Lemniscular carbon nanohoops with contiguous conjugation from planar chiral [2.2]paracyclophane: influence of the regioselective synthesis on topological chirality.

We report herein the regioselective synthesis of all-carbon lemniscular nanohoops bis-po-CC and bis-pm-TC by the rational control of ring closures at the different positions of planar chiral tetrasubstituted [2.2]paracyclophane. Topological analyses reveal that bis-pm-TC is topologically chiral while bis-po-CC is topologically achiral. X-ray crystal analysis demonstrates that bis-pm-TC adopts a lemniscular conformation with a contiguous conjugation. CD and CPL measurements further reveal that the chiroptical properties of bis-pm-TC are obviously different from those of bis-po-CC due to their different topological chiralities.

MicroRNA-214-3p facilitates M2 macrophage polarization by targeting GSK3B.

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. M2 macrophage polarization can reduce inflammation and repair tissue injury during AR development. Studies have substantiated the involvement of miRNAs in AR pathogenesis. Herein, the molecular mechanism of miR-214-3p in AR development was explored. To mimic the AR environment, ovalbumin (OVA) was used to treat macrophages. MiR-214-3p and glycogen synthase kinase 3 beta (GSK3B) expression in nasal mucus tissues and macrophages was assessed by RT-qPCR. The M2 phenotypic signature of CD206 in macrophages was assessed by flow cytometry. The protein expression of GSK3B and M2 macrophage markers (ARG-1 and IL-10) was evaluated by western blotting. The correlation between miR-214-3p and GSK3B was validated by a luciferase reporter assay. We found that miR-214-3p was overexpressed in macrophages and nasal mucus tissues from AR patients. MiR-214-3p facilitated M2 polarization of macrophages upon OVA stimulation. Mechanistically, miR-214-3p targeted the GSK3B 3' untranslated region in macrophages. In addition, GSK3B was downregulated in macrophages and nasal mucus tissues from AR patients. In rescue assays, GSK3B downregulation reversed the inhibitory effects of miR-214-3p silencing on M2 polarization of macrophages treated with OVA. Overall, miR-214-3p facilitates M2 macrophage polarization by targeting GSK3B.

Photocatalytic Synthesis of Quinolines via Povarov Reaction under Oxidant-Free Conditions.

We describe here an approach for synthesizing quinolines either from N-alkyl anilines or from anilines and aldehydes. A dual-catalyst system consisting of a photocatalyst and a proton reduction cocatalyst is employed. Without the use of any sacrificial oxidant and under extremely mild conditions, the reactions afford quinolines in excellent yields and produce H2 as a byproduct.

A new species (Begoniagiganticaulis) of Begoniaceae from southern Xizang (Tibet) of China.

Begoniagiganticaulis, a huge new species in Begoniasect.Platycentrum of Begoniaceae from southern Xizang (Tibet) of China, is described. Morphologically, it is mostly similar to B.longifolia and B.acetosella, but clearly differs from the former mainly by its dioecious and taller plants, sparse hairs on abaxial veins, longer inflorescence, unique shape of fruits, and differs from the latter mainly by its late and longer flowering time, 6-tepals of female flower and 3-loculed ovary. The phylogenetic analyses also support the separation of the new species from other taxa. Based on the current data, its conservation status is assigned to Endangered (B2a) according to the IUCN Red List Categories and Criteria.

Strategies for Discovering New Antibiotics from Bacteria in the Post-Genomic Era.

New antibiotics are urgently required in clinical treatment and agriculture with the development of antimicrobial resistance. However, products discovered by repeating previous strategies are either not antibiotics or already known antibiotics. There is a growing demand for efficient strategies to discover new antibiotics. With the continuous improvement of gene sequencing technology and genomic data, some mining strategies have emerged. These strategies are expected to alleviate the current dilemma of antibiotics. In this review, we discuss the recent advances in discovery of bacterial antibiotics from the following aspects: activation of silent gene clusters, genome mining and metagenome mining. In the future, we envision the discovery of natural antibiotic will be accelerated by the combination of these strategies.

A tree shrew model for steroid-associated osteonecrosis.

Osteonecrosis is a common human disease in orthopedics. It is difficult to treat, and half of patients may need artificial joint replacement, resulting in a considerable economic burden and a reduction in quality of life. Hormones are one of the major causes of osteonecrosis and high doses of corticosteroids are considered the most dangerous factor. Because of the complexity of treatment, we still need a better animal model that can be widely used in drug development and testing. Tree shrews are more closely related to primates than rodents. As such, we constructed a successful tree shrew model to establish and evaluate steroid-associated osteonecrosis (SAON). We found that low-dose lipopolysaccharide (LPS) combined with high-dose methylprednisolone (MPS) over 12 weeks could be used to establish a tree shrew model with femoral head necrosis. Serum biochemical and histological analyses showed that an ideal model was obtained. Thus, this work provides a useful animal model for the study of SAON and for the optimization of treatment methods.

Identification, characterization and expression profiles of PSEN2 in the Chinese tree shrew (Tupaia belangeri chinensis).

The gene PSEN2 encodes presenilin-2, a subunit of γ-secretase. Mutations in PSEN2 are not only related to Alzheimer's disease but are also involved in other diseases. The Chinese tree shrew (Tupaia belangeri chinensis) is a potential animal model for Alzheimer's disease, although little is known about its cDNA sequence, protein structure, and PSEN2 expression. To better understand PSEN2 in the tree shrew, we cloned this gene by rapid amplification of cDNA ends technology. Hence, we analyzed the sequence and molecular characteristics of PSEN2 mRNA, predicted its spatial structure, and analyzed its expression profiles. We found that tree shrew PSEN2 is 1539 base pairs in length and encodes 330 amino acids. It is homologous and genetically similar to humans (97.64% identity). The protein structure of tree shrew PSEN2 indicated similarities to human PSEN2, both being comprised of numerous transmembrane helices. However, tree shrew PSEN2 possesses seven α-helices, and thus lacks three compared with human PSEN2. Tree shrew PSEN2 mRNAs were ubiquitously detected in all tissues, with a tissue- and temporal-specific pattern. These results pave the way towards the function of tree shrew PSEN2, which will give insights into the mechanisms leading to neurodegenerative and other diseases in humans.

An Octanuclear Cobalt Cluster Protected by Macrocyclic Ligand: In Situ Ligand-Transformation-Assisted Assembly and Single-Molecule Magnet Behavior.

Macrocyclic molecules with multiple coordination sites have been widely used as promising ligands to build polynuclear metal clusters; however, cyclic silsesquioxane-based metal clusters are still rare. Herein, we report a new octanuclear Co-silsesquioxane cluster [Co8(OH)2{(MeSiO2)6}2(bpy)2(Obpy)2] (SD/Co8c; SD = SunDi), wherein the Co8 disc-like core is sandwiched by two hexamethylcyclohexasiloxanolate ligands (MeSiO2)6 at two poles and finally encircled by two bpy (bpy = 2,2'-bipyridine) and two Obpy (HObpy = 6-hydroxy-2,2'-bipyridine) ligands at the equatorial region. Interestingly, both MeSi(OMe)3 and bpy undergo in situ transformations to generate hexameric cyclic (MeSiO2)6 and Obpy, respectively. The unusual hydroxylation of bpy and the OH- anion in the center of Co8 core provide additional binding sites to induce the formation of the larger cluster instead of the traditional hexanuclear cluster. The solution stability and fragmentation route in the gas phase were studied by cold-spray ionization and collision-induced dissociation mass spectrometry, respectively. Both results reveal that the Co8 core is quite stable in solution as well as in the gas phase, even with increased collision voltage. Magnetic susceptibility studies of SD/Co8c show the slow magnetization relaxation indicative of single-molecule magnet (SMM) behavior. This work not only presents the multiple in situ ligand-transformation-assisted assembly of polynuclear cobalt cluster but also provides some new insights into the magnetism-structure relationship for SMMs.

Space Craft-like Octanuclear Co(II)-Silsesquioxane Nanocages: Synthesis, Structure, Magnetic Properties, Solution Behavior, and Catalytic Activity for Hydroboration of Ketones.

Two novel space craft-like octanuclear Co(II)-silsesquioxane nanocages, {Co8[(MeSiO2)4]2(dmpz)8} (SD/Co8a) and {Co8[(PhSiO2)4]2(dmpz)8} (SD/Co8b) (SD = SunDi; Hdmpz = 3,5-dimethylpyrazole), have been constructed from two similar multidentate silsesquioxane ligands assisted with a pyrazole ligand. The Co8 skeleton consists of eight tetrahedral Co(II) ions arranged in a ring and is further capped by two (MeSiO2)4 ligands up and down. The auxiliary dmpz- ligands seal the ring finally. Electrospray ionization mass spectrometry revealed SD/Co8a and SD/Co8b are highly stable in CH2Cl2. Magnetic analysis implies that SD/Co8a announces antiferromagnetic interactions between Co(II) ions. Moreover, both of them display good homogeneous catalytic activity for hydroboration of ketones in the presence of pinacolborane under mild conditions.

High glucose contributes to the proliferation and migration of non-small cell lung cancer cells via GAS5-TRIB3 axis.

Despite the growing number of studies exhibited an association of diabetes mellitus (DM) and lung cancer progression, the concrete mechanism of DM aggravating lung cancer has not been elucidated. This study was to investigate whether and how high glucose (HG) contribute to the proliferation and migration of non-small cell lung cancer (NSCLC) cells in vitro. In the present study, we confirmed that HG promoted the proliferation and migration of NSCLC cells, and also induced an anti-apoptosis effect on NSCLC cells. Moreover, HG inhibited the expression of GAS5 in NSCLC cells but elevated the protein level of TRIB3. GAS5 overexpression promoted the degradation of TRIB3 protein by ubiquitination and inhibited the HG induced-proliferation, anti-apoptosis and migration of NSCLC cells. Importantly, TRIB3 overexpression reversed the effects of GAS5 on the HG-treated NSCLC cells. Taken together, down-regulated GAS5 by HG significantly enhanced the proliferation, anti-apoptosis and migration in NSCLC cells through TRIB3, thus promoting the carcinogenesis of NSCLC.

Regeneration of islet ß-cells in tree shrews and rats.

BACKGROUD: Current understanding of injury and regeneration of islet ß-cells in diabetes is mainly based on rodent studies. The tree shrew is now generally accepted as being among the closest living relatives of primates, and has been widely used in animal experimentation. However, there are few reports on islet cell composition and regeneration of ß-cells in tree shrews. METHODS: In this study, we examined the changes in islet cell composition and regeneration of ß-cells after streptozotocin (STZ) treatment in tree shrews compared with Sprague-Dawley rats. Injury and regeneration of islet ß-cells were observed using hematoxylin and eosin (HE) staining and immunohistochemical staining for insulin, glucagon, somatostatin and PDX-1. RESULTS: Our data showed that in rats islet injury was most obvious on day 3 after injection, and islet morphologies were significantly restored by day 21. Regeneration of islet ß-cells was very pronounced in rats, and mainly involved regeneration of centro-acinar cells and transformation of extra-islet ductal cells. In tree shrews, the regeneration of islet ß-cells was not as significant. On days 3 and 7, only scattered regenerated cells were observed in the remaining islets. Further, no regeneration of centro-acinar cells was observed. CONCLUSION: The results suggest that the repair mechanism of islet ß-cells in tree shrews is similar to that of humans.

Assembly of silver Trigons into a buckyball-like Ag180 nanocage.

Buckminsterfullerene (C60) represents a perfect combination of geometry and molecular structural chemistry. It has inspired many creative ideas for building fullerene-like nanopolyhedra. These include other fullerenes, virus capsids, polyhedra based on DNA, and synthetic polynuclear metal clusters and cages. Indeed, the regular organization of large numbers of metal atoms into one highly complex structure remains one of the foremost challenges in supramolecular chemistry. Here we describe the design, synthesis, and characterization of a Ag180 nanocage with 180 Ag atoms as 4-valent vertices (V), 360 edges (E), and 182 faces (F)--sixty 3-gons, ninety 4-gons, twelve 5-gons, and twenty 6-gons--in agreement with Euler's rule V - E + F = 2. If each 3-gon (or silver Trigon) were replaced with a carbon atom linked by edges along the 4-gons, the result would be like C60, topologically a truncated icosahedron, an Archimedean solid with icosahedral (Ih) point-group symmetry. If C60 can be described mathematically as a curling up of a 6.6.6 Platonic tiling, the Ag180 cage can be described as a curling up of a 3.4.6.4 Archimedean tiling. High-resolution electrospray ionization mass spectrometry reveals that {Ag3}n subunits coexist with the Ag180 species in the assembly system before the final crystallization of Ag180, suggesting that the silver Trigon is the smallest building block in assembly of the final cage. Thus, we assign the underlying growth mechanism of Ag180 to the Silver-Trigon Assembly Road (STAR), an assembly path that might be further employed to fabricate larger, elegant silver cages.

Heptanuclear CoII5CoIII2 Cluster as Efficient Water Oxidation Catalyst.

Inspired by the transition-metal-oxo cubical Mn4CaO5 in photosystem II, we herein report a disc-like heptanuclear mixed-valent cobalt cluster, [CoII5CoIII2(mdea)4(N3)2(CH3CN)6(OH)2(H2O)2·4ClO4] (1, H2mdea = N-methyldiethanolamine), for photocatalytic oxygen evolution. The topology of the Co7 core resembles a small piece of cobaltate protected by terminal H2O, N3-, CH3CN, and multidentate N-methyldiethanolamine at the periphery. Under the optimal photocatalytic conditions, 1 exhibits water oxidation activity with a turnover number (TON) of 210 and a turnover frequency (TOFinitial) of 0.23 s-1. Importantly, electrospray mass spectrometry (ESI-MS) was used to not only identify the possible main active species in the water oxidation reaction but also monitor the evolutions of oxidation states of cobalt during the photocatalytic reactions. These results shed light on the design concept of new water oxidation catalysts and mechanism-related issues such as the key active intermediate and oxidation state evolution in the oxygen evolution process. The magnetic properties of 1 were also discussed in detail.

Functional analysis of serum microRNAs miR-21 and miR-106a in renal cell carcinoma.

OBJECTIVE: microRNAs (miRNAs) plays an important role in tumor development and progression and act as oncogenes or tumor suppressor genes in the carcinogenesis process. miRNA is stable in serum, and recent studies have demonstrated the feasibility of using circulating miRNA as biomarkers in cancer patients. However, currently, no serum biomarkers for the early diagnosis and prognosis of renal cell carcinoma (RCC) have been reported. Therefore, a new molecular marker for early diagnosis and evaluation of recurrence after surgery is required. Our purpose was to identify miRNA signatures that could distinguish the serum of RCC patients from matched healthy controls and validate identified miRNAs as potential biomarkers for RCC. METHOD: Serum samples from 30 RCC patients were collected before and 1 month after surgery. 30 cancer-free blood donor volunteers with no history of any cancer were recruited from the same institute. miR-21 and miR-106a expression levels were determined by real-time PCR. RESULT: The serum miR-21 level was significantly higher in RCC patients (median, 8.34) than in healthy control individuals (median, 0.70; p= 0.001). A month after surgery, serum miR-21 levels (median, 0.69) were significantly reduced (p= 0.032). The serum miR-106a level was higher in RCC patients (median, 8.99) compared with controls (median, 0.96; p= 0.000), while miR-106a levels (median, 1.01) were reduced a month after surgery (p= 0.028). The expression level of miR-21 and miR-106 a in RCC patients increased significantly, while miR-21 and miR-106a decreased after surgery. This outcome suggests that serum miR-21 and miR-106a expression level was closely related with kidney cancer tissue. CONCLUSION: We conclude that serum miR-21 and miR106a are expected to be molecular markers for RCC.

Impact of smoking status and cumulative smoking exposure on tumor recurrence of non-muscle-invasive bladder cancer.

OBJECTIVE: To investigate the effect of smoking status, cumulative smoking exposure and smoking cessation on the outcomes of patient with non-muscle-invasive bladder cancer (NMIBC). METHODS: We collected smoking data from 484 patients with NMIBC who were treated with transurethral resection (TUR); smoking status was categorized as (never smokers vs current smokers vs former smokers). Cumulative smoking exposure was categorized as high smoking exposure (cigarette index ≥400) versus low smoking exposure (cigarette index <400). Association with outcomes was examined by multivariable analyses after adjusting for the effects of standard clinicopathologic factors, and the Kaplan-Meier method was used to estimate the effect of smoking status and cumulative smoking exposure on RFS. RESULTS: A total of 168 (34.7 %) patients were never smoker, 121 (25 %) patients were current smokers, and 195 (40.3 %) patients were former smokers. The median follow-up was 25 months. By multivariate analysis, pathological grade (p = 0.013), history of recurrence (p < 0.001), number of tumors (p < 0.001) and size of tumors (p = 0.013) were significantly associated with tumor recurrence; nevertheless, smoking status did not influence tumor recurrence (p = 0.063). Among current and former smokers, cumulative smoking exposure was significantly associated with tumor recurrence (p < 0.001), compared to current smokers, patients with smoking cessation ≥10 years had a lower risk of tumor recurrence [hazard ratio (HR) 0.456, p = 0.007]. CONCLUSIONS: Smoking affects the prognosis of patient with NMIBC, which is still controversial; however, among ever smokers, a high cumulative exposure smoking can significantly increase the risk of tumor recurrence. Quitting smoking might be associated with a lower recurrence rate for patients with NMIBC.

Proprotein convertase subtilisin/kexin type 9 levels and aortic valve calcification: A prospective, cross sectional study.

OBJECTIVE: To investigate the possible association between plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and the incidence and severity of calcific aortic valve disease (CAVD). METHODS: This prospective, cross sectional study involved patients with and without (controls) aortic valve calcification diagnosed by transthoracic echocardiography and dual source computed tomography (DSCT) scan. Aortic valves calcification scores were calculated from DSCT scans and patients were graded: grade 1, no calcification; grade 2, mildly calcified; grade 3, moderately calcified; grade 4, heavily calcified. Plasma PCSK9 levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Forty patients were grade 1 (controls), 32 were grade 2, 48 were grade 3 and 32 were grade 4. Plasma levels of PCSK9 were significantly different between the four groups and the highest value was observed in the patients with grade 2 calcification. Only low-density lipoprotein cholesterol and lipoprotein (Lp)(a) were associated with the severity of CAVD. Regression analysis showed that age, Lp(a) and PCSK9 were independent predictors of CAVD. CONCLUSION: Data from this cross sectional study in a small sample of patients showed that plasma PCSK9 was correlated with the presence of CAVD but not its severity.

Hierarchical Assembly of a {Mn(II)15Mn(III)4} Brucite Disc: Step-by-Step Formation and Ferrimagnetism.

In search of functional molecular materials and the study of their formation mechanism, we report the elucidation of a hierarchical step-by-step formation from monomer (Mn) to heptamer (Mn7) to nonadecamer (Mn19) satisfying the relation 1 + Σn6n, where n is the ring number of the Brucite structure using high-resolution electrospray ionization mass spectrometry (HRESI-MS). Three intermediate clusters, Mn10, Mn12, and Mn14, were identified. Furthermore, the Mn19 disc remains intact when dissolved in acetonitrile with a well-resolved general formula of [Mn19(L)x(OH)y(N3)36-x-y](2+) (x = 18, 17, 16; y = 8, 7, 6; HL = 1-(hydroxymethyl)-3,5-dimethylpyrazole) indicating progressive exchange of N3(-) for OH(-). The high symmetry (R-3) Mn19 crystal structure consists of a well-ordered discotic motif where the peripheral organic ligands form a double calix housing the anions and solvent molecules. From the formula and valence bond sums, the charge state is mixed-valent, [Mn(II)15Mn(III)4]. Its magnetic properties and electrochemistry have been studied. It behaves as a ferrimagnet below 40 K and has a coercive field of 2.7 kOe at 1.8 K, which can be possible by either weak exchange between clusters through the anions and solvents or through dipolar interaction through space as confirmed by the lack of ordering in frozen CH3CN. The moment of nearly 50 NµB suggests Mn(II)-Mn(II) and Mn(III)-Mn(III) are ferromagnetically coupled while Mn(II)-Mn(III) is antiferromagnetic which is likely if the Mn(III) are centrally placed in the cluster. This compound displays the rare occurrence of magnetic ordering from nonconnected high-spin molecules.

Expression of chemokine receptor 4 was associated with poor survival in renal cell carcinoma.

Chemokines and their receptors are known to play important roles in tumor growth and metastasis of many malignancies. Recently, CC chemokine receptor 4 (CCR4) has been described as a prognostic marker in various tumors. However, the possible role of CCR4 in clear cell renal cell carcinoma (ccRCC) has not been well elucidated. In this study, we detected the expression of CCR4 in 53 ccRCC by immunohistochemistry and correlated it with clinicopathological parameters and prognosis. Immunohistochemistry was used to determine the expression of CCR4 in 53 ccRCC and 11 renal contusion tissue specimens. CCR4 expression between carcinoma and normal renal tissues was evaluated by χ(2) test. Correlation between CCR4 and clinicopathological data was tested by χ(2) test. Univariate survival analysis was performed by the Kaplan-Meier method, and differences among the groups were analyzed by the log-rank test. CCR4 expression in ccRCC tissue was significantly higher compared with normal renal tissue samples (χ(2) = 4.392, P = 0.036). CCR4 was correlated with the clinicopathological features including tumor stage (P = 0.009), lymph node metastasis (P = 0.003) and distant metastasis (P = 0.031). Further, CCR4 was the only dependent affecting factor in lymph node metastasis (P = 0.014). Univariate analysis showed that tumor stage, lymph node metastasis, distant metastasis and CCR4 were influential factors for poor prognosis in ccRCC patients; multivariate analysis revealed that CCR4 (P = 0.007) was the only independent risk factor for prognosis. In addition, Kaplan-Meier curve for overall survival (OS) indicated that prognosis was unfavorable for patients who had high CCR4 expression level (P = 0.010). CCR4 was correlated with tumor aggressive behavior in ccRCC. It might be involved in lymph node metastasis and have influence on patients' OS. Further research is needed to determine the potential of CCR4.

[Application of health education of house-to-house visit in malaria prevention and control].

OBJECTIVE: To evaluate the effects of health education of house-to-house visit in malaria prevention and control in the border and minority areas. METHODS: A health education of house-to-house visit in malaria prevention and control was carried out, and baseline and follow up surveys were conducted by qualitative and quantitative methods to document the changes of local villagers' knowledge, attitudes and behaviors (KAP) of malaria prevention and control in 2 counties of Yunnan Province, and the results before and after the interventions were analyzed and compared. RESULTS: After the intervention, the cognition rates about malaria symptoms and signs, transmission mode, preventive measures and health-seeking behaviors were 99.3%, 98.9%, 79.9% and 99.3% respectively in the local residents, and those were 39.2%, 8.2%, 47.0% and 49.9% respectively before the intervention, and all the differences were statistically significant (P all < 0.01). CONCLUSIONS: KAP related to malaria among the targeting population has improved after the interventions and the house-to-house visit is an effective community-based health education approach.

Motor Function in MPTP-Treated Tree Shrews (Tupaia belangeri chinensis).

The tree shrew, a new experimental animal model, has been used to study a variety of diseases, especially diseases of the nervous system. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the gold standard for toxin-based animal models of Parkinson's disease (PD) because MPTP treatment replicates almost all of the pathological hallmarks of PD. Therefore, in this study, the effects of MPTP on the motor function of the tree shrew were examined. After five daily injections of a 3 mg/kg dose of MPTP, the motor function of MPTP-injected tree shrews decreased significantly, and the classic Parkinsonian symptoms of action and resting tremor, bradykinesia, posture abnormalities, and gait instability were observed in most MPTP-injected tree shrews. HPLC results also showed significantly reduced striatal dopamine and 3,4-dihydroxyphenylacetic acid levels in tree shrews after MPTP injection. Increased oxidative stress levels are usually considered to be the cause of dopaminergic neuron depletion in the presence of MPTP and were observed in the substantia nigra of MPTP-treated tree shrews, as indicated by a significant reduction in superoxide dismutase and glutathione peroxidase activity and increased levels of malondialdehyde. In addition, elevated α-synuclein mRNA levels in the midbrain of MPTP-treated tree shrews were observed. Furthermore, MPTP-treated tree shrews showed the classic Parkinsonian symptoms at a lower MPTP dosage compared with other animal models. Thus, the MPTP-treated tree shrew may be a potential animal model for studying the pathogenesis of PD.