Recent advances in super-resolution optical imaging based on aggregation-induced emission.

Super-resolution imaging has rapidly emerged as an optical microscopy technique, offering advantages of high optical resolution over the past two decades; achieving improved imaging resolution requires significant efforts in developing super-resolution imaging agents characterized by high brightness, high contrast and high sensitivity to fluorescence switching. Apart from technical requirements in optical systems and algorithms, super-resolution imaging relies on fluorescent dyes with special photophysical or photochemical properties. The concept of aggregation-induced emission (AIE) was proposed in 2001, coinciding with unprecedented advancements and innovations in super-resolution imaging technology. AIE probes offer many advantages, including high brightness in the aggregated state, low background signal, a larger Stokes shift, ultra-high photostability, and excellent biocompatibility, making them highly promising for applications in super-resolution imaging. In this review, we summarize the progress in implementation methods and provide insights into the mechanism of AIE-based super-resolution imaging, including fluorescence switching resulting from photochemically-converted aggregation-induced emission, electrostatically controlled aggregation-induced emission and specific binding-regulated aggregation-induced emission. Particularly, the aggregation-induced emission principle has been proposed to achieve spontaneous fluorescence switching, expanding the selection and application scenarios of super-resolution imaging probes. By combining the aggregation-induced emission principle and specific molecular design, we offer some comprehensive insights to facilitate the applications of AIEgens (AIE-active molecules) in super-resolution imaging.

Cationic Conjugated Polyelectrolytes with Aggregation-Induced Ratiometric Fluorescence.

The molecular diversity of aggregation-induced emission remains a challenge due to the limitation of conventional synthesis methods. Here, a series of novel neutral and cationic conjugated polymers composed of various ratios of tetraarylethylene (TAE) containing a bridged oxygen (O) and fluorene (F) units is designed and synthesized via the geminal cross-coupling (GCC) of 1,1-dibromoolefins. The incorporation of TAE segments into the conjugated backbone of polyfluorene produces pronounced aggregation-induced ratiometric fluorescence, i.e., aggregation-induced emission (AIE) at 520-600 nm and grows synergistically with aggregations-caused quenching (ACQ) at 400-450 nm. The content of fluorene unit in the polymer backbones determines the intensity of the initial fluorescence in the blue light region. The huge distinction (about 150 nm) in dual emission wavelengths caused by the environment change makes these conjugated polyelectrolytes particularly suitable for ratiometric fluorescence sensing. Based on electrostatic interaction mechanism, the gradual addition of heparin into the cationic conjugated polymers aqueous solutions can induce dual-color fluorescence changes with a detection limit of 9 × 10-9 m. This work exhibits the great facility of using GCC reaction to synthesis the conjugated TAE polymers with superior AIE properties and special functions.

Reversible Three-Color Fluorescence Switching of an Organic Molecule in the Solid State via "Pump-Trigger" Optical Manipulation.

In photoswitches that undergo fluorescence switching upon ultraviolet irradiation, photoluminescence and photoisomerization often occur simultaneously, leading to unstable fluorescence properties. Here, we successfully demonstrated reversible solid-state triple fluorescence switching through "Pump-Trigger" multiphoton manipulation. A novel fluorescence photoswitch, BOSA-SP, achieved green, yellow, and red fluorescence under excitation by pump light and isomerization induced by trigger light. The energy ranges of photoexcitation and photoisomerization did not overlap, enabling appropriate selection of the multiphoton light for "pump" and "trigger" photoswitching, respectively. Additionally, the large free volume of the spiropyran (SP) moiety in the solid state promoted reversible photoisomerization. Switching between "pump" and "trigger" light is useful for three-color tunable switching cell imaging, which can be exploited in programmable fluorescence switching. Furthermore, we exploited reversible dual-fluorescence switching in a single molecular system to successfully achieve two-color super-resolution imaging.

Gut microbiota composition and functional prediction in diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is common and difficult to treat and its pathogenesis is closely related to gut microbiota. However, differences in gut microbiota of patients in different regions make it more difficult to elucidate the mechanism of IBS. We performed an analysis of gut microbiota composition and functional prediction in Chinese patients with diarrhea-predominant IBS (IBS-D). METHODS: Fecal samples were obtained from 30 IBS-D patients and 30 healthy controls (HCs) in Nanchang, China. Using 16S gene sequence profiles, we analyzed the abundance of dominant microbiota at different taxonomy levels. Based on 16S information, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predicting the function of gut microbiota. RESULTS: Compared to HCs, gut microbiota richness but not diversity was decreased in IBS-D patients. The abundant phyla Firmicutes, Fusobacteria and Actinobacteria decreased significantly, and Proteobacteria increased significantly in IBS-D patients. PICRUSt indicated that function expression of gut microbiota in IBS-D patients was up-regulated in metabolism of cofactors and vitamins, xenobiotics biodegradation and metabolism, and down-regulated in environmental adaptation, cell growth and death. CONCLUSIONS: Compared with the normal population in China, IBS-D patients are characterized by complex and unstable gut microbiota, which may influence inflammation and metabolism of the host.

miR-885 mediated cardioprotection against hypoxia/reoxygenation-induced apoptosis in human cardiomyocytes via inhibition of PTEN and BCL2L11 and modulation of AKT/mTOR signaling.

Ischemia/reperfusion (I/R) injury could cause the enhanced cell apoptosis of cardiomyocytes, which is one of key contributors for the development of ischemic heart disease. Recent studies emphasized the role of microRNAs (miRNAs) in regulating cardiomyocyte apoptosis. The study planned to elucidate the molecular actions of miR-885 on mediating human cardiomyocytes (HCMs) apoptosis induced by hypoxia/reoxygenation (H/R) and to explore the potential molecular mechanisms. The present data revealed that H/R stimulation inhibited HCM viability and potentiated HCM apoptosis, and more importantly, the expression of miR-885 in HCMs was markedly repressed after H/R stimulation. Further experimental examinations demonstrated that overexpression of miR-885 attenuated H/R-induced increased in HCM apoptotic rates, while miR-885 knockdown impaired HCM viability and increased HCM apoptotic rates. Moreover, the mechanistic studies showed that miR-885 inversely regulated the expression of phosphatase and tensin homolog (PTEN) and BCL2 like 11 (BCL2L11) in HCMs, and enforced expression of PTEN and BCL2L11 partially antagonized the protective actions of miR-885 overexpression on H/R-induced HCM injury. Moreover, H/R suppressed AKT/mTOR signaling, which was attenuated by miR-885 overexpression in HCMs. In conclusion, the present study for the first time showed the downregulation of miR-885 induced by H/R in HCMs, and provided the evidence that miR-885 attenuated H/R-induced cell apoptosis via inhibiting PTEN and BLC2L11 and modulation of AKT/mTOR signaling in HCMs.

Association between ADRB2, IL33, and IL2RB gene polymorphisms and lung cancer risk in a Chinese Han population.

PURPOSE: This study aimed to explore the associations between polymorphisms of a very important pharmacogene, ADRB2, two inflammation-related genes, IL33 and IL2RB, and the risk of lung cancer. METHODS: Six polymorphisms of ADRB2, IL33, and IL2RB were genotyped in 300 lung cancer patients and 300 healthy controls using MassARRAY. The relationship between genotypes and lung cancer risk was evaluated using chi-square tests. RESULTS: The minor allele of rs1042711 was a risk allele for lung cancer, whereas the minor alleles of rs7025417 and rs5756523 had protective effects against lung cancer (p＜0.05). The CT genotype of rs1042711 and the GT genotype of rs1560642 were associated with increased risk of lung cancer, whereas the CC and AA genotypes of rs7025417 and the CT and CC genotypes of rs5756523 were associated with decreased disease risk (p < 0.05). Genetic model analysis shows that rs1042711 and rs1560642 were associated with increased risk of lung cancer; whereas rs7025417, rs5756523, and rs2284033 were associated with decreased disease risk (p < 0.05). Stratification analysis showed that rs1042711 and rs1560642 were associated with increased risk of lung cancer in nonsmokers and smokers, respectively, whereas rs7025417 and rs5756523 were associated with decreased disease risk in both subgroups (p＜0.05). CONCLUSION: Our results shed new light on the association between polymorphisms of ADRB2, IL33, and IL2RB and the risk of lung cancer.

LncRNA DLX6-AS1 promotes tumor proliferation and metastasis in osteosarcoma through modulating miR-641/HOXA9 signaling pathway.

Osteosarcoma (OS) is the most common primary malignant bone tumor. Recently, increasing evidence has shown that the long noncoding RNA (lncRNA) DLX6-AS1 (distal-less homeobox 6 antisense 1) plays significant roles in various types of cancers. However, the functions and underlying mechanisms of DLX6-AS1 have not been explored in OS yet. In this study, we assessed the expression of DLX6-AS1 in OS tissues and cell lines and explored the underlying molecular mechanisms. DLX6-AS1 was found to be significantly upregulated in OS tissues and OS cell lines. High expression of DLX6-AS1 was significantly correlated with advanced TNM stage, high tumor grade, and distant metastasis of patients with OS. Knockdown of DLX6-AS1 suppressed OS cell proliferation, invasion, and migration, and induced cell apoptosis. Knockdown of DLX6-AS1 also suppressed in vivo tumor growth. Bioinformatics and luciferase assay analysis showed that DLX6-AS1 functioned as a competing endogenous RNA (ceRNA) to negatively regulate miR-641 expression. Furthermore, miR-641 was found to target the 3' untranslated region of homeobox protein Hox-A9 (HOXA9) and suppressed the expression of HOXA9. Mechanistic studies showed that DLX6-AS1 regulated OS cell proliferation, invasion, and migration via regulating HOXA9 by acting as a ceRNA for miR-641. Our results suggested that DLX6-AS1 functions as a ceRNA by targeting miR-641/HOXA9 signal pathway to suppress OS cell proliferation and metastasis. Our study may provide novel insights into understanding pathogenesis and development of OS.

The Long Non-Coding RNA SNHG1 Attenuates Cell Apoptosis by Regulating miR-195 and BCL2-Like Protein 2 in Human Cardiomyocytes.

BACKGROUND/AIMS: Long non-coding RNAs (lncRNAs) are theorized to play key roles in the development of heart diseases. However, the role of lncRNAs in cardiomyocyte apoptosis is largely unknown. The present study examined the role of lncRNA SNHG1 in the human cardiomyocytes (HCMs) apoptosis and explored the underlying molecular mechanisms. METHODS: SNHG1, miR-195 and mRNA expression was detected by qRT-PCR; protein level was determined by western blot; cell viability was detected by MTT assay; cell apoptosis was evaluated by flow cytometry and caspase-3 activity assay; the interaction between SNHG1 and miR195 was examined by using luciferase reporter assay. RESULTS: Hydrogen peroxide (H2O2) treatment significantly suppressed cell viability and increased cell apoptotic rate and caspase-3 activity in HCMs. Overexpression of SNHG1 attenuated the effects of H2O2 on HCMs viability and apoptosis; while SNHG1 exerted the opposite effects. SNHG1 was found to sponge miR-195 and suppress the expression of miR-195 in HCMs. Overexpression of miR-195 suppressed cell viability and induced apoptosis in HCMs, and miR-195 was found to negatively regulate the expression of BCL-2 like protein 2 (BCL2L2) via targeting its 3' untranslated region. Overexpression of BCL2L2 partially reversed the effects of miR-195 overexpression on cell viability and cell apoptosis of HCMs. MiR-195 overexpression or BCL2L2 knockdown attenuated the effects of SNHG1 overexpression on cell viability, cell apoptosis and protein levels of cleaved caspase-3, cleaved caspase-9 and Bax in H2O2-treated HCMs. CONCLUSION: Our results suggest a novel SNHG1/miR-195/BCL2L2 axis in the regulation of cardiomyocyte apoptosis. Modulation of SNHG1 may represent a novel strategy to treat cardiomyocyte apoptosis-related heart diseases.

Small Peptides Compound Isolated from Agkistrodon with Antiarthritic Effect in Collagen-Induced Arthritis Rats.

Agkistrodon in Chinese medicine has long been used as an effective treatment against rheumatoid arthritis (RA). The present research further investigated the effects of peptides extracted from the crude Agkistrodon on the RA rat model. Extracted peptides were separated by parameter-optimized ion-exchange chromatography (IEC), peptide fractions were further analysed by MALDI-TOF/TOF MS, and nano-LC-MS/MS acquired mass spectra were further characterized using Mascot software, which ranks the best matches in the NCBI database. RT-PCR results in RAW264.7 cells indicated that Agkistrodon peptide components had inhibitory effects against inflammatory cytokines. The therapeutic efficacy of Agkistrodon peptides was evaluated on the Wistar rats with collagen-induced arthritis. Symptom relief and reduced cartilage destruction and bone erosion were observed, which can be explained by the direct suppression of inflammatory cytokines in the joints. Agkistrodon peptides downregulate the expression of TNF-α, IL-1ß, and IL-6, which may alleviate cartilage destruction and bone erosion, thus relieving symptoms of RA.