Metallo-Helicoid with Double Rims: Polymerization Followed by Folding by Intramolecular Coordination.

In this study, we established a feasible strategy to construct a new type of metallo-polymer with helicoidal structure through the combination of covalent polymerization and intramolecular coordination-driven self-assembly. In the design, a tetratopic monomer (M) was prepared with two terminal alkynes in the outer rim for polymerization, and two terpyridines (TPYs) in the inner rim for subsequent folding by selective intramolecular coordination. Then, the linear covalent polymer (P) was synthesized by polymerization of M via Glaser-Hay homocoupling reaction. Finally, intramolecular coordination interactions between TPYs and Zn(II) folded the backbone of P into a right- or left-handed metallo-helicoid (H) with double rims. Owing to multiple positive charges on the inner rim of helicoid, double-stranded DNA molecules (dsDNA) could interact with H through electrostatic interactions. Remarkably, dsDNA allowed exclusive formation of H with right handedness by means of chiral induction.

Expression of Stanniocalcin 2 in Breast Cancer and Its Clinical Significance.

This study aims to explore the expression of stanniocalcin 2 (STC2) gene in breast cancer and its clinical significance. Female patients with breast cancer from Zhongnan Hospital of Wuhan University admitted during March 2014 to October 2014 were enrolled in this study. All the tissues used in this experiment included 50 cases of breast cancer tissues and corresponding 50 cases of paracancer normal breast tissues with complete patients' information. The real-time quantitative polymerase chain reaction (qPCR) was applied to detect the expression of STC2 gene in 50 cases of breast cancer and paracancer normal breast tissues. The results showed that the expression level of STC2 gene in 50 cases of breast cancer tissues was significantly higher than that in paracancer normal breast tissues (P<0.001). The expression of STC2 gene was correlated with lymph node metastasis, distant metastasis, TNM stage and histological grade (P<0.001). The expression level of STC2 gene was significantly higher in breast cancer tissues with higher expression of Ki-67 (P<0.001). The expression level of STC2 gene was significantly higher in estrogen receptor (ER) positive breast cancer tissues than in ER negative ones (P<0.001). However, different groups of age, pathological type, tumor size, PR expression and human epidermal growth factor receptor-2 (HER2) expression did not show significant differences in STC2 expression (P>0.05). In conclusion, the abnormal overexpression of STC2 gene may play a role in the development and progression of breast cancer, and it can be used as an independent metastasis and prognostic factor of breast cancer. In addition, STC2 gene probably promotes the development and metastasis of breast cancer by interacting with estrogen and ER, and it may become a new direction for breast cancer endocrine therapy.

Light-Controlled Generation of Singlet Oxygen within a Discrete Dual-Stage Metallacycle for Cancer Therapy.

Noninvasive control over the reversible generation of singlet oxygen (1O2) has found the practical significance in benefiting photodynamic therapy. In this study, we developed a new dual-stage metallacycle (M) by using a photosensitizer and photochromic switch as the functional building blocks, which enables the noninvasive "off-on" switching of 1O2 generation through the efficient intramolecular energy transfer. Due to the proximal placement of the functional entities within the well-defined metallacyclic scaffold, 1O2 generation in the ring-closed form state of the photochromic switch (C-M) is quenched by photoinduced energy transfer, whereas the generation of 1O2 in the ring-open form state (O-M) is activated upon light irradiation. More interestingly, the metallacycle-loaded nanoparticles with relatively high stability and water solubility were prepared, which allow for the delivery of metallacycles to cancer cells via endocytosis. Their theranostic potential has been systematically investigated both in vitro and in vivo. Under the light irradiation, the designed ring-open form nanoparticles (O-NPs) show remarkable higher cytotoxicity against cancer cells compared to the ring-closed form nanoparticles (C-NPs). In vivo experiments also revealed that tumors can be very efficiently eliminated by the designed nanoparticles under light irradiation with the ability to regulate in vivo generation of singlet oxygen. All these results demonstrated that the supramolecular coordination complexes with a dual-stage state provide a highly efficient nanoplatform for noninvasive control over the reversible generation of 1O2, thus allowing for their promising applications in tumor treatment and beyond.

Small-molecule Bifunctional Fluorescent Probes for the Differential Detection of Multiple Guests.

During the last few years, the preparation of bifunctional fluorescent probes, which exhibit differential response towards multiple analytes, has attracted considerable attention since they are cost-effective and highly desirable for real-time applications. This review focuses on the recent advances in the design principles, recognition mechanisms, and applications of multifunctional fluorescent probes for the differential detection of multiple guests.

Supramolecular Transformation of Metallacycle-linked Star Polymers Driven by Simple Phosphine Ligand-Exchange Reaction.

As a common phenomenon in biological systems, supramolecular transformations of biomacromolecules lead to specific biological functions as outputs, which thus inspire people to construct biomimetic dynamic systems through supramolecular transformation strategy. It should be noted that well-modulating the artificial macromolecules to fine-tune their properties is of great significance yet still remains a big challenge in polymer chemistry. In this study, through the combination of coordination-driven self-assembly and postassembly ring-opening polymerization, a six-armed star polymer linked by well-defined hexagonal metallacycle as core was successfully prepared. At the same time, the trans-platinum acetylide moieties as transformation sites were anchored onto the discrete metallacycle scaffold. Subsequently, the simple phosphine ligand-exchange reaction induced the conversions of platinum acetylide building blocks with the varied binding angles, which thus resulted in the successive hexagon-rhomboid-hexagon transformations of metallacyclic scaffold, therefore allowing for the corresponding supramolecular transformation of metallacycle-linked star polymers. More importantly, accompanied by such transformation process, property modulation of the resultant polymers has been successfully realized. In a word, by taking advantage of dynamic nature of metal-ligand coordination bonds and simple phosphine ligand-exchange reactions, facile architecture transformation of a star polymer to a linear polymer and back to a star polymer was successfully realized, which may provide a promising approach toward the construction of new dynamic polymeric materials.

Photoresponsive Chirality-Tunable Supramolecular Metallacycles.

Chirality-tunable supramolecular metallacycles containing two light-responsive dithienylethene units and two chiral 1,1'-bi-2-naphthol (BINOL) units have been successfully constructed via coordination-driven self-assembly. These new metallacycles are well-characterized with 1D multinuclear NMR (1 H and 31 P NMR), 2D 1 H-1 H COSY and DOSY, ESI-TOF-MS, and PM6 semiempirical molecular orbital methods. Interestingly, upon irradiation with ultraviolet and visible light, the conformation of these metallacycles can undergo reversible transformation between ring-open and ring-closed forms accompanied with the obvious change of CD signals. Further investigation reveals that the photoisomerization of the dithienylethene moieties induces the change in the dihedral angle of the binaphthyl rings, thus leading to the chiral modulation of supramolecular metallacycles. Thus, this study provides very few examples of the light-induced chirality-tunable metallosupramolecular assemblies, which may find potential application in mimicking the function of natural systems in the future.

Effect of Acupuncture on the Notch Signaling Pathway in Rats with Brain Injury.

OBJECTIVE: To observe the effect of acupuncture on the Notch signaling pathway in rats with traumatic brain injury and to explore the pathogenesis of acupuncture intervention on traumatic brain injury. METHODS: Feeney's freefall epidural impact method was used to establish a traumatic brain injury model in rats; the rats were randomly divided into a normal group, sham operation group, model group and acupuncture group. Acupuncture was performed in the Baihui (DU 20), Shuigou (DU 26), Fengfu (DU 16), Yamen (DU 15) and Hegu (LI 4) acupoints in the rat, and Yamen was punctured via Fengfu. Then, the rats in each group were randomly divided into three subgroups, namely the day 3 subgroup, day 7 subgroup and day 14 subgroup according to treatment duration. The modified neurological severity scores (mNss) method was used to perform neurobehavioral scoring for evaluating the degree of injury in the rats. The hematoxylin-eosin (HE) staining method was used to observe the pathological change in the brain tissue of rats in each group. Real-time fluorescent quantitative polymerase chain reaction (Q-PCR) technology was used to detect changes in the Notch1, Hes1 and Hes5 gene expression levels in the cortex on the injured side. Western blot was used to detect the protein expression changes. RESULTS: One day after modeling, the mNss scores in the model group and in the acupuncture group were significantly higher than those in the normal and sham operation groups (P<0.01) ; there was no statistically significant difference between the normal group and the sham operation group. The scores decreased with increased treatment time, and the scores in the acupuncture group decreased more significantly than those in the model group (P<0.01). The pathological examination by the HE staining method demonstrated that the brain tissue of the rats in the acupuncture and model groups relatively significantly changed. The Notch1 gene expression level in the acupuncture group was significantly higher than the level in all of the other groups (P<0.01) ; the Hes1 and Hes5 gene expression levels were also higher in the acupuncture group. The expression changes of the Notch1 and Hes1 protein were consistent with that of mRNA. In each experimental group, the mNss score and the pathological results by the HE staining method were consistent with the mRNA results. CONCLUSION: Acupuncture could significantly promote high expression levels of Notch1, Hes1 and Hes5 in the brain tissue of traumatic brain injury rats. Therefore, acupuncture might be an important intervention for inducing endogenous stem cell proliferation and for promoting nerve repair.

CO2 Stimuli-Responsive, Injectable Block Copolymer Hydrogels Cross-Linked by Discrete Organoplatinum(II) Metallacycles via Stepwise Post-Assembly Polymerization.

Supramolecular polymeric gels cross-linked by well-defined, discrete metal-organic macrocycles (MOMs) or metal-organic cages have become a prevailing topic within the field of supramolecular self-assembly. However, the realization of supramolecular polymeric hydrogels cross-linked by discrete organometallic architectures with good biocompatibility is still a great challenge. Herein, we present the successful preparation of CO2 stimuli-responsive, injectable block copolymer hydrogels cross-linked by discrete organoplatinum(II) metallacycles. Through the combination of coordination-driven self-assembly and stepwise post-assembly polymerization, star block copolymers (SBCPs) containing well-defined hexagonal metallacycles as cores were successfully prepared, which featured CO2 stimuli-responsive properties including CO2-triggered morphology transition and CO2-induced thermoresponsive behavior. Interestingly, the resultant SBCPs were capable of forming supramolecular hydrogels with MOMs as junctions near physiological temperature, which allowed the realization of a reversible gel-to-sol transformation through the removal and addition of CO2. More importantly, the resultant supramolecular hydrogels presented good cytocompatibility in vitro. Therefore, this study provides a new strategy for the construction of new "smart" supramolecular hydrogels with promising applications as biological materials.

Effects of acupuncture on cortical expression of Wnt3a, ß-catenin and Sox2 in a rat model of traumatic brain injury.

OBJECTIVE: To observe the effects of acupuncture treatment on the expression of Wnt/ß-catenin signalling pathway-related genes (Wnt3a, ß-catenin and Sox2) in the injured cerebral cortex of rats with traumatic brain injury (TBI). METHODS: A controlled impact model of TBI was established using Feeney's free-drop method. Seventy-eight Sprague-Dawley rats were randomly divided into the following three groups: a normal group (n=18) that was left untreated; a model group (n=30) that received no treatment after TBI; and an acupuncture group (n=30) that received acupuncture (at LI4, GV20, GV26 and GV16) after TBI. Rats in each group were randomly and equally divided into 3-day, 7-day and 14-day subgroups according to the duration of therapy. Real-time fluorescence quantitative PCR (RT-qPCR) was used to measure mRNA expression of Wnt3a, ß-catenin and Sox2. Western blots were performed to determine the expression levels of WNT3a, ß-Catenin and SOX2. RESULTS: Wnt3a mRNA was upregulated in the 7-day and 14-day acupuncture subgroups compared with the corresponding model subgroups (p<0.05). ß-catenin expression was significantly increased in the 7-day and 14-day acupuncture subgroups compared with the corresponding model subgroups (p<0.01). In the 3-day and 7-day acupuncture subgroups, Sox2 expression was significantly higher than that in the normal and model groups (p<0.01 each). The levels of WNT3a, ß-catenin and SOX2 were generally consistent with the corresponding mRNA levels. CONCLUSIONS: Acupuncture exerts a regulatory effect on the Wnt/ß-catenin signalling pathway, which may in turn influence the proliferation and differentiation of endogenous neural stem cells.