Integrating Photoactive Ligands into Crystalline Ultrathin 2D Metal-Organic Framework Nanosheets for Efficient Photoinduced Energy Transfer.

3D metal-organic frameworks (MOFs) have gained attention as heterogeneous photocatalysts due to their porosity and unique host-guest interactions. Despite their potential, MOFs face challenges, such as inefficient mass transport and limited light penetration in photoinduced energy transfer processes. Recent advancements in organic photocatalysis have uncovered a variety of photoactive cores, while their heterogenization remains an underexplored area with great potential to build MOFs. This gap is bridged by incorporating photoactive cores into 2D MOF nanosheets, a process that merges the realms of small-molecule photochemistry and MOF chemistry. This approach results in recyclable heterogeneous photocatalysts that exhibit an improved mass transfer efficiency. This research demonstrates a bottom-up synthetic method for embedding photoactive cores into 2D MOF nanosheets, successfully producing variants such as PCN-641-NS, PCN-643-NS, and PCN-644-NS. The synthetic conditions were systematically studied to optimize the crystallinity and morphology of these 2D MOF nanosheets. Enhanced host-guest interactions in these 2D structures were confirmed through various techniques, particularly solid-state NMR studies. Additionally, the efficiency of photoinduced energy transfer in these nanosheets was evidenced through photoborylation reactions and the generation of reactive oxygen species (ROS).

Crystal Structure and Optical Properties Characterization in Quasi-0D Lead-Free Bromide Crystals (C6H14N)3Bi2Br9·H2O and (C6H14N)3Sb3Br12.

Low dimensional organic inorganic metal halide materials have shown broadband emission and large Stokes shift, making them widely used in various fields and a promising candidate material. Here, the zero-dimensional lead-free bromide single crystals (C6H14N)3Bi2Br9·H2O (1) and (C6H14N)3Sb3Br12 (2) were synthesized. They crystallized in the monoclinic crystal system with the space group of P21 and P21/n, respectively. Through ultraviolet-visible-near-infrared (UV-vis-NIR) absorption analysis, the band gaps of (C6H14N)3Bi2Br9·H2O and (C6H14N)3Sb3Br12 are found to be 2.75 and 2.83 eV, respectively. Upon photoexcitation, (C6H14N)3Bi2Br9·H2O exhibit broad-band red emission peaking at 640 nm with a large Stokes shift of 180 nm and a lifetime of 2.94 ns, and the emission spectrum of (C6H14N)3Sb3Br12 are similar to those of (C6H14N)3Bi2Br9·H2O. This exclusive red emission is ascribed to the self-trapping exciton transition caused by lattice distortion, which is confirmed through both experiments and first-principles calculations. In addition, due to the polar space group structure and the large spin-orbit coupling (SOC) associated with the heavy elements of Bi and Br of crystal 1, an obvious Rashba effect was observed. The discovery of organic inorganic metal bromide material provides a critical foundation for uncovering the connection between 0D metal halide materials' structures and properties.

Advancing ASD identification with neuroimaging: a novel GARL methodology integrating Deep Q-Learning and generative adversarial networks.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects an individual's behavior, speech, and social interaction. Early and accurate diagnosis of ASD is pivotal for successful intervention. The limited availability of large datasets for neuroimaging investigations, however, poses a significant challenge to the timely and precise identification of ASD. To address this problem, we propose a breakthrough approach, GARL, for ASD diagnosis using neuroimaging data. GARL innovatively integrates the power of GANs and Deep Q-Learning to augment limited datasets and enhance diagnostic precision. We utilized the Autistic Brain Imaging Data Exchange (ABIDE) I and II datasets and employed a GAN to expand these datasets, creating a more robust and diversified dataset for analysis. This approach not only captures the underlying sample distribution within ABIDE I and II but also employs deep reinforcement learning for continuous self-improvement, significantly enhancing the capability of the model to generalize and adapt. Our experimental results confirmed that GAN-based data augmentation effectively improved the performance of all prediction models on both datasets, with the combination of InfoGAN and DQN's GARL yielding the most notable improvement.

Investigating the Cell Entry Mechanism, Disassembly, and Toxicity of the Nanocage PCC-1: Insights into Its Potential as a Drug Delivery Vehicle.

The porous coordination cage PCC-1 represents a new platform potentially useful for the cellular delivery of drugs with poor cell permeability and solubility. PCC-1 is a metal-organic polyhedron constructed from zinc metal ions and organic ligands through coordination bonds. PCC-1 possesses an internal cavity that is suitable for drug encapsulation. To better understand the biocompatibility of PCC-1 with human cells, the cell entry mechanism, disassembly, and toxicity of the nanocage were investigated. PCC-1 localizes in the nuclei and cytoplasm within minutes upon incubation with cells, independent of endocytosis and cargo, suggesting direct plasma membrane translocation of the nanocage carrying its guest in its internal cavity. Furthermore, the rates of cell entry correlate to extracellular concentrations, indicating that PCC-1 is likely diffusing passively through the membrane despite its relatively large size. Once inside cells, PCC-1 disintegrates into zinc metal ions and ligands over a period of several hours, each component being cleared from cells within 1 day. PCC-1 is relatively safe for cells at low micromolar concentrations but becomes inhibitory to cell proliferation and toxic above a concentration or incubation time threshold. However, cells surviving these conditions can return to homeostasis 3-5 days after exposure. Overall, these findings demonstrate that PCC-1 enters live cells by crossing biological membranes spontaneously. This should prove useful to deliver drugs that lack this capacity on their own, provided that the dosage and exposure time are controlled to avoid toxicity.

Single-cell analysis reveals dynamic changes of neural cells in developing human spinal cord.

During central nervous system development, neurogenesis and gliogenesis occur in an orderly manner to create precise neural circuitry. However, no systematic dataset of neural lineage development that covers both neurogenesis and gliogenesis for the human spinal cord is available. We here perform single-cell RNA sequencing of human spinal cord cells during embryonic and fetal stages that cover neuron generation as well as astrocytes and oligodendrocyte differentiation. We also map the timeline of sensory neurogenesis and gliogenesis in the spinal cord. We further identify a group of EGFR-expressing transitional glial cells with radial morphology at the onset of gliogenesis, which progressively acquires differentiated glial cell characteristics. These EGFR-expressing transitional glial cells exhibited a unique position-specific feature during spinal cord development. Cell crosstalk analysis using CellPhoneDB indicated that EGFR glial cells can persistently interact with other neural cells during development through Delta-Notch and EGFR signaling. Together, our results reveal stage-specific profiles and dynamics of neural cells during human spinal cord development.

Synthesis of Fluoro-Bridged Ho3+ and Gd3+ 1,3,5-Tris(4-carboxyphenyl)benzene Metal-Organic Frameworks from Perfluoroalkyl Substances.

A new fluoro-bridged rare-earth (RE) metal-organic framework consisting of 15-connected nonanuclear and 9-connected trinuclear clusters {[RE9-(µ3-F)14(H2O)6][RE3(µ3-F)(H2O)3](HCO2)3-(BTB)6}·(solvent)x 2 (RE = Ho3+ and Gd3+) was synthesized through the transformation of a dimeric complex formulated as bis(2,2'-bipyridine)tetrakis(µ-2-fluorobenzoato-O,O')-bis(2-fluorobenzoato)diRE(III) 1 with the bridging linker 1,3,5-tris(4-carboxyphenyl)benzene (H3BTB). The rare-earth metal ions Ho3+ and Gd3+ were also found to remove fluorine from other organo-fluorine compounds such as perfluorohexanoic acid (PFHxA) and perfluorooctanoic acid (PFOA), resulting in the new fluoro-bridged RE-MOFs.

Protective Effect of Illicium Verum Extract On Vascularization In Rats With Osteoporotic Fracture.

Objective: To investigate the protective effect of Illicium verum extract on the vascularization of osteoporotic fracture in rats, and to elucidate its potential mechanism. Methods: The osteoporotic fracture model was established in ovariectomized rats. Rats were infused with 0.05 ml/kg extract in the stomach every morning. Eighteen rats are then divided into control group, model group, and Illicium verum extract group with 6 rats in each group. To observe the therapeutic effect of Illicium verum extract on osteoporotic rats. Femoral bone mineral density and elastic segment end-point load were evaluated by dual-energy x-ray absorptiometry and three-point bending test. Hematoxylin-eosin staining was used to measure the number and area of callus blood vessels. The serum levels of VEGF and NO were detected by ELISA. Moreover, the expressions of NOX2, NOX4, NRF2, p-PI3K, CyclinD1, VEGF, HIF1α, and eNOS in HUVEC were detected by Western blot. CCK8 and wound healing assay were used to detect the proliferation and migration of HUVEC. Then, the ability of HUVEC to form blood vessels was detected by tube formation assay. Results: Firstly, control group showed the normal pathomorphology and density of femoral bone, and model group showed significantly decreased bone density and consistent with bone microstructure degeneration, destruction, thinning, and fracture of bone trabecular structure vs control group, and illicium verum extract significantly increased femoral density and maximum load, increased the number and area of callus blood vessels and increased VEGF and NO levels in serum vs model group. Then, Illicium verum extract promoted the expression of NRF2, p-PI3K, CyclinD1, VEGF, HIF1α, and eNOS protein in HUVEC, inhibited the expression of NOX2 and NOX4, and enhanced the cell proliferation, migration, and angiogenesis. However, the effect was reversed by the overexpression of NRF2 and the treatment with LY294002. Conclusion: Illicium verum extract protects the vascularization of the osteoporotic fracture model in rats.

Direct neuronal differentiation of neural stem cells for spinal cord injury repair.

Spinal cord injury (SCI) typically results in long-lasting functional deficits, largely due to primary and secondary white matter damage at the site of injury. The transplantation of neural stem cells (NSCs) has shown promise for re-establishing communications between separated regions of the spinal cord through the insertion of new neurons between the injured axons and target neurons. However, the inhibitory microenvironment that develops after SCI often causes endogenous and transplanted NSCs to differentiate into glial cells rather than neurons. Functional biomaterials have been shown to mitigate the effects of the adverse SCI microenvironment and promote the neuronal differentiation of NSCs. A clear understanding of the mechanisms of neuronal differentiation within the injury-induced microenvironment would likely allow for the development of treatment strategies designed to promote the innate ability of NSCs to differentiate into neurons. The increased differentiation of neurons may contribute to relay formation, facilitating functional recovery after SCI. In this review, we summarize current strategies used to enhance the neuronal differentiation of NSCs through the reconstruction of the SCI microenvironment and to improve the intrinsic neuronal differentiation abilities of NSCs, which is significant for SCI repair.

Electric field and strain engineering tuning Rashba spin splitting in quasi-one-dimensional organic-inorganic hybrid perovskites (MV)AI3Cl2 (MV = methylviologen, A = Bi, Sb).

We systematically study the Rashba spin texture of lead-free quasi-one-dimensional organic-inorganic hybrid perovskites (OIHP), (MV)AI3Cl2 (MV = methylviologen, A = Bi, Sb) with first-principles calculations. The kx-ky plane Rashba spin splitting was found to depend on the composition of Bi (Sb) and I atoms at band edges. Importantly, increasing ferroelectric polarization and the stretch along the z-direction can effectively enhance the amplitude of the Rashba spin splitting. This work provides an avenue for electric field and strain-controlled spin splitting and highlights the potential of quasi-one-dimensional OIHP for further applications in spin field effect transistors and photovoltaic cells.

Assembling Phenothiazine into a Porous Coordination Cage to Improve Its Photocatalytic Efficiency for Organic Transformations.

Photo-catalysis by small-molecules is often limited by catalyst degradation and low electron-transfer efficiency. Herein we report a stable N-phenyl-phenothiazine (PTH)-derived porous coordination cage (PCC) as a highly efficient photocatalyst. By the incorporation of the photocatalytic PTH moiety into a PCC, aggregation-induced quenching (AIQ) was shown to be reduced. An improvement in catalyst stability was discovered, ascribed to the synergistic effects of the PTH moieties. The catalyst, operating through a photolytic single-electron transfer, was utilized for photo-catalyzed dehalogenation and borylation. Evaluation of the catalytic mechanism in the borylation reaction showed that the improved performance results from the more efficient formation of the electron donor-acceptor (EDA) complex with the cage. This discovery provides a potential strategy to improve the photophysical properties and stabilities of small-molecule organic photocatalysts via supramolecular chemistry.

Homochiral Dodecanuclear Lanthanide "Cage in Cage" for Enantioselective Separation.

It is extremely difficult to anticipate the structure and the stereochemistry of a complex, particularly when the ligand is flexible and the metal node adopts diverse coordination numbers. When trivalent lanthanides (LnIII) and enantiopure amino acid ligands are utilized as building blocks, self-assembly sometimes yields rare chiral polynuclear structures. In this study, an enantiopure carboxyl-functionalized amino acid-based ligand with C3 symmetry reacts with lanthanum cations to give a homochiral porous coordination cage, (Δ/Λ)12-PCC-57. The dodecanuclear lanthanide cage has an unprecedented octahedral "cage-in-cage" framework. During the self-assembly, the chirality is transferred from the enantiopure ligand and fixed by the binuclear lanthanide cluster to give 12 metal centers that have either Δ or Λ homochiral stereochemistry. The cage exhibits excellent enantioselective separation of racemic alcohols, 2,3-dihydroquinazolinones, and multiple commercially available drugs. This finding exhibits a rare example of a multinuclear lanthanide complex with a dual-walled topology and homochirality. The highly ordered self-assembly and self-sorting of flexible amino acids and lanthanides shed light on the chiral transformation between different complicated artificial systems that mimic natural enzymes.

Tauroursodeoxycholic acid alleviates secondary injury in spinal cord injury mice by reducing oxidative stress, apoptosis, and inflammatory response.

BACKGROUND: Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid derivative, which has been demonstrated to have neuroprotective effects in different neurological disease models. However, the effect and underlying mechanism of TUDCA on spinal cord injury (SCI) have not been fully elucidated. This study aims to investigate the protective effects of TUDCA in the SCI mouse model and the related mechanism involved. METHODS: The primary cortical neurons were isolated from E16.5 C57BL/6 mouse embryos. To evaluate the effect of TUDCA on axon degeneration induced by oxidative stress in vitro, the cortical neurons were treated with H2O2 with or without TUDCA added and immunostained with Tuj1. Mice were randomly divided into sham, SCI, and SCI+TUDCA groups. SCI model was induced using a pneumatic impact device at T9-T10 level of the vertebra. TUDCA (200 mg/kg) or an equal volume of saline was intragastrically administrated daily post-injury for 14 days. RESULTS: We found that TUDCA attenuated axon degeneration induced by H2O2 treatment and protected primary cortical neurons from oxidative stress in vitro. In vivo, TUDCA treatment significantly reduced tissue injury, oxidative stress, inflammatory response, and apoptosis and promoted axon regeneration and remyelination in the lesion site of the spinal cord of SCI mice. The functional recovery test revealed that TUDCA treatment significantly ameliorated the recovery of limb function. CONCLUSIONS: TUDCA treatment can alleviate secondary injury and promote functional recovery by reducing oxidative stress, inflammatory response, and apoptosis induced by primary injury, and promote axon regeneration and remyelination, which could be used as a potential therapy for human SCI recovery.

Epidermal growth factor receptor-extracellular-regulated kinase blockade upregulates TRIM32 signaling cascade and promotes neurogenesis after spinal cord injury.

Nerve regeneration is blocked after spinal cord injury (SCI) by a complex myelin-associated inhibitory (MAI) microenvironment in the lesion site; however, the underlying mechanisms are not fully understood. During the process of neural stem cell (NSC) differentiation, pathway inhibitors were added to quantitatively assess the effects on neuronal differentiation. Immunoprecipitation and lentivirus-induced overexpression were used to examine effects in vitro. In vivo, animal experiments and lineage tracing methods were used to identify nascent neurogenesis after SCI. In vitro results indicated that myelin inhibited neuronal differentiation by activating the epidermal growth factor receptor (EGFR)-extracellular-regulated kinase (ERK) signaling cascade. Subsequently, we found that tripartite motif (TRIM) 32, a neuronal fate-determining factor, was inhibited. Moreover, inhibition of EGFR-ERK promoted TRIM32 expression and enhanced neuronal differentiation in the presence of myelin. We further demonstrated that ERK interacts with TRIM32 to regulate neuronal differentiation. In vivo results indicated that EGFR-ERK blockade increased TRIM32 expression and promoted neurogenesis in the injured area, thus enhancing functional recovery after SCI. Our results showed that EGFR-ERK blockade antagonized MAI of neuronal differentiation of NSCs through regulation of TRIM32 by ERK. Collectively, these findings may provide potential new targets for SCI repair.

Superparamagnetic iron oxide-gold nanoparticles conjugated with porous coordination cages: Towards controlled drug release for non-invasive neuroregeneration.

This paper reports a smart intracellular nanocarrier for sustainable and controlled drug release in non-invasive neuroregeneration. The nanocarrier is composed by superparamagnetic iron oxide-gold (SPIO-Au) core-shell nanoparticles (NPs) conjugated with porous coordination cages (PCCs) through the thiol-containing molecules as bridges. The negatively charged PCC-2 and positively charged PCC-3 are compared for intracellular targeting. Both types result in intracellular targeting via direct penetration across cellular membranes. However, the pyrene (Py)-PEG-SH bridge enabled functionalization of SPIO-Au NPs with PCC-3 exhibits higher interaction with PC-12 neuron-like cells, compared with the rhodamine B (RhB)-PEG-SH bridge enabled case and the stand-alone SPIO-Au NPs. With neglectable toxicities to PC-12 cells, the proposed SPIO-Au-RhB(Py)-PCC-2(3) nanocarriers exhibit effective drug loading capacity of retinoic acid (RA) at 13.505 µg/mg of RA/NPs within 24 h. A controlled release of RA is achieved by using a low-intensity 525 nm LED light (100% compared to 40% for control group within 96 h).

Polydatin promotes the neuronal differentiation of bone marrow mesenchymal stem cells in vitro and in vivo: Involvement of Nrf2 signalling pathway.

Bone marrow mesenchymal stem cell (BMSC) transplantation represents a promising repair strategy following spinal cord injury (SCI), although the therapeutic effects are minimal due to their limited neural differentiation potential. Polydatin (PD), a key component of the Chinese herb Polygonum cuspidatum, exerts significant neuroprotective effects in various central nervous system disorders and protects BMSCs against oxidative injury. However, the effect of PD on the neuronal differentiation of BMSCs, and the underlying mechanisms remain inadequately understood. In this study, we induced neuronal differentiation of BMSCs in the presence of PD, and analysed the Nrf2 signalling and neuronal differentiation markers using routine molecular assays. We also established an in vivo model of SCI and assessed the locomotor function of the mice through hindlimb movements and electrophysiological measurements. Finally, tissue regeneration was evaluated by H&E staining, Nissl staining and transmission electron microscopy. PD (30 µmol/L) markedly facilitated BMSC differentiation into neuron-like cells by activating the Nrf2 pathway and increased the expression of neuronal markers in the transplanted BMSCs at the injured spinal cord sites. Furthermore, compared with either monotherapy, the combination of PD and BMSC transplantation promoted axonal rehabilitation, attenuated glial scar formation and promoted axonal generation across the glial scar, thereby enhancing recovery of hindlimb locomotor function. Taken together, PD augments the neuronal differentiation of BMSCs via Nrf2 activation and improves functional recovery, indicating a promising new therapeutic approach against SCI.

Mechanics and Biology Interact in Intervertebral Disc Degeneration: A Novel Composite Mouse Model.

The aim of this study was to distinguish the characteristics of intervertebral disc degeneration (IVDD) originating from mechanics imbalance, biology disruption, and their communion, and to develop a composite IVDD model by ovariectomy combined with lumbar facetectomy for mimicking elderly IVDD with osteoporosis and lumbar spinal instability. Mice were randomly divided into four groups and subjected to sham surgery (CON), ovariectomy (OVX), facetectomy (mechanical instability, INS) or their combination (COM), respectively. Radiographical (n = 4) and histological changes (n = 8) of L4/5 spinal segments were analyzed. Tartrate-resistant acid phosphatase (TRAP) staining was conducted to detect osteoclasts, and expression of osterix (OSX), type I collagen (Col I), type II collagen (Col II) and vascular endothelial growth factor (VEGF) were evaluated by immunochemistry. OVX affected the body's metabolism but INS did not, as the body weight increased and uterus weight decreased in OVX and COM mice compared to CON and INS mice. OVX, INS, and COM caused IVDD in various degrees at 12 weeks after surgery. However, the major pathogeneses of OVX- and INS-induced IVDD were different, which focused on endplate (EP) remodeling and annulus fibrosus (AF) collapse, respectively. OVX induced osteopenia of vertebra. In contrast, INS promoted the stress-adaptive increase of subchondral bone trabeculae. The COM produced a reproducible severe IVDD model with characteristics of sparse vertebral trabeculae, cartilaginous EP ossification, subchondral bone sclerosis, fibrous matrix disorder, angiogenesis, disc stiffness, as well as space fusion. Additionally, all groups had elevated bone and cartilage turnover compared with CON group, as the quantity of trap + osteoclasts and the osteogenic OSX expression increased in these groups. Likewise, the VEGF expression levels were similar, accompanied by the altered matrix expression of disc, including the changed distribution and contents of Col II and Col I. The findings suggested that the composite mouse model to some extent could effectively mimic the interactions of biology and mechanics engaged in the onset and natural course of IVDD, which would be more compatible with the IVDD of elderly with vertebral osteoporosis and spinal instability and benefit to further clarify the complicated mechanobiological environment of elderly IVDD progression.

Catalytic reactions within the cavity of coordination cages.

Natural enzymes catalyze reactions in their substrate-binding cavities, exhibiting high specificity and efficiency. In an effort to mimic the structure and functionality of enzymes, discrete coordination cages were designed and synthesized. These self-assembled systems have a variety of confined cavities, which have been applied to accelerate conventional reactions, perform substrate-specific reactions, and manipulate regio- and enantio-selectivity. Many coordination cages or cage-catalyst composites have achieved unprecedented results, outperforming their counterparts in different catalytic reactions. This tutorial review summarizes recent developments of coordination cages across three key approaches to coordination cage catalysis: (1) cavity promoted reactions, (2) embedding of active sites in the structure of the cage, and (3) encapsulation of catalysts within the cage. Special emphasis of the review involves (1) introduction of the structure and property of the coordination cage, (2) discussion of the catalytic pathway mediated by the cage, (3) elucidation of the structure-property relationship between the cage and the designated reaction. This work will summarize the recent progress in supramolecular catalysis and attract more researchers to pursue cavity-promoted reactions using discrete coordination cages.

Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats.

BACKGROUND/AIMS: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats. METHODS: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1ß [IL-1ß], -IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism. RESULTS: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1ß, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway. CONCLUSION: TAN might have potential as a therapeutic agent for the treatment of RA.

Berberine inhibits the interleukin-1 beta-induced inflammatory response via MAPK downregulation in rat articular chondrocytes.

Osteoarthritis (OA) is one of the most chronic degenerative arthritic diseases, which gradually results in chondrocyte changes, articular cartilage degeneration, subchondral bone sclerosis, joint pain, swelling, and dysfunction. Berberine (BBR) has various confirmed biological activities, such as anti-inflammatory and antioxidant activities. However, the effect of BBR on the production of inflammation-associated proteins, including inducible nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, metalloproteinases (MMPs), Collagen II, TNF-α, and IL-6 via the MAPK (mitogen-activated protein kinases) pathway in IL-1ß-stimulated rat chondrocytes, has not yet been studied. Thus, the purpose of this study was to evaluate whether BBR would decrease the production of inflammation-associated proteins through the MAPK signal pathway. Rat chondrocytes were cultured and pretreated with BBR at different concentrations (0, 25, 50, and 100 µM) and then stimulated with or without IL-1ß (10 ng/mL). The mRNA expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 was measured by real-time polymerase chain reaction (RT-PCR), and the protein expression of iNOS, COX-2, Collagen II, MMP-3,MMP-13, and MAPKs were measured by Western blotting. The results showed that the expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 increased in the IL-1ß-treated group and BBR showed an ability to inhibit the elevated expression under the pretreatment. Furthermore, the IL-1ß-induced downregulation of Collagen II could be ameliorated by BBR. Moreover, the expression of MAPKs was significantly decreased by BBR. These results demonstrated that BBR had the anti-catabolic and anti-inflammation abilities that were through the MAPKs in IL-1ß-induced rat chondrocytes. These findings may provide a novel therapeutic choice for treatment of OA using BBR.

Investigating Subcellular Compartment Targeting Effect of Porous Coordination Cages for Enhancing Cancer Nanotherapy.

Understanding the key factors for successful subcellular compartment targeting for cargo delivery systems is of great interest in a variety of fields such as bionanotechnology, cell biology, and nanotherapies. However, the fundamental basis for intracellular transportation with these systems has thus far rarely been discussed. As a cargo vector, porous coordination cages (PCCs) have great potential for use in cancer nanotherapy and to elucidate fundamental insight regarding subcellular compartment targeting. Herein, it is shown that the transportation of PCC cargo vectors though various subcellular barriers of the mammalian cell can be manipulated by tuning the vector's electronic property and surface affinity. It is found that the PCCs become selectively aggregated at the cell membrane, the cytoplasm, or the nucleus, respectively. When a DNA topoisomerase inhibitor is delivered into the nucleus by a neutral and lipophilic PCC, the anticancer efficacy is dramatically improved. The findings shed light to tune the interactions at the "bio-nano" interface. This study provides a key strategy for future work in targeting specific cell organelles for cell imaging, cargo delivery, and therapy. This research also offers key insight into the engineering of nanoscopic materials for furnishing cell organelle-specificity.