Advances in regenerative rehabilitation in the rehabilitation of musculoskeletal injuries.

In the rapidly advancing field of regenerative medicine, relying solely on cell transplantation alone may be insufficient for achieving functional recovery, and rehabilitation before and after transplantation is crucial. Regenerative rehabilitation functions by synergizing the therapeutic effects of regeneration and rehabilitation to maximize tissue regeneration and patient function. We used the keywords "regenerative rehabilitation" to search across the database for published works; this review discusses the development of regenerative rehabilitation for the treatment of musculoskeletal injuries. Rehabilitation has become a crucial component of regenerative medicine because it can enhance patients' functional activity and facilitate their early return to society. Experimental data increasingly demonstrates that rehabilitation interventions support the regeneration of transplanted tissues.

Regenerative medicine concepts can be incorporated into rehabilitation to help patients achieve a better functional recovery outcome. Rehabilitation therapy can help patients return to society sooner following an injury. Regenerative medicine concepts can also be integrated into regenerative therapy to maximize its benefits when compared with traditional rehabilitation or regenerative therapy alone. The development of regenerative rehabilitation for the treatment of skeletal muscle, bone and bone junction injuries is reviewed in this article.

DTDNet: Dynamic Target Driven Network for pedestrian trajectory prediction.

Predicting the trajectories of pedestrians is an important and difficult task for many applications, such as robot navigation and autonomous driving. Most of the existing methods believe that an accurate prediction of the pedestrian intention can improve the prediction quality. These works tend to predict a fixed destination coordinate as the agent intention and predict the future trajectory accordingly. However, in the process of moving, the intention of a pedestrian could be a definite location or a general direction and area, and may change dynamically with the changes of surrounding. Thus, regarding the agent intention as a fixed 2-d coordinate is insufficient to improve the future trajectory prediction. To address this problem, we propose Dynamic Target Driven Network for pedestrian trajectory prediction (DTDNet), which employs a multi-precision pedestrian intention analysis module to capture this dynamic. To ensure that this extracted feature contains comprehensive intention information, we design three sub-tasks: predicting coarse-precision endpoint coordinate, predicting fine-precision endpoint coordinate and scoring scene sub-regions. In addition, we propose a original multi-precision trajectory data extraction method to achieve multi-resolution representation of future intention and make it easier to extract local scene information. We compare our model with previous methods on two publicly available datasets (ETH-UCY and Stanford Drone Dataset). The experimental results show that our DTDNet achieves better trajectory prediction performance, and conducts better pedestrian intention feature representation.

Controllable π-π coupling of intramolecular dimer models in aggregated states.

π-π coupling as a common interaction plays a key role in emissions, transport and mechanical properties of organic materials. However, the precise control of π-π coupling is still challenging owing to the possible interference from other intermolecular interactions in the aggregated state, usually resulting in uncontrollable emission properties. Herein, with the rational construction of intramolecular dimer models and crystal engineering, π-π coupling can be subtly modulated by conformation variation with balanced π-π and π-solvent interactions and visualized by green-to-blue emission switching. Moreover, it can rapidly respond to temperature, pressure and mechanical force, affording a facile way to modulate π-π coupling in situ. This work contributes to a deeper understanding of the internal mechanism of molecular motions in aggregated states.

Celastrol Alleviates Mitochondrial Oxidative Stress and Brain Injury After Intracerebral Hemorrhage by Promoting OPA1-Dependent Mitochondrial Fusion.

Mitochondrial oxidative stress is one of the characteristics of secondary brain injury (SBI) after intracerebral hemorrhage (ICH), contributing largely to the apoptosis of neurons. Celastrol, a quinone methide triterpene that possesses antioxidant and mitochondrial protective properties, has emerged as a neuroprotective agent. However, the activity of celastrol has not been tested in ICH-induced SBI. In this study, we found that celastrol could effectively alleviate neurological function deficits and reduce brain oedema and neuronal apoptosis caused by ICH. Through electron microscopy, we found that celastrol could significantly attenuate mitochondrial morphology impairment. Therefore, we tested the regulatory proteins of mitochondrial dynamics and found that celastrol could reverse the downwards trend of OPA1 expression after ICH. In view of this, by culturing OPA1-deficient primary neurons and constructing neuron-specific OPA1 conditional knockout mice, we found that the protective effects of celastrol on mitochondrial morphology and function after ICH were counteracted in the absence of OPA1. Further experiments also showed that OPA1 is indispensable for the protective effects of celastrol on ICH-induced secondary brain injury. In summary, we have demonstrated that celastrol is a potential drug for the treatment of ICH and have revealed a novel mechanism by which celastrol exerts its antioxidant effects by promoting OPA1-mediated mitochondrial fusion.

Improved Electrocatalytic Activity and Stability by Single Iridium Atoms on Iron-based Layered Double Hydroxides for Oxygen Evolution.

Full understanding to the origin of the catalytic performance of a supported nanocatalyst from the points of view of both the active component and support is significant for the achievement of high performance. Herein, based on a model electrocatalyst of single-iridium-atom-doped iron (Fe)-based layered double hydroxides (LDH) for oxygen evolution reaction (OER), we reveal the first completed origin of the catalytic performance of such supported nanocatalysts. Specially, besides the activity enhancement of Ir sites by LDH support, the stability of surface Fe sites is enhanced by doped Ir sites: DFT calculation shows that the Ir sites can reduce the activity and enhance the stability of the nearby Fe sites; while further finite element simulations indicate, the stability enhancement of distant Fe sites could be attributed to the much low concentration of OER reactant (hydroxyl ions, OH- ) around them induced by the much fast consumption of OH- on highly active Ir sites. These new findings about the interaction between the main active components and supports are applicable in principle to other heterogeneous nanocatalysts and provide a completed understanding to the catalytic performance of heterogeneous nanocatalysts.

["Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation].

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Engineering PtCu nanoparticles for a highly efficient methanol electro-oxidation reaction.

Achieving a highly efficient and durable methanol electro-oxidation catalyst in acid media is critical for the practical utilization of direct methanol fuel cells (DMFCs) at the commercial scale. Herein, we report a facile and effective one-pot strategy for the synthesis of carbon-supported PtCu alloy nanoparticles (PtCu NPs) with a Pt-rich surface, small particle size and uniform dispersion. The as-prepared PtCu NPs with the optimal alloy composition (Pt2Cu) exhibit a significantly improved electrochemical methanol oxidation reaction performance in terms of a high activity, superior CO tolerance and remarkable durability, in contrast to those of commercial Pt/C catalysts in acid media. Particularly, the Pt2Cu/C catalyst exerts a 4.5 times enhancement in the mass activity and a larger If/Ib value compared to those of commercial Pt/C (Pt/Ccomm). The enhanced catalytic activities can be ascribed to the high utilization of Pt and the high index facets of the surface. Also, the addition of Cu downshifts the d-band center of Pt and improves the CO tolerance during the methanol oxidation reaction process. This work provides an efficient strategy for designing desired Pt-based alloys for various catalytic reactions.

Malignant fibrous histiocytoma of the bone in a traumatic amputation stump: A case report and review of the literature.

BACKGROUND: Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas among adults. It is characterized by large size, high grade, and biological aggressiveness. There are many reports of MFH after local stimulation, such as bone fracture, implants, and chronic osteomyelitis. In this paper, we report a patient who developed MFH 6 years after amputation, suggesting that wound healing and mechanical force play a role in the local stimulation of this disease. CASE SUMMARY: A 66-year-old man complained of persistent pain in his residual mid-thigh. He had undergone amputation surgery due to a traffic accident 6 years prior. Physical examination showed tenderness but no abnormalities in appearance. X-ray radiographs and magnetic resonance imaging supported the diagnosis of a tumor, and a biopsy confirmed that the lesion was MFH. The patient received neoadjuvant chemotherapy and left hip disarticulation. During the 6-mo follow-up, there were no symptoms of recurrence. CONCLUSION: Postsurgery MFH has been reported before, and many studies have attributed it to the biological effects of implants. Our case report shows that this disease can develop without an implant and thus highlights the importance of local stimulation. The wound-healing process and mechanical force can both promote this tumor, but whether they directly cause MFH needs further investigation.

Experimental and Numerical Study on Interface Bond Strength and Anchorage Performance of Steel Bars within Prefabricated Concrete.

This study investigates the interface bond strength and anchorage performance of steel bars within prefabricated concrete. Twenty-two specimens were designed and manufactured to study the interface bond behavior of deformed and plain steel bars under a larger cover thickness. Diameter of steel bars, strength grade of concrete, and anchorage length were considered influential factors. The finite element method (ABAQUS) was used for the validation of experimental results. The interface bond's failure mechanism and the anchorage length in the prefabricated concrete under different concrete strength levels were explored and compared to national and international codes. A suitable value of the basic anchoring length for the prefabricated structure was recommended. The results show that the interface bond strength of prefabricated bridge members is directly proportional to the strength grade of the concrete, inversely proportional to the reinforcement diameter, and less related to anchorage length. The effect of the cover thickness of the surrounding concrete is negligible. Conversely, the bearing capacity of prefabricated bridge members depends on the strength of the concrete, the diameter of the steel bar, and the anchorage length. Furthermore, it is concluded that the mechanical bond strength accounts for 88% of the bond strength within prefabricated concrete.

Electrochemical Production of Formic Acid from CO2 with Cetyltrimethylammonium Bromide-Assisted Copper-Based Catalysts.

The electrochemical reduction of CO2 (ERC) to valuable chemicals has attracted extensive attention. However, the relatively low selectivity and efficiency of the reaction remain challenges. In this study, Cu electrodes derived from Cu2 O with predominant (111) facets are synthesized by cetyltrimethylammonium bromide-assisted preparation. The optimized electrode shows a high faradaic efficiency of 90 % for HCOOH obtained by ERC at -2.0 V (vs.SCE), which surpasses most reported Cu electrodes. Based on a comprehensive analysis of the relationship between the catalytic activity and the thickness of the Cu2 O layer, the catalytic activity of the unit active site on the Cu2 O-derived Cu electrodes is found to be higher than that on the blank Cu electrode. DFT calculations indicate that OCHO* would be produced preferentially over *COOH in the presence of cetyltrimethylammonium bromide (CTAB). This deduction is verified by testing of the effects of CTAB and KBr addition on HCOO- selectivity.

Bradykinin Activates the Bradykinin B2 Receptor to Ameliorate Neuronal Injury in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury.

Bradykinin and bradykinin B2 receptors (B2R) play important roles in both the peripheral and central nervous systems. The aim of this study was to explore the changes of bradykinin and B2R in spinal cord ischemic injury (SCII) and whether bradykinin treatment would improve the neurologic function of SCII rats. The rats were divided into the sham group, the SCII group, and three doses of bradykinin (50, 100, 150 µg/kg) groups. The neurologic function was assessed by the Basso, Beattie, and Bresnahan (BBB) score at -1, 1, 3, 5, and 7 days postsurgery. Bradykinin concentration in serum and IL-6, TNF-α, and MCP-1 levels in the spinal cord were detected by ELISA. The mRNA expressions of B2R, IL-6, TNF-α, MCP-1, COX-2, and iNOS in the spinal cord were determined by RT-PCR. The protein expressions of B2R, COX-2, iNOS, p65, and p-p65 were detected by Western blot. Immunohistochemical staining was used to examine B2R expression in the L4-6 segments of the spinal cord. Bradykinin levels in serum and B2R expression in the spinal cord were downregulated in SCII rats. Bradykinin treatment significantly improved the hind limb motor function of SCII rats and increased B2R expression, inhibiting COX-2, iNOS, and p-p65 expression in the spinal cord of SCII rats together with a decrease of the inflammatory mediators of IL-6, TNF-α, and MCP-1 levels. Bradykinin administration activated B2R in the spinal cord of SCII rats, which may improve hind limb locomotor recovery by regulating the NF-κB signaling pathway to inhibit the inflammatory response. These findings may provide a theoretical basis for the clinical application of bradykinin in SCII.

A novel sandwich shaped {CoCoMo} cluster with a Co triangle encapsulated in two capped CoIIICoMoO40 fragments.

A novel discrete {Co14Mo24} nanoscale cluster, {CoIII2CoII10Cl2(dpbt)3(H2O)2[CoIIMoV12O31(CH3O)9]2}·24CH3OH (1) (here, dpbt = 5,5'-di(pyridin-2-yl)-3,3'-bi(1,2,4-triazole)), with a triangular Co4 core encapsulated in two novel capped Co-substituted Keggin-type Co5Mo12O40 anions, has been isolated from alkaline methanol solution. The high-resolution electrospray ionization mass spectrum (HRESI-MS) of microcrystalline 1 in MeOH/CH2Cl2 (v : v = 2 : 1) was recorded. Two prominent overlapping peaks in the range of m/z = 2740-2840 and 1820-1880 for the discrete fragments of [CoIII2CoII12MoV24O62Cl2(dpbt)3(H2O)2(CH3O)x(OH)18-x-2H]2- (x = 9-18, F1) and [CoIII2CoII12MoV24O62Cl2(dpbt)3(H2O)2(CH3O)x(OH)19-x-2H]3- (x = 6-13, F2), respectively, are obtained, confirming the {Co14Mo24} composition in 1. In addition, weak anti-ferromagnetic interactions in 1 are observed.

Combination Therapy With Hyperbaric Oxygen and Erythropoietin Inhibits Neuronal Apoptosis and Improves Recovery in Rats With Spinal Cord Injury.

BACKGROUND: Apoptosis plays an important role in various diseases, including spinal cord injury (SCI). Hyperbaric oxygen (HBO) and erythropoietin (EPO) promote the recovery from SCI, but the relationship between apoptosis and the combination therapeutic effect is not completely clear. OBJECTIVE: The purpose of this study was to investigate the effects of HBO and EPO on SCI and the mechanisms that underlie their therapeutic benefits. DESIGN: The study was designed to explore the effects of HBO and EPO on SCI through a randomized controlled trial. METHODS: Sixty young developing female Sprague-Dawley rats were randomly divided into groups of 12 rats receiving sham, SCI, HBO, EPO, or HBO plus EPO. The SCI model was modified with the Allen method to better control consistency. HBO was performed for 1 hour per day for a total of 21 days, and EPO was given once per week for a total of 3 weeks. Both methods were performed 2 hours after SCI. Locomotor function was evaluated with the 21-point Basso-Beattie-Bresnahan Locomotor Rating Scale, an inclined-plane test, and a footprint analysis. All genes were detected by Western blotting and immunohistochemistry. The level of cell apoptosis was determined by Hoechst staining. RESULTS: The results showed that HBO and EPO promoted the recovery of locomotor function in the hind limbs of rats by inhibiting the apoptosis of neurons. During this period, the expression of B-cell lymphoma/leukemia 2 protein (Bcl-2) increased significantly, whereas the expression of Bcl-2-associated X protein (Bax) and cleaved caspase 3 decreased significantly, indicating the inhibition of apoptosis. Meanwhile, the expression of G protein-coupled receptor 17 decreased, and that of myelin basic protein increased, suggesting that there may be a potential connection between demyelination and neuronal apoptosis. LIMITATIONS: The limitations of the study include deviations in the preparation of SCI models; lack of reverse validation of molecular mechanisms; absence of in vitro cell experiments; and only one time point after SCI was studied. CONCLUSIONS: HBO and EPO treatments are beneficial for SCI, especially when the 2 therapies are combined.

In vitro and in vivo antitumor activities of three novel binuclear platinum(II) complexes with 4'-substituted-2,2':6',2″-terpyridine ligands.

Herein, we report the design and synthesis of three novel binuclear platinum(II) complexes, [Pt(tpbtpy)Cl][Pt(DMSO)Cl3] (tpbtpy-Pt), [Pt(dthbtpy)Cl][Pt(DMSO)Cl3]⋅CH3OH (dthbtpy-Pt), and [Pt(qlbtpy)Cl][Pt(DMSO)Cl3]⋅CH3OH (qlbtpy-Pt) with 4'-(3-thiophenecarboxaldehyde)-2,2':6',2″-terpyridine (tpbtpy), 4'-(3,5-bis (1,1-dimethylethyl)-2-hydroxy-benzaldehyde)-2,2':6',2″-terpyridine (dthbtpy) and 4'-(2-quinolinecarboxaldehyde)-2,2':6',2″-terpyridine (qlbtpy) as ligands, respectively. All three novel binuclear platinum(II) complexes tpbtpy-Pt, dthbtpy-Pt, and qlbtpy-Pt were characterized by single-crystal X-ray diffraction analysis, spectroscopic analysis (ESI-MS, IR, 1H NMR), and elemental analysis. Additionally, the cytotoxicity of tpbtpy-Pt, dthbtpy-Pt and qlbtpy-Pt was assessed with human non-small cell lung cancer cell line (NCIH460 cells), yielding IC50 values in the range of 0.35-12.09 µM with tpbtpy-Pt as the most potent and qlbtpy-Pt as the least potent complexes. Mechanistic studies indicated that tpbtpy-Pt and dthbtpy-Pt induced apoptosis through mitochondrial dysfunction and telomerase inhibition. In a NCIH460 xenograft model, when administered at 10.0 mg kg-1 every 2 days, tpbtpy-Pt was shown to significantly reduce tumor growth (tumor growth inhibition rate (IR) = 70.1%, p < 0.05). Therefore, tpbtpy-Pt is a promising Pt(II) complex for further translational studies and clinical evaluation as an antitumor agent.

Airway microbiome is associated with respiratory functions and responses to ambient particulate matter exposure.

BACKGROUND: Ambient particulate matter (PM) exposure has been associated with respiratory function decline in epidemiological studies. We hypothesize that a possible underlying mechanism is the perturbation of airway microbiome by PM exposure. METHODS: During October 2016-October 2017, on two human cohorts (n = 115 in total) in Shanghai China, we systematically collected three categories of data: (1) respiratory functions, (2) airway microbiome from sputum, and (3) PM2.5 (PM of ≤ 2.5 µm in diameter) level in ambient air. We investigated the impact of PM2.5 on airway microbiome as well as the link between airway microbiome and respiratory functions using linear mixed regression models. RESULTS: The respiratory function of our primary interest includes forced vital capacity (FVC) and forced expiratory volume in 1st second (FEV1). FEV1/FVC, an important respiratory function trait and key diagnosis criterion of COPD, was significantly associated with airway bacteria load (p = 0.0038); and FEV1 was associated with airway microbiome profile (p = 0.013). Further, airway microbiome was significantly influenced by PM2.5 exposure (p = 4.48E-11). CONCLUSIONS: To our knowledge, for the first time, we demonstrated the impact of PM2.5 on airway microbiome, and reported the link between airway microbiome and respiratory functions. The results expand our understanding on the scope of PM2.5 exposure's influence on human respiratory system, and point to novel etiological mechanism of PM2.5 exposure induced diseases.

Bio3Air, an integrative system for monitoring individual-level air pollutant exposure with high time and spatial resolution.

BACKGROUND: Air pollution is a leading cause of global disease burden. Lack of suitable methods for long term measuring exposure level at individual level is crippling environmental epidemiology research of air pollution. METHODS: We report an integrative system, Bio3Air, for long term measurement of individual level air pollution exposure, currently focusing on ambient particulate matter (PM). The novel system in real-time quantifies individual's outdoor/indoor status, geological location, lung ventilation rate and PM concentration of individual's surrounding environment, and these metrics are subsequently incorporated in calculating PM exposure. RESULTS: The system is fully developed and tested in China, USA and Canada, and has been successfully applied in epidemiology study. Bio3Air offers high reliability, sensitivity, reproducibility (>99%) and accuracy. It has high time- and spatial- resolution (≤ 2 min and ≤ 20 m, respectively). Bio3Air achieved 91.89% consistency with "gold-standard" method (membrane collection and off-line analysis). CONCLUSIONS: Bio3Air represents a substantial methodological advance in environmental health research of air pollution. It captures information relevant in measuring individual's PM exposure (e.g. real-time outdoor/indoor status, location and lung ventilation rate). Such information is typically missed by conventional approaches. Additional features of Bio3Air include easy-to-use, cost-effectiveness and automated data collection, making it a powerful tool facilitating studies of air pollution exposure and health consequences.

Synthesis, structure and magnetic properties of two mixed-valence icosanuclear nanocages.

The reactions of 3,3'-bis(5-mercapto-1,2,4-triazole) with Co(ii) and Ni(ii) ions, respectively, gave two nanospheric mixed-valence icosanuclear cage-like complexes [M20L12](SO4)2·6DMF·CH3OH·3H2O (M = Co, 1; Ni, 2) with the in situ generated oxalyldithiosemicarbazide (H4L) as ligand. The eight octahedral M(ii) ions and twelve square-planar M(iii) ions in the two complexes are linked by twelve three-connecting linkers of L4- to build an icosanuclear [MII8MIII12L12]4+ nanocage with an inner cubic MII8 cage core. Their cage skeletons are stable in water. The sulphate anions reside over the cage portals. The magnetic measurements of the two complexes revealed the presence of dominant antiferromagnetic interactions between the metal ions in both complexes.

Novel tacrine platinum(II) complexes display high anticancer activity via inhibition of telomerase activity, dysfunction of mitochondria, and activation of the p53 signaling pathway.

In this work, we designed and synthesized tacrine platinum(II) complexes [PtClL(DMSO)]⋅CH3OH (Pt1), [PtClL(DMP)] (Pt2), [PtClL(DPPTH)] (Pt3), [PtClL(PTH)] (Pt4), [PtClL(PIPTH)] (Pt5), [PtClL(PM)] (Pt6) and [PtClL(en)] (Pt7) with 4,4'-dimethyl-2,2'-bipyridine (DMP), 4,7-diphenyl-1,10-phenanthroline (DPPTH), 1,10-phenanthroline (PTH), 2-(1-pyrenecarboxaldehyde) imidazo [4,5-f]-[1,10] phenanthroline (PIPTH), 2-picolylamine (PM) and 1,2-ethylenediamine (en) as telomerase inhibitors and p53 activators. Biological evaluations demonstrated that Pt1Pt7 exhibited cytotoxic activity against the tested NCIH460, Hep-G2, SK-OV-3, SK-OV-3/DDP and MGC80-3 cancer cell lines, with Pt5 displaying the highest cytotoxicity. Pt5 exhibited an IC50 value of 0.13 ±â€¯0.16 µM against SK-OV-3/DDP cancer cells and significantly reduced tumor growth in a Hep-G2 xenograft mouse model (tumor growth inhibition (TGI) = 40.8%, p < 0.05) at a dose of 15.0 mg/kg. Interestingly, Pt1Pt7 displayed low cytotoxicity against normal HL-7702 cells. Mechanistic studies revealed that these compounds caused cell cycle arrest at the G2/M and S phases, and regulated the expression of CDK2, cyclin A, p21, p53 and p27. Further mechanistic studies showed that Pt5 induced SK-OV3/DDP cell apoptosis via dysfunction of mitochondria, inhibition of the telomerase activity by directly targeting the c-myc promoter, and activation of the p53 signaling pathway. Taken together, Pt5 has the potential to be further developed as a new antitumor drug.

Hierarchical Assembly of a {Co24} Cluster from Two Vertex-Fused {Co13} Clusters and Their Single-Molecule Magnetism.

We present the synthesis, structural characterization, and magnetic properties of two high-nuclearity cobalt clusters formulated as [Co13(µ3-OH)3(µ3-Cl)(dpbt)5(ptd)Cl10][Co(H2O)2Cl2]·(CH3)2CHOH (1) and [Co24(µ3-OH)6(µ3-Cl)2(dpbt)10(ptd)2Cl16]·2CH3CH2OH (2), respectively (H2dpbt = 5,5'-bis(pyridin-2-yl)-3,3'-bis(1,2,4-triazole) and H2ptd = 3-(pyridin-2-yl)-1,2,4-triazine-5,6-diol). Compound 1 is composed of an inner [Co4(µ3-OH)3(µ3-Cl)] cubane and an outer [Co9(dpbt)5(ptd)Cl10] defective adamantane. Compound 2 reveals a giant {Co24} cluster possessing a dual-[Co12] skeleton from 1. The hierarchical assembly from 1 to 2 has been established and tracked through high-resolution electrospray ionization (HRESI-MS) analyses from the solvothermal reaction mother solution. Magnetic studies of 1 and 2 revealed the highly correlated spins, a glasslike magnetic phase transition at ca. 8 K, and slow relaxation behavior of SMM nature in the lower-temperature region (below 4 K).

Schiff base complex conjugates of bovine serum albumin as artificial metalloenzymes for eco-friendly enantioselective sulfoxidation.

Artificial metalloenzymes (BSA-ML) have been prepared by non-covalent insertion of transition metal Schiff-base complexes, ML (L = 2-hydroxynaphthalen-1-naphthaldehyde and 3,4-diaminobenzenesulfonic acid; M = Co, Mn, V, Fe, Cr), into bovine serum albumin (BSA) as the host protein and were characterized by UV-visible spectroscopy, ESI-TOF mass spectrometry and molecular docking studies. The catalytic activities of the BSA-ML in the selective oxidation of various prochiral sulfides in aqueous media, using H2O2 as oxidant, have been evaluated. During the optimization process, pH and the concentrations of catalyst and oxidant were found to have a remarkable influence on both yield and enantioselectivity. In certain cases, BSA-ML gave satisfactory results in the oxidation of organic sulfides to sulfoxides (up to 100% conversion, 100% chemoselectivity, 96% ee and 500 h-1 turnover frequency).