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This article reports the first optically active macroporous materials constructed by helical substituted polyacetylene and prepared by a high internal phase emulsion (HIPE) technique. The macroporous (∼3 μm) materials were fabricated simply through polymerization of the continuous phase in HIPEs. The porous structures of the resulting materials can be adjusted by varying the fraction of the dispersed phase. The obtained materials were characterized by regular pore morphology, high porosity, and low density. Circular dichroism and UV-vis absorption spectra demonstrated that the substituted polyacetylene forming the materials adopted chirally helical conformations, which endowed the materials with considerable optical activity. The optically active porous materials were used as chiral inducers and efficiently induced enantioselective crystallization of threonine and alanine racemates. l-Threonine and l-alanine were preferably induced to form crystals from the respective racemic solutions. The prepared materials open a new type of functional chiral materials with potential applications in asymmetric catalysis, chiral resolution, etc.

Competing endogenous RNA (ceRNA) network is dysregulated in the initiation and progression of tumors. In the present study, we explored the regulatory mechanism of ceRNA in endometrial carcinoma (EC) and the potential key molecules with potential value in the diagnosis, treatment, and prognosis of EC. The long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression profiles (552 EC tissues and 35 nontumor tissues) and microRNAs (miRNAs) expression profiles (546 EC tissues and 33 nontumor tissues) were downloaded from The Cancer Genome Atlas database to identify differentially expressed RNAs (DERNAs) in EC. An integrated bioinformatics analysis was used to construct an EC-specific ceRNA network and select key molecules. As a result, 96 differentially expressed lncRNAs (DElncRNAs), 29 differentially expressed miRNAs (DEmiRNAs), and 77 differentially expressed mRNAs (DEmRNAs) were identified. An EC-specific ceRNA network was built based on nine DElncRNAs significantly associated with overall survival. CCNB1 was found as a key gene in EC through the weighted gene coexpression network analysis and protein-protein interaction network analysis. Our ceRNA network showed C2orf48 and LINC00483 might upregulate CCNB1 via competing with miR-183. In addition, we found a subnetwork which contained survival-associated DERNAs (AC110491.1, LINC00483-miR-192-GRHL1). The results of reverse transcription quantitative polymerase chain reaction supported the relative expressions of C2orf48, LINC00483 were upregulated and that of AC110491.1 was downregulated in EC. We further found C2orf48 was upregulated in serous EC, endometrioid EC, and mixed serous and endometrioid EC. LINC00483 was upregulated in mixed serous and endometrioid EC compared with that in the normal tissues according to UALCAN database. In addition, candidate small molecular drugs were screened out by ConnectivityMap based on the 77 DEmRNAs in the ceRNA network. Eventually, C2orf48, LINC00483, and AC110491.1 were identified as three key lncRNAs in EC.

Aims The association of strictly defined metabolic healthy obese (MHO) with subclinical cardiac function was unclear. Our study aims to examine the role of MHO in subclinical cardiac dysfunction in a Chinese population. Methods and results The study subjects were recruited from Danyang from 2017 to 2019. Obesity was defined by body mass index (BMI) categories (normal weight, overweight and obesity). Metabolic health was strictly defined as having neither any of the guidelines recommended metabolic syndrome components nor insulin resistance. Thus, subjects were grouped by BMI categories and metabolic health status as six groups. Preclinical systolic (global longitudinal strain [GLS]) and diastolic function were assessed by 2D speckle tracking, and transmitral and tissue Doppler imaging, respectively. The 2757 participants (mean age ± standard deviation, 52.7 ± 11.7 years) included 1613 (58.5%) women, 999 (36.2%) obese, 2080 (75.4%) metabolically unhealthy and 93 (3.4%) MHO participants. After adjustment for covariates, the trend was similar for left ventricular (LV) ejection fraction (P trend ≥ 0.07) but significantly worse for GLS, e′ and E/e′ (P trend ≤ 0.02) across the six groups or passing from normal weight to obese individuals irrespective of metabolic status. MHO participants had lower GLS (20.4 vs. 21.4%) and e′ (9.6 vs. 10.6 cm/s) compared with controls (P

Atherosclerosis is now the major cause of mortality and morbidity worldwide. Formation of macrophage-derived foam cells is a hallmark of atherosclerosis, which is regulated by cholesterol uptake, intracellular metabolism, and efflux. PPARγ-LXRα-ABCA1/ABCG1 pathway plays an important part in regulating cholesterol efflux and this pathway could be a promising target for treating atherosclerosis. However, due to undesirable systemic effects, PPARγ agonist therapy for atherosclerosis remains challenging. Many traditional Chinese medicine has been well accepted and applied in atherosclerosis treatment. Yin-xing-tong-mai decoction (YXTMD) has been applied for treating atherosclerosis for decades. However, the mechanism remains to be explored. Here, we showed that YXTMD effectively attenuated atherosclerosis in ApoE-/- mice. YXTMD increased cholesterol efflux of foam cell by upregulation of ABCA1 and ABCG1 in vivo and in vitro. Through bioinformatic analysis and experimental validation, we found that PPARγ was an important downstream effector of YXTMD in macrophages. Reduction of PPARγ significantly decreased LXRα, ABCA1, and ABCG1 expression in macrophages, with reduced cholesterol efflux. In conclusion, these findings confirmed that YXTMD attenuated atherosclerosis by activating the PPARγ-LXRα- ABCA1/ABCG1 pathway to enhance cholesterol efflux.

The association of albuminuria, as measured by urine albumin-to-creatinine ratio (UACR) concentration, with subclinical cardiac dysfunction in hypertensive patients is unclear. Our study aimed to examine its relationship in hypertensive patients compared with that in normotensive patients. The study participants were recruited from Danyang, a city of Jiangsu Province from 2017 to 2019. Categorical and continuous analyses were performed with sex-specific UACR tertiles and natural logarithmically transformed UACR, respectively. Comprehensive echocardiography including conventional imaging, tissue Doppler imaging, and 2D speckle tracking was performed using Philips CX50 device. The 2857 participants (mean age = 52.7 ± 11.8 years) included 1673 (58.6%) women, 1125 (39.4%) hypertensive patients, 546 (19.1%) patients with microalbuminuria, and 38 (1.3%) patients with macroalbuminuria. Comorbidities were increasingly prevalent across the tertiles of UACR. Increased left ventricular (LV) mass index, decreased global longitudinal strain (GLS) and LV ejection fraction, lower E/A ratio and e' velocity, and higher E/e' ratio were significantly associated with higher UACR on unadjusted analyses (p ≤ .01). After adjustment for covariates, UACR was only independently associated with lower GLS (tertile 3 = 20.7% vs. tertile 1 = 20.9%; p = .04). The results of hypertensive patients (p ≤ .04) but not normotensive patients (p ≥ .16) were similar to those of the total cohort. Subgroup analyses revealed similar results in patients without coronary artery disease, or without LV hypertrophy, or without diabetes. In conclusion, increased UACR is associated with worse subclinical systolic function in Chinese hypertensive patients but not in normotensive participants.

Hybrid materials are interesting because they combine the advantages of multiple components in one material entity. This article reports on a new type of chiral porous hybrid particle constructed by helical substituted polyacetylene and silica. To prepare the hybrid particles, chirally helical substituted acetylene copolymers containing pendent Si–O–Et groups were first synthesized and subsequently used as macromolecular silane couplers to perform a sol–gel reaction with TEOS. After aging, the designed hybrid particles were fabricated. Phase separation in the sol–gel reaction endowed the hybrid particles with abundant pores. In the resulting hybrid particles, inorganic silica constituted the rigid framework, whereas the organic helical substituted polyacetylene bonded with the framework and offered optical activity. SEM images confirmed the formation of spherical particles with regular morphology and porous structure. Circular dichroism and UV-vis absorption spectra demonstrated that the helical polymer chains had a preferential helicity and considerable optical activity in the hybrid particles. The hybrid materials demonstrated the capability of enantioselectively releasing cinchona alkaloid, which was used to model chiral drugs. The release process was found to be influenced by temperature: low temperature was more favorable for enantio-differentiating release.

Polylactide (PLA, two enantiomers: PLLA and PDLA) is well-known for its biocompatibility, biodegradability, and good mechanical capacity. However, PLLA and PDLA have been rarely explored in spite of the well-known significance of chirality and chiral (macro)molecules. This work aims to investigate PLLA and PDLA’s chirality in terms of enantioselectivity towards chiral guests. For this purpose, PLA-based chiral particles were successfully prepared and demonstrated enantioselectivity in releasing chiral drug, naproxen. The PLLA- and PDLA-based particles both showed enantioselectivity towards the chiral drug, i.e. preferably releasing S-naproxen over the R-enantiomer. Moreover, PDLA-based particles showed enantioselectivity only in racemic release mode but not in single enantiomer release mode. We accordingly propose that enantio-differentiating effects not only occur in release process, but also in drug loading process. The intriguing findings are essentially different from other chiral polymers investigated earlier, and deserve much more interest due to the extensive uses of PLA as biomaterials.

The present work reports on the synthesis of chiral particles consisting of helical polylactide (PLA) and helical substituted polyacetylene, aiming to investigate the chiral synergetic effects of the two helical components in enantioselectivity. For this purpose, polylactide with polymerizable terminal alkynyl group was prepared and subsequently used as macromer to copolymerize with chiral alkynyl monomer to form the target particles. SEM images demonstrate that the particles possessed porous structures. Circular dichroism shows that the helical substituted polyacetylene had an influence on the helical screw sense of polylactide chains, thereby affecting the enantioselectivity of the chiral particles in releasing the model chiral drug naproxen. Compared with our earlier study on enantioselectivity of PLA, copolymerizing PLA with chiral alkynyl monomer improves PLA’s enantioselectively discriminating ability in naproxen release and even can reverse the particles’ preferential enantioselectivity in releasin...

Background: KDM lysine demethylase family members are related to lung cancer clinical outcomes and are potential biomarkers for chemotherapeutics. However, little is known about epigenetic alterations in KDM genes and their roles in lung cancer survival. Methods: Tumor tissue samples of 1230 early-stage non-small cell lung cancer (NSCLC) patients were collected from the five independent cohorts. The 393 methylation sites in KDM genes were extracted from epigenome-wide datasets and analyzed by weighted random forest (Ranger) in discovery phase and validation dataset, respectively. The variable importance scores (VIS) for the sites in top 5% of both discovery and validation sets were carried forward for Cox regression to further evaluate the association with patient's overall survival. TCGA transcriptomic data were used to evaluate the correlation with the corresponding DNA methylation. Results: DNA methylation at sites cg11637544 in KDM2A and cg26662347 in KDM1A were in the top 5% of VIS in both discovery phase and validation for squamous cell carcinomas (SCC), which were also significantly associated with SCC survival (HRcg11637544 = 1.32, 95% CI, 1.16-1.50, P = 1.1 x 10(-4); HRcg26662347 = 1.88, 95% CI, 1.37-2.60, P = 3.7 x 10(-3)), and correlated with corresponding gene expression (cg11637544 for KDM2A, P = 1.3 x 10(-10); cg26662347 for KDM1A P = 1.5 x 10(-5)). In addition, by using flexible criteria for Ranger analysis followed by survival classification tree analysis, we identified four clusters for adenocarcinomas and five clusters for squamous cell carcinomas which showed a considerable difference of clinical outcomes with statistical significance. Conclusions: These findings highlight the association between somatic DNA methylation in KDM genes and early-stage NSCLC patient survival, which may reveal potential epigenetic therapeutic targets.

Incorporating multi-functions into a single entity can provide various novel materials, well exemplified by interpenetrating polymer networks. In this contribution, we prepared the first chiral porous interpenetrating polymer networks (IPNs) by incorporating functional boronic acid-containing polymers to a pre-formed chiral porous framework which was constructed by chirally helical substituted polyacetylenes. The pore size in the resulting chiral IPNs can be tuned by adjusting the content of the boronic acid-containing polymer. Circular dichroism and UV-vis absorption spectra demonstrated that the helical polymer chains in both the pre-formed chiral porous framework and the final IPNs took preferential helicity, which rendered the IPNs with considerable optical activity. The as-prepared IPNs could adsorb glucose through esterification reaction occurring between the boronic acid groups contained in the networks and cis-diol in glucose. More importantly, the successful combination of boronic acid groups with the chiral framework enabled the IPNs to simultaneously exhibit enantioselectivity and pH sensitivity in the glucose adsorption process. The reversibility of the boronic acid-derived ester structure facilitated the IPNs to be easily recycled, thus endowing the novel IPNs with diverse promising applications.

The double helix is one of the most basic and exquisite architectures in nature, and thus has received much attention in multiple disciplines. However, the types of artificial polymeric double helices and their synthetic methods are severely limited. The present contribution develops a novel 3-step methodology for preparing double helices consisting of helical substituted polyacetylenes (DHSPs): (1) an optically inactive helical polymer is synthesized using an achiral monomer; (2) the as-obtained polymer is induced to form a one-handed helix by “locking” a chiral monomer in the helical grooves; (3) the “locked” chiral monomer undergoes helically twining polymerization along the pre-formed one-handed helical polymer chains, thereby constructing the DHSPs. Circular dichroism and UV-vis absorption spectra in combination with high resolution TEM images demonstrate the optical activity, double helical structure, and helix sense of the DHSPs. The convenient synthetic strategy is expected to provide various kinds of double helical polymers.

Objective. Type 2 diabetes (T2DM) is a global epidemic and increases mortality due to its vascular complications. Chemerin has been found to exert a major role in glucose and lipid metabolism. The aim of this study was to explore the correlation between plasma chemerin levels and microangiopathy in patients with T2DM. Methods. A total of 598 T2DM patients were classified into two groups: with and without microvascular complications. Anthropometric parameters and blood pressure were taken. The amounts of glycosylated hemoglobin, glucose, lipid profiles, creatinine, and chemerin concentrations in the blood were determined. The presence and severity of nephropathy, retinopathy, and neuropathy were also evaluated by specific tests. Results. Plasma levels of chemerin in diabetic subjects with microvascular complications were markedly elevated compared to those without. The number of microvascular complications increased with high plasma chemerin levels. Patients with high chemerin levels had an increased incidence of nephropathy and retinopathy. Furthermore, the chemerin plasma concentrations increased with the progression of diabetic nephropathy with highest values in macroalbuminuria groups. In contrast, no significant difference was observed in plasma chemerin levels between subjects with and without peripheral neuropathy. Pearson correlation analysis showed that plasma chemerin levels were positively related to duration of diabetes, serum creatinine, and 24-hour urine albumin excretion, even after multiple adjustments. Using logistic regression analysis, plasma chemerin concentrations were independently associated with the presence of nephropathy and retinopathy, not neuropathy. Conclusion. This study elucidated a positive correlation between increased chemerin levels and the development of some subtypes of diabetic microangiopathy.

A judicious combination of chiral structure with other functionalities in one entity may provide novel materials. For this purpose, boronic acid functional group was integrated with optically active helical substituted polyacetylene microspheres. To prepare the designed functional microspheres, two substituted acetylene monomers, i.e. chiral monomer M1 and achiral monomer M2 which was prepared from a boronic acid derivative, were synthesized and copolymerized through suspension polymerization for constructing polymeric microspheres. SEM images demonstrated the successful formation of the microspheres. X-ray photoelectron spectroscopy was measured to determine boronic acid content on the surface of the as-prepared microspheres. Circular dichroism spectra showed that one-handed helices were formed in the copolymer chains constructing the microspheres, which enabled the microspheres to exhibit enantio-differentiating adsorption capacity towards 3,4-dihydroxy-l-phenylalanine (l-DOPA), whereas 3,4-dihydroxy-d-phenylalanine (d-DOPA) was preferentially released. Amazing synergistic effects occurred in the helical polymer chains and the pendant boronic acid moieties. Desorption capacity and recyclability of the microspheres were also clearly verified. The unprecedented optically active microspheres hold practical applications for developing materials used for chiral adsorption, enantiomeric drug controlled release, etc.

The importance of chiral compounds has been widely recognized. Enantioselectively controlled release of the desired enantiomer from a racemate while retarding the other isomer provides a novel route toward practical applications of biologically chiral molecules. Such processes may maximize the efficacy while minimizing the dosage and frequency of chiral compounds. So far, exciting achievements have been made in enantioselective release (ESR), which can be classified into two main groups according to the essential strategy: (1) chiral interactions occurring between chiral compounds and chiral matrices (“enantioselective interaction” strategy); and (2) recognizing sites inside molecular-imprinting polymers (MIPs; “key-to-lock” strategy). The chiral compounds of interest are not limited to chiral drugs, but also include other biologically important chiral compounds (e.g., amino acids). Based on our studies, this article reviews the state-of-the-art techniques and materials systems toward ESR. The emphasis is...

While obesity and fat intake have been associated with the risk and prognosis of epithelial ovarian cancer, the association between the lipid levels and epithelial ovarian cancer phenotype remains controversial. We conducted a retrospective study of 349 epithelial ovarian cancer patients who received treatment at Jiangsu Cancer Hospital, China between 2011 and 2017. We analyzed age at diagnosis, blood pressure, plasma glucose content, body mass index (BMI), lipid levels and clinical parameters. Severity of epithelial ovarian cancer was classified according to the International Federation of Gynecology and Obstetrics (FIGO) grading system. Univariate analysis of the clinical factors according to the severity of epithelial ovarian cancer was followed by logistic regression analysis to identify clinical factors significantly associated with epithelial ovarian cancer severity. Univariate analysis indicated that age, BMI, triglyceride (TG), and high density lipoproteins (HDL) differed significantly among different stages of epithelial ovarian cancer (P < 0.05). In the logistic regression model, elevated TG (OR: 1.883; 95% CI = 1.207– 2.937), and low HDL (OR: 0.497; 95% CI = 0.298–0.829) levels were significantly associated with the high severity epithelial ovarian cancer. Our data indicate that high TG and low HDL levels correlate with a high severity of epithelial ovarian cancer. These data provide important insight into the potential relationship between the lipid pathway and epithelial ovarian cancer phenotype and development.

Using biomacromolecule-based nanorods as a chiral source is a creative way to fabricate broadband chiroptically active nanoarchitectures. Herein, right-handedly twisted cellulose nanocrystal (CNC) nanorods, serving simultaneously as a chiral template and a building block, were combined with CuO for constructing composite nanoflowers that showed broadband chiroptical activity. Through calcination, the CuO/CNC nanoflowers can transform into chiral CuO with a flower-like architecture. The established preparation technology is expected to provide various novel broadband chiroptically active nanoarchitectures originating from CNCs and metal oxides.

Background KDM lysine demethylase family members are related to lung cancer clinical outcomes and are potential biomarkers for chemotherapeutics. However, little is known about epigenetic alterations in KDM genes and their roles in lung cancer survival. Methods Tumor tissue samples of 1230 early-stage non-small cell lung cancer (NSCLC) patients were collected from the five independent cohorts. The 393 methylation sites in KDM genes were extracted from epigenome-wide datasets and analyzed by weighted random forest (Ranger) in discovery phase and validation dataset, respectively. The variable importance scores (VIS) for the sites in top 5% of both discovery and validation sets were carried forward for Cox regression to further evaluate the association with patient’s overall survival. TCGA transcriptomic data were used to evaluate the correlation with the corresponding DNA methylation. Results DNA methylation at sites cg11637544 in KDM2A and cg26662347 in KDM1A were in the top 5% of VIS in both discovery phase and validation for squamous cell carcinomas (SCC), which were also significantly associated with SCC survival (HRcg11637544 = 1.32, 95%CI, 1.16–1.50, P = 1.1 × 10−4; HRcg26662347 = 1.88, 95%CI, 1.37–2.60, P = 3.7 × 10−3), and correlated with corresponding gene expression (cg11637544 for KDM2A, P = 1.3 × 10−10; cg26662347 for KDM1A P = 1.5 × 10−5). In addition, by using flexible criteria for Ranger analysis followed by survival classification tree analysis, we identified four clusters for adenocarcinomas and five clusters for squamous cell carcinomas which showed a considerable difference of clinical outcomes with statistical significance. Conclusions These findings highlight the association between somatic DNA methylation in KDM genes and early-stage NSCLC patient survival, which may reveal potential epigenetic therapeutic targets. Electronic supplementary material The online version of this article (10.1186/s13148-018-0474-3) contains supplementary material, which is available to authorized users.

This article reports a novel type of polymeric microspheres derived from a renewable biomass, eugenol, via a facile and effective suspension polymerization approach. On the basis of eugenol and methacryloyl chloride, we first synthesized and then structurally identified the monomer eugenyl methacrylate (E-MA). By using E-MA as the sole monomer and simultaneously as the cross-linking agent, we successfully prepared cross-linked polymeric microspheres through suspension polymerization in aqueous media with 2,2-azoisobutyronitrile (AIBN) as the initiator and poly(vinyl alcohol) (PVA) as the stabilizer. The resulting microspheres were obtained in high yield with diameters ranging 500–800 μm and exhibited remarkably large oil absorbency in a relatively high speed. The microspheres can be reused for at least five times with little change in maximum absorption. The preparative strategy for the polymeric microspheres can be taken as a versatile platform for preparing more functional polymeric microspheres, which ...

This article reports optically active microspheres consisting of chiral helical substituted polyacetylene and β-cyclodextrin-derivative (β-CD-A). The microspheres showed remarkable adsorption toward various organic compounds in water. To prepare the microspheres, an acetylenic-derived helical macro-monomer was synthesized and then underwent aqueous suspension copolymerization with octadecyl acrylate and butyl acrylate by using azobis(isobutyronitrile) as initiator and β-CD-A simultaneously as comonomer and cross-linking agent. The helical macro-monomer chains enabled the microspheres to exhibit desirable enantio-differentiating adsorption capacity toward chiral compounds respectively dissolved in organic solvent, dispersed in water, and dissolved in water. The saturated absorbency toward (R)-(+)- and (S)-(-)-1-phenylethylamine was 29 and 12 mg · g(-1), respectively. The microspheres also showed large oil absorbency (e.g., 22 g · g(-1) CCl4) and a large adsorption toward methyl red (as a model for organic dyes) dispersed in water. The presence of β-CD-A moieties improved the adsorption performance of the microspheres. The present optically active microspheres open a new approach for preparing adsorbents particularly chiral adsorbents with potentials for wastewater treatment.

Chiral molecularly imprinted polymer microspheres (MIPMs) reported so far are majorly limited to being constructed by using achiral polymer together with chiral template. The present contribution reports on a unique type of chiral MIPMs consisting of chirally helical substituted polyacetylene, which are prepared through suspension polymerization by using (a)chiral acetylenics as monomer and chiral Boc-d/l-proline as template. The resulting MIPMs after removing the template show optical activity that is derived from the chirally helical structures of substituted polyacetylene. The microspheres demonstrate enantio-differentiating ability in releasing the enantiopure templates. A complete release of the template provides the chiral MIPMs. Worthy to mention is that the two chiral sources (chirally helical conformation and chiral template configuration) work in a synergistic way, obviously increasing the MIPMs' enantiodiscrimination ability. The present study develops a strategy for preparing chiral MIPMs, which are expected to find significant applications in chiral separation, enantioselective release of chiral drugs, etc.

This article reports an original, versatile strategy to chirally functionalize graphene oxide (GO) with optically active helical-substituted polyacetylene. GO was first converted into alkynyl-GO containing polymerizable -C≡C moieties, which took part in the polymerization of another chiral acetylenic monomer, yielding the expected GO hybrid covalently grafted with chiral helical polyacetylene chains. Transmission electron microscopy, atomic force microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analyses verified the successful attachment of substituted polyacetylene chains on GO by covalent chemical bonding. Moreover, circular dichroism effects and UV-vis absorption demonstrated that the GO hybrid possessed fascinating optical activity. It also largely improved the dispersibility of GO in tetrahydrofuran. The GO-derived hybrid was further used as a chiral inducer toward enantioselective crystallization of alanine enantiomers. l-Alanine was preferably induced to crystallize, forming rodlike crystals.