TMB Signature-Related RCAN2 Promotes Apoptosis by Upregulating EHF/DR5 Pathway in Hepatocellular Carcinoma.

BACKGROUND: The tumour mutation burden (TMB) is a valuable indicator of the accumulation of somatic mutations, and is thought to be associated with the biological behaviour and prognosis of tumours. However, the related genetic mechanism for these association is still unclear. The aim of the present study was to identify the key gene(s) associated with TMB in hepatocellular carcinoma (HCC) and to investigate its biological functions, downstream transcription factors, and mechanism of action. METHODS: Patients in The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database were classified according to TMB signature-related genes. Key genes related to the TMB signature and tumour prognosis were identified. Immunohistochemistry and Quantitative Real-Time Polymerase Chain Reaction (qPCR) were then used to assess gene expression in clinical HCC tissues and HCC cells. Cells with altered gene expression were evaluated for the effect on cell proliferation and apoptosis, both in vitro and in vivo. Three independent databases and cell sequencing data were used to identify the mechanisms involved and the downstream transcription factors. The mechanism was also studied by altering the expression of downstream transcription factors in vitro. RESULT: The integrated cluster (IC) 2 group, characterized by 99 TMB signature-related genes, showed a significant different TMB score compared to the IC1 group (p < 0.001), as well as more favourable tumour prognosis (p = 0.031). We identified five key prognostic genes that were differentially expressed between IC2 and IC1 and were associated with overall survival. The expression of one of these key prognostic genes, RCAN2, was negatively correlated with TMB in 18 out of 33 tumour types examined. A high level of RCAN2 was correlated with better overall survival in HCC (p = 0.0009). Overexpression of RCAN2 enhanced apoptosis in vitro and in vivo, whereas knockdown of RCAN2 attenuated apoptosis. The mechanism by which RCAN2 promotes apoptosis may involve upregulation of the expression of ETS homologous factor (EHF) and of death receptor 5 (DR5). CONCLUSIONS: Downregulation of RCAN2 expression was found to correlate with elevated TMB in multiple cancer types. RCAN2 was also found to be a biomarker of HCC prognosis, and to promote the apoptosis of HCC cells through the EHF/DR5 pathway. These findings provide a new perspective on systemic treatment for advanced HCC with a high TMB.

Correction: The {Cu2I2} cluster bearing metal organic frameworks: crystal structures and fluorescence detecting performances towards cysteine and explosive molecules.

Correction for 'The {Cu2I2} cluster bearing metal organic frameworks: crystal structures and fluorescence detecting performances towards cysteine and explosive molecules' by Jiang Jiang et al., Dalton Trans., 2024, 53, 706-714, https://doi.org/10.1039/d3dt03363e.

The {Cu2I2} cluster bearing metal organic frameworks: crystal structures and fluorescence detecting performances towards cysteine and explosive molecules.

Two {Cu2I2} cluster-bearing metal organic frameworks (MOFs) of {[Eu(CuI)2(INA)3DMF]·0.95DMF}n (Eu-CuI-INA) and {K[(CH3)2NH2]Sr4(INA)2(DMF)2{(Cu2I2)2(INA)8}·2H2O}n (Sr-K-CuI-INA, HINA = isonicotinic acid, DMF = N,N-dimethyl formamide) were prepared and characterized in this work. Both materials feature a three-dimensional (3-D) structure, in which the {Cu2I2} clusters and Eu3+ (or Sr2+) metal ions are coordinated by INA- ligands with pyridine and carboxylic groups, respectively. Impressively, Sr-K-CuI-INA exhibits sensitive fluorescence sensing behaviors towards cysteine and nitro-bearing molecules, demonstrating potential FL sensing applications for bio and explosive molecules. This work would provide a good reference for designing fluorescent MOF probes containing CuI molecules.

A Soluble Porous Coordination Polymer for Fluorescence Sensing of Explosives and Toxic Anions under Homogeneous Environment.

In the past decades, porous coordination polymers (PCPs) based fluorescent (FL) sensors have received intense attention due to their promising applications. In this work, a soluble Zn-PCP is presented as a sensitive probe towards explosive molecules, chromate, and dichromate ions. In former reports, PCP sensors were usually ground into fine powders and then dispersed in solvents to form FL emulsion for sensing applications. However, their insoluble characters would cause the sensing accuracy which is prone to interference from environmental effects. While in this work, the as-made PCP could be directly soluble in organic solvents to form a clear solution with bright blue emission, representing the first soluble PCP based fluorescence sensor to probe explosive molecules under a homogeneous environment. Moreover, the FL PCP solution also shows sensitive detection behaviors towards the toxic anions of CrO42- and Cr2O72-, which exhibit a good linear relationship between the fluorescence intensity of Zn-PCP and the concentrations of both analytes. This work provides a reference for designing task-specific PCP sensors utilized under a homogeneous environment.

Confinement of 1D Chain and 2D Layered CuI Modules in K-INA-R Frameworks via Coordination Assembly: Structure Regulation and Semiconductivity Tuning.

Herein, we present a new series of CuI-based hybrid materials with tunable structures and semiconducting properties. The CuI inorganic modules can be tailored into a one-dimensional (1D) chain and two-dimensional (2D) layer and confined/stabilized in coordination frameworks of potassium isonicotinic acid (HINA) and its derivatives (HINA-R, R = OH, NO2, and COOH). The resulting CuI-based hybrid materials exhibit interesting semiconducting behaviors associated with the dimensionality of the inorganic module; for instance, the structures containing the 2D-CuI module demonstrate significantly enhanced photoconductivity with a maximum increase of five orders of magnitude compared to that of the structures containing the 1D-CuI module. They also represent the first CuI-bearing hybrid chemiresistive gas sensors for NO2 with boosted sensing performance and sensitivity at multiple orders of magnitude over that of the pristine CuI. Particularly, the sensing ability of CuI-K-INA containing both 1D- and 2D-CuI modules is comparable to those of the best NO2 chemiresistors reported thus far.

Confinement of Pyridine Derivatives into a Metal-Organic Framework Host as Electron Acceptors to Achieve Photoinduced Electron-Transfer.

The photoinduced electron-transfer (ET) process plays an irreplaceable role in chemical and biological fields exemplified by enzymatic catalysis, artificial photosystems, solar energy conversion, and so forth. Searching for a new photoinduced ET system is of great importance for the development of functional materials. Herein, a series of host-guest compounds based on a magnesium metal-organic framework (Mg-MOF) as a host and pyridine derivatives as guests have been presented. Notably, strong O-H···N hydrogen bond between the oxygen atom of µ2-H2O and the nitrogen atom of pyridine enables proton delocalization between water molecule and pyridine guest. Despite the absence of photochromic modules in these host-guest compounds, long-lived charge-separated states with distinct color changes can be formed after UV-light irradiation. The substituents in pyridines and the proton delocalization ability between the host and guests have a great influence on their photoinduced ET process to endow the MOF materials with tunable photoinduced charge-separated states.

A Cerium Organic Framework with {Cu2I2} Cluster and {Cu2I2}n Chain Modules: Structure and Fluorescence Sensing Properties.

In this work, a copper iodine module bearing a coordination polymer (CP) with a formula of [(Cu2I2)2Ce2(INA)6(DMF)3]·DMF (1, HINA = isonicotinic acid, DMF = N,N'-dimethyl formamide) is presented. The title compound features a three dimensional (3D) structure, in which the {Cu2I2} cluster and {Cu2I2}n chain modules are coordinated by N atoms from a pyridine ring in INA- ligands, while the Ce3+ ions are bridged by the carboxylic groups of INA- ligands. More importantly, compound 1 exhibits an uncommon red fluorescence (FL) with a single emission band maximized at 650 nm belonging to near infrared (NIR) luminescence. The temperature dependent FL measurement was applied to investigate the FL mechanism. Remarkably, 1 could be used as a FL sensor to cysteine and the nitro-bearing explosive molecule of trinitropheno (TNP) with high sensitivity, demonstrating its potential FL sensing applications for biothiol and explosive molecules.

A Robust Strontium Coordination Polymer with Selective and Sensitive Fluorescence Sensing Ability for Fe3+ Ions.

Exploration of sensitive and selective fluorescence sensors towards toxic metal species is of great importance to solve metal pollution issues. In this work, a three-dimensional (3D) strontium coordination polymer of Sr2(tcbpe) (H4tcbpe = 1,1,2,2-tetrakis(4-(4-carboxy-phenyl)phenyl)ethene) has been synthesized and developed as a fluorescent sensor to Fe3+ ions. Sr2(tcbpe) shows a mechanochromic fluorescence with emission shifting from blue of the pristine to green after being ground. Notably, based on a fluorescence quenching mechanism, Sr2(tcbpe) displays a sensitive and selective fluorescent sensing behavior to Fe3+ ions with a detection limit of 0.14 mM. Moreover, Sr2(tcbpe) exhibits high tolerance to water in a wide pH range (pH = 3-13), demonstrating that Sr2(tcbpe) is a potential fluorescent sensor of Fe3+ in water.

Single-Crystal Superstructures via Hierarchical Assemblies of Giant Rubik's Cubes as Tertiary Building Units.

Intricate superstructures possess unusual structural features and promising applications. The preparation of superstructures with single-crystalline nature are conducive to understanding the structure-property relationship, however, remains an intriguing challenge. Herein we put forward a new hierarchical assembly strategy towards rational and precise construction of intricate single-crystal superstructures. Firstly, two unprecedented superclusters in Rubik's cube's form with a size of ≈2×2×2 nm3 are constructed by aggregation of eight {Pr4 Sb12 } oxohalide clusters as secondary building units (SBUs). Then, the Rubik's cubes further act as isolable tertiary building units (TBUs) to assemble diversified single-crystal superstructures. Importantly, intermediate assembly states are captured, which helps illustrate the evolution of TBU-based superstructures and thus provides a profound understanding of the assembly process of superstructures at the atomic level.

An Iron-NDC Framework with a Cage Structure and an Optothermal Conversion in NIR Window.

Pursuing novel materials with efficient photothermal conversion under irradiation at the near-infrared region windows (NIR, 750-850 nm; NIR-I and NIR-II, 1000-1320 nm)) is of great importance due to their irreplaceable applications, especially in the biomedical field. Herein, on the basis of a coordination chemistry strategy, an iron-based metal-organic framework (MOF) of [N(CH3)4]2[Fe3(NDC)4]·DMF·3H2O (Fe-NDC, 1,4-H2NDC = 1,4-naphthalenedicarboxylic acid, N(CH3)4+ = tetramethyl-ammonium, and DMF = N,N-dimethylformamide) was prepared and characterized. Due to the d-d transition effect introduced by coordination with the transition-metal ion of iron and the highly conjugated naphthalenic moiety in 1,4-H2NDC, guaranteeing an energy transfer between iron and the organic module, Fe-NDC shows a remarkable broad absorption, which could be extended into the NIR-II section. As a result, Fe-NDC could be irradiated by NIR laser (both 808 and 1064 nm) to achieve photothermal conversion. This work sets a good example to inspire the future designation of NIR light-irradiated photothermal materials based on the first-row transition metals.

Achieving a blue-excitable yellow-emitting Ca-LMOF phosphor via water induced phase transformation.

Luminescent metal-organic frameworks (LMOFs) with diverse structural features and promising fluorescence-based applications have attracted wide attention in the past two decades. In this work, a LMOF with the formula [Ca4(tcbpe-F)2(H2O)3] (1, LMOF-411) has been constructed from calcium (Ca) and 1,1,2,2-tetrakis(4-(4-carboxyphenyl)phenyl)ethene (H4tcbpe-F). Compound 1 features a three-dimensional framework with a 10-nodal net topology. Due to the relatively high hydration energy of Ca2+, compound 1 readily transforms into a new phase formulated as [Ca(H2tcbpe-F)(H2O)2] (1') upon exposure to water. Combining experimental characterization and theoretical calculations, we elucidated the mechanism of H2O-induced phase transition from 1 to 1'. Notably, the water induced phase transformation can be detected visibly from the change in luminescence, which originates from the fluorescent linker. Compound 1 emits green light (λ em = 490 nm) under UV excitation, while compound 1' emits bright yellow light (λ em = 550 nm) under blue excitation (450 nm). Compound 1' represents the first Ca based LMOF yellow phosphor and its luminescence quantum yield reaches 68%. It can be coated directly onto a commercial blue light-emitting-diode (LED) chip to fabricate a white LED (WLED).

[Ba13Sb36Cl34O54]8-: high-nuclearity cluster for the assembly of nanocluster-based compounds.

Herein, we report two nanocluster-based compounds built on an unprecedented cluster [Ba13Sb36Cl34O54]8-, which represents the first example of a discrete alkaline earth (AE)-containing oxochloride cluster and the largest Sb-based oxohalide cluster to date; the proton-conducting property of the compounds was investigated.

Effects of interleukin-7/interleukin-7 receptor on RANKL-mediated osteoclast differentiation and ovariectomy-induced bone loss by regulating c-Fos/c-Jun pathway.

To explore the effects of IL-7/IL-7R on the RANKL-mediated osteoclast differentiation in vitro and OVX-induced bone loss in vivo. BMMs and RAW264.7 were transfected with IL-7, IL-7R siRNA, c-Fos siRNA, and c-jun siRNA and later stimulated by RANKL. TRAP and toluidine blue staining were used to observe osteoclast formation and bone resorption, respectively. HE and TRAP staining were used to detect trabecular bone microstructure and osteoclasts of mice, respectively. qRT-PCR and Western blot analysis were used to examine expression. IL-7 unregulated the expression of CTSK, NFATc1, MMP9, and the phosphorylation of p38 and Akt by activating the c-Fos/c-Jun pathway, which increased osteoclast numbers and bone resorption in RANKL-stimulated macrophages. While IL-7R siRNA and c-Fos siRNA decreased the expression, as well as and the phosphorylation of p38 and Akt.IL-7 decreased the BMD and OPG expression in OVX-induced mice and increased the TRAP positive cells, the mRNA expression of c-fos, c-jun, and RANKL, which was contradictory to IL-7R siRNA, and c-Fos siRNA. Furthermore, IL-7R siRNA and c-Fos siRNA caused thicker trabeculae, increased trabecular number, and decreased osteolysis in OVX mice. IL-7/IL-7R can promote RANKL-mediated osteoclast formation and bone resorption by activating the c-Fos/c-Jun pathway, as well as inducing bone loss in OVX mice.

Mg2+ incorporated Co-based MOF precursors for hierarchical CNT-containing porous carbons with ORR activity.

In this paper, we introduced light and abundant metal magnesium into a cobalt-based metal organic framework (Co-MOF, [(CH3)2NH2]2[Co3(bpdc)4]·5DMF·4CH3OH) (1, H2bpdc = 4,4'-biphenyldicarboxylic acid, DMF = N,N-dimethylformamide) as a heteroatom to synthesize Mg-Co bimetallic MOFs, namely [(CH3)2NH2]2[MgCo2(bpdc)4]·4DMF·5CH3OH (2) and [(CH3)2NH2]2[Mg1.2Co1.8(bpdc)4] 4DMF·4CH3OH·6H2O (3). Based on the formation of a rather low density framework after the introduction of the light Mg2+, such bimetallic MOFs exhibited higher gas adsorption abilities than the isostructural Co-based MOF 1. N2 adsorption measurements demonstrate that the BET surface area of 3 is 305.4 m2 g-1, exhibiting three times that of 1 (104.4 m2 g-1). Significantly, due to the introduction of the low-melting Mg2+, the Mg-Co MOFs could be further utilized as precursors for porous carbons only by calcination at a mild temperature of 600 °C which could exhibit a BET surface as high as 712.78 m2 g-1. Furthermore, after post-synthetic modification with a N/S heteroatom at 900 °C, the obtained hierarchical carbons exhibit superior activity in the oxygen reduction reaction (ORR) that is comparative to the commercial Pt/C catalyst. TEM results indicate that Co-embedded carbon nanotube (CNT)-containing hierarchically nanoporous carbons have been obtained. This study may offer a new avenue to prepare porous carbons utilizing Mg-containing bimetallic MOFs as sacrificial templates.

A series of Mg-Zn heterometallic coordination polymers: synthesis, characterization, and fluorescence sensing for Fe3+, CS2, and nitroaromatic compounds.

Herein, the solvothermal preparations, crystal structures, and fluorescence properties of three Mg-Zn heterometallic coordination polymers (CPs), i.e. [Mg2Zn2(OH)2(1,4-NDC)3(H2O)2]·6H2O (1), [Mg1.13Zn1.87(1,4-NDC)3(dppe)(CH3OH)] (2), and [Mg1.17Zn1.83(1,4-NDC)3(py)2]·1.5py (3), based on the mixed ligands of 1,4-naphthalene dicarboxylic acid (1,4-H2NDC) and N-containing ligands of 1,3-di(4-pyridyl)propane (dppe) or pyridine (py) are presented. In the title compounds, Zn and Mg are statistically distributed, as confirmed by single crystal analysis, and the ratios of Zn and Mg have been identified by inductively coupled plasma (ICP) measurements. In compound 1, the metal ions are tetra- or hexa-coordinated by the oxygen atoms of the carboxylate and µ3-OH group to form a one-dimensional (1D) ribbon, and these 1D ribbons are further bridged by 1,4-NDC linkers to grow into a 3D framework with 1D channels along the b axis. In compounds 2 and 3, the metal ions also adopt tetra- or hexa-coordination modes and are inter-bridged by carboxylate oxygen atoms to form a tri-nuclear secondary building unit (SBU). Due to the introduction of N-containing ligands acting as terminal molecules, these SBUs are linked by 1,4-NDC ligands to form a 2D network. Photoluminescence (PL) studies indicated that the title compounds showed strong blue emissions. Significantly, compound 1 demonstrated sensitive fluorescence sensing for Fe3+, carbon disulfide (CS2), and nitroaromatic compounds at low concentrations. The fluorescence sensing properties of compound 2 were also comparatively investigated in detail.

A Mg-CP with in Situ Encapsulated Photochromic Guest as Sensitive Fluorescence Sensor for Fe3+/Cr3+ Ions and Nitro-Explosives.

Here we report a fluorescent magnesium coordination polymer (Mg-CP), namely, [CH3-dpb]2[Mg3(1,4-NDC)4(µ-H2O)2(CH3OH)(H2O)]·1.5H2O (1, 1,4-H2NDC = 1,4-naphthalene dicarboxylic acid, dpb = 1,4-bis(pyrid-4-yl)benzene). Compound 1 possesses a three-dimensional (3D) host-guest structure constructed by the 1,4-NDC linkers bridging the linear trinuclear secondary building units of [Mg3(COO)8(µ-H2O)2]. The dpb molecules were in situ reacted with CH3OH resulting in photochromic cations of [CH3-dpb]+ that acted as guests located in the channels parallel to the b-axis. Photoluminescence (PL) studies indicated that 1 showed a strong green emission demonstrating sensitive fluorescence sensing of Fe3+/Cr3+ metal ions and nitro-explosive compounds. Compound 1 represents the first PL Mg-CP as a fluorescent probe for detecting metal ions. Moreover, because of the in situ encapsulation of photochromic [CH3-dpb]+ guests, 1 exhibited reversible photochromic behavior.

Fine decoration of carbon nanotubes with metal organic frameworks for enhanced performance in supercapacitance and oxygen reduction reaction.

Efficient electrode material is crucial for energy conversion from renewable sources such as solar electricity. We present a method for preparation of carbon nanotubes (CNTs) with zeolitic imidazolate frameworks (ZIFs, e.g., ZIF-8) via an in situ pyrolysis process. The resultant materials are completely new carbon composites with desirable hierarchical porosity and nitrogen-doped features. Electron microscopy images show that CNTs with small external diameters enable more uniform dispersion of ZIF-8-derived carbons, subsequently yielding a unique hierarchically porous structure. Such carbon shows superior activity in oxygen reduction reaction (ORR) and high performance of supercapacitance, making it a valuable metal-free electrode material and a competent alternative to the state-of-the-art Pt/C catalyst. The electrocatalytic performance of CNTs can be dramatically improved by the incorporation of ZIF-8-derived carbons, which is attributed to the combination of good conductivity, abundant accessible dopant species, as well as proper porosity. Our method offers a new avenue for constructing electrocatalysts by effective integration of ZIF-8-derived carbon and the CNTs skeleton.

MicroRNA-145 Mediates Steroid-Induced Necrosis of the Femoral Head by Targeting the OPG/RANK/RANKL Signaling Pathway.

OBJECTIVE: To investigate the role of microRNA-145 (miR-145) in steroid-induced necrosis of the femoral head (SINFH) by evaluating its effects on the OPG/RANK/RANKL signaling pathway. METHODS: A rat model of SINFH was constructed via injection of the lentiviral vector pLV-shRNA-miR-145. Pathological observation was performed via tartrate-resistant acid phosphatase (TRAP) staining, and serum OPG levels were detected by ELISA. The mRNA expression levels of miR-145, OPG, RANK and RANKL in THP-1 cells were assessed by RT-PCR, and the protein expression levels of OPG, RANK and RANKL were assessed by western blotting. RESULTS: The expression of miR-145 in the lentivirus-mediated miR-145 group was significantly up-regulated compared with that in the control and normal groups (both P < 0.01). Serum OPG levels were decreased in SINFH rats compared with control and normal rats. The mRNA and protein expression levels of OPG in THP-1 cells decreased after transfection (all P < 0.05). By contrast, the mRNA and protein expression levels of RANK and RANKL in THP-1 cells increased after transfection (all P < 0.05). After transfection of 293T cells with an miR-145 overexpression vector, miR-145 expression in 293T cells increased significantly, while OPG mRNA and protein expression decreased significantly (all P < 0.05). CONCLUSION: MiR-145 plays a role in the occurrence of SINFH by targeting the OPG/RANK/RANKL signaling pathway.

Dual-Emission Luminescence of Magnesium Coordination Polymers Based on Mixed Organic Ligands.

Presented herein are two luminescent magnesium coordination polymers (Mg-CPs), namely [Mg2 (H2O)2 (2-NDC)4 (1,10-phen)2] (1) and [Mg2 (H2O)(1,4-NDC)2 (1,10-phen)] (2), in which 2-NDCH=2-naphthalenecarboxylic acid, 1,4-NDCH2 =1,4-naphthalene dicarboxylic acid, and 1,10-phen=1,10-phenanthroline. Based on the mixed ligands, the title compounds exhibit linker-based photoluminescence (PL) properties thanks to the unique configuration of the Mg(2+) ions. The two compounds show interesting dual emission on excitation of the different luminophores of the mixed linkers. In particular, the emissions of compound 2 could be tuned from green to yellow simply by varying the excitation energies. Furthermore, 2 could be excited by using a commercial λ=450 nm blue LED chip to generate white-light emission, which allows the fabrication of a white-light-emitting diode (WLED) with 20 lm W(-1) luminous efficacy. This work may provide a new method for designing tunable PL CPs by using the low-cost and abundant magnesium ion.

Tunable photoluminescence and direct white-light emission in Mg-based coordination networks.

The bpy, dpe and dppe were introduced as auxiliary ligands, respectively, to construct three magnesium-1,4-NDC coordination polymers (Mg-CPs) that exhibited tunable photoluminescence (PL) and direct white-light emission upon varying the excitation light.