Progress of lymphocyte activation gene 3 and programmed cell death protein 1 antibodies for cancer treatment: A review.

The application of immune checkpoint inhibitors has proven to be an effective treatment for cancer. Immune checkpoints such as programmed cell death protein 1/programmed cell death protein 1 ligand 1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T-cell immunoglobulin-3 (TIM-3), T-cell immunoglobulin and ITIM domain (TIGIT), and lymphocyte activation gene-3 (LAG-3) have received extensive attention, and the efficacy of antibodies or inhibitors against these checkpoints (either alone or in combination) has been evaluated in many tumors. This paper provides a brief overview of the PD-1 and LAG-3 checkpoints, and then shifts focus to the combined use of PD-1 and LAG-3 antibodies in both in vivo and in vitro experiments. In the in vitro experiments, we examined the correlation between the expression and activation of these inhibitors on T cells, and also assessed toxicity in animals in preparation for in vivo experiments. The effects of the combined use of PD-1 and LAG-3 antibodies were then summarized in animal models of melanoma, MC38 carcinoma, and other tumors. In clinical studies, the combined application of these antibodies was assessed in patients with melanoma, colorectal, breast, and renal cell cancers, as well as other solid tumors. In general, the combination of PD-1 and LAG-3 antibodies has shown promising results in both in vivo and in vitro studies.

Expanded Azahelicenes with Large Dissymmetry Factors.

Expanded azahelicenes, as heteroanalogues of helically chiral helicenes, hold significant potential for chiroptical materials. Nevertheless, their investigation and research have remained largely unexplored. Herein, we present the facile synthesis of a series of expanded azahelicenes NHn (n=1-5) consisting of 11, 19, 27, 35, and 43 fused rings, mainly by Suzuki coupling followed by Bi(OTf)3-mediated cyclization of vinyl ethers. The structures of NH2, NH3 and NH4 were confirmed through X-ray crystallography analysis, and their (P)- and (M)- enantiomers were also isolated with chiral high performance liquid chromatography. The enantiomers exhibit large absorption (abs) and luminescence (lum) dissymmetry factors, with |gabs|max=0.044; |glum|max=0.003 for NH2, |gabs|max=0.048; |glum|=0.014 for NH3, and |gabs|max=0.043; |glum|max=0.021 for NH4, which are superior to their respective all-carbon analogues.

Analysis and identification of oxidative stress-ferroptosis related biomarkers in ischemic stroke.

Studies have shown that a series of molecular events caused by oxidative stress is associated with ferroptosis and oxidation after ischemic stroke (IS). Differential analysis was performed to identify differentially expressed mRNA (DEmRNAs) between IS and control groups. Critical module genes were identified using weighted gene co-expression network analysis (WGCNA). DEmRNAs, critical module genes, oxidative stress-related genes (ORGs), and ferroptosis-related genes (FRGs) were crossed to screen for intersection mRNAs. Candidate mRNAs were screened based on the protein-protein interaction (PPI) network and the MCODE plug-in. Biomarkers were identified based on two types of machine learning algorithms, and the intersection was obtained. Functional items and related pathways of the biomarkers were identified using gene set enrichment analysis (GSEA). Finally, single-sample GSEA (ssGSEA) and Wilcoxon tests were used to identify differential immune cells. An miRNA-mRNA-TF network was created. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the expression levels of biomarkers in the IS and control groups. There were 8287 DE mRNAs between the IS and control groups. The genes in the turquoise module were selected as critical module genes for IS. Thirty intersecting mRNAs were screened for overlaps. Seventeen candidate mRNAs were also identified. Four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) were identified using two types of machine-learning algorithms. GSEA results indicated that the biomarkers were associated with steroid biosynthesis. Nine types of immune cells (activated B cells and neutrophils) were markedly different between the IS and control groups. We identified 3747 miRNA-mRNA-TF regulatory pairs in the miRNA-mRNA-TF regulatory network, including hsa-miR-4469-CDKN1A-BACH2 and hsa-miR-188-3p-GPX4-ATF2. CDKN1A, PRDX1, and PRDX6 were upregulated in IS samples compared with control samples. This study suggests that four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) are significantly associated with IS. This study provides a new reference for the diagnosis and treatment of IS.

[Effect of sodium alginate-g-deferoxamine/chitosan microspheres on osteogenic differentiation of rat bone mesenchymal stem cells].

PURPOSE: To explore the effect of sodium alginate-g-deferoxamine/chitosan (SA-g-DFO/CS) microspheres on proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs). METHODS: A kind of SA-g-DFO/CS microsphere was developed through electrostatic interaction between porous chitosan microspheres and sodium alginate chemically grafted on the surface of DFO. Its morphology, porosity rate, pore size and sustained release of DFO in vitro were examined. Rat BMSCs were isolated and co-cultured with microspheres in osteogenic differentiation medium. MTT assay was used to study the influence of cell proliferation, and Calcein-AM/PI staining was used to observe the cell viability. Alkaline phosphatase (ALP) activity assay was conducted. PCR was used to detect the expression of genes related to angiogenesis and osteogenesis. Statistical analysis was performed using SPSS 22.0 software package. RESULTS: The SA-g-DFO/CS porous microspheres were successfully prepared with a sustained re6lease of DFO. Compared with SA/CS microspheres, the SA-g-DFO/CS microspheres were conducive to cell proliferation and differentiation, with the increases in expression level of ALP, related angiogenesis genes HIF-1α, VEGF and osteogenesis genes COLI, OCN. CONCLUSIONS: The SA-g-DFO/CS porous microspheres can provide a new choice for the development of alveolar bone regeneration.

3,5,6-Trichloro-2-pyridinol confirms ototoxicity in mouse cochlear organotypic cultures and induces cytotoxicity in HEI-OC1 cells.

The metabolite of organophosphate pesticide chlorpyrifos (CPF), 3,5,6-Trichloro-2-pyridinol (TCP), is persistent and mobile toxic substance in soil and water environments, exhibiting cytotoxic, genotoxic, and neurotoxic properties. However, little is known about its effects on the peripheral auditory system. Herein, we investigated the effects of TCP exposure on mouse postnatal day 3 (P3) cochlear culture and an auditory cell line HEI-OC1 to elucidate the underlying molecular mechanisms of ototoxicity. The damage of TCP to outer hair cells (OHC) and support cells (SC) was observed in a dose and time-dependent manner. OHC and SC were a significant loss from basal to apical turn of the cochlea under exposure over 800 µM TCP for 96 h. As TCP concentrations increased, cell viability was reduced whereas reactive oxygen species (ROS) generation, apoptotic cells, and the extent of DNA damage were increased, accordingly. TCP-induced phosphorylation of the p38 and JNK MAPK are the downstream effectors of ROS. The antioxidant agent, N-acetylcysteine (NAC), could reverse TCP-mediated intracellular ROS generation, inhibit the expressive level of cleaved-caspase 3 and block phosphorylation of p38/JNK. Overall, this is the first demonstration of TCP damaging to peripheral sensory HCs and SC in organotypic cultures from the postnatal cochlea. Data also showed that TCP exposure induced oxidase stress, cell apoptosis and DNA damage in the HEI-OC1 cells. These findings serve as an important reference for assessing the risk of TCP exposure.

Facile Synthesis and Chiral Resolution of Expanded Helicenes with up to 35 cata-Fused Benzene Rings.

Expanded helicenes are expected to show enhanced chiroptical properties as compared to the classical helicenes but the synthesis is very challenging. Herein, we report the facile synthesis of a series of expanded helicenes Hn (n=1-4) containing 11, 19, 27 and 35 cata-fused benzene rings through Suzuki coupling-based oligomerization followed by Bi(OTf)3 -mediated regioselective cyclization of vinyl ethers. Their structures were determined by X-ray crystallographic analysis. Enantiopure H2, H3, and H4 can be isolated by chiral HPLC and they all exhibit strong chiroptical responses with high absorption dissymmetry factor (|gabs |) values (0.020 for H2, 0.021 for H3, and 0.021-0.024 for H4).

Protective role of muscones on astrocytes under a mechanical-chemical damage model.

Background: Traumatic spinal cord injury (SCI) is a major clinical concern and a life-changing neurological condition with substantial socioeconomic implications. The initial mechanical force applied to the spinal cord at the time of injury is known as the primary injury. After the primary injury, ischemia and hypoxia induce cell death and autolysis, which are associated with the release of a group of inflammatory factors and biologically active substances, such as superoxide dismutase (SOD), malonaldehyde (MDA), lactate dehydrogenase (LDH), and tumor necrosis factor-α (TNF-α). These processes are called the secondary injury, and may lead to an excess of extracellular glutamate (Glu), which in turn promotes the neuronal injuries. Muscone has been shown to have anti-inflammatory effects in the treatment of brain diseases and other diseases. However, to date, no study has examined the effects of muscone in the treatment of SCI. Methods: Astrocytes were separated and purified by the method of short-term exposure combining with differential sticking wall. Astrocyte was identified by glial fibers acidic protein (GFAP) selecting cell immunochemical staining. A mechanical-chemical damage (MCD) model was established via the primary spinal astrocytes of rats, and treatment was administered with different concentrations of muscone. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) was detected at 6, 12, 24, 48 and 72 h. SOD, MDA, LDH, TNF-alpha and intracellular calcium was detected at 3, 6 and 12 h. Glu in supernatant was detected respectively at 3, 6 and 12 h by enzyme-linked immunosorbent assay (ELISA) method. Intracellular calcium was detected respectively at 3, 6 and 12 h by flow cytometry method. MRNA expression of excitatory amino acid transporters (EAATs) and GFAP were detected by the quantitative reverse transcription polymerase chain reaction (qRT-PCR) method and protein expression of those by western blot at 6 h. Results: Muscone reduced the levels of LDH, TNF-α, and MDA after injury, and upregulated the level of SOD. Muscone also reduced the density of extracellular Glu and suppressed the intracellular calcium level. Additionally, it decreased the expression levels of EAATs and GFAPs. Conclusions: Muscone has a protective effect on astrocytes in a MCD and inhibits astrocytes' proliferation.

[Research on the Effects of NOX-Mediated Oxidative Stress and Hearing Loss].

Hearing loss is one of the most common chronic developmental diseases.The available studies have demonstrated that the occurrence and development of hearing loss is closely related to oxidative damage caused by oxidative stress.Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase,NOX) contribute to the production of reactive oxygen and are classified into seven subtypes (NOX1,NOX2,NOX3,NOX4,NOX5,DUOX1,and DUOX2).To explore the relationship between oxidative stress and hearing loss,this paper reviews the latest research progress in the pathological mechanism of NOX-mediated oxidative stress and hearing loss.

Protective effects of muscone on traumatic spinal cord injury in rats.

Background: Traumatic spinal cord injury (SCI) is a major clinical concern, and it is a life-changing neurological condition with substantial socioeconomic implications. Muscone has been widely used in traditional Chinese medicinal formulations for its anti-inflammatory activity. However, its protective effects on traumatic SCI have not been explored. This study investigated whether muscone plays a protective role in SCI and compared its effects with those of methylprednisolone sodium succinate (MPSS). Methods: Rats were divided into five groups: normal saline (NS; n=24), methylprednisolone (MP; w=24), and muscone 1 (MO1), muscone 2 (MO2), and muscone 3 (MO3) (n=24 in each group, collectively called the MOx groups). The SCI rat model was established by the modified Allen's method. The rats were administered muscone (MO1: 2.5 mg/kg, MO2: 5 mg/kg, and MO3: 10 mg/kg) or MP (30 mg/kg), or an equivalent volume of saline. The rats were kept under observation for 4 weeks. Malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA). The expression of glial fibrillary acidic protein (GFAP), B-cell lymphoma-2 (BCL-2), and caspase3 was detected by western blot analysis. Hematoxylin-eosin (HE), Nissl, and immunocytochemistry (ICC) staining was performed for pathological observation. Basso-Beattie-Bresnahan motor function scores were evaluated for assessment of neural functions after acute SCI. Results: Muscone inhibited immune-inflammatory reactions, neuronal necrosis, and apoptosis. The lower limb function recovery was better in the MOx groups compared with NS and MP groups according to Basso-Beattie-Bresnahan scores. The changes were remarkable in the MO2 group compared with the other groups. Conclusions: Muscone alleviates secondary injury after SCI by reducing immune-inflammatory reactions, neuronal necrosis, and apoptosis.

Conditional overexpression of neuritin in supporting cells (SCs) mitigates hair cell (HC) damage and induces HC regeneration in the adult mouse cochlea after drug-induced ototoxicity.

Hearing loss due to the loss of auditory hair cells is normally irreversible because mammalian hair cells do not regenerate. Using neurotrophic factors to induce the regeneration of hair cells (HCs) from adjacent nonsensory supporting cells (SCs) may be a promising strategy to treat hearing loss. Here, we demonstrate that overexpression of neuritin in SCs could mitigate drug-induced HC damage and directly induce HC regeneration from SCs by inhibiting the Notch signaling pathway. Using neuritin conditional knock-in mice, we found that upregulation of neuritin in SCs results in preserved HCs and partial recovery of hearing, inducing the regeneration of HCs from the transdifferentiation of SCs in ears damaged by kanamycin. Furthermore, neuritin overexpression in SCs downregulates the expression levels of Notch receptor Notch intracellular domain (NICD) and hairy and enhancer of split-1 (HES1) protein, two core components of the Notch signaling pathway. These observations confirmed in vitro that in cultured neonatal mouse cochleae, neuritin overexpression in SCs significantly inhibited gentamicin-induced HC damage and induced regeneration of HCs from the transdifferentiation of SCs, and that these effects were eliminated by adding the Notch ligand Jagged-1. These findings may provide a new avenue to stimulate HC regeneration after HC loss and highlight the therapeutic potential of neuritin for sensorineural hearing loss.

Association of blood pressure in the first-week of hospitalization and long-term mortality in patients with acute left ventricular myocardial infarction.

BACKGROUND: Previous studies have shown that optimal blood pressure (BP) control is necessary to outcomes in patients with acute myocardial infarction (AMI). Acute left ventricular MI is a prevalent type of AMI with poor prognosis. We aimed to analyze the associations between BP control in the first 7 days of hospitalization and long-term mortality specific to patients with isolated left ventricular MI. METHODS: A total of 3108 acute left ventricular MI patients were included in this analysis. The average BP on the first seven days of hospitalization was categorized into 10-mmHg increments. The primary and secondary outcomes were all-cause death and cardiac death, respectively. Cox models were used to assess the association of outcomes with BP during hospitalization. RESULTS: The median length-of-stay was 7 (IQR 6-10) days. The relationship between systolic BP (SBP) or diastolic BP (DBP) followed a U-shaped curve association with outcomes. All-cause mortality was higher in patients with lower SBP (≤90 mmHg) (adjusted hazard ratios (HRs) 7.12, 95% confidence interval (CI) 3.13-16.19; p < 0.001) and DBP (<60 mmHg) (HR 1.76, 95% CI 1.14-2.71; p = 0.011) [reference: 110 < SBP ≤120 mmHg; 70 < DBP ≤ 80 mmHg], respectively. Furthermore, primary outcome was higher in patients with higher SBP (>130 mmHg) (HR 1.51, 95% CI 1.12-2.03; p = 0.007) and DBP (>80 mmHg) (HR 1.61, 95% CI 1.20-2.18; p = 0.002), respectively. CONCLUSION: Maintaining a SBP from 90 to 130 mmHg and a DBP from 60 to 80 mmHg may be beneficial to patients with acute left ventricular MI in the long run.

Giant Concentric Metallosupramolecule with Aggregation-Induced Phosphorescent Emission.

Fluorescent metallosupramolecules have received considerable attention due to their precisely controlled dimensions as well as the tunable photophysical and photochemical properties. However, phosphorescent analogues are still rare and limited to small structures with low-temperature phosphorescence. Herein, we report the self-assembly and photophysical studies of a giant, discrete metallosupramolecular concentric hexagon functionalized with six alkynylplatinum(II) bzimpy moieties. With a size larger than 10 nm and molecular weight higher than 26 000 Da, the assembled terpyridine-based supramolecule displayed phosphorescent emission at room temperature. Moreover, the supramolecule exhibited enhanced aggregation-induced phosphorescent emission compared to the ligand by tuning the aggregation states through intermolecular interactions and significant enhancement of emission to CO2 gas.

Polylactide pins can effectively fix severely comminuted and unsalvageable radial head fracture: A retrospective study of 40 patients.

BACKGROUND: The treatment of comminuted unsalvageable radial head fracture remains controversial. Open reduction and internal fixation with metallic plates and screws are hard to achieve. Conventional techniques include radial head resection and arthroplasty. Both methods have inevitable complications. The purpose of this retrospective study is to prove the feasibility of treating unsalvageable radial head fractures with absorbable polylactide pins. METHODS: A total of 17 patients with severely comminuted Mason type III radial head fractures were treated with open reduction and internal fixation using polylactide pins and 23 with metallic plates and screws. Patients receiving both modalities were followed-up for a mean of 24 months (standard deviation SD: 2.6). Radiographic analysis was conducted 2, 30, 60, and 120 days after surgery. Measurements of range of motion (ROM), disability of arm shoulder and hands, Mayo elbow performance score, and Broberg and Morrey elbow score were recorded, with treatments compared using a Mann-Whitney U test. RESULT: By the time of last follow up, All fractures in both groups healed successfully. The duration (134 min SD:21 min to 131 min SD:19 min) and blood loss (121 ml SD: 25 ml to 124 ml SD: 27 ml) during surgery of polylactide pin and metallic implant group have no statistical differences. The MEPI score (91 SD:7 to 94 SD:9), the Broberg and Morrey score (93 SD:3 to 93 SD:5), the DASH outcome measures (4.5 SD: 3.0 to 3.7 SD: 3.5), the range of motion also shows no statistical differences. Complications were infrequent and did not cause disability in both groups. All patients were satisfied with the surgical outcomes. CONCLUSION: Polylactide pins can feasibly treat severely comminuted radial head fractures, which usually are considered unreducible. This technique provides an optional treatment plan in addition to resection or arthroplasty, especially for young patients that refuse that form of treatment.

Comparative analysis of the efficacy of a transverse process bone graft with other bone grafts in the treatment of single-segment thoracic spinal tuberculosis.

BACKGROUND: There was a controversy about bone grafting of spinal tuberculosis treatment. The aim of this study was to compare the clinical efficacy of a new bone grafting method-transverse bone grafting (TBG)-with iliac bone grafting (IBG) and titanium mesh grafting (TMG) in the treatment of single-segment thoracic spinal tuberculosis. MATERIAL AND METHODS: TBG was undertaken in 30 patients (group A), IBG was carried out in 28 patients (group B), and TMG was performed in 36 patients (group C). The operative time, intraoperative blood loss, postoperative drainage amount, postoperative complications, length of hospital stay, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, visual analog scale (VAS) score for back pain, Oswestry dysfunction index (ODI), intervertebral height, and time to bone graft fusion were compared. Changes in the Cobb angle of kyphosis, intervertebral height, and loss to the final follow-up were measured. Neurological function recovery was evaluated according to the criteria of the American Spinal Injury Association (ASIA). RESULTS: The operative times in group A was significantly shorter than those in groups B and C (PAB = 0.036, PAC = 0.005, PBC = 0.901). The hospital stay in group A was significantly shorter than that in groups B and C (PAB = 0.022, PAC = 0.031, PBC = 0.424). The intraoperative blood loss in group A was significantly less than that in groups B and C (PAB = 0.045, PAC = 0.004, PBC = 0.586). The VAS score, ODI, ESR level, CRP level, Cobb angle of kyphosis, and intervertebral height of the affected segment were significantly improved compared with those before surgery (P < 0.05). CONCLUSION: For the treatment of single-segment thoracic spinal tuberculosis, the new interbody fusion technique using transverse process bone grafting is a safe, reliable, effective, and ideal bone grafting method.

Radical-Induced Hierarchical Self-Assembly Involving Supramolecular Coordination Complexes in Both Solution and Solid States.

To explore a new supramolecular interaction as the main driving force to induce hierarchical self-assembly (HSA) is of great importance in supramolecular chemistry. Herein, we present a radical-induced HSA process through the construction of well-defined rhomboidal metallacycles containing triphenylamine (TPA) moieties. The light-induced radical generation of the TPA-based metallacycle has been demonstrated, which was found to subsequently drive hierarchical self-assembly of metallacycles in both solution and solid states. The morphologies of nanovesicle structures and nanospheres resulting from hierarchical self-assembly have been well-illustrated by using TEM and high-angle annular dark-field STEM (HAADF-STEM) micrographs. The mechanism of HSA is supposed to be associated with the TPA radical interaction and metallacycle stacking interaction, which has been supported by the coarse-grained molecular dynamics simulations. This study provides important information to understand the fundamental TPA radical interaction, which thus injects new energy into the hierarchical self-assembly of supramolecular coordination complexes (SCCs). More interestingly, the stability of TPA radical cations was significantly increased in these metallacycles during the hierarchical self-assembly process, thereby opening a new way to develop stable organic radical cations in the future.

High-temperature Requirement Protein A1 Regulates Odontoblastic Differentiation of Dental Pulp Cells via the Transforming Growth Factor Beta 1/Smad Signaling Pathway.

INTRODUCTION: Dentinogenesis includes odontoblast differentiation and extracellular matrix maturation as well as dentin mineralization. It is regulated by numerous molecules. High-temperature requirement protein A1 (HtrA1) plays crucial roles in bone mineralization and development and is closely associated with the transforming growth factor beta (TGF-ß) signal in osteogenesis differentiation. Simultaneously, the TGF-ß1/small mother against decapentaplegic (Smad) signaling pathway is an important signaling pathway in various physiological processes and as a downstream regulation factor of HtrA1. However, the role of HtrA1 and its relationship with the TGF-ß1/Smad signaling pathway in dentin mineralization is unknown. METHODS: We detected the role of HtrA1 and its relationship with the TGF-ß1/Smad signaling pathway in odontoblastic differentiation of human dental pulp cells (hDPCs) in this study. First, hDPCs were cultured in mineralized medium, and odontoblastic differentiation was confirmed by investigating mineralized nodule formation, alkaline phosphatase (ALP) activity, and the expression of mineral-associated genes, including ALP, collagen I, and dentin sialophosphoprotein. Then, the expression of HtrA1 and TGF-ß1/Smad in hDPCs was investigated in hDPCs during mineralized induction. After HtrA1 knockdown by lentivirus, the mineralized nodule formation, ALP activity, and expression of mineral-associated genes and TGF-ß1/Smad genes were investigated to confirm the effect of HtrA1 on odontoblastic differentiation and its relationship with the TGF-ß1/Smad signaling pathway. RESULTS: The expression of HtrA1 and TGF-ß1 was increased during odontoblastic differentiation of hDPCs along with the messenger RNA expression of downstream factors of the TGF-ß1/Smad signaling pathway. In addition, lentivirus-mediated HtrA1 knockdown inhibited the process of mineralization and the expression of HtrA1 and TGF-ß1/Smad genes. CONCLUSIONS: These findings suggest that HtrA1 might positively regulate odontoblastic differentiation of hDPCs through activation of the TGF-ß1/Smad signaling pathway.

Synthesis and pharmacological evaluation of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as sigma-2 receptor ligands.

Increasing evidences have implicated that sigma-2 receptor is a biomarker and significantly over-expressed in many proliferative cancer cells with no or low expression in normal cells. Sigma-2 receptor selective ligands have been successfully used as valuable tools to study its pharmacological functions, tumor imaging, and cancer therapeutics or adjuvants. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolinylalkyl benzamides are among a few categories of structures that have demonstrated high affinities and selectivities for sigma-2 receptor and been used extensively as study tools in various tumor imaging and therapy. As a continuous effort, we have synthesized a new series of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives and evaluated their affinities for both sigma-1 and sigma-2 receptors. Most of these newly developed analogs showed good to excellent binding affinities for sigma-2 receptor with no or low affinities for sigma-1 receptor. In particular, compounds 3b, 3e, 4b, and 4e demonstrated Ki values of 5-6 nM affinities and excellent selectivities for sigma-2 receptor. In addition, these analogs also demonstrated moderate anticancer activities against human liver Huh-7 tumor cells and human esophagus KYSE-140 cancer cells. But their cytotoxicities seem not to be correlated with their sigma-2 receptor affinities.

Hierarchical Self-Assembly of an Alkynylplatinum(ll) Bzimpy-Functionalized Metallacage via Pt···Pt and π-π Interactions.

A new discrete supramolecular metallacage functionalized with an alkynylplatinum(ll) 2,6-bis(benzimidazole-2'-yl)-pyridine (bzimpy) moiety has been successfully constructed via coordination-driven self-assembly. A study on the hierarchical self-assembly behavior of the obtained metallacage revealed that it displayed a solvent-induced emission switch accompanied by enhancement of the emission intensity as a result of the change in intermolecular Pt···Pt and π-π interactions. More interestingly, the metallacage has been found to spontaneously self-assemble into a transparent metallogel at room temperature without a heating-cooling process.

Formation of a series of stable pillar[5]arene-based pseudo[1]-rotaxanes and their [1]rotaxanes in the crystal state.

A series of mono-amide-functionalized pillar[5]arenes with different lengths of N-ω-aminoalkyl groups as the side chain on the rim were designed and synthesized, which all formed pseudo[1]rotaxanes in the crystal state. And these pseudo[1]rotaxanes could be transformed into [1]rotaxanes or open forms in the crystal state. In addition, they were also studied in solution by (1)H NMR spectroscopy.

[Therapeutic evaluation of intertransverse bone graft for single segmental thoracic spinal tuberculosis].

OBJECTIVE: ?To explore the effectiveness of intertransverse bone graft after debridement and fusion combined with posterior instrumentation in patients with single segmental thoracic tuberculosis. METHODS: ?Between March 2014 and May 2015, 17 cases of thoracic tuberculosis were treated by the surgery of intertransverse bone graft after debridement and fusion combined with posterior instrumentation. There were 10 males and 7 females with an average age of 48.5 years (range, 18-70 years), and with a mean disease duration of 4 months (range, 1-9 months). The affected segments included T4, 5 in 2 cases, T6, 7 in 5 cases, T7, 8 in 3 cases, T9, 10 in 2 cases, T10, 11 in 4 cases, and T11, 12 in 1 case. The operation time, intraoperative blood loss, and hospitalization time were recorded. Postoperative plain radiography was taken to assess the decompression and internal fixation, and the fusion effect was evaluated by X-ray or CT examination. The erythrocyte sedimentation rate (ESR), C reactive protein (CRP), visual analogue scale (VAS), Oswestry disability index (ODI), and Kyphosis angle were recorded and compared; the nerve function was evaluated by American Spinal Injury Association (ASIA). RESULTS: ?The mean operation time, intraoperative blood loss, and hospitalization time were 184 minutes (range, 165-220 minutes), 231 mL (range, 150-800 mL), and 18 days (range, 12-26 days) respectively. No complication of hematoma or wound dehiscence was found. All patients were followed up 17.9 months on average (range, 9-22 months). No bone graft failure, internal fixation broken, pleural effusion, cerebrospinal fluid leakage, wound infection, fistula formation, and other complications occurred. Satisfactory intervertebral fusion was obtained in all patients at 3-8 months (mean, 5.3 months) after surgery. The ESR, CRP, VAS score, ODI score, and Kyphosis angle were significantly improved at immediate after operation and last follow-up when compared with preoperative ones (P<0.05), and the ESR, CRP, VAS score and ODI score at last follow-up were significantly better than those at immediate after operation (P<0.05). At last follow-up, the nerve function was recovered to ASIA grade E from grade C (1 case) and grade D (6 cases). CONCLUSIONS: ?Intertransverse bone graft is a reliable, safe, and effective way of bone graft applied to the single segmental thoracic spinal tuberculosis.