Identification and Validation of Tumor Microenvironment-Associated Signature in Clear-Cell Renal Cell Carcinoma through Integration of DNA Methylation and Gene Expression.

The tumor microenvironment (TME) is crucial in tumor development, metastasis, and response to immunotherapy. DNA methylation can regulate the TME without altering the DNA sequence. However, research on the methylation-driven TME in clear-cell renal cell carcinoma (ccRCC) is still lacking. In this study, integrated DNA methylation and RNA-seq data were used to explore methylation-driven genes (MDGs). Immune scores were calculated using the ESTIMATE, which was employed to identify TME-related genes. A new signature connected with methylation-regulated TME using univariate, multivariate Cox regression and LASSO regression analyses was developed. This signature consists of four TME-MDGs, including AJAP1, HOXB9, MYH14, and SLC6A19, which exhibit high methylation and low expression in tumors. Validation was performed using qRT-PCR which confirmed their downregulation in ccRCC clinical samples. Additionally, the signature demonstrated stable predictive performance in different subtypes of ccRCC. Risk scores are positively correlated with TMN stages, immune cell infiltration, tumor mutation burden, and adverse outcomes of immunotherapy. Interestingly, the expression of four TME-MDGs are highly correlated with the sensitivity of first-line drugs in ccRCC treatment, especially pazopanib. Molecular docking indicates a high affinity binding between the proteins and pazopanib. In summary, our study elucidates the comprehensive role of methylation-driven TME in ccRCC, aiding in identifying patients sensitive to immunotherapy and targeted therapy, and providing new therapeutic targets for ccRCC treatment.

Multi-stimuli-responsive luminescence enabled by crown ether anchored chiral antimony halide phosphors.

Stimuli-responsive optical materials have provided a powerful impetus for the development of intelligent optoelectronic devices. The family of organic-inorganic hybrid metal halides, distinguished by their structural diversity, presents a prospective platform for the advancement of stimuli-responsive optical materials. Here, we have employed a crown ether to anchor the A-site cation of a chiral antimony halide, enabling convenient control and modulation of its photophysical properties. The chirality-dependent asymmetric lattice distortion of inorganic skeletons assisted by a crown ether promotes the formation of self-trapped excitons (STEs), leading to a high photoluminescence quantum yield of over 85%, concomitant with the effective circularly polarized luminescence. The antimony halide enantiomers showcase highly sensitive stimuli-responsive luminescent behaviours towards excitation wavelength and temperature simultaneously, exhibiting a versatile reversible colour switching capability from blue to white and further to orange. In situ temperature-dependent luminescence spectra, time-resolved luminescence spectra and theoretical calculations reveal that the multi-stimuli-responsive luminescent behaviours stem from distinct STEs within zero-dimensional lattices. By virtue of the inherent flexibility and adaptability, these chiral antimony chlorides have promising prospects for future applications in cutting-edge fields such as multifunctional illumination technologies and intelligent sensing devices.

Bosea beijingensis sp. nov., Telluria beijingensis sp. nov. and Agrococcus beijingensis sp. nov., isolated from baijiu mash.

The baijiu fermentation environment hosts a variety of micro-organisms, some of which still remain uncultured and uncharacterized. In this study, the isolation, cultivation and characterization of three novel aerobic bacterial strains are described. The cells of strain REN20T were Gram-negative, strictly aerobic, motile and grew at 26-37 °C, at pH 6.0-9.0 and in the presence of 0-5.0   % (w/v) NaCl. The cells of strain REN29T were Gram-negative, strictly aerobic, motile and grew at 15-30 °C, at pH 6.0-9.0 and in the presence of 0-10.0   % (w/v) NaCl. The cells of strain REN33T were Gram-positive, strictly aerobic, motile and grew at 15-37 °C, at pH 5.0-10.0 and in the presence of 0-7.0   % (w/v) NaCl. The digital DNA-DNA hybridization and average nucleotide identity by orthology values between type strains in related genera and REN20T (20.3-36.8 % and 79.8-89.9  %), REN29T (20.3-36.8  % and 74.5-88.5  %) and REN33T (22.6-48.6  % and 75.8-84.2  %) were below the standard cut-off criteria for the delineation of bacterial species, respectively. Based on polyphasic taxonomy analysis, we propose three new species, Bosea beijingensis sp. nov. (=REN20T=GDMCC 1.2894T=JCM 35118T), Telluria beijingensis sp. nov. (=REN29T=GDMCC 1.2896T=JCM 35119T) and Agrococcus beijingensis sp. nov. (=REN33T=GDMCC 1.2898T=JCM 35164T), which were recovered during cultivation and isolation from baijiu mash.

Precise Preparation of Triarylboron-Based Graphdiyne Analogues for Gas Separation.

A series of triarylboron-based graphdiyne analogues (TAB-GDYs) with tunable pore size were prepared through copper mediated coupling reaction. The elemental composition, chemical bond, morphology of TAB-GDYs were well characterized. The crystallinity was confirmed by selected area electron diffraction (SAED) and stacking modes were studied in combination with high resolution transmission electron microscope (HRTEM) and structure simulation. The absorption and desorption isotherm revealed relatively high specific surface area of these TAB-GDYs up to 788 m2 g-1 for TMTAB-GDY, which decreased as pore size enlarged. TAB-GDYs exhibit certain selectivity for CO2 /N2 (21.9), CO2 /CH4 (5.3), CO2 /H2 (41.8) and C2 H2 /CO2 (2.3). This work has developed a series of boron containing two-dimensional frameworks with clear structures and good stability, and their tunable pore sizes have laid the foundation for future applications in the gas separation field.

Analysis of the potential ferroptosis mechanism and multitemporal expression change of central ferroptosis-related genes in cardiac ischemia-reperfusion injury.

Acute myocardial infraction is the most severe type of coronary artery disease and remains a substantial burden to the health care system globally. Although myocardial reperfusion is critical for ischemic cardiac tissue survival, the reperfusion itself could cause paradoxical injury. This paradoxical phenomenon is known as ischemia-reperfusion injury (IRI), and the exact molecular mechanism of IRI is still far from being elucidated and is a topic of controversy. Meanwhile, ferroptosis is a nonapoptotic form of cell death that has been reported to be associated with various cardiovascular diseases. Thus, we explored the potential ferroptosis mechanism and target in cardiac IRI via bioinformatics analysis and experiment. GSE4105 data were obtained from the GEO database and consist of a rat IRI model and control. After identifying differentially expressed ferroptosis-related genes (DEFRGs) and hub genes of cardiac IRI, we performed enrichment analysis, coexpression analysis, drug-gene interaction prediction, and mRNA-miRNA regulatory network construction. Moreover, we validated and explored the multitemporal expression of hub genes in a hypoxia/reoxygenation (H/R)-induced H9C2 cell injury model under different conditions via RT-qPCR. A total of 43 DEFRGs and 7 hub genes (tumor protein p53 [Tp53], tumor necrosis factor [Tnf], hypoxia-inducible factor 1 subunit alpha [Hif1a], interleukin 6 [Il6], heme oxygenase 1 [Hmox1], X-box binding protein 1 [Xbp1], and caspase 8 [Casp8]) were screened based on bioinformatics analysis. The functional annotation of these genes revealed apoptosis, and the related signaling pathways could have association with the pathogenesis of ferroptosis in cardiac IRI. In addition, the expression of the seven hub genes in IRI models were found higher than that of control under different H/R conditions and time points. In conclusion, the analysis of 43 DEFRGs and 7 hub genes could reveal the potential biological pathway and mechanism of ferroptosis in cardiac IRI. In addition, the multitemporal expression change of hub genes in H9C2 cells under different H/R conditions could provide clues for further ferroptosis mechanism exploring, and the seven hub genes could be potential biomarkers or therapeutic targets in cardiac IRI.

Neutrophil CD64: a potential biomarker for the diagnosis of infection in patients with haematological malignancies.

METHODS: The clinical data of 76 patients with haematological malignancies and infection who were treated in our department between January 2014 and October 2019 were retrospectively analysed. To evaluate the diagnostic value of some biomarkers, infection indexes such as white blood cell count (WBC), neutrophil count (NEUT), neutrophil CD64 and procalcitonin (PCT) were compared across the patients with confirmed infection status and infection-control status. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) were also determined. RESULTS: The WBC and NEUT did not differ significantly, whereas the neutrophil CD64 and PCT levels were significantly elevated in patients with a confirmed infection status (p < 0.05), with sensitivity of 31.0%, 45.2%, 76.2% and 50%, respectively, and specificity of 90.5%, 69%, 71.4% and 64.3%, respectively. The AUC of WBC, NEUT, neutrophil CD64 and PCT was 0.528, 0.517, 0.844 and 0.599, respectively. Further highlighting their diagnostic value, the neutrophil CD64 and PCT levels in neutropenia patients were significantly upregulated in patients with infection status (p < 0.05) but the WBC and NEUT were unchanged, with sensitivity of 73.7%, 63.2%, 68% and 68.4%, respectively, and specificity of 68.4%, 52.6%, 57.9% and 63.2%, respectively. The AUC of neutrophil CD64, PCT, WBC and NEUT was 0.864, 0.593, 0.419 and 0.403, respectively. CONCLUSION: These results indicate that neutrophil CD64 is a promising biomarker with superior sensitivity and specificity for diagnosing infection in patients with haematological malignancies, especially neutropenia patients.

Sporosarcina beigongshangi sp. nov., isolated from pit mud of Baijiu.

A Gram-positive, aerobic and short rod-shaped bacterium designated REN13T, was isolated from pit mud of Baijiu, in Sichuan province, China. Strain REN13T could grow at 10-50 â„ƒ, pH 6.0-9.0 and 0-2% (w/v) NaCl, with the optimal growth occurred at 28 â„ƒ, pH 7.0, and 2% (w/v) NaCl. 16S rRNA gene sequence analysis showed that strain REN13T was closely related to Sporosarcina globispora DSM 4T (98.6%). The DNA G + C content of strain REN13T was 41.1 mol %. DDH and ANI value between strain REN13T and S. globispora DSM 4T was 24.4% and 67.6%, respectively. The major fatty acids were iso-C15:0 and antesio-C15:0. The respiratory quinone was MK-7, and the polar lipids were phosphatidylethanolamine, phospholipids, phosphatidylglycerol and diphosphatidylglycerol. Based on the above polyphasic taxonomic analysis, strain REN13T represents a novel species of the genus Sporosarcina, for which the name Sporosarcina beigongshangi sp. nov. is proposed. The type strain is strain REN13T (= JCM 34409T = GDMCC 1.2151T).

Umezawaea beigongshangensis sp. nov., Isolated From the Mash of Baijiu.

A Gram-positive, aerobic and non-motile actinobacterial strain, designated REN6T, was isolated from the mash of Baijiu (Chinese spirits, a kind of distilling liquor is made by cooking, saccharification, fermentation and distillation) collected from Sichuan Province Region, China, and characterized using a polyphasic approach. Morphological and chemotaxonomic properties of strain REN6T were consistent with the description of the genus Umezawaea, such as the spore arrangement, the abundant aerial mycelium and the fragmented substrate mycelium. The diamino acid of peptidoglycan is meso-diaminopimelic acid. The diagnostic phospholipids were DPG (diphosphatidylglycerol), PG (phosphatidylglycerol), PI (phosphatidylinositol), PE (phosphatidylethanolamine). The major fatty acids were C16:0, C17:0, Iso-C16:0, Iso-C16:1 H, C17:1ω6c and C17:1 ω8c. Menaquinone-9 (MK-9) (H4) was the predominant menaquinones. The genomic DNA G + C contents were 72.7 mol%. Phylogenetic analysis based on 16S rDNA gene sequences demonstrated that strain REN6T should also be classified in the genus Umezawaea, with U. tangerina (98.7%) and U. endophytica (98.7%). However, it can be distinguished from the closest strains U. tangerina JCM 10302T based on the low levels of DNA-DNA hybridization 22.1%. Based upon the morphological, physiological, chemotaxonomic and molecular characteristics differences from other members of the genus, a novel species, Umezawaea beigongshangensis sp. nov., is proposed, with REN6T (= JCM 33954T = CGMCC 19205T) as the type strain.

Pseudoxanthomonas beigongshangi sp. nov., a novel bacteria with predicted nitrite and nitrate reduce ability isolated from pit mud of Baijiu.

A Gram-negative and rod-shape bacterium designated REN9T, was isolated from pit mud of Baijiu in Sichuan, China. The 16S rRNA sequence of strain REN9T had a high similarity to Pseudoxanthomonas indica P15T (99.21%), P. mexicana AMX 26BT (97.74%) and P. japonensis 12-3T (97.43%). Phylogenetic analysis showed that REN9T belongs to the genus Pseudoxanthomonas and formed distinct cluster. The ANI and DDH values between strains REN9T and P15T were 80.94% and 24%, respectively. Strain REN9T grew optimally at 37 °C, pH 7.0 and 2% NaCl. PE (phosphatidylethanolamine), PG (phosphatidylglycerol) and DPG (diphosphatidylglycerol) were the major polar lipids of REN9T. Ubiquinone 8 (Q-8) was the predominant quinone, and Iso-C15:0 (64.32%), anteiso-C15:0 (12.04%) and Iso-C14:0 (4.56%) were the majority fatty acids. The DNA G + C content of strain REN9T was 67.3 mol%. Genomic analysis showed that strain REN9T had two secondary metabolite biosynthesis gene clusters. Moreover, strain REN9T had 43 glycoside hydrolases, 41 glycosyl transferases and 41 carbohydrate esterases. Based on the polyphasic taxonomic analysis, strain REN9T is recommended as a novel species within the genus Pseudoxanthomonas, for which the name Pseudoxanthomonas beigongshangi is proposed. The type stain is REN9T (= JCM 33961T = GDMCC 1.2210T).

Brevibacterium renqingii sp. nov., isolated from the Daqu of Baijiu.

Two bacterial strains, designated REN4T and REN4-1, were isolated from daqu sample collected from baijiu factory located in Shanxi, China. The two strains shared highly similar 16S rRNA gene sequences (99.67% identities) and formed a monophyletic clade within the Brevibacterium 16S rRNA gene tree, showing 97.56-97.85% 16S rRNA gene sequence identities with type strains Brevibacterium permense VKM Ac-2280 T, Brevibacterium sediminis FXJ8.269 T, Brevibacterium oceani BBH7T and Brevibacterium epidermidis NCIMB 702286 T. They contained MK-8(H2) as the most predominant menaquinone, antesio-C15:0, antesio-C17:0, Iso-C16:0 and Iso-C17:0 as the major cellular fatty acids, DPG (diphosphatidylglycerol), PG (phosphatidylglycerol), PGL (phosphatidylglycerollipids), and PL (phospholipids) as the main polar lipids. The genomic DNA G + C content of strains REN4 and REN4-1 were 64.35, 65.82 mol%. Moreover, the low DNA-DNA relatedness values, physiological and biochemical characteristics, and taxonomic analysis allowed the differentiation of strains REN4T and REN4-1 from the other recognized species of the genus Brevibacterium. Therefore, strain REN4T represents a novel species of the genus Brevibacterium, for which the name Brevibacterium renqingii sp. nov. is proposed, with the type strain REN4T (= JCM 33953 T = KCTC 49366 T).

Multi-functional Nanodrug Based on a Three-dimensional Framework for Targeted Photo-chemo Synergetic Cancer Therapy.

Targeted synergistic therapy has broad prospects in tumor treatments. Here, a multi-functional nanodrug GDYO-CDDP/DOX@DSPE-PEG-MTX (GCDM) based on three traditional anticancer drugs (doxorubicin (DOX), cisplatin (CDDP) and methotrexate (MTX)) modified graphdiyne oxide (GDYO) is described, for diagnosis and targeted cancer photo-chemo synergetic therapy. In this system, for the first time, these three traditional anti-cancer drugs have played new roles and can reduce multidrug resistance through synergistic anti-tumor effects. Cisplatin can be hybridized with GDYO to form a multifunctional and well-dispersed three-dimensional framework, which can not only be used as nano-drug carriers to achieve high drug loading rates (40.3%), but also exhibit excellent photothermal conversion efficiency (47%) and good photodynamic effects under NIR irradiation. Doxorubicin (DOX) is loaded onto GDYO-CDDP through π-π stacking, which is used as an anticancer drug and as a fluorescent probe for nanodrug detection. Methotrexate (MTX) can be applied in tumor targeting and play a role in synergistic chemotherapy with DOX and CDDP. The synthesized multi-functional nanodrug GCDM has good biocompatibility, active targeting, long-term retention, sustained drug release, excellent fluorescence imaging capabilities, and remarkable photo-chemo synergistic therapeutic effects.

MiR-1231 decrease the risk of cancer-related mortality in patients combined with non-small cell lung cancer and diabetes mellitus.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a deadly human malignancy, and previous studies support the contribution of microRNAs (miRNAs) to cancer assessment. It has been reported that miR-1231 can be used as a biomarker to assess prognosis in different cancers. However, the prognostic value of miR-1231 in NSCLC patients with comorbid diabetes mellitus (DM) remains unclear. The present study evaluated the risk factors for NSCLC with DM and developed a predictive model for it. METHODS: A real-world study was conducted, including data from 108 patients with NSCLC combined with DM from April 1, 2010, to June 1, 2015. MiR-1231 was recorded during hospital admission. Cox-proportional hazards model was applied for survival analysis of risk factors for cancer-related mortality and to create nomograms for prediction. The accuracy of the model was evaluated by C-index and calibration curves. RESULTS: The mortality rate in the high miR-1231 level (≥ 1.775) group was 57.4%. On the basis of univariate analysis, we put factors (P < 0.05) into multivariate regression models, and high miR-1231 levels (P < 0.001, HR = 0.57), surgery (P < 0.001, HR = 0.37) and KPS score > 80 (P = 0.01, HR = 0.47) had a better prognosis and were considered as independent protective factors. These independently relevant factors were used to create nomograms to predict long-term patient survival. Nomogram showed good accuracy in risk estimation with a guide-corrected C-index of 0.691. CONCLUSION: MiR-1231 reduced the risk of cancer-related death in patients with combined NSCLC and DM. Nomogram based on multivariate analysis showed good accuracy in estimating the overall risk of death.

HRD1, an Important Player in Pancreatic ß-Cell Failure and Therapeutic Target for Type 2 Diabetic Mice.

Inadequate insulin secretion in response to glucose is an important factor for ß-cell failure in type 2 diabetes (T2D). Although HMG-CoA reductase degradation 1 (HRD1), a subunit of the endoplasmic reticulum-associated degradation complex, plays a pivotal role in ß-cell function, HRD1 elevation in a diabetic setting contributes to ß-cell dysfunction. We report in this study the excessive HRD1 expression in islets from humans with T2D and T2D mice. Functional studies reveal that ß-cell-specific HRD1 overexpression triggers impaired insulin secretion that will ultimately lead to severe hyperglycemia; by contrast, HRD1 knockdown improves glucose control and response in diabetic models. Proteomic analysis results reveal a large HRD1 interactome, which includes v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), a master regulator of genes implicated in the maintenance of ß-cell function. Furthermore, mechanistic assay results indicate that HRD1 is a novel E3 ubiquitin ligase that targets MafA for ubiquitination and degradation in diabetic ß-cells, resulting in cytoplasmic accumulation of MafA and in the reduction of its biological function in the nucleus. Our results not only reveal the pathological importance of excessive HRD1 in ß-cell dysfunction but also establish the therapeutic importance of targeting HRD1 in order to prevent MafA loss and suppress the development of T2D.

Sodium Selenate Ameliorates Cardiac Injury Developed from High-Fat Diet in Mice through Regulation of Autophagy Activity.

Obesity is often accompanied by dyslipidemia, high blood glucose, hypertension, atherosclerosis, and myocardial dysfunction. Selenate is a vital antioxidant in the cardiovascular system. The beneficial effects of selenate on obesity-associated cardiac dysfunction and potential molecular mechanism were identified in both H9C2 cells and C57BL/6J mice hearts. The cardiac histological preformation in C57BL/6J mice were evaluated by cross-sectional area (CSA) of cardiomyocytes and percent area of fibrosis in the left ventricles. The cardiac autophagy flux in H9C2 cells and C57BL/6J mice hearts was analyzed by Western blots and the number of autophagosomes and autolysosome in H9C2 cells. In the present study, we found that lipid overload caused increases in serum lipid, CSA, and percent area of fibrosis. We further found that lipid-induced accumulation of autophagosomes  was due to depressed autophagy degradation, which was not restored in the pretreatment with 3-methyladenine and chloroquine, whereas, it was improved by rapamycin. Moreover, we demonstrated that increased levels of serum lipid, CSA, percent area of fibrosis and mRNA expression related to cardiomyocytes hypertrophy and fibrosis were significantly reduced after selenate treatments of mice. We also found selenate treatment significantly down-regulated activity of the Akt pathway, which was activated in response to lipid-overload. Furthermore, selenate dramatically improved cardiac autophagic degradation which was suppressed after exposure to lipid-overload in both H9C2 cells and C57BL/6J mice hearts. Taken together, selenate offers therapeutic intervention in lipid-related metabolic disorders, and protection against cardiac remodeling, likely through regulation of the activity of autophagic degradation and Akt pathway.

Pontibacter beigongshangensis sp. nov., Isolated from the Mash of Wine.

A Gram-negative, aerobic, oval-shaped, and light red pigmented bacterium, designated T6-1T, was isolated from the mash of wine collected from a wine-making laboratory simulated fermenter located in Beijing, China. The optimal growth of T6-1T occurred at 30 °C, pH 7.0 with 1% NaCl. The sole respiratory quinone was menaquinone-7 (MK-7). The principal cellular fatty acids (>5%) were iso-C15:0, iso-C17:0 3OH, C16:1 ω5c, and iso-C17:0. The major polar lipids were PE (phosphatidylethanolamine), PL (unidentified phospholipid), and L1-2 (unidentified lipids). 16S rRNA phylogenetic analysis indicated that strain T6-1T belonged to the genus Pontibacter. The 16S rRNA gene sequence of strain T6-1T was most similar to Pontibacter amylolyticus 9-2T (95.92%). The genomic DNA G+C content of strain T6-1 was 50.34 mol%. The digital DNA-DNA relatedness and average nucleotide identity value between T6-1T and 9-2T was 20.20% and 74.18%, respectively. Polyphasic taxonomy analysis indicated that strain T6-1T represents a novel species of the genus Pontibacter, for which the name Pontibacter beigongshangensis sp. nov. is proposed, with the type strain T6-1T (= CGMCC 1.17104T = KCTC 72413T).

An integrated targeting drug delivery system based on the hybridization of graphdiyne and MOFs for visualized cancer therapy.

Multimodal therapies have been regarded as promising strategies for cancer treatment as compared to conventional drug delivery systems that have various drawbacks in either low loading content, uncontrolled release, non-targeting or biotoxicity. We have developed a multifunctional three-dimensional tumor-targeting drug delivery system, Fe3O4@UIO-66-NH2/graphdiyne (FUGY), based on the hybridization of a novel two-dimensional material, graphdiyne (GDY), with a metal organic framework (MOFs) structure, Fe3O4@UIO-66-NH2 (FU). The FU MOF structure has superior ability for magnetic targeting, and was constructed by an in situ growth method in which it was surface-installed with GDY via amide bonds, as a carrier of anticancer drugs. The anticancer drug doxorubicin (DOX) was loaded onto FUGY and served as both an anticancer drug to treat the tumor and a fluorescence probe to ascertain the location of FUGY. The results show that FUGY exhibits a high drug loading content of 43.8% and an effective drug release around the tumor cells at pH 5.0. In particular, fluorescence imaging demonstrates that FUGY can deliver more anticancer drugs to tumor tissue than conventional drug delivery systems. Furthermore, FUGY exhibits superior therapeutic efficiencies with negligible side effects as compared to the direct administration of free DOX, both in vitro and in vivo. The obtained FUGY drug delivery system possesses ideal biocompatibility, sustained drug release, effective chemotherapeutic efficacy, and specific targeting abilities. Such a multimodal therapeutic system can facilitate new possibilities for multifunctional drug delivery systems.

A novel amphiphilic fluorescent probe BODIPY-O-CMC-cRGD as a biomarker and nanoparticle vector.

Fluorescent probes have been demonstrated to be promising candidates as biomarkers and biological carriers. Our study focuses on the development of a novel amphiphilic fluorescent probe with good photostability, high water solubility, excellent specificity and promising loading capability for tumor diagnosis and treatment. At first, BODIPY dye and O-carboxymethyl chitosan were prepared via a chemical reaction. Then, the prepared BODIPY dye and cRGD were bonded to O-carboxymethyl chitosan successively via an acylation reaction. Finally, we obtained the desired amphiphilic fluorescent probe: BODIPY-O-CMC-cRGD, which was based on the fluorescence resonance energy transfer (FRET) principle for selective visualization of tumors in vitro. Through a series of experiments, we found that this fluorescent probe possessed better fluorescence characteristics and tumor targeting properties. Simultaneously, by self-assembly, the amphiphilic probe encapsulated the other flexible structure of BODIPY2 and the rigid structure of porphyrin, which formed distinct nanoparticles with different particle sizes. Hence, we could observe different phagocytosis processes of the two nanoparticles in the tumor cells via the fluorescence of dyes by confocal laser scanning microscopy. Therefore, the results suggest that the fluorescent probe has advantages in tumor detection, and the constructed tumor-specific nanoparticles show high clinical potential to be utilized not only in visual and precise diagnosis but also in excellent drug delivery for tumor treatment. Henceforth, we will prepare new targeted and visualized pharmaceuticals by replacing BODIPY2 and porphyrin with antineoplastic drugs for future tumor treatment.

Organized chromophoric assemblies for nonlinear optical materials: towards (sub)wavelength scale architectures.

Photonic circuits are expected to greatly contribute to the next generation of integrated chips, as electronic integrated circuits become confronted with bottlenecks such as heat generation and bandwidth limitations. One of the main challenges for the state-of-the-art photonic circuits lies in the development of optical materials with high nonlinear optical (NLO) susceptibilities, in particular in the wavelength and subwavelength dimensions which are compatible with on-chip technologies. In this review, the varied approaches to micro-/nanosized NLO materials based on building blocks of bio- and biomimetic molecules, as well as synthetic D-π-A chromophores, have been categorized as supramolecular self-assemblies, molecular scaffolds, and external force directed assemblies. Such molecular and supramolecular NLO materials have intrinsic advantages, such as structural diversities, high NLO susceptibilities, and clear structure-property relationships. These "bottom-up" fabrication approaches are proposed to be combined with the "top-down" techniques such as lithography, etc., to generate multifunctionality by coupling light and matter on the (sub)wavelength scale.

O antigen is the receptor of Vibrio cholerae serogroup O1 El Tor typing phage VP4.

Bacteriophage VP4 is a lytic phage of the Vibrio cholerae serogroup O1, and it is used in phage subtyping of V. cholerae biotype El Tor. Studies of phage infection mechanisms will promote the understanding of the basis of phage subtyping as well as the genetic differences between sensitive and resistant strains. In this study, we investigated the receptor that phage VP4 uses to bind to El Tor strains of V. cholerae and found that it infects strains through adsorbing the O antigen of V. cholerae O1. In some natural isolates that are resistant to VP4 infection, mutations were identified in the wb* cluster (O-antigen gene cluster), which is responsible for the biosynthesis of O antigen. Mutations in the manB, wbeE, and wbeU genes caused failure of adsorption of VP4 to these strains, whereas the observed amino acid residue mutations within wbeW and manC have no effect on VP4 infection. Additionally, although mutations in two resistant strains were found only in manB and wbeW, complementing both genes did not restore sensitivity to VP4 infection, suggesting that other resistance mechanisms may exist. Therefore, the mechanism of VP4 infection may provide a basis for subtyping the phage. Elaborate mutations of the O antigen may imbue V. cholerae strains with resistance to phage infection.

Gold nanoparticle-based monitoring of the reduction of oxidized to reduced glutathione.

We demonstrate the reduction of oxidized to reduced glutathione in the presence of glutathione reductase enzyme based on the modulation in photoluminescent quenching efficiency between the perylene bisimide chromophore TPPCA and gold nanoparticles (AuNPs). The TPPCA-AuNPs assembly shows a turn-on fluorescent signal in the presence of reduced glutathione, which provides a new concept to measure the balance of glutathione in a creature.