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Controllable synthesis of sophisticated aggregations has attracted wide attention from scientists. In this work, homo- and heterometallic {Co III Co II 12 M II 6 } ( M = Co II /Cd II ) aggregates with similar skeletons, composed of two [Co 3 M 3 (dpbt) 3 ] peripheries and a central [Co 7 (OH) 8 ] vertex-fused double-cubane, were constructed from prefabricated {Co 14 } clusters and characterized by single-crystal X-ray diffraction and XPS, ICP-MS, SEM (EDX), and so on. And then, the structure and magnetic differences of them had been further analyzed under dotted with paramagnetic Co II ions and/or diamagnetic Cd II ions. Interestingly, the spin canting behavior in {Co III Co II 18 } was suppressed in {Co III Co II 12 Cd II 6 } , upon the introducing of Cd II ions.

Hierarchical supramolecular frameworks are being designed and constructed for various applications, yet the controlled assembly and process understanding incorporating giant building blocks remains a great challenge. Here, we report a strategy of "rivet" substitution and "hinge" linkage for the controlled assembly of the hierarchical supramolecular framework. The replacement of two "rivet" ethylene glycol (EG) molecules for triangular prism [Zn 9 ] (a small block in 1) with a 1,3-propanediol (PDO) provides space for a "hinge" linkage from adjacent ligands, thus providing a hierarchical (from micro- to mesopores, from the internal cavity to external surface) supramolecular framework (2) based on a coordinative subblock with the record number of zinc ions ([Zn 54 ]). Time-dependent powder X-ray diffraction and ESI-MS technology were used to assess the in situ evolution process: logically progressing from [Zn 9 ] to [Zn 18 ], then to [Zn 27 ], and finally to [Zn 54 ]. The sequential transformation entails two types of half-opening cavities and two types of internal microcages. Further aggregation of [Zn 54 ] in dia topology engenders the formation of a one-dimensional channel (10 Å), and an additional mesocage with a volume of 16 × 16 × 55 Å 3 . The diverse pore system exhibits an impressive uptake capability (3.19 g g -1 ) for iodine vapor at 75 °C and effective ethylene purification. Our investigations represent a valuable avenue for assembling a giant subblock and hierarchical supramolecular framework, facilitating multi-functional molecular accommodation., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Since the concept of metal ion stimulation-mediated chemodynamic therapy was proposed by Bu and Shi's group in 2016, increasing attention has been directed toward the fabrication of efficient, safe and stable Fenton/Fenton-like catalysts to advance clinical translation. In particular, metal-based complexes with inherent metal catalytic centers have received extensive attention as potential alternatives/complements for traditional CDT agents. Among them, copper-based complexes, which possess excellent redox properties, extensive adaptability and abundant availability, enable the efficient generation of ROS through Fenton-like reactions in CDT, thereby causing oxidative damage to lipids, proteins, and DNA in cancer cells. In this brief review, we summarize the recent progress on various discrete copper-based metal complexes aimed at enhancing the therapeutic efficacy of CDT as well as their application in combination therapy. We hope that this review will attract active attention toward metal complexes in advancing more accurate and efficient chemodynamic therapy and encourage further in-depth research to facilitate clinical translation.

Large metal-phosphonate clusters typically exhibit regular polyhedral, wheel-shaped, spherical, or capsule-shaped morphologies more effectively than high-aspect ratio topologies. A system of elongated lanthanide core topologies has now been synthesized by the reaction of lanthanide 1-naphthylmethylphosphonates and four differently terminated pyrazinyl hydrazones. Four new rod-shaped dysprosium phosphonate clusters, [Dy 6 (O 3 PC 11 H 9 ) 4 (L 1 ) 4 (μ 4 -O)(DMF) 4 ]·2DMF·3MeCN·3H 2 O ( 1 ), [Dy 8 (O 3 PC 11 H 9 ) 4 (L 2 ) 4 (μ 3 -O) 4 (CO 2 ) 4 (H 2 O) 4 ]·6DMF·4MeCN·3H 2 O ( 2 ), [Dy 12 Na(O 3 PC 11 H 9 ) 6 (L 3 ) 6 (μ 3 -O) 2 (pyr) 6 ]·DMF·2MeCN·H 2 O ( 3 ), and [Dy 14 (O 3 PC 11 H 9 ) 12 (L 4 ) 8 (μ 3 -O) 2 (DMF) 4 (MeOH) 2 (H 2 O) 4 ]·5DMF·2MeCN·H 2 O ( 4 ), were obtained. Four single-pyrazinyl hydrazones function as pentadentate bis-chelate terminal co-ligands, coordinating the periphery of dysprosium phosphonate rods. A sodium ion serves as a cation template for constructing heterobimetallic 3 by occupying the void, demonstrating the ability to reliably control cluster length by modifying the hydrazone co-ligand structure and cation template. Additionally, it was observed that the elongation of the rods has a significant directional impact on the magnetic relaxation behavior, transitioning from a one-step process in 1 to a three-step process in 2 , a two-step process in 3 , and finally a two-step process in 4 .

The accurate manipulation of the species and locations of catalytic centers is crucial for regulating the catalytic activity of catalysts, which is essential for their efficient design and development. Metal-organic frameworks (MOFs) with coordinated metal sites are ideal materials for investigating the origin of catalytic activity. In this study, we present a Ni 2 -MOF featuring novel Ni-based binuclear nodes with open metal sites (OMSs) and saturated metal sites (SMSs). The nickel was replaced by iron to obtain Ni 1 Fe 1 -MOF. In the electrocatalytic oxygen evolution reaction, Ni 1 Fe 1 -MOF exhibited an overpotential and Tafel slope of 370 mV@10 mA cm -2 and 87.06 mV dec -1 , respectively, which were higher than those of Ni 2 -MOF (283 mV@10 mA cm -2 and 39.59 mV dec -1 , respectively), demonstrating the superior performance of Ni 1 Fe 1 -MOF. Furthermore, theoretical calculations revealed that iron as an SMS may effectively regulate the electronic structure of the nickel catalytic center to reduce the free energy barrier Δ G *OH of the rate-determining step.

An Fe-catalyzed visible-light induced condensation of alkylbenzenes with anthranilamides has been developed. Upon irradiation, the trivalent iron complex could generate chlorine radicals, which successfully abstracted the hydrogen of benzylic C-H bonds to form benzyl radicals. And these benzyl radicals were converted into oxygenated products under air conditions, which subsequently reacted with anthranilamides for the synthesis of quinazolinones.

A visible-light-induced chemodivergent synthesis of tetracyclic quinazolinones and 3-iminoisoindoliones has been developed. This chemodivergent reaction afforded two kinds of different products by substrate control. A detailed investigation of the reaction mechanism revealed that this consecutive photoinduced electron transfer (ConPET) cascade cyclization involved a radical process, and the aryl radical was the crucial intermediate. This method employed 4-DPAIPN as a photocatalyst and i -Pr 2 NEt as a sacrificial electron donor leading to metal-free conditions.

Marbofloxacin (MB) is a newly developed fluoroquinolone antibiotic used especially as a veterinary drug. It may be regarded as the improved version of enrofloxacin owing to its antibacterial activity, enhanced bioavailability, and pharmacokinetic-pharmacodynamic (PK-PD) properties. In this study, nine heavy rare-earth ions (Y, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) were selected in light of their potential antibacterial activity and satisfactory biosafety to afford the corresponding rare-earth metal complexes of MB: the MB-Ln series. Their chemical structures and coordination patterns were characterized using IR spectroscopy, HRMS, TGA, and X-ray single-crystal diffraction analysis. Our results confirmed that all the MB-Ln complexes yielded the coincident coordination modes with four MB ligands coordinating to the Ln(III) center. In vitro antibacterial screening on five typical bacteria strains revealed that the MB-Ln complexes exhibited antibacterial activities comparable with MB, as indicated by the MIC/MBC values, in which Escherichia coli and Salmonella typhi were the most sensitive ones to MB-Ln. Furthermore, the MB-Ln complexes were found to be much less toxic in vivo than MB, as suggested by the evaluated LD 50 (50% lethal dose) values. All the MB-Ln series complexes fell in the LD 50 range of 5000-15 000 mg kg -1 , while the LD 50 value of MB was only 1294 mg kg -1 . Furthermore, MB-Lu, as the selected representative of MB-Ln, could effectively inhibit the activity of DNA gyrase, the same as MB, suggesting the primary antibacterial mechanism of the MB-Ln series. The results demonstrated the good prospects and potential of metal-based veterinary drugs with better drug performance.

Two double-stranded metallo-triangles, Dy9 and Dy24, with hexaple-C 10 H 7 PO 3 2- bridges were constructed, and their magnetic properties were explored. Compared with the field-induced relaxation phenomenon of Dy9 templated with a chloride anion, Dy24 templated with a sodium cation exhibited zero-field single-molecule-magnet behavior.

An atomically precise Cu(I) macrocyclic complex Cu8I was developed for chemodynamic therapy (CDT) research. The {Cu 8 } macrocyclic skeleton gradually forms with the selective recognition of iodide ions, and the monitoring of intermediate fragments during Cu8I formation using time-dependent electrospray ionization mass spectrometry indicates the following possible formation process: [Cu 1 ] → [Cu 2 ] → [Cu 3 ] → [Cu 4 ] → [Cu 5 I] → [Cu 6 I] → [Cu 7 I] → [Cu 8 I] when recognized by iodide ions. Furthermore, the Cu(I)-mediated Fenton-like reaction in Cu8I catalyzes the production of toxic ˙OH from H 2 O 2 , which results in efficient tumor suppression.

Our group has previously demonstrated elevated serum-soluble ST2 in patients with active systemic lupus erythematosus, suggesting a role of IL-33 in the underlying pathogenesis. However, inconsistent results have been reported on the effect of exogenous IL-33 on murine lupus activity, which may be mediated by concerted actions of various immune cells in vivo. This study aimed to examine the function of IL-33 on macrophage polarization and regulatory T cells (Treg) and their interactive effects in the lupus setting by in vitro coculture experiments of macrophages and T cells that were performed in the presence or absence of IL-33-containing medium. Compared to IL-4-polarized bone marrow-derived macrophages (BMDM) from MRL/MpJ mice, adding IL-33 enhanced mRNA expression of markers of alternatively activated macrophages, including CD206 and Arg1. IL-33 and IL-4 copolarized BMDM produced higher TGF-β but not IL-6 upon inflammatory challenge. These BMDM induced an increase in the Foxp3+CD25+ Treg population in cocultured allogeneic T cells from MRL/MpJ and predisease MRL/lpr mice. These copolarized BMDM also showed an enhanced suppressive effect on T cell proliferation with reduced IFN-γ and IL-17 release but increased TGF-β production. In the presence of TGF-β and IL-2, IL-33 also directly promoted inducible Treg that expressed a high level of CD25 and more sustained Foxp3. Unpolarized BMDM cocultured with these Treg displayed higher phagocytosis. In conclusion, TGF-β was identified as a key cytokine produced by IL-4 and IL-33 copolarized alternatively activated macrophages and the induced Treg, which may contribute to a positive feedback loop potentiating the immunoregulatory functions of IL-33., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Increasing the reactive oxygen species (ROS) content at the tumor site is one of the effective strategies to promote intracellular oxidative stress and improve therapeutic efficiency. Herein, an atomically precise cinnamaldehyde-derived metal-organic Cu(I) complex (denoted as DC-OD-Cu) was rationally constructed. DC-OD-Cu could preferentially accumulate in the mitochondria of HeLa cells due to the mitochondria-targeting ability of triphenylphosphine, which was accompanied by the generation of large amounts of highly toxic hydroxyl radicals (˙OH) via Cu(I)-mediated Fenton-like reactions. Meanwhile, greater ROS generation jointly results in mitochondrial damage under white LED light irradiation. Furthermore, the in vitro and in vivo results suggested that DC-OD-Cu possesses favorable cytotoxicity and inhibits tumor growth. We believe that this research might provide a controllable strategy to construct multifunctional metal organic complexes for ROS-involved CDT.

The innate cytokine IL-33 is increasingly recognised to possess biological effects on various immune cells. We have previously demonstrated elevated serum level of soluble ST2 in patients with active systemic lupus erythematosus suggesting involvement of IL-33 and its receptor in the lupus pathogenesis. This study sought to examine the effect of exogenous IL-33 on disease activity of pre-disease lupus-prone mice and the underlying cellular mechanisms. Recombinant IL-33 was administered to MRL/lpr mice for 6 weeks, whereas control group received phosphate-buffered saline. IL-33-treated mice displayed less proteinuria, renal histological inflammatory changes, and had lower serum levels of pro-inflammatory cytokines including IL-6 and TNF-α. Renal tissue and splenic CD11b+ extracts showed features of M2 polarisation with elevated mRNA expression of Arg1, FIZZI, and reduced iNOS. These mice also had increased IL-13, ST2, Gata3, and Foxp3 mRNA expression in renal and splenic tissues. Kidneys of these mice displayed less CD11b+ infiltration, had downregulated MCP-1, and increased infiltration of Foxp3-expressing cells. Splenic CD4+ T cells showed increased ST2-expressing CD4+Foxp3+ population and reduced IFN-γ+ population. There were no differences in serum anti-dsDNA antibodies and renal C3 and IgG2a deposit in these mice. Exogenous IL-33 was found to ameliorate disease activity in lupus-prone mice with induction of M2 polarisation, Th2 response, and expansion of regulatory T cells. IL-33 likely orchestrated autoregulation of these cells through upregulation of ST2 expression., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

A triphenylphosphine coordinated Cu(I) complex of Fc-OD-Cu was rationally designed for chemodynamic therapy (CDT) of cancer. The complex was capable of generating a highly toxic hydroxyl radical (˙OH) via a Fenton-like reaction induced by Cu(I) moieties and simultaneously mediated by ferrocene moieties. As a result, the CDT efficiency of Fc-OD-Cu is higher than that of Ba-OD-Cu (without ferrocene moieties) and Fc-OD (without Cu(I) moieties).

Using the polydentate ligand of H 4 L with the Co II ion, a triangular prism-type nine-nucleus cluster [Co 9 (L) 3 (CH 2 OCH 2 OH) 6 ]·3.5H 2 O ({Co9}-Eg, H 4 L = 6,6'-(1 H ,1' H -[3,3'-bi(1,2,4-triazole)]-5,5'-diyl)dipicolinic acid) was constructed. Ion fragmentation during the formation of the {Co9}-Eg cluster was tracked using time-dependent electrospray ionization mass spectrometry. In addition, we proposed two possible formation processes (i) H 4 L → CoL → Co 2 L → Co 6 L 3 → Co 7 L 3 → Co 9 L 3 and (ii) H 4 L → CoL → Co 2 L → Co 3 L → Co 5 L 2 → Co 7 L 3 → Co 9 L 3 . Magnetic studies show that {Co9}-Eg exhibits slow relaxation under a static zero field at low temperature, which is the main characteristic of single molecule magnets (SMMs).

Objective: The objective of the present study was to examine the clinical factors influencing the pregnancy rate of infertile patients with endometriosis and establish a predictive model., Patients and Methods: This study included 158 patients (158 cycles) with infertility and endometriosis who underwent laparoscopic surgery, and in vitro fertilization and embryo transfer (IVF-ET) were evaluated retrospectively between January 2019 and December 2020. The clinical factors in the pregnant and non-pregnant group were analyzed by univariate analysis. Statistically significant variables were subsequently used for multivariate logistic regression to establish the prediction model., Results: Multivariate logistic regression analyses showed that GnRH-a treatment after operation (OR, 6.562; 95% CI: 2.782-15.477; p<0.01), ASRM stage (OR, 0.218; 95% CI: 0.093-0.509; p<0.05), the number of high-quality transferred embryos (OR, 3.155; 95% CI: 1.647-6.047; p<0.05) were independently associated with successful pregnancy. The area under the curve (AUC) of the prediction model was 0.774 (95% CI: 0.700-0.847). According to Hosmer-Lemeshow, the model was well fitted (p>0.05). We applied the bootstrapping method to internal validation, and the result showed that the pregnancy rate predicted by the model and the real data were consistent., Conclusions: The models for predicting pregnancy rates after IVF-ET in infertility and endometriosis patients showed high accuracy. The effective methods to increase the number of high-quality embryos need further study.

Chemodynamic therapy (CDT), which uses agents to induce cell death by decomposing endogenous hydrogen peroxide (H 2 O 2 ) into highly toxic hydroxyl radicals (˙OH), has been recognized as a promising approach to treat cancer. However, improving the efficiency of ˙OH production is considered one of the biggest challenges that limits the therapeutic efficacy of CDT. Herein, to controllably and efficiently induce oxidative damage through the production of ˙OH, we developed a new metal complex CDT agent with atomically precise structural characteristics as a deviation from traditional nanomaterial-CDT agents. The obtained CDT agent, a cinnamaldehyde derived copper(I) complex (denoted Cin-OD-Cu), was found to be continuously enriched in the mitochondria of A2780 ovarian carcinoma cells, which was accompanied by the generation of large amounts of ˙OH via Cu(I)-mediated Fenton-like reactions of H 2 O 2 , thereby stimulating oxidative stress in the mitochondria and eventually leading to cell death. Moreover, in vivo experiments showed that Cin-OD-Cu was capable of effectively inhibiting tumor growth with excellent biocompatibility. We believe this research enriches the limited selection of atomically precise metal complex CDT agents in particular for reactive oxygen species-mediated treatments aimed at inducing mitochondria oxidative damage; we anticipate that it will provide new insights into the development of novel, atomically precise agents for CDT.

Doxorubicin (DOX) is an anthraquinone drug used for the efficient treatment of a variety of tumors in human beings. Unfortunately, its poor biodegradability causes incomplete metabolism in the body. Therefore, it is of great significance to synthesize a sensitive and selective material for DOX detection. In this paper, we report a water-soluble Tb 12 cluster and track its step-by-step formation (L → Tb 1 L 1 → Tb 2 L 1 → Tb 2 L 2 → Tb 3 L 2 → Tb 4 L 2 → Tb 12 L 6 ). Tb 12 can be used to determine the presence of DOX, which quenches the luminescence of the Tb 12 aqueous solution, and the detection limit can reach 13 nM ( K SV = 8.7 × 10 5 M -1 ). Tb 12 has advantages of high sensitivity and high selectivity for the detection of DOX in a simulated environment of human urine and serum.

Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19), with macrophages as one of the main cell types involved. It is urgent to understand the interactions among permissive cells, macrophages, and the SARS-CoV-2 virus, thereby offering important insights into effective therapeutic strategies. Here, we establish a lung and macrophage co-culture system derived from human pluripotent stem cells (hPSCs), modeling the host-pathogen interaction in SARS-CoV-2 infection. We find that both classically polarized macrophages (M1) and alternatively polarized macrophages (M2) have inhibitory effects on SARS-CoV-2 infection. However, M1 and non-activated (M0) macrophages, but not M2 macrophages, significantly up-regulate inflammatory factors upon viral infection. Moreover, M1 macrophages suppress the growth and enhance apoptosis of lung cells. Inhibition of viral entry using an ACE2 blocking antibody substantially enhances the activity of M2 macrophages. Our studies indicate differential immune response patterns in distinct macrophage phenotypes, which could lead to a range of COVID-19 disease severity., (© 2022. The Author(s).)

A triphenylphosphine-modified tetra-nuclear Cu(I) coordinated cluster was constructed for enhanced chemodynamic therapy (CDT) by increasing the number of metal centers. Once inside human bladder cancer (T24) cells, a larger amount of copper accumulated compared with the mono-nuclear Cu(I) complex; the additional copper could generate more •OH and then induce more obvious apoptosis via a Fenton-like reaction, thus further increasing the tumor inhibition effect and ultimately improving the CDT efficiency.

The single crystals of two novel chiral tetranucleate copper(II)-based complexes (TNCu-A and TNCu-B) containing L -methioninol-derived Schiff-bases were obtained. Their single structures were characterized by X-ray single crystal diffraction, infrared (IR) rays, elemental analysis, and liquid chromatography-mass spectrometry analysis. TNCu-A can effectively inhibit human umbilical vein endothelial cells (HUVECs) to form a tubular structure and it induces apoptosis of human triple-negative breast cancer MDA-MB-231 cells and HUVECs in vitro in a mitochondria dependent manner. Moreover, in vivo TNCu-A can remarkably inhibit the growth of triple-negative breast cancer from which MDA-MB-231 cells were xenografted into severely immunodeficient nude mice by inhibiting proliferation, inducing apoptosis of MDA-MB-231 cells by dramatically inhibiting the expression of the anti-apoptotic protein Bcl-2 and up-regulating the expressions of proapoptotic proteins caspase-9 and Bax, and simultaneously inhibiting tumor angiogenesis by decreasing the density of vascular endothelial cells and suppressing migration and even partially inducing apoptosis.

A simple and feasible atom-precise biotinylated Cu(i) complex, which can catalyze H 2 O 2 overexpressed commonly in the tumor microenvironment to produce ˙OH through a Fenton-like reaction, was prepared and employed as an effective agent for tumor-targeted chemodynamic therapy.

The Dark photon as an ultralight dark matter candidate can interact with the standard model particles via kinetic mixing. We propose to search for the ultralight dark photon dark matter using radio telescopes with solar observations. The dark photon dark matter can efficiently convert into photons in the outermost region of the solar atmosphere, the solar corona, where the plasma mass of photons is close to the dark photon rest mass. Because of the strong resonant conversion and benefiting from the short distance between the Sun and the Earth, the radio telescopes can lead the dark photon search sensitivity in the mass range of 4×10^{-8}-4×10^{-6}  eV, corresponding to the frequency 10-1000 MHz. As a promising example, the low-frequency array telescope can reach the kinetic mixing ε∼10^{-13} (10^{-14}) within 1 (100) h of solar observations. The future experiment square kilometer array phase 1 can reach ε∼10^{-16}-10^{-14} with 1 h of solar observations.

An unprecedented inner [Mn 18 (CO 3 ) 9 ] inorganic core and [Mn 20 ] metal-organic periphery compose a high-nuclearity homometallic single-valent {Mn II 38 } molecular aggregate with a [Mn 6 ] ⊂ [Mn 12 ] ⊂ [Mn 8 ] ⊂ [Mn 12 ] matryoshka doll-like skeleton that displays a significant magnetocaloric effect (MCE).

The controllable construction and function expansion of some sophisticated aggregations represent a current hot topic in scientific research. In this paper, using a prefabricated {Co 14 } cluster as a synthetic precursor, a homometallic {Co 24 } and a heterometallic {Co 12 Cd 12 } giant cluster possessing similar dual-[M 12 ] (M = Co/Cd) skeletons was prepared by reacting the precursor with excess CoCl 2 and Cd(OAc) 2 salts, respectively. The detailed structural information on {Co 24 } and {Co 12 Cd 12 } was characterized by single-crystal X-ray diffraction and further analyzed by X-ray photoelectron spectroscopy, inductively coupled plasma-mass spectroscopy, and scanning electron microscopy with energy dispersive X-ray (EDX) spectroscopy in the solid state. Compared to the {Co 14 } precursor, magnetic difference revealed that spin-canting and magnetic ordering had been enhanced in {Co 24 } and suppressed in {Co 12 Cd 12 } when dotted with diamagnetic Cd 2+ ions.

{Dy16(μ6-C10H7PO3)2(μ5-C10H7PO3)8(spch)8(μ3-OH)2(μ2-OH)2(μ2-AcO)6(μ3-COO)2(DMF)2(H2O)6}·0.5CH3OH·4.5H2O (1) and {Dy16(μ5-C10H7PO3)4(μ3-C10H7PO3)12(μ2-C10H7PO3H)8(opch)4(DMF)8(MeOH)4}·2.5CH3OH·3H2O (2), where H2spch is ((E)-N'-(2-hydroxybenzylidene)pyrazine-2-carbohydrazide, C10H7PO3H2 is 1-naphthylphosphonic acid and H2opch is (E)-N'-(2-hydroxy-3-methoxybenzylidene)pyrazine-2-carbohydrazide, were successfully synthesized by varying the hydrazone ligands in the Dy-phosphonate system. It is important that the ellipsoidal core experiences a ring forming structural transformation to the supramolecular square motif upon the incorporation of an ortho-methoxy substituent into the hydrazone. Alternating-current (ac) magnetic susceptibility studies of 1 and 2 suggest that similar single molecule magnet behaviors occur for these two complexes. The result represents an effective molecular assembly tactic to develop highly complicated lanthanide coordination clusters through the multicomponent self-assembly of the coalescence of phosphonate- and hydrazone-based ligands and metal salts.

Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies. Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection. Among the hPSC-derived lung cells, alveolar type II and ciliated cells are the major cell populations expressing the viral receptor ACE2 and co-effector TMPRSS2, and both were highly permissive to viral infection. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 and IL-18, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper-inflammatory response mediated by M1 macrophages., Competing Interests: Competing Financial Interests The authors have no financial conflicts of interest.

The single crystals of two novel copper(ii)-based complexes containing l-methioninol-derived Schiff bases were obtained and characterized. The nanoparticles of these complexes were prepared and their cellular uptake was measured in MDA-MB-231 cells and HUVECs. It was found that these complexes could remarkably induce apoptosis, inhibit proliferation, suppress migration and metastasis, and inhibit angiogenesis and the growth of triple-negative breast cancer derived from MDA-MB-231 cells in vitro. Meanwhile, these complexes exhibit anticancer and antiangiogenic functions by activating the important protein molecules VEGFR2, FAK, AKT and Erk1/2 or their phosphorylated molecules p-VEGFR2, p-FAK, p-AKT, and p-Erk1/2 in the VEGF/VEGFR2 signaling pathway, collapsing the mitochondrial membrane potential, and damaging the level of reactive oxygen species.

A novel discrete {Co14Mo24} nanoscale cluster, {CoIII2CoII10Cl2(dpbt)3(H2O)2[CoIIMoV12O31(CH3O)9]2}·24CH3OH (1) (here, dpbt = 5,5'-di(pyridin-2-yl)-3,3'-bi(1,2,4-triazole)), with a triangular Co4 core encapsulated in two novel capped Co-substituted Keggin-type Co5Mo12O40 anions, has been isolated from alkaline methanol solution. The high-resolution electrospray ionization mass spectrum (HRESI-MS) of microcrystalline 1 in MeOH/CH2Cl2 (v : v = 2 : 1) was recorded. Two prominent overlapping peaks in the range of m/z = 2740-2840 and 1820-1880 for the discrete fragments of [CoIII2CoII12MoV24O62Cl2(dpbt)3(H2O)2(CH3O)x(OH)18-x-2H]2- (x = 9-18, F1) and [CoIII2CoII12MoV24O62Cl2(dpbt)3(H2O)2(CH3O)x(OH)19-x-2H]3- (x = 6-13, F2), respectively, are obtained, confirming the {Co14Mo24} composition in 1. In addition, weak anti-ferromagnetic interactions in 1 are observed.

In this study, four in situ hydro(solvo)thermal metal-ligand reactions, including oxidation (H 2 L 1 ), C-C coupling (H 4 L 2 ), nitration (H 2 L 3 ), and condensation (HL 4-6 ), based on bis[3-(pyridin-2-yl)-1 H -1,2,4-triazol-5-yl]methane (H 2 L 0 ), in the presence of Dy III ions, were carried out. The in situ metal-ligand reaction gave six new ligands existing in eight novel Dy III coordination complexes, which were characterized by crystal structure, mass spectrometry, and magnetism.

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We present the synthesis, structural characterization, and magnetic properties of two high-nuclearity cobalt clusters formulated as [Co 13 (μ 3 -OH) 3 (μ 3 -Cl)(dpbt) 5 (ptd)Cl 10 ][Co(H 2 O) 2 Cl 2 ]·(CH 3 ) 2 CHOH (1) and [Co 24 (μ 3 -OH) 6 (μ 3 -Cl) 2 (dpbt) 10 (ptd) 2 Cl 16 ]·2CH 3 CH 2 OH (2), respectively (H 2 dpbt = 5,5'-bis(pyridin-2-yl)-3,3'-bis(1,2,4-triazole) and H 2 ptd = 3-(pyridin-2-yl)-1,2,4-triazine-5,6-diol). Compound 1 is composed of an inner [Co 4 (μ 3 -OH) 3 (μ 3 -Cl)] cubane and an outer [Co 9 (dpbt) 5 (ptd)Cl 10 ] defective adamantane. Compound 2 reveals a giant {Co 24 } cluster possessing a dual-[Co 12 ] skeleton from 1. The hierarchical assembly from 1 to 2 has been established and tracked through high-resolution electrospray ionization (HRESI-MS) analyses from the solvothermal reaction mother solution. Magnetic studies of 1 and 2 revealed the highly correlated spins, a glasslike magnetic phase transition at ca. 8 K, and slow relaxation behavior of SMM nature in the lower-temperature region (below 4 K).

In this study, two Ni(II) complexes, namely [Ni(HL1)₂(OAc)₂] ( 1 ) and [Ni(L2)₂] ( 2 ) (where HL1 and HL2 are ( E )-1-((1-(2-hydroxyethyl)-1 H -pyrazol-5-ylimino)methyl)-naphthalen-2-ol) and ( E )-ethyl-5-((2-hydroxynaphthalen-1-yl)methyleneamino)-1-methyl-1 H -pyrazole-4-carboxylate, respectively), were synthesized and characterized by X-ray crystallography, Electrospray Ionization Mass Spectrometry (ESI-MS), elemental analysis, and IR. Their uptake in biological macromolecules and cancer cells were preliminarily investigated through electronic absorption (UV-Vis), circular dichroism (CD) and fluorescence quenching measurements. Bovine serum albumin (BSA) interaction experiments were investigated by spectroscopy which showed that the complexes and ligands could quench the intrinsic fluorescence of BSA through an obvious static quenching process. The spectroscopic studies indicated that these complexes could bind to DNA via groove, non-covalent, and electrostatic interactions. Furthermore, in vitro methyl thiazolyl tetrazolium (MTT) assays and Annexin V/PI flow cytometry experiments were performed to assess the antitumor capacity of the complexes against eight cell lines. The results show that both of the complexes possess reasonable cytotoxicities., Competing Interests: The authors declare no conflict of interest.

Four different transition metal complexes containing dipyridyl triazole ligands, namely [Cu(abpt)2Cl2]·2H2O (1), [Cu(abpt)2(ClO4)2] (2), [Co2(abpt)2(H2O)2Cl2]·Cl2·4H2O (3) and [Co2(Hbpt)2(CH3OH)2(NO3)2] (4) have been designed, synthesized and further structurally characterized by X-ray crystallography, ESI-MS, elemental analysis, IR and Raman spectroscopy. In these complexes, the both ligands act as bidentate ligands with N, N donors. DNA binding interactions with calf thymus DNA (ct-DNA) of the ligand and its complexes 1~4 were investigated via electronic absorption, fluorescence quenching, circular dichroism and viscosity measurements as well as confocal Laser Raman spectroscopy. The results show these complexes are able to bind to DNA via the non-covalent mode i.e. intercalation and groove binding or electrostatic interactions. The interactions with bovine serum albumin (BSA) were also studied using UV-Vis and fluorescence spectroscopic methods which indicated that fluorescence quenching of BSA by these compounds was the presence of both static and dynamic quenching. Moreover, the in vitro cytotoxic effects of the complexes against four cell lines SK-OV-3, HL-7702, BEL7404 and NCI-H460 showed the necessity of the coordination action on the biological properties on the respective complex and that all four complexes exhibited substantial cytotoxic activity., (Copyright © 2016. Published by Elsevier B.V.)

Three new matrine-type alkaloids, (+)-5α-hydroxyoxysophocarpine (1), (-)-12β-hydroxyoxysophocarpine (2), and (+)-5α-hydroxylemannine (3), along with 14 known analogues, (-)-sophocarpine (4), (-)-5α-hydroxysophocarpine (5), (-)-9α-hydroxysophocarpine (6), (+)-12α-hydroxysophocarpine (7), (-)-12β-hydroxysophocarpine (8), (+)-oxysophocarpine (9), (+)-matrine (10), (+)-sophoranol (11), (+)-9α-hydroxymatrine (12), (-)-14β-hydroxymatrine (13), (+)-oxymatrine (14), (+)-5α-hydroxyoxymatrine (15), (-)-14β-hydroxyoxymatrine (16), and (+)-sophoramine (17), were isolated from the rhizomes of Sophora tonkinensis. Their structures were elucidated via spectrometric data analyses, and the absolute configurations were established by single-crystal X-ray diffraction and ECD data. Alkaloids 2, 6, 11, and 13 exhibited antiviral activity against the Coxsackie virus B3 (CVB3), with IC50 values of 26.62-252.18 μM, and alkaloids 7, 8, and 17 inhibited influenza virus A/Hanfang/359/95 (H3N2) replication with IC50 values of 63.07-242.46 μM.

Objective: Regulatory T cells (Tregs) with the plasticity of producing proinflammatory cytokine IL-17 have been demonstrated under normal and pathogenic conditions. However, it remains unclear whether IL-17-producing Tregs lose their suppressive functions because of their plasticity toward Th17 in autoimmunity. The aim of this study was to investigate IL-17-producing Tregs from patients with rheumatoid arthritis (RA), and characterise their regulatory capacity and clinical significance., Methods: Foxp3 and IL-17 coexpression were evaluated in CD4 T lymphocytes from RA patients. An in vitro T cell polarisation assay was performed to investigate the role of proinflammatory cytokines in IL-17-producing Treg polarisation. The suppressive function of IL-17-producing Tregs in RA was assessed by an in vitro suppression assay. The relationship between this Treg subset and clinical features in RA patients was analysed using Spearman's rank correlation test., Results: A higher frequency of IL-17-producing Tregs was present in the peripheral blood of RA patients compared with healthy subjects. These cells from peripheral blood showed phenotypic characteristics of Th17 and Treg cells, and suppressed T cell proliferation in vitro. Tregs in RA synovial fluid lost suppressive function. The Th17 plasticity of Tregs could be induced by IL-6 and IL-23. An increased ratio of this Treg subset was associated with decreased levels of inflammatory markers, including the erythrocyte sedimentation rate and C-reactive protein level, in patients with RA., Conclusions: Increased levels of IL-17-producing Tregs were identified in RA patients. This Treg subset with Th17 plasticity in peripheral blood retained suppressive functions and was associated with milder inflammatory conditions, suggesting that this Treg population works as a negative regulator in RA, but in RA synovial site it may be pathogenic., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

An intuitional hierarchical assembly, metaphorically referred to as a "blossom and yield fruit" process, from a discrete cluster {[Co14(CH3O)4(dpbt)6Cl12]·14CH3OH, ()} to 2D cluster organic frameworks {[Co14(CH3O)10(dpbt)6 Cl6]·12CH3OH, ()}, has been established. The magnetic ordering of was obviously improved compared with .

Two doubly interpenetrated coordination polymers [Co2(BDC)2(bpt)2]·nSolvent based on dimeric secondary building units and crystallizing with distinct solvent molecules (-H2O and -MeOH for nSolvent = 2H2O and MeOH·H2O, respectively) were obtained by employing 1,4-benzenedicarboxylate (BDC) and 1H-3,5-bis(4-pyridyl)-1,2,4-triazole) (bpt) as linkers. The structures consist of a square grid of dimers bridged by BDC and pillared by bpt. Thermogravimetry and PXRD indicate that the frameworks are stable and are retained up to 400 °C, but the structures are modified irreversibly. -H2O, high-symmetry Pna21, exhibits antiferromagnetic coupling within the dimer, while -MeOH, low-symmetry P21/n, exhibits ferromagnetic coupling. Upon desolvation, the -de and -de couplings are antiferromagnetic but reduced. Subsequent resolvation to -H2O and -MeOH resulted in a slight increase of the antiferromagnetic coupling without attaining the virgin states. The interesting difference of magnetic properties between -H2O and -MeOH, the solvated/desolvated phases, particularly at low temperature, indicates that there is a prominent solvent effect.

Naphthalene, the most common polycyclic aromatic hydrocarbon, causes airway epithelium injury in mice. Repeated exposure of mice to naphthalene induces airway epithelia that are resistant to further injury. Previous studies revealed that alterations in bioactivation enzymes and increased levels of gamma-glutamylcysteine synthase in the bronchioles protect tolerant mice from naphthalene and its reactive metabolites. In our current study, tolerance was induced in male ICR mice using a total of 7 daily intraperitoneal injections of naphthalene (200 mg/kg). Both naphthalene-tolerant and non-tolerant mice were challenged with a dose of 300 mg/kg naphthalene on day 8 to investigate metabolite differences. The lungs, liver, and kidneys were collected for histopathology 24 h after the challenge dose. Bronchial alveolar lavage fluid (BALF) and both hydrophilic and hydrophobic extracts from each organ were analyzed using nuclear magnetic resonance (NMR)-based metabolomics. The histological results showed no observable injuries to the airway epithelium of naphthalene-tolerant mice when compared with the control. In contrast, airway injuries were observed in mice given a single challenge dose (injury mice). The metabolomics analysis revealed that the energy metabolism in the lungs of tolerant and injury mice was significantly perturbed. However, antioxidant metabolites, such as glutathione and succinate, were significantly increased in the lungs of tolerant mice, suggesting a role for these compounds in the protection of organs from naphthalene-induced electrophilic metabolites and free radicals. Damage to the airway cellular membrane, as shown by histopathological results and increased acetone in the BALF and perturbation of hydrophobic lung extracts, including cholesterol, phosphorylcholine-containing lipids, and fatty acyl chains, were observed in injury mice. Consistent with our histopathological results, fewer metabolic effects were observed in the liver and kidney of mice after naphthalene treatments. In conclusion, NMR-based metabolomics reveals possible mechanisms of naphthalene tolerance and naphthalene-induced toxicity in the respiratory system of mice.

In spite of considerable interest in the field, reprogramming induced pluripotent stem cells (iPSCs) directly from cancer cells has encountered considerable challenges, including the extremely low reprogramming efficiency and instability of cancer-derived iPSCs (C-iPSCs). In this study, we aimed to identify the main obstacles that limit cancer cell reprogramming. Through a detailed multidimensional kinetic optimization, a highly optimized protocol is established for reprogramming C-iPSCs using nonviral plasmid vectors. We demonstrated how the initial cancer cell density seeded could be the most critical factor ultimately affecting C-iPSCs reprogramming. We have consistently achieved an unprecedented high C-iPSC reprogramming efficiency, establishing stable colonies with typical iPSC morphology, up to 50% of which express the iPSC phenotypic (Oct3/4, Sox2, Nanog) and enzymatic (alkaline phosphatase) markers. Furthermore, established C-iPSC lines were shown to be capable of forming teratomas in vivo, containing cell types and tissues from each of the embryonic germ layers, fully consistent with their acquisition of pluripotency. This protocol was tested and confirmed in two completely unrelated human lung adenocarcinoma (A549) and mouse melanoma (B16f10) cancer cell lines and thus offers a potentially valuable method for generating effectively virus-free C-iPSCs for future applications.

The first example of rare earth metal-catalyzed [3 + 2] cycloaddition of organic azides with nitroolefins and subsequent elimination reaction is described. In the presence of a catalytic amount of Ce(OTf)3, both benzyl and phenyl azides react with a broad range of aryl nitroolefins containing a range of functionalities selectively producing 1,5-disubstituted 1,2,3-triazoles in good to excellent yields.

Regulatory B cells (Breg) have attracted increasing attention for their roles in maintaining peripheral tolerance. Interleukin 33 (IL-33) is a recently identified IL-1 family member, which leads a double-life with both pro- and anti-inflammatory properties. We report here that peritoneal injection of IL-33 exacerbated inflammatory bowel disease in IL-10-deficient (IL-10(-/-)) mice, whereas IL-33-treated IL-10-sufficient (wild type) mice were protected from the disease induction. A phenotypically unconventional subset(s) (CD19(+)CD25(+)CD1d(hi)IgM(hi)CD5(-)CD23(-)Tim-1(-)) of IL-10 producing Breg-like cells (Breg(IL-33)) was identified responsible for the protection. We demonstrated further that Breg(IL-33) isolated from these mice could suppress immune effector cell expansion and functions and, upon adoptive transfer, effectively blocked the development of spontaneous colitis in IL-10(-/-) mice. Our findings indicate an essential protective role, hence therapeutic potential, of Breg(IL-33) against mucosal inflammatory disorders in the gut., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

Diosgenin (DIO) is the active ingredient of Dioscorea species. The interaction of DIO with bovine serum albumin (BSA) was investigated through spectroscopic methods under simulated physiological conditions. The fluorescence quenching data revealed that the binding of DIO to BSA without or with Co(2+) or Zn(2+) was a static quenching process. The presence of Co(2+) or Zn(2+) both increased the static quenching constants K SV and the binding affinity for the BSA-DIO system. In the sight of the competitive experiment and the negative values of ΔH (0) and ΔS (0), DIO bound to site I of BSA mainly through the hydrogen bond and Van der Waals' force. In addition, the conformational changes of BSA were studied by Raman spectra, which revealed that the secondary structure of BSA and microenvironment of the aromatic residues were changed by DIO. The Raman spectra analysis indicated that the changes of conformations, disulfide bridges, and the microenvironment of Tyr, Trp residues of BSA induced by DIO with Co(2+) or Zn(2+) were different from that without Co(2+) or Zn(2+).

Glioma is the most common primary brain tumor, yet the high cost of diagnostic imaging has made early detection of asymptomatic glioma a formidable challenge. Thus, the development of a convenient, sensitive, and cost-effective diagnostic strategy, such as enzyme-linked immunosorbent assay (ELISA) based on glioma-specific and World Health Organization (WHO) grade-specific autoantibody serum markers, is necessary. To this end, a comparative proteomic analysis based on two-dimensional western blotting was carried out with the sera of glioma patients and normal controls. Of the 11 novel glioma-expressed autoantibodies, the autoantibody against glial fibrillary acidic protein (GFAP) showed the highest differential expression. To investigate the potential clinical utility of the GFAP autoantibody as an early diagnostic marker for glioma, an ELISA-based assay was developed and validated with sera from glioma patients with WHO grades II (n = 19), III (n = 17), and IV (n = 24). The GFAP autoantibody level directly correlated with WHO grade and tumor volume. Sera from patients of non-glioma brain tumors, as well as non-brain tumors, showed much lower levels of GFAP autoantibody than those of the glioma patients, indicating that elevated GFAP autoantibody is specific to glioma patients. Analysis of the receiver operating characteristics curve suggested that the new ELISA has good distinguishing power and sensitivity for diagnosing glioma patients. This is the first ELISA assay developed for an autoantibody of a glioma antigen and may prove valuable for the clinical detection of glioma.

The title compound, C13H6Br2O4, derived from xanthone, a fundamental structural framework of active ingredients in many medicinal plants, and was synthesized by bromination of 1,3-di-hydroxyxanthen-9-one with N-bromo-succinimide. The mol-ecular conformation is essentially planar, the dihedral angle between the benzene rings being 1.1 (4)°. This conformation is favorable for the formation of an intra-molecular O-H⋯O hydrogen bond between a hy-droxy group and the xanthone carbonyl group. In the crystal, mol-ecules are associated into chains along the b-axis direction via C=O⋯H-O hydrogen bonds involving the other hy-droxy group.

Papillary meningioma is a rare subtype of malignant meningiomas, which is classified by the World Health Organization as Grade III. Because of lack of large sample size case studies, many of the specific characteristics of papillary meningioma are unclear. This study investigated by retrospective analysis the clinical, radiological and histopathological findings of 17 papillary meningioma patients who underwent surgical resection or biopsy, to assess the characteristics of papillary meningioma. Eight female and nine male patients were included, with a mean age of 40 (range: 6 to 55) years. Tumors were mostly located in the cerebral convexity and showed irregular margins, absence of a peritumoral rim, heterogeneous enhancement and severe peritumoral brain edema on preoperative images. Brain invasion was often confirmed during the operations, with abundant to exceedingly abundant blood supply. Intratumoral necrosis and mitosis was frequently observed on routinely stained sections. The average MIB-1 labeling index was 6.9%. Seven cases experienced tumor recurrence or progression, while seven patients died 6 to 29 months after operation. Radiation therapy was given in 52.9% of all cases. Univariate analysis showed that only the existence of intratumoral necrosis and incomplete resection correlated with tumor recurrence. The 3-year progression free survival was 66.7% after gross total resection and 63.6% for other cases. The 3-year mortality rate was 50% after gross total resection and 63.6% for other cases. Papillary meningioma has specific clinical and histopathological characteristics. Tumor recurrence (or progression) and mortality are common. Gross total tumor resection resulted in less recurrence and mortality.

Interleukin (IL)-33 is a recently identified pleiotropic cytokine, which can orchestrate complex innate and adaptive immune responses in immunity and disease. It has been characterized as a cytokine of the IL-1 family and affects a wide range of immune cells by signalling through its receptor ST2L. Accumulating evidence suggests a crucial role of IL-33/ST2 in inducing and modifying host immune responses against a variety of pathogens including parasites, bacteria, viruses and fungi as well as sterile insults of both endogenous and exogenous source. In this review, we endeavour to give a comprehensive overview of the current knowledge about the role of IL-33 and its receptor ST2 in host defence against infections.