Bis(2,2′-bipyridine-κ2 N,N′)bis­(1H-indole-2-carboxyl­ato-κ2 O,O′)cadmium–2,2′-bipyridine–water (1/0.5/2)

The asymmetric unit of title compound, [Cd(C9H6NO2)2(C10H8N2)2]·0.5C10H8N2·2H2O, consists of one complex mol­ecule, one half of an uncoordinated 2,2′-bipyridine mol­ecule and two solvent water mol­ecules. The uncoordinated 2,2′-bipyridine mol­ecule is located on a center of symmetry. Within the complex mol­ecule, the CdII atom is coordinated by four N atoms from two 2,2′-bipyridine ligands and three O atoms from two 1H-indole-2-carboxyl­ate anion ligands, completing a distorted CdN4O3 penta­gonal bipyra­mid. The mol­ecules are assembled into one-dimensional chains along the [100] direction through classical hydrogen bonds (O—H⋯N, N—H⋯O and O—H⋯O). The resulting chains are further connected into two-dimensional supra­molecular layers parallel to the (110) direction by inter­molecular classical hydrogen bonds (N—H⋯O and O—H⋯O) from adjacent chains. A three-dimensional supra­molecular network is formed via interlayer and O—H⋯O hydrogen bonds

Functionalized layered double hydroxide nanoparticles as an intelligent nanoplatform for synergistic photothermal therapy and chemotherapy of tumors

In this work, a novel layered double hydroxide (LDH)-based multifunctional nanoplatform was built for synergistic temperature photothermal therapy (PTT)/chemotherapy. The platform was modified using the peptide B3int to target cancer cells with overexpression of integrin αvβ3. Indocyanine green (ICG) and doxorubicin (DOX) were loaded into the nanocarrier (LDH-PEG-B3int NPs) to form a system having a high DOX drug loading (18.62%) and a remarkable photothermal conversion efficiency of 25.38%. It also showed pH-responsive and near-infrared (NIR)-triggered DOX release. In vitro and in vivo studies indicated that the anti-tumor activity of the combined delivery system was significantly higher than that of a single delivery system. This co-delivery nanosystem may be helpful for future application in the clinical treatment of cancer

Cell-Cycle-Regulated Interaction between Mcm10 and Double Hexameric Mcm2-7 Is Required for Helicase Splitting and Activation during S Phase

Mcm2-7 helicase is loaded onto double-stranded origin DNA as an inactive double hexamer (DH) in G1 phase. The mechanisms of Mcm2-7 remodeling that trigger helicase activation in S phase remain unknown. Here, we develop an approach to detect and purify the endogenous DHs directly. Through cellular fractionation, we provide in vivo evidence that DHs are assembled on chromatin in G1 phase and separated during S phase. Interestingly, Mcm10, a robust MCM interactor, co-purifies exclusively with the DHs in the context of chromatin. Deletion of the main interaction domain, Mcm10 C terminus, causes growth and S phase defects, which can be suppressed through Mcm10-MCM fusions. By monitoring the dynamics of MCM DHs, we show a significant delay in DH dissolution during S phase in the Mcm10-MCM interaction-deficient mutants. Therefore, we propose an essential role for Mcm10 in Mcm2-7 remodeling through formation of a cell-cycle-regulated supercomplex with DHs

Brucella Dysregulates Monocytes and Inhibits Macrophage Polarization through LC3-Dependent Autophagy

Brucellosis is caused by infection with Brucella species and exhibits diverse clinical manifestations in infected humans. Monocytes and macrophages are not only the first line of defense against Brucella infection but also a main reservoir for Brucella. In the present study, we examined the effects of Brucella infection on human peripheral monocytes and monocyte-derived polarized macrophages. We showed that Brucella infection led to an increase in the proportion of CD14++CD16− monocytes and the expression of the autophagy-related protein LC3B, and the effects of Brucella-induced monocytes are inhibited after 6 weeks of antibiotic treatment. Additionally, the production of IL-1β, IL-6, IL-10, and TNF-α from monocytes in patients with brucellosis was suppressed through the LC3-dependent autophagy pathway during Brucella infection. Moreover, Brucella infection inhibited macrophage polarization. Consistently, the addition of 3-MA, an inhibitor of LC3-related autophagy, partially restored macrophage polarization. Intriguingly, we also found that the upregulation of LC3B expression by rapamycin and heat-killed Brucella in vitro inhibits M2 macrophage polarization, which can be reversed partially by 3-MA. Taken together, these findings reveal that Brucella dysregulates monocyte and macrophage polarization through LC3-dependent autophagy. Thus, targeting this pathway may lead to the development of new therapeutics against Brucellosis

Immune Checkpoint Axes Are Dysregulated in Patients With Alcoholic Hepatitis

Alcoholic hepatitis (AH) is a severe inflammatory liver disease that develops in some heavy drinkers. The immune system in patients with AH is hyperactive and yet dysfunctional. Here, we investigated whether this immune‐dysregulated state is related to the alcoholic impact on immune checkpoints (ICPs). We used multiplex immunoassays and enzyme‐linked immunosorbent assay to quantify plasma levels of 18 soluble ICPs (sICPs) from 81 patients with AH, 65 heavy drinkers without liver diseases (HDCs), and 39 healthy controls (HCs) at baseline, 33 patients with AH and 32 HDCs at 6‐month follow‐up, and 18 patients with AH and 29 HDCs at 12‐month follow‐up. We demonstrated that baseline levels of 6 sICPs (soluble T‐cell immunoglobulin and mucin domain 3 [sTIM‐3], soluble cluster of differentiation [sCD]27, sCD40, soluble Toll‐like receptor‐2 [sTLR‐2], soluble herpesvirus entry mediator [sHVEM], and soluble lymphotoxin‐like inducible protein that competes with glycoprotein D for herpes virus entry on T cells [sLIGHT]) were up‐regulated, while 11 sICPs (soluble B‐ and T‐lymphocyte attenuator [sBTLA], sCD160, soluble cytotoxic T‐lymphocyte‐associated protein 4 [sCTLA‐4], soluble lymphocyte‐activation gene 3 [sLAG‐3], soluble programmed death 1 [sPD‐1], sPD ligand 1 [sPD‐L1], sCD28, soluble glucocorticoid‐induced tumor necrosis factor receptor‐related protein [sGITR], sGITR ligand [sGITRL], sCD80, and inducible T‐cell costimulator [sICOS]) were down‐regulated in patients with AH compared to HDCs. The up‐regulated sICPs except sLIGHT and down‐regulated sCD80, sCD160, sCTLA‐4, and sLAG‐3 correlated positively or negatively with AH disease severity, bacterial translocation, and inflammatory factors. At follow‐up, abstinent patients with AH still had higher levels of several sICPs compared to HDCs. We also compared expression of 10 membrane‐bound ICPs (mICPs) on peripheral blood mononuclear cells (PBMCs) from patients with AH and HCs by flow cytometry and found that several mICPs were dysregulated on blood cells from patients with AH. The function and regulation of sICPs and mICPs were studied using PBMCs from patients with AH and HCs. Recombinant sHVEM affected tumor necrosis factor (TNF)‐α and interferon‐γ production by T cells from patients with AH and HCs. Conclusion: Both sICPs and mICPs were dysregulated in patients with AH, and alcohol abstinence did not fully reverse these abnormalities. The HVEM axis plays a role in regulating T‐cell function in patients with AH