors and interacts with CatC at the plasma membrane via palmitoylation. CatC is phosphorylated mainly at Tyr-210 and is activated by STRK1. The phosphorylation mimic form CatCY210D exhibits higher catalase activity both in vitro and in planta, and salt stress enhances STRK1-mediated tyrosine phosphorylation on CatC. Compared with wild-type plants, STRK1-overexpressing plants exhibited higher catalase activity and lower accumulation of H2O2 as well as higher tolerance to salt and oxidative stress. Our findings demonstrate that STRK1 improves salt and oxidative tolerance by phosphorylating and activating CatC and thereby regulating H2O2 homeostasis. Moreover, overexpression of STRK1 in rice not only improved growth at the seedling stage but also markedly limited the grain yield loss under salt stress conditions. Together, these results offer an opportunity to improve rice grain yield under salt stress.

Prognostic impact of tumor length in esophageal Cancer: a systematic review and Meta-analysis.

BACKGROUND: In clinical studies, it has been observed that esophageal cancer (EC) patient prognosis can be very different even for those patients with tumors of the same TNM stage. Tumor length has been analysed as a possible independent prognostic factor in many studies, but no unanimous conclusion has been reached. Therefore, this review used a meta-analysis to evaluate the association between tumor length and prognosis in EC patients. METHODS: A systematic search for relevant articles was performed in PubMed, Web of Science, and Embase. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effective measures to estimate the correlation between tumor length and prognosis, including overall survival, disease-free survival, progression-free survival, disease-specific survival, and cancer-specific survival. STATA 15.0 software was used to perform the meta-analysis and the data synthesis. RESULTS: Finally, 41 articles with 28,973 patients were included in our study. The comprehensive statistical results showed that long tumors are an independent prognostic parameter associated with poor overall survival (OS) (HR = 1.30; 95% CI: 1.21-1.40, p < .001) and disease-free survival (DFS) (HR = 1.38; 95% CI: 1.18-1.61, p < .001) in EC patients. Subgroup analyses also suggested a significant correlation between long tumors and poor OS. Sensitivity analysis and publication bias evaluation confirmed the reliability and stability of the results. Similar results were obtained in the analyses of progression-free survival (PFS), disease-specific survival (DSS), and cancer-specific survival (CSS). CONCLUSION: The results of this meta-analysis showed that long tumors were related to poor OS, DFS, PFS, DSS and CSS in EC patients. Tumor length might be an important predictor of prognosis in EC patients, and it can be used as an independent staging index. Further well-designed and large-scale prospective clinical studies are needed to confirm these findings.

Anion-Dependent Electron Transfer in the Cyanide-Bridged [Fe2Co2] Capsules.

A family of molecular capsules, {[(Tp*)Fe(CN)3Co(bpyC═N(CH2)7N═Cbpy)]2[X]2}·sol (1, X = ClO4, sol = 6DMF; 2, X = PF6, sol = 6DMF; 3, X = OTf, sol = 6DMF; 4, X = BPh4, sol = 2DMF; Tp* = hydrotris(3,5-dimethylpyrazol-1-yl)borate; bpy = 2,2'-bipyridine), were prepared via the Schiff-base condensation of the aldehyde-substituted bpy (bpyCHO) and 1,7-diaminoheptane (H2N(CH2)7NH2). All the complexes contain the same cyanide-bridged cationic square cores ([Fe2Co2]2+), which are encapsuled by the flexible alkyl chains. Variable-temperature single-crystal X-ray diffraction, FT-IR spectra, and magnetic studies reveal the abrupt and complete, thermo- and photo-induced electron-transfer-coupled spin transition for 1-3, while the pure high-spin phase for 4. Such distinct behavior is attributed to the effective long-range cooperative interactions mediated by the intercluster π-π couplings in 1-3, which, however, are significantly blocked in 4 due to the steric effect of interstitial BPh4- anions. Furthermore, the shift in the thermally induced transition temperatures of 254 K for 1, 233 K for 2, and 187 K for 3, respectively, is likely correlated to the variable H···O and H···F interactions between the solvent molecules, anions, and the bipyridine ligands of the [Fe2Co2] squares, suggesting the significant anion-dependent effect in such a system.

A Dicobalt(II) Single-Molecule Magnet via a Well-Designed Dual-Capping Tetrazine Radical Ligand.

The recent years have witnessed the glory development for the construction of high-performance mononuclear single molecule magnets (SMMs) within a specific coordination geometry, which, however, is not well applied in cluster-based SMMs due to the synthetic challenges. Given that the monocobalt(II) complexes within a trigonal-prismatic (TPR) coordination geometry have been classified as excellent SMMs with huge axial anisotropy (D ≈ -100 cm-1), here we designed and synthesized a new dual-capping tetrazine ligand, 3,6-bis(6-(di(1H-pyrazol-1-yl)methyl)pyridin-2-yl)-1,2,4,5-tetrazine (bpptz), and prepared a novel dicobalt(II) complex, [Cp2CoIII][{(hfac)CoII}2(bpptz•-)][hfac]2·2Et2O (1, hfac = hexafluoroacetylacetonate). In the structure of 1, the bpptz•- radical ligand enwraps two Co(II) centers within quasi-TPR geometries, which are further bridged by the tetrazine radical in the trans mode. The magnetic study revealed that the interaction between the Co centers and the tetrazine radical is strongly antiferromagnetic with a coupling constant (J) of -65.8 cm-1 (in the -2J formalism). Remarkably, 1 exhibited the typical SMM behavior with an effective energy barrier of 69 cm-1 under a 1.5 kOe dc field, among the largest for polynuclear transition metal SMMs. In addition, DFT and ab initio calculations suggested that the presence of a strong Co(II)-radical magnetic interaction effectively quenches the QTM effect and enhances the barrier height for the magnetization reversal.

Strong Coupling and Slow Relaxation of the Magnetization for an Air-Stable [Co4] Square with Both Tetrazine Radicals and Azido Bridges.

Introducing both tetrazine radical and azido bridges afforded two air-stable square complexes [MII4(bpztz•-)4(N3)4] (MII = Zn2+, 1; Co2+, 2; bpztz = 3,6-bis(3,5-dimethylpyrazolyl)-1,2,4,5-tetrazine), where the metal ions are cobridged by µ1,1-azido bridges and tetrazine radicals. Magnetic studies revealed strong antiferromagnetic metal-radical interaction with a coupling constant of -64.7 cm-1 in the 2J formalism in 2. Remarkably, 2 exhibits slow relaxation of magnetization with an effective barrier for spin reverse of 96 K at zero applied field.

ZLM-7 inhibits the occurrence and angiogenesis of breast cancer through miR-212-3p/Sp1/VEGFA signal axis.

BACKGROUND: Breast cancer (BC) is a common malignant tumor with poor prognosis. Angiogenesis is related to the growth and progression of solid tumors and associated with prognosis. ZLM-7, SP1, VEGFA and miR-212-3p were associated with BC angiogenesis and proliferation, however the detailed mechanism was not clear. This study aimed to reveal the regulatory mechanism of angiogenesis of BC. METHODS: BC cell lines were treated with 10 nM ZLM-7 for 8 h. We detected protein expression level by western blot and RNA expression level by qRT-PCR. Overexpression or inhibition of miR-212-3p is performed using miR-212-3p mimics or miR-212-3p inhibitor, Sp1 overexpression using pcDNA3.1 vector. Angiogenesis was analyzed by co-culturing BC cell lines and HUVEC cells. To evaluate regulatory relationship between miR-212-3p and Sp1, dual luciferase assay was performed. Besides, the direct interaction between Sp1 and VEGFA was analyzed by ChIP. Migration and invasion were analyzed by transwell assay and proliferation was detected by clone formation assay. In mice xenograft model developed using BC cells, we also detected angiogenesis marker CD31 through immunohistochemistry. RESULTS: ZLM-7 up-regulated miR-212-3p and inhibited invasion, migration, proliferation and angiogenesis of BC, while miR-212-3p inhibitor antagonized such effects. Binding sequence was revealed between miR-212-3p and Sp1, and expression of Sp1 was inhibited by miR-212-3p on both protein and mRNA level. Sp1 could interact with VEGFA and promoted its expression. Overexpression of miR-212-3p inhibited migration, invasion, proliferation and angiogenesis of BC cell lines, while Sp1 overexpression showed the opposite effect and could antagonize these effects of miR-212-3p overexpression. ZLM-7 decreased VEGFA expression, which was rescued by co-transfection with miR-212-3p inhibitor. Similar, ZLM-7 could inhibit tumor growth and angiogenesis through the miR-212-3p/Sp1/VEGFA axis in vivo. CONCLUSIONS: ZLM-7 could directly up-regulate miR-212-3p in BC. MiR-212-3p could inhibit VEGFA expression through Sp1, thereby inhibiting angiogenesis and progression of BC.