Ultrasound targeted microbubble destruction-mediated SOCS3 attenuates biological characteristics and epithelial-mesenchymal transition (EMT) of breast cancer stem cells

SOCS3 is low-expressed in breast cancer and may be a potential target. Ultrasound targeted microbubble destruction (UTMD) improved the efficiency of gene transfection. We explored the effects of UTMD-mediated transfection of SOCS3 on the biological characteristics and epithelial-mesenchymal transition (EMT) of breast cancer stem cells (BCSCs). The expression of SOCS3 in breast cancer (BC) and its association with prognosis were evaluated by GEPIA and The Cancer Genome Atlas (TCGA) websites. BCSCs were sorted by flow cytometry and immunomagnetic bead method, followed by sphere formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and xenograft assays to test their effects in vitro and in vivo. The levels of SOCS3, EMT- and STAT3 pathway-related genes were determined by RT-qPCR and Western blot, respectively. The effects of liposome and UTMD on BCSCs and mice were compared by the gain-of-function experiments. Low expression of SOCS3 was associated with poor prognosis of BC patients, and found in BC and BCSCs. BCSCs were successfully sorted, with high viability and tumorigenicity. UTMD increased the transfection rate of SOCS3. Moreover, UTMD- and liposome-mediated SOCS3 reduced cell viability, proliferation, migration and invasion, blocked cell cycle, inhibited sphere formation in BCSCs, and retarded tumor growth in mice. Mechanistically, overexpressed SOCS3 inhibited the expressions of EMT-related genes and the activation of STAT3 pathway in BCSCs and mice. The regulatory effects of UTMD-mediated SOCS3 on the above-mentioned biological characteristics were better than liposome-mediated SOCS3. UTMD-mediated SOCS3 has a better therapeutic effect in BC, providing new experimental evidence for the treatment of BC.</p

Table_1_Predictive factors and prognosis of immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer patients.docx

ObjectiveTo investigate the influencing factors and prognosis of immune checkpoint inhibitor-related pneumonitis (CIP) in advanced non-small cell lung cancer (NSCLC) patients during or after receiving immune checkpoint inhibitors(ICIs).MethodsThe clinical and laboratory indicator data of 222 advanced NSCLC patients treated with PD-1/PD-L1 inhibitors at the First Affiliated Hospital of Zhengzhou University between December 2017 and November 2021 were collected retrospectively. The patients were divided into a CIP group (n=41) and a non-CIP group (n=181) according to whether they developed CIP or not before the end of follow-up. Logistic regression was used to evaluate risk factors of CIP, and Kaplan‒Meier curves were used to describe the overall survival (OS) of different groups. The log-rank test was used to compare the survival of different groups.ResultsThere were 41 patients who developed CIP, and the incidence rate of CIP was 18.5%. Univariate and multivariate logistic regression analyses showed that low pretreatment hemoglobin (HB) and albumin (ALB) levels were independent risk factors for CIP. Univariate analysis suggested that history of chest radiotherapy was related to the incidence of CIP. The median OS of the CIP group and non-CIP were 15.63 months and 30.50 months (HR:2.167; 95%CI: 1.355-3.463, PConclusionLower pretreatment HB and ALB levels were independent risk factors for CIP. A high NLR level, a low ALB level and the development of CIP were independent risk factors for the prognosis of advanced NSCLC patients treated with ICIs.</p

New Two-Dimensional Metal−Organic Networks Constructed from 1,2,4,5-Benzenetetracarboxylate and Chelate Ligands

Two novel nickel coordination polymers [Ni2(2,2‘-bipy)2(OH)2(H2btec)]3n (1) and [Ni2(1,10‘-phen)2(H2O)2(btec)]n (2) (btec = 1,2,4,5-benzenetetracarboxylate) have been hydrothermally synthesized and characterized by elemental analyses, IR and XPS spectra, TG analysis, X-ray powder diffraction, and single crystal X-ray diffraction. Crystal data for 1:  C90H66N12O30Ni6, monoclinic P21/c, a = 10.905(2) Å, b = 18.006(4) Å, c = 20.551(4) Å, β = 94.91(3)°, Z = 2. Crystal data for 2:  C34H22N4O10Ni2, monoclinic P21/n, a = 10.122(2) Å, b = 9.3106(19) Å, c = 15.690(3) Å, β = 92.03(3)°, Z = 2. Compound 1 exhibits a novel one-dimensional chainlike structure, in which the dinuclear Ni centers are linked by the btec ligands. Furthermore, the adjacent chains are linked into a 2-D wavelike layer via the strong OH···O hydrogen bonding interactions. Compound 2 possesses an unusual two-dimensional steplike network with interesting rhombic grids. Both compounds exhibit unprecedented metal−organic ligand construction modes in {M/btec/L} (M = transition metal; L = chelate ligands) systems. The magnetic behaviors of compounds 1 and 2 have been studied

New Two-Dimensional Metal−Organic Networks Constructed from 1,2,4,5-Benzenetetracarboxylate and Chelate Ligands

Two novel nickel coordination polymers [Ni2(2,2‘-bipy)2(OH)2(H2btec)]3n (1) and [Ni2(1,10‘-phen)2(H2O)2(btec)]n (2) (btec = 1,2,4,5-benzenetetracarboxylate) have been hydrothermally synthesized and characterized by elemental analyses, IR and XPS spectra, TG analysis, X-ray powder diffraction, and single crystal X-ray diffraction. Crystal data for 1:  C90H66N12O30Ni6, monoclinic P21/c, a = 10.905(2) Å, b = 18.006(4) Å, c = 20.551(4) Å, β = 94.91(3)°, Z = 2. Crystal data for 2:  C34H22N4O10Ni2, monoclinic P21/n, a = 10.122(2) Å, b = 9.3106(19) Å, c = 15.690(3) Å, β = 92.03(3)°, Z = 2. Compound 1 exhibits a novel one-dimensional chainlike structure, in which the dinuclear Ni centers are linked by the btec ligands. Furthermore, the adjacent chains are linked into a 2-D wavelike layer via the strong OH···O hydrogen bonding interactions. Compound 2 possesses an unusual two-dimensional steplike network with interesting rhombic grids. Both compounds exhibit unprecedented metal−organic ligand construction modes in {M/btec/L} (M = transition metal; L = chelate ligands) systems. The magnetic behaviors of compounds 1 and 2 have been studied

New Two-Dimensional Metal−Organic Networks Constructed from 1,2,4,5-Benzenetetracarboxylate and Chelate Ligands

Two novel nickel coordination polymers [Ni2(2,2‘-bipy)2(OH)2(H2btec)]3n (1) and [Ni2(1,10‘-phen)2(H2O)2(btec)]n (2) (btec = 1,2,4,5-benzenetetracarboxylate) have been hydrothermally synthesized and characterized by elemental analyses, IR and XPS spectra, TG analysis, X-ray powder diffraction, and single crystal X-ray diffraction. Crystal data for 1:  C90H66N12O30Ni6, monoclinic P21/c, a = 10.905(2) Å, b = 18.006(4) Å, c = 20.551(4) Å, β = 94.91(3)°, Z = 2. Crystal data for 2:  C34H22N4O10Ni2, monoclinic P21/n, a = 10.122(2) Å, b = 9.3106(19) Å, c = 15.690(3) Å, β = 92.03(3)°, Z = 2. Compound 1 exhibits a novel one-dimensional chainlike structure, in which the dinuclear Ni centers are linked by the btec ligands. Furthermore, the adjacent chains are linked into a 2-D wavelike layer via the strong OH···O hydrogen bonding interactions. Compound 2 possesses an unusual two-dimensional steplike network with interesting rhombic grids. Both compounds exhibit unprecedented metal−organic ligand construction modes in {M/btec/L} (M = transition metal; L = chelate ligands) systems. The magnetic behaviors of compounds 1 and 2 have been studied

New High-Dimensional Networks Based on Polyoxometalate and Crown Ether Building Blocks

Three novel supramolecular assemblies constructed from polyoxometalate and crown ether building blocks, [(DB18C6)Na(H2O)1.5]2Mo6O19·CH3CN, 1, and [{Na(DB18C6)(H2O)2}3(H2O)2]XMo12O40·6DMF·CH3CN (X = P, 2, and As, 3; DB18C6 = dibenzo-18-crown-6; DMF = N,N-dimethylfomamide), have been synthesized and characterized by elemental analyses, IR, UV−vis, EPR, TG, and single crystal X-ray diffraction. Compound 1 crystallizes in the tetragonal space group P4/mbm with a = 16.9701(6) Å, c = 14.2676(4) Å, and Z = 2. Compound 2 crystallizes in the hexagonal space group P63/m with a = 15.7435(17) Å, c = 30.042(7) Å, γ = 120°, and Z = 2. Compound 3 crystallizes in the hexagonal space group P63/m with a = 15.6882(5) Å, c = 29.9778(18) Å, γ = 120°, and Z = 2. Compound 1 exhibits an unusual three-dimensional network with one-dimensional sandglasslike channels based on the extensive weak forces between the oxygen atoms on the [Mo6O19]2- polyoxoanions and the CH2 groups of crown ether molecules. Compounds 2 and 3 are isostructural, and both contain a novel semiopen cagelike trimeric cation [{Na(DB18C6)(H2O)2}3(H2O)2]3+. In their packing arrangement, an interesting 2-D “honeycomblike” “host” network is formed, in which the [XMo12O40]3- (X = As and P) polyoxoanion “guests” resided

Syntheses, Structures, and Photoluminescence of a Novel Class of d¹⁰ Metal Complexes Constructed from Pyridine-3,4-dicarboxylic Acid with Different Coordination Architectures

Two novel d10 metal coordination polymers [Zn(PDB)]n (1) and [Cd3(PDB)2(OH)2(H2O)2]n (2) (H2PDB = pyridine-3,4-dicarboxylic acid) have been synthesized under hydrothermal conditions and characterized by elemental analysis, IR, TG analysis, and single-crystal X-ray diffraction. Crystal data for 1:  C7H3NO4Zn, orthorhombic Pna21, a = 8.423(17) Å, b = 6.574(13) Å, c = 12.899(3) Å, Z = 4. Crystal data for 2:  C14H12N2O12Cd3, monoclinic C2/c, a = 20.130(4) Å, b = 6.692(13) Å, c = 13.081(3) Å, β = 102.78(3)°, Z = 4. Both compounds exhibit novel three-dimensional frameworks. Compound 1 not only possesses a one-dimensional rectangular channel but also contains infinite double-stranded helical chains. Compound 2 has two different types of channels, one being built up from pyridine rings and {CdO5N} and {CdO6} building units and the other being constructed from pyridine rings and {CdO5N} building units. Furthermore, both compounds show strong photoluminescence properties at room temperature

Syntheses, Structures, and Photoluminescence of a Novel Class of d¹⁰ Metal Complexes Constructed from Pyridine-3,4-dicarboxylic Acid with Different Coordination Architectures

Two novel d10 metal coordination polymers [Zn(PDB)]n (1) and [Cd3(PDB)2(OH)2(H2O)2]n (2) (H2PDB = pyridine-3,4-dicarboxylic acid) have been synthesized under hydrothermal conditions and characterized by elemental analysis, IR, TG analysis, and single-crystal X-ray diffraction. Crystal data for 1:  C7H3NO4Zn, orthorhombic Pna21, a = 8.423(17) Å, b = 6.574(13) Å, c = 12.899(3) Å, Z = 4. Crystal data for 2:  C14H12N2O12Cd3, monoclinic C2/c, a = 20.130(4) Å, b = 6.692(13) Å, c = 13.081(3) Å, β = 102.78(3)°, Z = 4. Both compounds exhibit novel three-dimensional frameworks. Compound 1 not only possesses a one-dimensional rectangular channel but also contains infinite double-stranded helical chains. Compound 2 has two different types of channels, one being built up from pyridine rings and {CdO5N} and {CdO6} building units and the other being constructed from pyridine rings and {CdO5N} building units. Furthermore, both compounds show strong photoluminescence properties at room temperature

Syntheses, Structures, and Photoluminescence of a Novel Class of d¹⁰ Metal Complexes Constructed from Pyridine-3,4-dicarboxylic Acid with Different Coordination Architectures

Two novel d10 metal coordination polymers [Zn(PDB)]n (1) and [Cd3(PDB)2(OH)2(H2O)2]n (2) (H2PDB = pyridine-3,4-dicarboxylic acid) have been synthesized under hydrothermal conditions and characterized by elemental analysis, IR, TG analysis, and single-crystal X-ray diffraction. Crystal data for 1:  C7H3NO4Zn, orthorhombic Pna21, a = 8.423(17) Å, b = 6.574(13) Å, c = 12.899(3) Å, Z = 4. Crystal data for 2:  C14H12N2O12Cd3, monoclinic C2/c, a = 20.130(4) Å, b = 6.692(13) Å, c = 13.081(3) Å, β = 102.78(3)°, Z = 4. Both compounds exhibit novel three-dimensional frameworks. Compound 1 not only possesses a one-dimensional rectangular channel but also contains infinite double-stranded helical chains. Compound 2 has two different types of channels, one being built up from pyridine rings and {CdO5N} and {CdO6} building units and the other being constructed from pyridine rings and {CdO5N} building units. Furthermore, both compounds show strong photoluminescence properties at room temperature

Regio- and Diastereoselective Annulation of α,β-Unsaturated Aldimines with Alkenes via Allylic C(sp³)–H Activation by Rare-Earth Catalysts

The [3 + 2] or [4 + 2] annulation of α,β-unsaturated aldimines with alkenes via β′- or γ-allylic C(sp3)–H activation is, in principle, an atom-efficient route for the synthesis of five- or six-membered-ring cycloalkylamines, which are important structural motifs in numerous natural products, bioactive molecules, and pharmaceuticals. However, such a transformation has remained undeveloped to date probably due to the lack of suitable catalysts. We report herein for the first time the regio- and diastereoselective [3 + 2] and [4 + 2] annulations of α,β-unsaturated imines with alkenes via allylic C(sp3)–H activation by half-sandwich rare-earth catalysts having different metal ion sizes. The reaction of α-methyl-substituted α,β-unsaturated aldimines with alkenes by a C5Me4SiMe3-ligated scandium catalyst took place in a trans-diastereoselective [3 + 2] annulation fashion via C(sp3)–H activation at the α-methyl group (β′-position), exclusively affording alkylidene-functionalized cyclopentylamines with excellent trans-diastereoselectivity. In contrast, the reaction of β-methyl-substituted α,β-unsaturated aldimines with alkenes by a C5Me5-ligated cerium catalyst proceeded in a cis-diastereoselective [4 + 2] annulation fashion via γ-allylic C(sp3)–H activation, selectively yielding multisubstituted 2-cyclohexenylamines with excellent cis-diastereoselectivity. The mechanistic details of these transformations have been elucidated by deuterium-labeling experiments, kinetic isotope effect studies, and the isolation and transformations of key reaction intermediates. This work offers an efficient and selective protocol for the synthesis of a new family of cycloalkylamine derivatives, featuring 100% atom efficiency, high regio- and diastereoselectivity, broad substrate scope, and an unprecedented reaction mechanism