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Novel ZIF-8/gold nanocomposites with significantly enhanced ROS generation capability for boosting the photobactericidal activity of MOFs are fabricated by combining the LSPR effect of AuNRs and the photosensitization feature of ultrasmall AuNCs under visible light illumination.

Incorporating synthetic macrocycles with unique structures and distinct conformations into conjugated macrocycle polymers (CMPs) can endow the resulting materials with great potentials in gas uptake and pollutant adsorption. Here, four CMPs (CMP-n, n=1-4) capable of reversibly capturing iodine and efficiently separating carbon dioxide are constructed from per-triflate functionalized leaning tower[6]arene (LT6-OTf) and [2]biphenyl-extended pillar[6]arene (BpP6-OTf) via Pd-catalyzed Sonogashira-Hagihara cross-coupling reaction. Intriguingly, owing to the appropriate cavity size of LT6-OTf and the numerous aromatic rings in the framework, the newly designed CMP-4 possesses an outstanding I2 affinity with a large uptake capacity of 208 wt % in vapor and a great removal efficiency of 94 % in aqueous solutions. To our surprise, with no capacity to accommodate nitrogen, CMP-2 constructed from BpP6-OTf is able to specifically capture carbon dioxide at ambient conditions.

Molybdenum disulfide quantum dots (MoS2 QDs) have drawn increasing attention owing to their distinct optical properties and potential applications in many fields such as biosensing, photocatalysis and cell imaging. Elucidating the relationship between the surface chemistry of MoS2 QDs and their optical properties as well as biological behaviors is critical for their practical applications, which remain largely unclear. Herein, by adopting a sulfur vacancy modification strategy, a toolbox of MoS2 QDs functionalized with different thiolate ligands was prepared. The effect of surface chemistry on the optical properties of MoS2 QDs was systematically explored by various spectroscopic techniques, revealing the important role of surface ligands in defining their absorption band gap and luminescence quantum yield. Furthermore, cellular experiments showed that the cytotoxicity and intracellular fate (i.e., lysosomal accumulation) of MoS2 QDs are closely related to the properties of surface ligands. Our results underscore the important roles of surface ligands in regulating the properties and biological interactions of these QDs, which will facilitate the future development of MoS2-based materials with precisely controlled functions for biomedical applications.

A series of covalent organic frameworks substituted with azo groups (AzoCOFs) have been synthesized via imine condensation. The obtained frameworks show crystallinity and high stability. More importantly, the AzoCOFs exhibit exceptionally high ideal adsorption solution theory (IAST) selectivity in adsorption of C2H2 (35-2891) over CH4 at 273 K and 1 bar, owing to the favorable interactions between azo groups and acetylene molecules. The dependence of the gas adsorption property on pore size and polarity of the frameworks was also studied. The triethylene glycol substituted Tg-AzoCOF shows the highest C2H2/CH4 selectivity (IAST selectivity of 2891), which represents the highest reported for all porous materials. The AzoCOFs also exhibit high IAST adsorption selectivity of C2H4/CH4 (11-20), C2H6/CH4 (15-22), and CO2/CH4 (12-37), which is comparable with most porous materials, thus showing their great potential in gas separation applications.

Gold nanoclusters (AuNCs) are an emerging type of ultrasmall nanomaterials possessing unique physicochemical characteristics. Metal-organic frameworks (MOFs), a singular kind of porous solid and crystalline material, have attracted tremendous attention in recent years. The combination of AuNCs and MOFs can integrate and improve the prominent properties of both components, such as high catalytic activities, tunable optical properties, good biocompatibility, surface functionality and stability, which make the composites of MOFs and AuNCs promising for sensing applications. This review systematically summarizes the recent progress on the sensing of various analytes via MOFs-mediated AuNCs assemblies based on strategies of luminescence sensing, colorimetric sensing, electrochemiluminescence sensing, and electrochemical and photoelectrochemical sensing. A brief outlook regarding the future development of MOFs-mediated AuNCs assemblies for sensing application is presented as well.

Cationic nanoparticles (NPs) have shown great potential in biological applications owing to their distinct features such as favorable cellular internalization and easy binding to biomolecules. However, our current knowledge of cationic NPs' biological behavior, i.e., NP-protein interactions, is still rather limited. Herein, we choose ultrasmall-sized fluorescent gold nanoclusters (AuNCs) coated by (11-mercaptoundecyl) - N, N, N - trimethylammonium bromide (MUTAB) as representative cationic NPs, and systematically study their interactions with different serum proteins at nano-bio interfaces. By monitoring the fluorescence intensity of MUTAB-AuNCs, all proteins are observed to bind with roughly micromolar affinities to AuNCs and quench their fluorescence. Transient fluorescence spectroscopy, X-ray photoelectron spectroscopy and isothermal titration calorimetry are also adopted to characterize the physicochemical properties of MUTAB-AuNCs after the protein adsorption. Concomitantly, circular dichroism spectroscopy reveals that cationic AuNCs can exert protein-dependent conformational changes of these serum proteins. Moreover, protein adsorption onto cationic AuNCs can significantly influence their cellular responses such as cytotoxicity and uptake efficiency. These results provide important knowledge towards understanding the biological behaviors of cationic nanoparticles, which will be helpful in further designing and utilizing them for safe and efficient biomedical applications.

Molybdenum disulfide quantum dots (MoS2 QDs) have drawn increasing attention owing to their distinct optical properties and potential applications in many fields such as biosensing, photocatalysis and cell imaging. Elucidating the relationship between the surface chemistry of MoS2 QDs and their optical properties as well as biological behaviors is critical for their practical applications, which remain largely unclear. Herein, by adopting a sulfur vacancy modification strategy, a toolbox of MoS2 QDs functionalized with different thiolate ligands was prepared. The effect of surface chemistry on the optical properties of MoS2 QDs was systematically explored by various spectroscopic techniques, revealing the important role of surface ligands in defining their absorption band gap and luminescence quantum yield. Furthermore, cellular experiments showed that the cytotoxicity and intracellular fate (i.e., lysosomal accumulation) of MoS2 QDs are closely related to the properties of surface ligands. Our results underscore the important roles of surface ligands in regulating the properties and biological interactions of these QDs, which will facilitate the future development of MoS2-based materials with precisely controlled functions for biomedical applications.

Left ventricular assist device (LVAD) associated infections (LVADIs) have substantial morbidity and mortality. We aim to describe the incidence and epidemiology of LVADIs in an Asian cohort. This is currently not well studied.We conducted a retrospective review of 52 patients who underwent LVAD implantation from 1 May 2009-31 December 2014 in National Heart Centre Singapore. LVADIs were defined based on definitions proposed by the International Society for Heart and Lung Transplantation.There were 39 males and 13 females. Seventy-three percent had Heartmate II LVAD implant while 27% received Heartware HVAD. Eighty-one percent were implanted as bridge to heart transplantation, 19% as destination therapy. Forty-five episodes of LVADIs occurred in 25 patients. Overall LVADI incidence was 47.5 cases per 100 patient-years. Driveline infections (58%) were the commonest type of LVADI. The commonest causative organisms were coagulase-negative staphylococci (33%), Staphylococcus aureus (31%) and Corynebacterium species (19%). Twelve percent of patients with LVADI required surgical debridement and one patient required pump exchange due to pump pocket infection. All-cause mortality was 13%.The findings of our study add to the understanding and epidemiology of LVADIs, particularly in the Asian setting. This can contribute to the development of evidence based strategies to prevent and manage LVADIs.

Myocardial ischemia-reperfusion (I/R) injury is a common complication following reperfusion therapy that involves a series of immune or apoptotic reactions. Studies have revealed the potential roles of miRNAs in I/R injury. Herein, we established a myocardial I/R model in rats and a hypoxia/reoxygenation (H/R) model in H9c2 cells and investigated the effect of miR-145-5p on myocardial I/R injury. After 3 h or 24 h of reperfusion, left ventricular end-systolic pressure (LVESP), ejection fraction (EF), and fractional shortening (FS) were obviously decreased, and left ventricular end-diastolic pressure (LVEDP) was increased. Meanwhile, I/R induced an increase in myocardial infarction area. Moreover, a decrease in miR-145-5p and increase in (NADPH) oxidase homolog 1 (NOH-1) were observed following I/R injury. With this in mind, we performed a luciferase reporter assay and demonstrated that miR-145-5p directly bound to NOH-1 3' untranslated region (UTR). Furthermore, miR-145-5p mimics decreased the levels of tumor necrosis factor (TNF)-α, IL-1β, and IL-6 via oxygen and glucose deprivation/reperfusion (OGD/R) stimulation. Upregulation of miR-145-5p increased cell viability and reduced apoptosis accompanied by downregulation of Bax, cleaved caspase-3, cleaved poly(ADP-ribose) polymerase (PARP) and upregulation of Bcl2. In addition, miR-145-5p overexpression increased superoxide dismutase (SOD) activity and reduced reactive oxygen species (ROS) and malondialdehyde (MDA) content under OGD/R stress. Notably, NOH-1 could significantly abrogate the above effects, suggesting that it is involved in miR-145-5p-regulated I/R injury. In summary, our findings indicated that miR-145-5p/NOH-1 has a protective effect on myocardial I/R injury by inhibiting the inflammatory response and apoptosis.

Incorporating synthetic macrocycles with unique structures and distinct conformations into conjugated macrocycle polymers (CMPs) can endow the resulting materials with great potentials in gas uptake and pollutant adsorption. Here, four CMPs (CMP-n, n=1-4) capable of reversibly capturing iodine and efficiently separating carbon dioxide are constructed from per-triflate functionalized leaning tower[6]arene (LT6-OTf) and [2]biphenyl-extended pillar[6]arene (BpP6-OTf) via Pd-catalyzed Sonogashira-Hagihara cross-coupling reaction. Intriguingly, owing to the appropriate cavity size of LT6-OTf and the numerous aromatic rings in the framework, the newly designed CMP-4 possesses an outstanding I

Herein, we reported a new strategy to simultaneously regulate both the physicochemical properties and biological behaviors of fabricated nanomaterials. Upon precisely pre-tailoring the number of charged groups of bovine serum albumin (BSA), the resultant BSA-templated gold nanoclusters (BSA-AuNCs) exhibit remarkably different fluorescence properties and strong biotemplate-dependent cellular uptake behavior.

We report a new approach towards the design of multi-stimuli responsive "gated scaffolds" based on the combination of capped metal-organic frameworks (MOFs) and supramolecular[2]pseudorotaxanes. These mechanized Zr-MOFs showed negligible premature release, high drug encapsulation, low cytotoxicity and good biocompatibility. Around or inside the bone tumour cells, the pH, lysosomal pH, and osteoclast pH are observed to be lowered (acidosis), and thus the resulting osteolysis increases the Ca

Adenosine triphosphate (ATP) plays an important role in various biological processes and the ATP level is closely associated with many diseases. Herein, a novel ratiometric fluorescence assay for ATP was developed based on the excimer-monomer transfer of a perylene probe. By encapsulating a perylene probe, N,N'-bis(6-caproic acid)-3,4:9,10-perylenediimide (PDI), into zeolitic imidazolate framework-8 (ZIF-8) nanocrystals, fluorescent nanocomposites (PDI@ZIF-8) with significant excimer emission of the perylene probe were prepared for the first time. The presence of ATP will trigger the decomposition of PDI@ZIF-8 due to much stronger coordination between ATP and Zn2+ than that of 2-methylimidazole and Zn2+. As a result, the encapsulated PDI probes were released, leading to significantly increased monomer emission accompanying the decrease in the excimer emission. The excimer-monomer transition signal was utilized for ratiometric ATP sensing and its potential application for detecting ATP in cell lysates was also successfully demonstrated.

Finding a cost-effective, environmental benign, economical and technologically viable way to selectively capture, storage and/or purify energy and light gases represents one of the most urgent needs from energetic, biological, and environmental standpoints. Two 3D low-density supramolecular organic frameworks (SOFs) with solution-processibility were constructed using low-cost and readily available synthetic macrocyclic compounds, namely pillar[5]arene (P5) and pillar[6]arene (P6), via strong O-H···O, C-H···O, C-H···π, π···π interactions. These SOFs offer unusual topology, interconnecting pores and extremely high selective CO2 capture and separation properties for multiple gas mixtures (e.g. 30/70 mixture of CO2/H2, up to 3733/1, 298 K), making them great promising candidates for practical gas separation of steam-methane re-former (SMR) off-gas, flue gas, natural gas, biogas, syngas, paraffin/olefin, etc.

Atherosclerosis is the underlying contributing factor of cardiovascular disease, which is a process of inflammation and lipid-rich lesion. Macrophage-derived foam cell is a key hallmark of atherosclerosis and connected with various factors of lipid metabolism. Here, we showed that fatty acid binding protein 3 (FABP3) was upregulated in the aorta of ApoE-/- mice with high-fat-diet (HFD) feeding. Knockdown of FABP3 in HFD-fed ApoE-/- mice notably facilitated cholesterol efflux, inhibited macrophage foam cell formation, and thus prevented atherogenesis. Furthermore, FABP3 silencing decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ). Mechanistic studies had disclosed the involvement of PPARγ signaling in balancing cholesterol uptake and efflux and diminishing foam cell formation. These findings firstly revealed an anti-atherogenic role of FABP3 silencing in preventing foamy macrophage formation partly through PPARγ, which might be a beneficial approach for therapying atherosclerosis.

Supramolecular organic frameworks (SOFs) represent a class of microporous solids with excellent light-gas selectivity, as well as good solubility/dispersibility in common organic solvents. We created new mixed-matrix membrane (MMM) materials by blending the microporous, solid supramolecular organic framework material, pillar[5]arene (P5-SOF) with the commercial polymer, Matrimid-5218™, and tested their light gas separation performance. These purely organic MMM materials were found to have very high (light gas/CH 4 ) selectivity values (CO 2 /CH 4 : 180, N 2 /CH 4 : 6.5, and H 2 /CH 4 : 600), illustrating that they have promise as membranes for high-purity CH 4 separations.

We report the high hydrocarbon storage capacity and adsorption selectivity of two low-density pillar[n]arene-based SOFs. Our study would open new perspectives in the development of pillar[n]arene-based SOFs and study of their great potential in gas-storage and gas-separation applications.

Purpose To evaluate the efficacy of infrared (IR) ocular thermography in screening for dry eye disease (DED). Methods IR ocular thermography was performed on 62 dry eye and 63 age- and sex-matched control subjects. Marking of ocular surface and temperature acquisition was done using a novel ‘diamond’ demarcation method. 30 static- and 30 dynamic-metrics were studied and receiver operating characteristic curves were plotted. Efficacy of the temperature metrics in detecting DED were evaluated singly and in combination in terms of their area under the curve (AUC), Youden’s index and discrimination power (DP). Results Absolute temperature of the extreme nasal conjunctiva 5 s and 10 s after eye opening were best detectors for DED. With threshold value for the first metric set at 34.7 °C, sensitivity and specificity was 87.1% (95% CI: 76.2–94.3%) and 50.8% (95% CI: 37.9–63.6%) respectively. With threshold value for the second metric set at 34.5 °C, sensitivity and specificity was 77.6% (95% CI: 64.7–87.5%) and 61.9% (95% CI: 48.8–73.9%) respectively. The two metrics had moderate accuracy and limited performances with AUC of 72% (95% CI: 63–81%) and 73% (95% CI: 64–82%); Youden index of about 0.4 and DP of 1.07 and 1.05 respectively. None of the dynamic metrics was good detector for DED. Combining metrics was not able to increase the AUC. Conclusions This work suggests some utility for the application of IR ocular thermography for evaluation of dry eye patients.

// Hao Guo 1, * , Shuni Zhou 2, * , Lili Tan 1 , Xiaoyu Wu 3 , Zhenfeng Wu 3 , Ruizhi Ran 1 1 Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefacture, Enshi, Hubei 445000, China 2 Department of Chinese Medicine and Cardiology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefacture, Enshi, Hubei 445000, China 3 Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 1 Nanjing 210029, China * These authors contributed equally to this work Correspondence to: Ruizhi Ran, email: ruizhiran56@hotmail.com Keywords: NSCLC, WIF-1, methylation, tumor suppressor gene, drug target Received: September 12, 2016 Accepted: November 15, 2016 Published: November 29, 2016 ABSTRACT Methylation of the WIF-1 gene can lead to the loss of WIF-1 expression which has been observed in numerous types of cancer including NSCLC. However, the association and clinicopathological significance between WIF-1 promoter hypermethylation and NSCLC remains unclear. In the present study, we performed a meta-analysis to evaluate the clinicopathological significance of WIF-1 hypermethylation in NSCLC. A systematic literature search was carried out using Pubmed, EMBASE, Web of Science and CNKI. The Cochrane software Review manager 5.2 was used. The frequency of WIF-1 hypermethylation was significantly increased in NSCLC compared with normal lung tissue; the pooled OR was 8.67 with 95% CI 1.64-45.88, p = 0.01. The rate of WIF-1 hypermethylation was higher in SCC than in AC, OR was 1.74 with 95% CI 0.97-3.11, p = 0.06. In addition, WIF-1 loss was correlated with low 5-year survival rate. In summary, WIF-1 hyper methylation is a potential biomarker for diagnosis of NSCLC. WIF-1 hypermethylation is predominant in squamous cell carcinoma (SCC), suggesting that WIF-1 methylation contributes to the development of NSCLC, especially SCC.

Purpose To investigate the inter-image, inter-occasion and inter-examiner repeatability of NEC infrared thermo-tracer TH 9260 in assessing healthy and dry eyes. Methods Ocular surface temperature (OST) was recorded using NEC infrared thermo-tracer TH 9260 on 21 healthy and 15 dry eyes. Data from the right eyes were analyzed. Marking of the ocular surface and OST acquisition was performed using a new ‘diamond’ demarcation method. Twelve OST indices were obtained at three different time points following a blink: 0 s, 5 s and 10 s. Inter-image, inter-occasion and inter-examiner repeatability of the infrared ocular thermography was evaluated by calculating coefficients of repeatability (COR). Results Ten out of the twelve tested OST indices had good repeatability with small inter-image variability (%COR: 0.2–0.9), inter-occasion variability (%COR: 2.1–3.7) and inter-examiner variability (%COR: 1.5–3.7) for the three studied time points. Two of the OST indices (temperature standard deviation of the region of interest and radial temperature difference) had poor repeatability with much larger inter-image variability (%COR: 8.9–140.7), inter-occasion variability (%COR: 47.5–153.5) and inter-examiner variability (%COR: 54.7–142.0) for the three studied time points. Conclusions Most of the metrics adopted in this assessment can be considered to be highly repeatable.

We report a new approach towards the design of multi-stimuli responsive “gated scaffolds” based on the combination of capped metal–organic frameworks (MOFs) and supramolecular[2]pseudorotaxanes. These mechanized Zr-MOFs showed negligible premature release, high drug encapsulation, low cytotoxicity and good biocompatibility. Around or inside the bone tumour cells, the pH, lysosomal pH, and osteoclast pH are observed to be lowered (acidosis), and thus the resulting osteolysis increases the Ca2+ concentration (hypercalcemia). The drug release from the mechanized MOFs was triggered by the simultaneous variations of pH and Ca2+ concentration in bone tumour cells. Hyperthermia (also called thermal therapy or thermotherapy) as a popular type of cancer treatment technique can also control drug release in the above-mentioned system. This design opens up the possibility of developing smart biomaterials for bone regeneration and cancer therapy.

Herein, cationic MUTAB-Ag NPs of different sizes were synthesized and their interactions with a negatively charged perylene probe, N,N′-bis(6-caproic acid)-3,4:9,10-perylenediimide (PDI-COOH), were investigated. MUTAB-Ag NPs could result in significant monomer quenching and excimer formation by inducing probe aggregation due to the strong electrostatic attractive interactions between them. Moreover, significant excimer emission could be observed at extremely low probe concentration when induced by larger MUTAB-Ag NPs. A possible mechanism of metal-enhanced fluorescence was proposed, which is evidenced by the strong dependence between surface plasmon resonance absorption spectra of MUTAB-Ag NPs and the excimer emission spectra of PDI-COOH, together with the sharp decrease in fluorescence lifetime of excimer compared with that induced by poly(allylamine). Consequently, ratiometric fluorescence sensors for heparin and heparinase were developed based on the Ag NP-induced excimer emission of PDI-COOH. The adsorption of heparin on the surface of MUTAB-Ag NPs led to the release of monomer, while the degradation of heparin by heparinase facilitated the formation of PDI-COOH excimer. The monomer-excimer transition signal was harnessed for heparin and heparinase sensing, which exhibited good sensitivity and excellent selectivity. Finally, application of the present system for detection of heparin and heparinase in human serum sample was successfully demonstrated.

To investigate the effect of miR-17-5p on vascular lesion and expression of very low density lipoprotein receptor (VLDLR) in atherosclerotic (AS) mice.The results of HE staining showed thatcompared with the NC group, the AS model group had obvious plaques in vascular endothelium, smooth muscle cell disorder and intimal hyperplasia, while the antagomiR-17-5p treated mice had significantly less lesions compared with the NC miRNA group. The intimal area of mice in the AS model group was bigger compared with NC group, but decreased after the inhibition of miR-17-5p. There was no statistically significant difference in the area of the media in each group. Vascular lumen area was smaller and intima/media ratio (I/M) values were lower in the AS model group and the NC miRNA group compared with the NC group, while the antagomiR-17-5p group alleviated this effect (miR-17-5p inhibitors may effectively alleviate the pathological changes of arterial vessels in AS mice by up-regulating the expression of VLDLR in arterial tissues, and may become a new therapeutic target for AS disease.

By gut microbiota metagenomic analysis, we found that the abundance of sulfatase-secreting bacteria (SSB) in the gut of mice fed chondroitin sulfate (CS) increases with significant individual difference. The fluctuation of lipopolysaccharide (LPS) and pro-inflammatory indicators with significant individual and tissue variations was also observed. After mice were fed mixed with CS or injected separately with LPS, the breast cancer-related transcriptional factor genes, BCL11A and RUNX1, were upregulated, whereas the tumor suppressor gene, TP53BP1, were downregulated. Further, the mammary myopithelium marker CK5/6, the mammary hyperplasia marker Ki-67, and other tumor markers were also upregulated. While the exogenous estradiol does not induce the expression of BCL11A, RUNX1, and TP53BP1, the estrogen receptor (ER) agonist Fulvestrant that mimics estradiol action not only elevates estradiol concentrations, but also upregulates tumor marker expression levels, revealing that ER inflammatory inactivation and hyperestrogenemia induction might be the etiological cues of breast cancer origin. This study has preliminarily established a possible correlation of gut microbiota dysbiosis and chronic low-grade inflammation with the early-phase onset of breast cancer in mice. The statistical insignificance of test data was attributed to the individual difference of gut microbiota compositions, which determining the individual and tissue variations of systemic inflammation.

BackgroundAlthough dietary patterns are recognized to affect health by interfering with gut microbiota homeostasis, whether live or dead bacteria-bearing spring mineral water (MW) would also exert beneficial effects on health upon curing gut dysbiosis remains unknown.ResultsDue to harboring live bacteria, the heated but unboiled MW from Bama, where centenarians are ubiquitously inhabited, reshapes the gut microbiota from a traveler-type to a local resident-type except for Prevotella. While chondroitin sulfate, a component occurring in livestock and poultry meats, increases the richness of sulfatase-secreting bacteria and sulfate-reducing bacteria, Bama MW dampens the overgrowth of those colon-thinning bacteria and hampers the overexpression of multiple genes responsible for anti-inflammation, anti-oxidation, anti-hypoxia, anti-mutagenesis, and anti-tumorigenesis.ConclusionsBama spring MW prevents the early-phase onset of breast cancer by curating gut dysbiosis. MW also compromises chromosomal DNA damage and ameliorate mitochondrial dysfunctions, implying it may extend lifespan.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor and the leading cause of cancer-related death worldwide. Biphenyldicarboxylate (BPDC), an intermediate of schisandrin C fromSchisandra chinensis, has been used as a hepatoprotective agent that compromises hepatic injuries in China for decades. Whether BPDC is also implicated in the prevention of HCC remains understood. Here, we report that the bacterial endotoxin lipopolysaccharide (LPS) promotes hepatic inflammation and hyperplasia, during which the common tumor markers, alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA), were unregulated, whereas the tumor suppressors, PTEN, FOXO1 and MEN1, were downregulated through increasing the microRNAs, miR-21, miR-122 and miR-24. In contrast, BPDC dampened hepatic inflammation and hyperplasia accompanied by the upregulation of PTEN, FOXO1 and MEN1 through decreasing miR-21, miR-122 and miR-24. However, BPDC failed to downregulate the tumor marker AEG-1 via increasing miR-195. Taken together, BPDC exerts anti-tumor effects by upregulating tumor suppressors upon decreases of miRNAs rather than downregulating tumor markers by increases of miRNAs.

BackgroundThe origin of breast cancer remains poorly understood. Here, we testify a putative mechanism of “breast cancer origin from inducible nitric oxide synthase (iNOS) activation and oestrogen receptor alpha (ERα) inactivation”, which are classified as the essential outcomes of chronic inflammatory responses.MethodsTo reverse breast cancer status, iNOS was downregulated by short-hairpin RNA (shRNA)-guidedNOS2knockdown from human triple-negative breast cancer (TNBC) cells. To re-enact breast cancer origin, ERα was downregulated by shRNA-directedESR1knockdown in human mammary epithelial cells.ResultsUponNOS2knockdown from HCC1937 cells, the specific TNBC transcription factor genes,RUNX1andBCL11A, were downregulated, hypoxia was compromised, Warburg effects were attenuated, and tumourigenic proliferation was halted, accompanied by an increase in the tumour marker cyclin D1 (CD1) and a decrease in the tumour suppressor cyclin-dependent kinase inhibitor (CKI). In contrast,ESR1knockdown from MCF-10A cells led to upregulatedBCL11AandRUNX1expression, augmented hypoxic responses, pronounced Warburg effects, and enhanced PI3K/Akt/mTOR signalling, together with low levels of CD1 and high levels of CKI induction.ConclusionsBreast cancer should originate from inflammatory signalling, during which iNOS activation and ERα inactivation elicit hypoxia, oxidation, mitochondrial dysfunction, and breast cancer-like hyperplasia, demonstrating that iNOS inhibitors and ERα activators represent promising candidate prodrugs enabling breast cancer prevention in the early stage.

Spurred on by recent advances in materials chemistry and drug delivery, a new stimuli-responsive theranostic hybrid platform, based on mechanized monodisperse nano metal–organic frameworks (NMOFs) gated by carboxylatopillar[5]arene (CP5) switches with bio-friendly pH-triggered cargo release capabilities, has been constructed for the first time. This nanoscale smart cargo delivery system showed pH- and/or competitive binding agent-triggered controlled cargo release with negligible premature release, large pore sizes for drug encapsulation, low cytotoxicity, good biodegradability and biocompatibility, and potential application in cell imaging, which offers a new tool in targeted drug delivery and the controlled release of therapeutic agents.

Background The aim of this study was to describe the prevalence and risk factors of symptomatic dry eye disease (SDED) in Singapore. Methods A cross-sectional dry eye survey was carried out using the McMonnies dry eye questionnaire. Members of the public were interviewed at the 46 (out of 62) randomly-selected mass rapid transit (MRT) stations and their vicinity. A total of 1,004 questionnaires were collected from participants aged between 15 and 83 years. Symptomatic dry eye disease (SDED) was defined as at least one of five self-reported symptoms that were reported as often or constantly. Non-dry eye (NDE) subjects were those with no related symptoms reported. Prevalence of symptomatic dry eye disease in the studied population and confidence interval (CI) were calculated. Risk factors were also evaluated using logistic regression analysis at 95% CI. Results The prevalence for symptomatic dry eye disease was found to be 12.3 per cent with prevalence greater in females than males. Symptomatic dry eye disease was significantly associated with contact lens wear (odds ratio [OR] 2.96, 95% CI: 1.81 to 4.83), those having had previous treatment for dry eye (OR 2.09, 95% CI: 1.33 to 3.29), those taking medication (OR 1.84, 95% CI: 0.99 to 3.44), those with unusual sensitivity of eyes (OR 3.04, 95% CI: 1.92 to 4.83), constant mucous membrane dryness (OR 4.11, 95% CI: 1.62 to 10.45) and irritation on waking (OR 2.38, 95% CI: 1.34 to 4.22). Smoking was not found to be associated with symptomatic dry eye disease. Conclusion Singapore has a symptomatic dry eye disease prevalence of 12.3 per cent and was associated with contact lens wear, those who had previous treatment for dry eye, medication, those having unusual sensitivity of eyes, mucous membrane dryness and waking irritation. These new data will be of value to the eye-care community in Singapore and elsewhere.

Although artemisinin has been used as anti-malarial drug, accumulating evidence on the extended therapeutic potential of artemisinin emerges. Apart from anti-malaria and anti-tumor, artemisinin can also exert beneficial effects on some metabolic disorders, such as obesity, diabetes, and aging-related diseases. However, whether artemisinin should be applied to treatment of the wide-spectrum diseases is debating. Here, we discuss the predisposition of a raised risk of malarial resistance to artemisinin from consideration of the multi-target and non-specific features of artemisinin.

BackgroundWhether insulin enhances or represses tumor cell proliferation remains debating and inconclusive although epidemiological data indicated insulin use raises a risk of cancer incidence in patients with diabetes mellitus (DM).Methodology/Principle FindingsWe cultured rat pituitary adenoma cells in a high-glucose medium to simulate hyperglycemia occurring in DM patients. Upon incubation with or without insulin, repressed tumor cell proliferation and downregulated tumor marker expression occur accompanying with mitigated oxidative stress and compromised apoptosis. Mechanistically, insulin resistance-abrogated glucose uptake was suggested to create an intracellular low-glucose milieu, leading to cellular starvation resembling calorie restriction (CR). While downregulation of insulin-like growth factor 1 (IGF-1) occurring in CR was validated, oncogene downregulation and tumor suppressor gene upregulation seen in CR was also replicated byNOS2knockdown.Conclusions/SignificanceCellular starvation can exert CR-like anti-tumor effects regardless of insulin presence or absence.

It remains obscure how to medically manage visceral obesity that predisposes metabolic disorders. Here, we show for the first time that a trace amount of artemisinin (0.25 mg/kg) reduces adipose weight in an inflammatory obese mouse model induced by a high-fat diet with lipopolysaccharide (HFD+LPS). HFD+LPS trigger pro-inflammatory responses, upregulate NOS2 expression, elicit potent nitric oxide (NO) burst, and reinforce adipose mitochondrial dysfunctions that facilitate adipogenesis for visceral weight gain. By targeting mitochondrial complexes, artemisinin resembles the NO donor nitroglycerin to exert anti-inflammatory effects, downregulate NOS2 expression, maintain stable NO release, and augment adipose mitochondrial functions that necessitate adipolysis for visceral weight loss. Taken together, artemisinin plays adipose weight-reducing roles by rectifying inflammation-driven mitochondrial dysfunctions.

BackgroundAn interaction of the food types with the gut microbiota changes is deeply implicated in human health and disease. To verify whether animal-based diets would lead to gut dysbiosis, systemic inflammation and inflammatory pathogenesis, we fed mice with chondroitin sulfate (CS), a sulfate-containing O-glycan naturally occurring in livestock and poultry products, and monitored the dynamic changes of microbial flores, inflammatory signatures, and pathogenic hallmarks.ResultsA metagenomic gut microbiota analysis revealed the overgrowth of sulfatase-secreting bacteria and sulfate-reducing bacteria in the gastrointestinal tracts of mice upon daily CS feeding. Sulfatase-secreting bacteria compromise gut integrity through prompting mucin degradation and mucus lesions, which were evident from the upregulation of secretary leukocyte protease inhibitor (SLPI) and mucin 1/4 (MUC-1/4). A synchronous elevation of lipopolysaccharide (LPS) and tumor necrosis factor α (TNF-α) levels in the serum as well as cerebral, hepatic, cardiac and muscular tissues suggests bacterial endotoxinemia, chronic low-grade inflammation and mitochondrial dysfunction, eventually leading to the onset of global inflammatory pathogenesis towards arthritis, dementia, tumor, and fatty liver.ConclusionsCS triggers the early-phase and multi-systemic pathogenesis like arthritis, dementia, tumor, and fatty liver by enhancing gut opportunistic infection and evoking low-grade inflammation in mice. A plausible reason for the inconsistency of CS in treatment of osteoarthritis (OA) was also discussed.

SUMMARYWhether chondroitin sulfate (CS), a common ingredient naturally occurring in livestock and poultry products, improves osteoarthritis remains debating. Here, we show for the first time that CS induces steatogenesis, atherogenesis, and dementia-like pathogenesis in mice. Gut microbiome analysis revealed the sulfatase-secreting bacteria Rikenella and the sulfate-reducing bacteria Desulfovibrio are enriched. Surprisingly, berberine use boosts CS-induced multi-loci inflammatory manifestations by further increasing the abundance of Rikenella and Desulfovibrio, whereas cephalosporin reinforces the colon mucus barrier via flourishing Akkermansia muciniphila and upregulating mucin expression. Mechanistically, berberine aggravates mucus lining injury by prompting mucin degradation, endotoxin leakage, neutralizing antibody induction, pro-inflammatory cytokine burst, lactic acid accumulation and energy currency depletion in multiple organs and tissues. Taken together, CS evokes the early-phase pathogenesis toward steatohepatitis, atherosclerosis, and dementia upon augmenting gut opportunistic infection, and a sustained antibiotic monotherapy does not deprive the risk of CS-driven systemic inflammatory disorders.

As a rapidly developing class of synthetic macrocycles with intrinsic characteristics and properties, pillarenes (or pillararenes) have become more and more attractive on account of their unique features and potentials in fabricating functional materials. This feature article provides an overview of molecular recognition and self-assembly of pillarenes. The host–guest motifs, building strategies, topological architectures, stimuli-responsiveness, functionalities and various supramolecular assemblies including mechanically interlocked molecules containing rotaxanes, polyrotaxanes and catenanes, self-inclusion complexes, supramolecular dimers and polymers, micelles, vesicles, tubes and artificial transmembrane channels are comprehensively discussed. Prospects about future research directions and applications in this research area are predicted.

In recent years,with the low carbon environmental protection consciousness into the social and economic,shallow geothermal energy which is one of the clean energy of is applied widely.This paper states the conditions of resource utilization and collecting technology in Shijiazhuang.It also states the present development situation and the application examples of Shallow Geothermal Energy heat source heating (cold) system , which can provide beneficial reference data.

Smart delivery systems have gained momentum over the last few decades due to their potential to realize enhanced therapeutic efficacy. Poly(glycidyl methacrylate)s (PGMAs), which spring up like mushrooms, have drawn great attention in the theranostics field, especially in multifunctional theranostic systems. The marriage of PGMAs with functional inorganic cores is expected to integrate diagnosis (e.g., fluorescence, X-ray computed tomography, magnetic resonance, photoacoustic and upconversion luminescence imaging), treatment, or multimodal synergistic therapies (e.g., chemotherapy, gene therapy, photothermal therapy) in one pot for personalized medicine. In this review, recent progress in various PGMA-coated nanohybrids based on the type of integrated inorganic nanoparticle, including silica nanoparticles, magnetic nanoparticles, quantum dots, gold nanoparticles, gold nanorods, metal-organic frameworks, cellulose nanocrystals, and their core-shell nanostructures is systematically reviewed. Future work in this field is anticipated to be devoted to developing efficient real-time-imaging-guided multimodal synergistic therapies.

A highly efficient one-pot procedure for the preparation of fluorescein-based dyes with relatively high yield was investigated. Significantly, introduction of these fluoro and chloro functional groups and forming host-guest complexes with cyclodextrins partially enhanced the photostability of these dyes.