Smurf1-targeting microRNA-136-5p-modified bone marrow mesenchymal stem cells combined with 3D-printed ß-tricalcium phosphate scaffolds strengthen osteogenic activity and alleviate bone defects.

Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR-136-5p or Smurf1 expression were transfected into BMSCs. The effects of miR-136-5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR-136-5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR-136-5p/BMSCs/ß-TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro-CT and HE staining. Elevating miR-136-5p-3p or suppressing Smurf1 could stimulate OD of BMSCs. miR-136-5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR-136-5p on the OD of BMSCs. miR-136-5p/BMSCs/ß-TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1-targeting miR-136-5p-modified BMSCs combined with 3D-printed ß-TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.

A ratiometric radio-photoluminescence dosimeter based on a radical excimer for X-ray detection.

A novel radio-photoluminescence material featuring fluorochromic responses toward UV or X-ray irradiation has been obtained. Such a unique monomer- to excimer-based luminescence transition allows for dosimetry of ionizing radiation in a ratiometric manner. Rather than quenching the luminescence, the radiation-induced radical species of Th-105 boost the excimer emission, rendering it as a rare material possessing radical-excimers.

Adsorption and Detection of Iodine Species by a Thorium-Based Metal-Organic Framework.

Actinide-bearing metal-organic frameworks (MOFs) encompass intriguing structures and properties, but the radioactivity of actinide cripples their applications. Herein, we have constructed a new thorium-based MOF (Th-BDAT) as a bifunctional platform for the adsorption and detection of radioiodine, a more radioactive fission product that can readily spread through the atmosphere in its molecular form or via solution as anionic species. The iodine capture within the framework of Th-BDAT from both the vapor phase and the cyclohexane solution has been verified, showing that Th-BDAT features maximum I2 adsorption capacities (Qmax) of 959 and 1046 mg/g, respectively. Notably, the Qmax of Th-BDAT toward I2 from cyclohexane solution ranks among the highest value for Th-MOFs reported to date. Furthermore, incorporating highly extended and π-electron-rich BDAT4- ligands renders Th-BDAT as a luminescent chemosensor whose emission can be selectively quenched by iodate with a detection limit of 1.367 µM. Our findings thus foreshadow promising directions that might unlock the full potential of actinide-based MOFs from the point of view of practical application.

A robust thorium-organic framework as a bifunctional platform for iodine adsorption and Cr(VI) sensitization.

Simple synthetic modulation based on thorium nitrate and tris((4-carboxyl)phenylduryl)amine (H3TCBPA) gives rise to a new thorium-based metal-organic framework, Th-TCBPA, which features excellent hydrolytic and thermal stabilities. Incorporating electron-rich TCBPA3- linkers not only endows Th-TCBPA with high adsorption capacity toward radioiodine vapor, but also makes it a luminescence sensor for the highly sensitive and selective detection of Cr(VI) anions.

Stepwise Crystallization of Millimeter Scale Thorium Cluster Single Crystals as a Bifunctional Platform for X-ray Detection and Shielding.

Monitoring and shielding of X-ray radiation are of paramount importance across diverse fields. However, they are frequently realized in separate protocols and a single material integrating both functions remained elusive. Herein, a hexanuclear cluster [Th6 (µ3 -OH)4 (µ3 -O)4 (H2 O)6 ](pba)6 (HCOO)6 (Th-pba-0D) incorporating high-Z thorium cations and 3-(pyridin-4-yl)benzoate ligands that can function as a brand-new dual-module platform for visible detection and efficient shielding of ionizing radiation is demonstrated. Th-pba-0D exhibits rather unique reversible radiochromism upon alternating X-ray and UV irradiation. Moreover, the millimeter scale crystal size of Th-pba-0D renders the penetration depth of X-ray visible to naked eye and leads to the unearthing of its high X-ray attenuation efficiency. Indeed, the shielding efficacy of Th-pba-0D is comparable to that of lead glass containing 40% PbO, and a Th-pba-0D pellet with a thickness of merely 1.2 mm can shield 99.73% X-ray (16 keV). These studies portend the possible utilization of thorium-bearing materials as a bifunctional platform for radiation detection and shielding.

Ginsenoside Re Attenuates Cisplatin-Induced Intestinal Toxicity via Suppressing GSK-3ß-Dependent Wnt/ß-Catenin Signaling Pathway In Vivo and In Vitro.

Previous reports have confirmed that crude saponins (ginsenosides) in Panax ginseng have a preventive effect on chemotherapy-induced intestinal injury. However, the protective effects and possible mechanisms of ginsenoside Re (G-Re, a maker saponin in ginseng) against chemotherapy-induced intestinal damage have not been thoroughly studied. In this work, a series of experiments in vivo and in vitro on the intestinal toxicity caused by cisplatin have been designed to verify the improvement effect of G-Re, focusing on the levels of Wnt3a and [Formula: see text]-catenin. Mice were intragastric with G-Re for 10 days, and intestinal injury was induced by intraperitoneal administration of cisplatin at a dose of 20 mg/kg. Histopathology, gastrointestinal digestive enzyme activities, inflammatory cytokines, and oxidative status were evaluated to investigate the protective effect. Furthermore, in IEC-6 cells, G-Re statistically reverses cisplatin-induced oxidative damage and cytotoxicity. The TUNEL and Hoechst 33258 staining demonstrated that G-Re possesses protective effects in cisplatin-induced apoptosis. Additionally, pretreatment with G-Re significantly alleviated the apoptosis via inhibition of over-expressions of B-associated X (Bax), as well as the caspase family members, such as caspase 3 and 9, respectively, in vivo and in vitro. Notably, western blotting results showed that G-Re treatment decreased Wnt3a, Glycogen synthase kinase [Formula: see text] (GSK-[Formula: see text]), and [Formula: see text]-catenin expression, suggesting that nuclear accumulation of [Formula: see text]-catenin was attenuated, thereby inhibiting the activation of GSK-[Formula: see text]-dependent Wnt/[Formula: see text]-catenin signaling, which was consistent with our expected results. Therefore, the above evidence suggested that G-Re may be a candidate drug for the treatment of intestinal injury.

Luminometric dosimetry of X-ray radiation by a zwitterionic uranium coordination polymer.

A novel X-ray dosimeter based on a uranium coordination polymer U-Cbdcp was obtained by the judicious synergy between the luminescent uranyl centres and zwitterionic tritopic ligands. Notably, U-Cbdcp exhibits luminescence quenching upon increasing X-ray dose, which in combination with its excellent radiolytic stability, makes it suitable for X-ray dosimetry.

Recent advances in the applications of thorium-based metal-organic frameworks and molecular clusters.

This perspective highlights the recent advances in the structural and practical aspects of thorium-based metal-organic frameworks (Th-MOFs) and molecular clusters. Thorium, as an underexplored actinide, features surprisingly rich coordination geometries and accessibility of the 5f orbital. These features lead to a myriad of topologies and electronic structures, many of which are undocumented for other tetravalent metal-containing MOFs or clusters. Moreover, Th-MOFs inherit the modularity, structural tunability, porosity, and versatile functionality of the state-of-the-art MOFs. Recognizing the radioactive nature of these thorium-bearing materials that may limit their practical uses, Th-MOFs and Th-clusters still have great potential for various applications, including radionuclide sequestration, hydrocarbon storage/separation, radiation detection, photoswitch, CO2 conversion, photocatalysis, and electrocatalysis. The objective of this updated perspective is to propose pathways for the renaissance of interest in thorium-based materials.

Study the effects of dry-wet cycles and cadmium pollution on the mechanical properties and microstructure of red clay.

In order to study the effect of cadmium ions on the mechanical properties and micro-structure characteristics of the red clay in Guilin, we have conducted triaxial test and the scanning electron microscope tests to analyze the effects of cadmium ion concentration and the number of dry and wet cycles on the mechanical properties and micro-structure changes of the red clay. The results showed the effects of cadmium ions and dry-wet cycles destroy the structure of red clay. The cohesive force of red clay decreases with the increase of cadmium ion concentration, and the internal friction angle first increases and then decreases. With the rise in the number of dry and wet cycles, the cohesive force of cadmium-contaminated red clay first increases and then decreases, and the angle of internal friction rises gradually. Under the action of different cadmium ion concentrations, the stress-strain curve is strain hardening. With the concentration of cadmium ions increases, the strain hardening becomes more apparent; the peak value reached faster. and the axial strain corresponding to the peak value of the line decreases. With the increase in the number of wet and dry cycles, the volume of cadmium-contaminated red clay shrinks and its compactness increases; it gets the peak shear strength faster during the shearing process, and its peak value becomes larger and larger. The main reason for the phenomenon is that cadmium ions destroy the cementation between the particles. The soil particles are mainly in point contact which loosens the structure of the soil; on the other hand, the thickness of the surface diffusion layer of the clay particles increases through chemical action, The exchange of cations increases the porosity of the soil and weakens its strength. The dry-wet cycle shrinks the volume of the red clay, and the soil particles are mainly in surface contact; as the number of dry-wet cycles increases, the soil particles connection is closer, the soil porosity decreases and the strength increases.

A New Concept of Radiation Detection Based on a Fluorochromic and Piezochromic Nanocluster.

Developing materials that possess colorimetric responses to external stimuli is a promising strategy for addressing the current challenges in radiation dosimetry. Currently, colorimetric ionizing-radiation-responsive materials remain underexplored, and those with multistimuli response are rare. Herein, the integration of thorium cation and photoresponsive terpyridine carboxylate ligand gives rise to a thorium nanocluster, Th-101, which displays the second case of fluorochromic response and unprecedented piezochromic behavior among all actinide materials. The emission color of Th-101 exhibits a gradual transition from blue to cyan to green upon irradiation with accumulated dose, which renders colorimetric dosimetry of ionizing radiation based on a red-green-blue (RGB) concept. Further fabricating Th-101 into a custom-built optoelectronic device allows for on-site quantification of radiation dose with merits of ease of operation, rapid readout, and cost-effectiveness.

Emergence of Thorium-Based Polyoxo Clusters as a Platform for Selective X-ray Dosimetry.

A brand-new application of thorium-bearing clusters in the field of ionizing radiation detection is exemplified by two novel hexanuclear thorium clusters, Th-bppCOO-1 and Th-bppCOO-2, which incorporate carboxylate-functionalized 2,6-di(pyrazol-1-yl)pyridine ligands. Notably, Th-bppCOO-1 is composed of an unprecedented [Th6(OH)4O4(H2O)5]12+ secondary building unit, the Th6 core of which is decorated by five H2O molecules. Furthermore, selective photoluminescence quenching responses of Th-bppCOO-1 and Th-bppCOO-2 toward X-ray over UV radiation have been demonstrated for the first time.

Protective Effect of 20(R)-Ginsenoside Rg3 Against Cisplatin-Induced Renal Toxicity via PI3K/AKT and NF-[Formula: see text]B Signaling Pathways Based on the Premise of Ensuring Anticancer Effect.

Although the protective effect of ginsenoside on cisplatin-induced renal injury has been extensively studied, whether ginsenoside interferes with the antitumor effect of cisplatin has not been confirmed. In this paper, we verified the main molecular mechanism of 20(R)-ginsenoside Rg3 (R-Rg3) antagonizing cisplatin-induced acute kidney injury (AKI) through the combination of in vivo and in vitro models. It is worth mentioning that the two cell models of HK-2 and HepG2 were used simultaneously for the first time to explore the effect of the activation site of tumor-associated protein p53 on apoptosis and tumor suppression. The results showed that a single injection of cisplatin (20 mg/kg) led to weight loss, the kidney index of the mice increased, and creatinine (CRE) and blood urea nitrogen (BUN) levels in mice sharply increased. Continuous administration of R-Rg3 at doses of 10 and 20 mg/kg for 10 days could significantly alleviate this symptom. Similarly, R-Rg3 treatment reduced oxidative stress damage caused by cisplatin. Moreover, R-Rg3 could observably reduce the apoptosis and inflammatory infiltration of renal tubular cells induced by cisplatin. We used western blotting analysis to demonstrate that R-Rg3 restored cisplatin-induced AKI might be related to PI3K/AKT and NF-[Formula: see text]B mediated apoptosis and inflammation pathways. In the meantime, we also verified that R-Rg3 could activate different sites of p53 to control renal cell apoptosis induced by cisplatin without affecting its antitumor effect.

Emergence of a thorium-organic framework as a radiation attenuator for selective X-ray dosimetry.

By first applying a thorium-organic framework (Th-SINAP-2) as a radiation attenuator and by incorporating a terpyridine derivative (Htpbz) as a photo-responsive guest, selective photochromism in response to X-rays was achieved in the host-guest assembly of Htpbz@Th-SINAP-2. Such a combination endows the afforded material with the lowest detection limit of X-ray dose among all photochromic sensors and a brand-new function of X-ray dosimetry for thorium containing materials.

Interpenetration Control in Thorium Metal-Organic Frameworks: Structural Complexity toward Iodine Adsorption.

The rational design and synthesis of metal-organic frameworks with well-controlled interpenetration have been active research areas of inquiry, particularly for porosity-related applications. Herein, we extend the use of the ligand steric modulation strategy to initiate the first study of the interpenetration control of thorium-based MOFs. The approximate "hardness" of the Th4+ cation, which was conjugated with aromatic substitutions and delicately modified synthetic conditions, allows for the crystallization of single crystals of seven new Th-MOFs with five distinct topologies. Solvothermal reactions of Th(NO3)4 with the triphenyl H2TPDC ligand under variable conditions exclusively gave rise to an interpenetrated Th-MOF with a hex topology, namely Th-SINAP-16. Modifications of the ligand sterics with two pendant methyl groups to 2',5'-Me2TPDC2- and 2,2″-Me2TPDC2- afforded two noninterpenetrated UiO-68-type Th-MOFs (Th-SINAP-17 and Th-SINAP-20, respectively) with record-high pore volumes (74.8% and 75.3%, respectively) among all the thorium MOFs. Moreover, another four Th-MOFs Th-SINAP-n (n = 18, 19, 21, and 22) with three different topologies were obtained by a simple synthetic modulation. Notably, Th-SINAP-16 and Th-SINAP-21 represent the second rare examples of interpenetrated Th-MOFs reported to date. These findings revealed the unprecedented structural complexity and synthetic accessibility of Th-MOFs among all tetravalent metal containing MOFs. Such features make Th-MOFs as an ideal platform to elucidate the structure-property relationship for various applications, e.g. iodine adsorption.

A cationic thorium-organic framework with triple single-crystal-to-single-crystal transformation peculiarities for ultrasensitive anion recognition.

Single-crystal-to-single-crystal transformation of metal-organic frameworks has been met with great interest, as it allows for the creation of new materials in a stepwise manner and direct visualization of structural transitions when subjected to external stimuli. However, it remains a peculiarity among numerous metal-organic frameworks, particularly for the ones constructed from tetravalent metal cations. Herein, we present a cationic thorium-organic framework displaying unprecedented triple single-crystal-to-single-crystal transformations in organic solvents, water, and NaIO3 solution. Notably, both the interpenetration conversion and topological change driven by the SC-SC transformation have remained elusive for thorium-organic frameworks. Moreover, the single-crystal-to-single-crystal transition in NaIO3 solution can efficiently and selectively turn the ligand-based emission off, leading to the lowest limit of detection (0.107 µg kg-1) of iodate, one of the primary species of long-lived fission product 129I in aqueous medium, among all luminescent sensors.

Evaluating Surgical Risk Using FMEA and MULTIMOORA Methods under a Single-Valued Trapezoidal Neutrosophic Environment.

BACKGROUND: Human errors during operations may seriously threaten patient recovery and safety and affect the doctor-patient relationship. Therefore, risk evaluation of the surgical process is critical. Risk evaluation by failure mode and effect analysis (FMEA) is a prospective technology that can identify and evaluate potential failure modes in the surgical process to ensure surgical quality and patient safety. In this study, a hybrid surgical risk-evaluation model was proposed using FMEA and multiobjective optimization on the basis of ratio analysis plus full multiplicative form (MULTIMOORA) method under a single-valued trapezoidal neutrosophic environment. This work aimed to determine the most critical risk points during the surgical process and analyze corresponding solutions. METHODS: A team for FMEA was established from domain experts from different departments in a hospital in Hunan Province. Single-valued trapezoidal neutrosophic numbers (SVTNNs) were used to evaluate potential risk factors in the surgical process. Cmprehensive weights combining subjective and objective weights were determined by the best-worst method and entropy method to differentiate the importance of risk factors. The SVTNN-MULTIMOORA method was utilized to calculate the risk-priority order of failure modes in a surgical process. RESULTS: The hybrid FMEA model under the SVTNN-MULTIMOORA method was used to calculate the ranking of severity of 21 failure modes in the surgical process. An unclear diagnosis is the most critical failure in the surgical process of a hospital in Hunan Province. CONCLUSION: The proposed model can identify and evaluate the most critical potential failure modes of the surgical process effectively. In addition, such a model can help hospitals to reduce surgical risk and improve the safety of surgery.

Rare Ginsenoside 20(R)-Rg3 Inhibits D-Galactose-Induced Liver and Kidney Injury by Regulating Oxidative Stress-Induced Apoptosis.

Oxidative stress is considered as a major factor in aging and exacerbates aging process through a variety of molecular mechanisms. D-galactose, a normal reducing sugar with high dose can cause the accumulation of reactive oxygen species (ROS) or stimulate free radical production indirectly by the formation of advanced glycation end products in tissues, finally resulting in oxidative stress. 20(R)-ginsenoside Rg3 (20(R)-Rg3), a major and representative component isolated from red ginseng (Panax ginseng C.A Meyer), has been shown to observably have an anti-oxidative effect. We thereby investigated the beneficial effects of 20(R)-Rg3 on D-galactose-induced oxidative stress injury and its underlying mechanisms. Our results showed that continuous injection of D-galactose with 800[Formula: see text]mg/kg/day for 8 weeks increased the levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). However, such increases were attenuated by the treatment of 20(R)-Rg3 for 4 weeks. Meanwhile, 20(R)-Rg3 markedly inhibited D-galactose-caused oxidative stress in liver and kidney. The anti-oxidants, including catalase (CAT) and superoxide dismutase (SOD), were elevated in the mice from 20(R)-Rg3-treated group compared with that from D-galactose group. In contrast, a significant decrease in levels of cytochrome P450 E1 (CYP2E1) and the lipid peroxidation product malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were observed in the 20(R)-Rg3-treated group. These effects were associated with a significant increase of AGEs. More importantly, 20(R)-Rg3 effectively attenuated D-galactose induced apoptosis in liver and kidney via restoring the upstream PI3K/AKT signaling pathway. Taken together, our study suggests that 20(R)-Rg3 may be a novel and promising anti-oxidative therapeutic agent to prevent aging-related injuries in liver and kidney.

Red ginseng protects against cisplatin-induced intestinal toxicity by inhibiting apoptosis and autophagy via the PI3K/AKT and MAPK signaling pathways.

Although growing evidence has shown that ginseng (Panax ginseng C.A. Meyer.) exerts strong protective and preventive effects on cisplatin-induced side effects, including nephrotoxicity, ototoxicity and cardiotoxicity, the ameliorative effects of ginseng on intestinal damage caused by cisplatin are unknown to date. Red ginseng (RG), a major processed product of the roots of Panax ginseng C.A. Meyer, can be used to control chemotherapy drug-induced multiple toxicity. In the present work, an animal model of cisplatin-induced intestinal injury was established to evaluate the ameliorative effects of RG and their underlying molecular mechanism for the first time. The results showed that a single cisplatin injection (20 mg kg-1) leads to loss of body weight, shrinkage of the small intestine, and sharp increase of the intestinal function index of diamine oxidase (DAO). These symptoms were remarkably relieved after the administration of RG at 300 and 600 mg kg-1 for 10 continuous days, respectively. In addition, RG markedly reduced the increase in malondialdehyde (MDA) levels and the consumption of superoxide dismutase (SOD) and catalase (CAT) caused by cisplatin-induced oxidative stress. Furthermore, RG pretreatment dramatically improved the cisplatin-induced apoptosis of intestinal villous cells, irregular nuclear arrangement, ablation of crypt cells, and damage to the mechanical barrier. In this study, pharmacological methods have been used to prove that RG can inhibit cisplatin intestinal toxicity by activating the PI3K/AKT signaling pathway to inhibit apoptosis and by antagonizing the MAPK-mediated autophagy pathway.

Ultrastable Thorium Metal-Organic Frameworks for Efficient Iodine Adsorption.

Two novel thorium-based metal-organic frameworks (MOFs), namely Th-SINAP-7 and Th-SINAP-8, have been synthesized via the solvothermal reactions of thorium nitrate and 1,4- or 2,6-naphthalenedicarboxylic acid in the presence of acid modulators. Bearing the rigid aromatic architectures, Th-SINAP-7 and Th-SINAP-8 exhibit exceptional chemical (from pH 1 to 12) and thermal stabilities (up to 520 °C), as well as ionizing radioresistance (2 × 105 Gy ß and γ irradiations). The highly porous nature and conjugated π-electrons of naphthalene on the organic linkers endow high affinity of both MOFs toward I2 molecules owning to the charge transfer between π-electrons of the host networks and the guest iodine molecules, as evidenced by combined techniques including of FTIR, PXRD, SEM-EDS, UV-vis spectroscopy, XPS, and Raman spectroscopy. Particularly, Th-SINAP-8 can efficiently remove >99% I2 from cyclohexane solution and exhibit guest uptake of iodine vapor with an adsorption capacity of 473 mg/g.

[Ln6O8] Cluster-Encapsulating Polyplumbites as New Polyoxometalate Members and Record Inorganic Anion-Exchange Materials for ReO4 - Sequestration.

Various types of polyoxometalates (POMs) have been synthesized since the 19th century, but their assortment has been mostly limited to Groups 5 and 6 metals. Herein, a new family of POMs composed of a carbon group element as the addenda atoms with two distinct phases, LnPbOClO4-1 (Ln = Sm to Ho, Y) and LnPbOClO4-2 (Ln = Er and Tm) is reported. Both structures are built from [Ln6O8] rare-earth metal hexamers being incorporated in [Pb18O32]/[Pb12O24] polyplumbites, and unbound perchlorates as charge-balancing anions. Impressively, YPbOClO4-1 and ErPbOClO4-2 exhibit exceptional uptake capacities (434.7 and 427.7 mg g-1) toward ReO4 -, a chemical surrogate for the key radioactive fission product in the nuclear fuel cycle 99TcO4 -, which are the highest values among all inorganic anion-exchange materials reported until now. The sorption mechanism is clearly elucidated and visualized by single-crystal-to-single-crystal structural transformation from ErPbOClO4-2 to a perrhenate-containing complex ErPbOReO4 , revealing a unique ReO4 - uptake selectivity driven by specific interaction within Pb···O-ReO3 - bonds.