Heteroepitaxial Growth to Construct Hexagonal/Hexagonal ß-NaYF4:Yb,Tm/Cs4PbBr6 Multi-Code Emitting Core/Shell Nanocrystals.

Synthesis of upconversion nanoparticles (UCNPs)-metal halide perovskites (MHPs) heterostructure is garnered immense attentions due to their unparalleled photophysical properties. However, the obvious difference in their structural forms makes it a huge challenge. Herein, hexagonal ß-NaYF4 and hexagonal Cs4PbBr6 are filtrated to construct the UCNP/MHP heterostructural luminescent material. The similarity in their crystal structures facilitate the heteroepitaxial growth of Cs4PbBr6 on the surface of ß-NaYF4 NPs, leading to the formation of high-quality ß-NaYF4:Yb,Tm/Cs4PbBr6 core/shell nanocrystals (NCs). Interestingly, this heterostructure endows the core/shell NCs with typically narrow-band green emission centered at 524 nm under 980 nm excitation, which should be attributed to the Förster resonance energy transfer (FRET) from Tm3+ to Cs4PbBr6. It is noteworthy that the FRET efficiency of ß-NaYF4:Yb,Tm/Cs4PbBr6 core/shell NCs (58.33%) is much higher than that of the physically mixed sample (1.84%). In addition, the reduced defect density, lattice anchoring effect, as well as diluted ionic bonding proportion induced by the core/shell structure further increase the excellent water-resistance and thermal cycling stability of Cs4PbBr6. These findings open up a new way to construct UCNP/MHP heterostructure with better multi-code luminescence performance and stability and promote its wide optoelectronic applications.

Elongin B promotes breast cancer progression by ubiquitinating tumor suppressor p14/ARF.

Elongin B (ELOB), a pivotal element in the ELOB/c-Cullin2/5-SOCS-box E3 ubiquitin-protein ligase complex, plays a significant role in catalyzing the ubiquitination and subsequent degradation of a broad spectrum of target proteins. Notably, it is documented to facilitate these processes. However, the regulatory role of ELOB in breast cancer remains ambiguous. In this study, through bio-informatic analysis of The Cancer Genome Atlas and Fudan University Shanghai Cancer Center database, we demonstrated that ELOB was over-expressed in breast cancer tissues and was related to unfavorable prognosis. Additionally, pathway enrichment analysis illustrated that high expression of ELOB was associated with multiple cancer promoting pathways, like cell cycle, DNA replication, proteasome and PI3K - Akt signaling pathway, indicating ELOB as a potential anticancer target. Then, we confirmed that both in vivo and in vitro, the proliferation of breast cancer cells could be significantly suppressed by the down-regulation of ELOB. Mechanically, immunoprecipitation and in vivo ubiquitination assays prompted that, as the core element of Cullin2-RBX1-ELOB E3 ligase (CRL2) complex, ELOB regulated the ubiquitination and the subsequent degradation of oncoprotein p14/ARF. Moreover, the anticancer efficacy of erasing ELOB could be rescued by simultaneous knockdown of p14/ARF. Finally, through analyzing breast cancer tissue microarrays and western blot of patient samples, we demonstrated that the expression of ELOB in tumor tissues was elevated in compared to adjacent normal tissues. In conclusion, ELOB is identified to be a promising innovative target for the drug development of breast cancer by promoting the ubiquitination and degradation of oncoprotein p14/ARF.

A Tumor-Targeting Dual-Modal imaging probe for nitroreductase in vivo.

Nitroreductase (NTR) overexpression often occurs in tumors, highlighting the significance of effective NTR detection. Despite the utilization of various optical methods for this purpose, the absence of an efficient tumor-targeting optical probe for NTR detection remains a challenge. In this research, a novel tumor-targeting probe (Cy-Bio-NO2) is developed to perform dual-modal NTR detection using near-infrared fluorescence and photoacoustic techniques. This probe exhibits exceptional sensitivity and selectivity to NTR. Upon the reaction with NTR, Cy-Bio-NO2 demonstrates a distinct fluorescence "off-on" response at 800 nm, with an impressive detection limit of 12 ng/mL. Furthermore, the probe shows on-off photoacoustic signal with NTR. Cy-Bio-NO2 has been successfully employed for dual-modal NTR detection in living cells, specifically targeting biotin receptor-positive cancer cells for imaging purposes. Notably, this probe effectively detects tumor hypoxia through dual-modal imaging in tumor-bearing mice. The strategy of biotin incorporation markedly enhances the probe's tumor-targeting capability, facilitating its engagement in dual-modal imaging at tumor sites. This imaging capacity holds substantial promise as an accurate tool for cancer diagnosis.

Correlation of retrobulbar perfusion deficits with glaucomatous visual field defects.

PURPOSE: This study is to evaluate the correlation between retrobulbar perfusion deficits and glaucomatous visual field defects. METHODS: Eighty-four patients with glaucoma and 17 normal subjects serving as controls were selected. Color Doppler imaging (CDI) was used to measure the changes in blood flow parameters in the retrobulbar ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCAs). Visual field testing was performed using a Humphrey perimeter, categorizing the visual field deficits into four stages according to the Advanced Glaucoma Intervention Study (AGIS) scoring method. Subsequently, the correlation of retrobulbar hemodynamic parameter alterations among glaucomatous patients with varying visual field defects was examined. RESULTS: The higher the visual field stage, the lower the peak systolic velocity (PSV) of the OA, CRA, and SPCAs in glaucomatous patients. The CRA had the highest sensitivity to changes in its PSV. The PSV of the temporal SPCA (TSPCA-PSV) was lower in advanced glaucoma than in early-stage glaucoma. The PSVs of the OA, CRA, and TSPCA, as well as the resistance index of the CRA (CRA-RI), were positively correlated with the visual field index and the mean deviation. Except for that of OA, the PSV of the retrobulbar vessels was negatively correlated with the pattern standard deviation (PSD). The OA-PSV and end-diastolic velocity (EDV) of the CRA and TSPCA were lower in patients with superior visual field defects than in those with inferior visual field defects. CONCLUSIONS: Greater severity of visual field defects corresponded to poorer retrobulbar blood flow in glaucomatous patients. Patients suffered significant perfusion impairments in the CRA at the early stage, accompanied by SPCA perfusion disorder at the advanced stage. The presence of a bow-shaped defect in the superior or inferior region of the visual field in moderate-stage glaucoma was closely correlated with retrobulbar vascular EDV. TRIAL REGISTRATION: ChiCTR2200059048 (2022-04-23).

Near-Infrared Fluorescent Nanoprobes for Adenosine Triphosphate-Guided Imaging in Cancer and Fatty Liver Mice.

Adenosine triphosphate (ATP), as an indispensable biomolecule, is the main energy source of cells and is used as a marker for diseases such as cancer and fatty liver. It is of great significance to design a near-infrared fluorescent nanoprobe with excellent performance and apply it to various disease models. Here, a near-infrared fluorescent nanoprobe (ZIF-90@SiR) based on a zeolitic imidazole framework is proposed. The fluorescent nanoprobes are synthesized by encapsulating the dye (SiR) into the framework of ZIF-90. Upon the addition of ATP, the structure of the ZIF-90@SiR nanoprobe is disrupted and SiR is released to generate near-infrared fluorescence at 670 nm. In the process of ATP detection, ZIF-90@SiR shows high sensitivity and good selectivity. Moreover, the ZIF-90@SiR nanoprobe has good biocompatibility due to its low toxicity to cells. It is used for fluorescence imaging of ATP in living cells and thus distinguishing normal cells and cancer cells, as well as distinguishing fatty liver cells. Due to excellent near-infrared fluorescence properties, the ZIF-90@SiR nanoprobe can not only distinguish normal mice and tumor mice but also differentiate normal mice and fatty liver mice for the first time.

Long-Term Imaging of Cys in Cells and Tumor Mice by a Solid-State Fluorescence Probe.

Cysteine is an important biological thiol and is closely related to cancer. It remains a challenge to develop a probe that can provide long-term fluorescence detection and imaging of Cys in cells as well as in living organisms. Here, a solid-state fluorophore HTPQ is combined with an acrylate group to construct a solid-state fluorescent probe HTPQC for Cys recognition. The fluorescence of the probe is quenched when the photoinduced electron transfer (PET) process is turned on and the excited-state intramolecular proton transfer (ESIPT) process is turned off. In the presence of Cys, an obvious solid-state fluorescence signal can be observed. The double quenching mechanism makes the probe HTPQC have the advantages of high sensitivity, good selectivity, and high contrast of biological imaging. Due to low cytotoxicity, the probe HTPQC can be used to detect exogenous and endogenous Cys in living cells and is capable of imaging over long periods of time. By making full use of long wavelengths, the probe can be applied for the detection of Cys levels in tumor mice and equipped with the ability to conduct long-term imaging in vivo.

A near-infrared fluorescent probe for detecting hydrogen sulfide with high selectivity in cells and ulcerative colitis in mice.

Although hydrogen sulfide (H2S) is a well-known toxic gas, its vital role as a gas transmitter in various physiological and pathological processes of living systems cannot be ignored. Relevant investigations indicate that endogenous H2S is involved in the development of ulcerative colitis pathology and is overexpressed in ulcerative colitis, and hence can be considered as an ulcerative colitis biomarker. Herein, an isophorone-xanthene-based NIR fluorescent probe (IX-H2S) was constructed to image H2S. Owing to its large conjugated structure, the probe exhibits a near-infrared emission wavelength of 770 nm with a large Stokes shift (186 nm). Moreover, IX-H2S has excellent selectivity for the detection of H2S without interference from other analytes including thiols. In addition, the probe has been successfully applied not only in fluorescence imaging of endogenous and exogenous H2S in living cells, but also in imaging of H2S in normal and ulcerative colitis mice. Encouraged by the eminent performance, IX-H2S is expected to be a potent "assistant" for the diagnosis of ulcerative colitis.

Anti-CD40 Antibodies Fused to CD40 Ligand Have Superagonist Properties.

CD40 is a potent activating receptor within the TNFR family expressed on APCs of the immune system, and it regulates many aspects of B and T cell immunity via interaction with CD40 ligand (CD40L; CD154) expressed on the surface of activated T cells. Soluble CD40L and agonistic mAbs directed to CD40 are being explored as adjuvants in therapeutic or vaccination settings. Some anti-CD40 Abs can synergize with soluble monomeric CD40L. We show that direct fusion of CD40L to certain agonistic anti-CD40 Abs confers superagonist properties, reducing the dose required for efficacy, notably greatly increasing total cytokine secretion by human dendritic cells. The tetravalent configuration of anti-CD40-CD40L Abs promotes CD40 cell surface clustering and internalization and is the likely mechanism of increased receptor activation. CD40L fused to either the L or H chain C termini, with or without flexible linkers, were all superagonists with greater potency than CD40L trimer. The increased anti-CD40-CD40L Ab potency was independent of higher order aggregation. Moreover, the anti-CD40-CD40L Ab showed higher potency in vivo in human CD40 transgenic mice compared with the parental anti-CD40 Ab. To broaden the concept of fusing agonistic Ab to natural ligand, we fused OX40L to an agonistic OX40 Ab, and this resulted in dramatically increased efficacy for proliferation and cytokine production of activated human CD4+ T cells as well as releasing the Ab from dependency on cross-linking. This work shows that directly fusing antireceptor Abs to ligand is a useful strategy to dramatically increase agonist potency.

Identification and characterization of a heme exporter from the MRP family in Drosophila melanogaster.

BACKGROUND: The heme group constitutes a major functional form of iron, which plays vital roles in various biological processes including oxygen transport and mitochondrial respiration. Heme is an essential nutrient, but its pro-oxidant nature may have toxic cellular effects if present at high levels, and its synthesis is therefore tightly regulated. Deficiency and excess of heme both lead to pathological processes; however, our current understanding of metazoan heme transport is largely limited to work in mammals and the worm Caenorhabditis elegans, while functional analyses of heme transport in the genetically amenable Drosophila melanogaster and other arthropods have not been explored. RESULTS: We implemented a functional screening in Schneider 2 (S2) cells to identify putative heme transporters of D. melanogaster. A few multidrug resistance-associated protein (MRP) members were found to be induced by hemin and/or involved in heme export. Between the two plasma membrane-resident heme exporters CG4562 and CG7627, the former is responsible for heme transit across the intestinal epithelium. CG4562 knockdown resulted in heme accumulation in the intestine and lethality that could be alleviated by heme synthesis inhibition, human MRP5 (hMRP5) expression, heme oxygenase (HO) expression, or zinc supplement. CG4562 is mainly expressed in the gastric caeca and the anterior part of the midgut, suggesting this is the major site of heme absorption. It thus appears that CG4562 is the functional counterpart of mammalian MRP5. Mutation analyses in the transmembrane and nucleotide binding domains of CG4562 characterized some potential binding sites and conservative ATP binding pockets for the heme transport process. Furthermore, some homologs in Aedes aegypti, including that of CG4562, have also been characterized as heme exporters. CONCLUSIONS: Together, our findings suggest a conserved heme homeostasis mechanism within insects, and between insects and mammals. We propose the fly model may be a good complement to the existing platforms of heme studies.

Clinicopathological significance of Obg-like ATPase 1 and its association with Snail in gastric cancer.

Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear. In the present study, mRNA level of OLA1 in gastric cancer (GC) was detected in 2 datasets downloaded from the open Gene Expression Omnibus database and 30 cancer tissues. Immunohistochemistry was performed on GC and its association with Snail in 334 GC patients. The results showed that OLA1 mRNA and protein were elevated in GC tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumour size, lymph-node-metastasis and tumour-nodus-metastases stage ( p = 0.0146, p = 0.0037, p < 0.001, respectively). Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival ( p = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and a combination of them revealed improved prognostic accuracy for GC patients. High expression of OLA1 predicts poor prognosis in GC patients and may be serviced as a novel target for GC.

Catalytic Gasification of Petroleum Coke with Different Ratios of K2CO3 and Evolution of the Residual Coke Structure.

The catalytic gasification of petroleum coke with different ratios of K2CO3 was investigated by a thermogravimetric analyzer (TGA) using the non-isothermal method. The initial, peak, and final gasification temperatures of the petroleum coke decreased greatly as the amount of K2CO3 increased, and the catalytic reaction became saturated at a concentration of K+ higher than 5 mmol/g; with the further increase in catalyst; the gasification rate varied slightly, but no inhibition effect was observed. The vaporization of the catalyst was confirmed during the gasification at high temperatures. The structural evolution of the residual coke with different carbon conversions was examined by X-ray diffraction (XRD), Raman spectroscopy, and N2 adsorption analyses during gasification with and without the catalyst. The results showed that the carbon crystallite structure of the residual coke varied in the presence of the catalyst. As the carbon conversion increased, the structure of the residual coke without the catalyst became more ordered, and the number of aromatic rings decreased, while the graphitization degree of the residual coke in the presence of the catalyst decreased. Meanwhile, the surface area and pore volume of petroleum coke increased in the gasification process of the residual coke, irrespective of the presence of the catalyst. However, the reactivity of the residual coke did not change much with the variation in the carbon and pore structure during the reaction.

Profiling Cystathionine ß/γ-Lyase in Complex Biosamples Using Novel Activatable Fluorogens.

Cystathionine lyase, the key enzyme in transsulfuration and reverse transsulfuration pathways, is involved in a wide array of physiological and pathophysiological processes in both mammals and nonmammals. Though the biological significance of the hydrogen sulfide/cystathionine lyase system in disease states is extensively discussed, the absence of molecular methods for direct monitoring of cystathionine lyase in complex biosamples renders the result unreliable and perplexing. Here, we present the first attempt at designing and developing effective activatable fluorescent probes for cystathionine lyase based on the naphthylamide scaffold. CBLP and CSEP were designed based on the catalytic preference of cystathionine ß-lyase (CBL) and cystathionine γ-lyase (CSE). Briefly, incorporation of cysteine/homocysteine as the recognition moiety and a carbamate ethyl sulfide group as a self-immolated linker proved to be an effective strategy for cystathionine lyase fluorescence reporting. CBLP exhibits high selectivity and sensitivity in vitro in semiquantifying CBL levels in roots of wild-type Arabidopsis thaliana and cbl mutants (cbl knockout: SALK_014740C, overexpressed: OE-CBL). Meanwhile, CSEP successfully detected CSE levels in HCC-LM3 cells, zebrafish models, and upregulated CSE in frozen section slides from the liver tissue of cecal ligation and puncture (CLP)-induced septic rats, which was also validated by Western blotting and immunohistochemical analysis. In summary, the practical design strategy facilitates profiling of cystathionine lyase activity in biological processes. It may pave the way for the development of accurate and efficient methods for the direct estimation of cystathionine lyase.

A Dual-Channel Fluorescent Nanoprobe for Sequential Detection of ATP and Peroxynitrite to Accurately Distinguish between Normal Cells and Cancer Cells.

Cancer is one of the biggest public enemies of global health with its high morbidity and mortality. Achieving early diagnosis is the most effective means of reducing cancer harm, which requires the use of powerful tools to accurately identify biomarkers. However, most of the reported fluorescent probes for cancer diagnosis can only detect one substance, which makes it difficult to meet the requirements of high accuracy. Here, a fluorescent nanoprobe (CPQ@ZIF-90) for sequential detection of ATP and ONOO- is constructed by encapsulating the ONOO- sensitive unit CPQ within ZIF-90. CPQ@ZIF-90 first reacts with ATP to release CPQ, which greatly enhances the fluorescence at 740 nm. Then, the released CPQ continues to react with ONOO- and is oxidatively cleaved by ONOO- to form a coumarin product with a small π-conjugated structure, which significantly enhances the fluorescence at 510 nm. CPQ@ZIF-90 shows high sensitivity and selectivity for the detection of ATP and then ONOO-. Moreover, CPQ@ZIF-90 has good biocompatibility and successfully realizes the sequential detection of a dual-channel fluorescence change of ATP and ONOO- in living cells and zebrafish and accurately distinguishes normal cells from cancer cells. CPQ@ZIF-90 is expected to be a potential tool for accurate cancer diagnosis through sequential detection of two cancer markers.

Cu(I)-Catalyzed C-H Alkenylation of Tertiary C(sp3)-H Bonds of 3-Aryl Benzofuran-2(3H)-ones to Give Z- and E-Styrene Containing Quaternary Carbon Centers with 99/1 Regioselectivity.

The synthesis of isomerically pure olefins containing all-carbon quaternary centers is a challenging issue. Herein, we developed an efficient protocol for the synthesis of (Z)-olefins (27 examples, yield up to 97%, Z/E up to 99/1) and (E)-olefins (16 examples, yield up to 94%, E/Z up to 99/1) containing all-carbon quaternary centers. This protocol is adopted for the copper-catalyzed regioselective C-H alkenylation of the tertiary C(sp3)-H bond of 3-aryl benzofuran-2(3H)-ones with alkyne and alkenes. A diverse range of functional groups in the substrates is well-tolerated, such as F, Cl, Br, Me, OMe, ester, CF3, etc. A gram scale experiment was performed in good yield, and the radical mechanisms are also proposed based on the control experiments.

A nitrobenzoxadiazole-based near-infrared fluorescent probe for the specific imaging of H2S in inflammatory and tumor mice.

As a common gaseous signaling molecule, hydrogen sulfide (H2S) plays a vital role in physiology and pathology. The development of fluorescent probes for detecting H2S has attracted widespread attention. However, most of the reported fluorescent probes with nitrobenzoxadiazole (NBD) as the recognition group have been widely used to simultaneously detect biothiols and H2S, instead of specifically detecting H2S. Herein, a novel NBD-based near-infrared (NIR) fluorescent probe named CX-N for the detection of H2S is synthesized. The selectivity of CX-N for H2S is significantly higher than that for biothiols and other potential interferences. After reacting with H2S, CX-N shows a significant increase in NIR fluorescence (75-fold), large Stokes shift (155 nm) and fast response (4 min). And the possible response mechanism of CX-N to H2S is given and confirmed by HPLC and HRMS. Based on the low cytotoxicity of CX-N, it has been used for H2S imaging in live cells and zebrafish. More importantly, CX-N has also been successfully applied for the real-time imaging of H2S in inflammatory and tumor mice based on its NIR emission, which provides a reliable platform for the specific recognition of H2S in complex biological systems.

H2S aids osmotic stress resistance by S-sulfhydration of melatonin production-related enzymes in Arabidopsis thaliana.

KEY MESSAGE: Hydrogen sulfide closed Arabidopsis thaliana stomata by increasing the transcription of melatonin-producing enzymes and the post-translational modification levels to combat osmotic stress. Hydrogen sulfide (H2S) and melatonin (MEL) reportedly have similar functions in many aspects of plant growth, development and stress response. They regulate stomatal movement and enhance drought resistance. However, their physiological relationship is not well understood. Here, their crosstalk involved in osmotic stress resistance in Arabidopsis thaliana was studied. Exogenous H2S and MEL closed stomata under normal or osmotic stress conditions and increased the relative water contents of plants under osmotic stress conditions. At the same time, exogenous H2S and MEL responded to osmotic stress by increasing the content of proline and soluble sugar, and reducing malondialdehyde (MDA) content and relative conductivity. Using mutants in the MEL-associated production of serotonin N-acetyltransferase (snat), caffeic acid O-methyltransferase (comt1) and N-acetylserotonin methyltransferase (asmt), we determined that H2S was partially dependent on MEL to close stomata. Additionally, the overexpression of ASMT promoted stomatal closure. Exogenous H2S increased the transcription levels of SNAT, ASMT and COMT1. Furthermore, exogenous H2S treatments increased the endogenous MEL content significantly. At the post-translational level, H2S sulfhydrated the SNAT and ASMT, but not COMT1, enzymes associated with MEL production. Thus, H2S appeared to promote stomatal closure in response to osmotic stress by increasing the transcription levels of MEL synthesis-related genes and the sulfhydryl modification of the encoded enzymes. These results increased our understanding of H2S and MEL functions and interactions under osmotic stress conditions.

Transcriptional response of Asarum heterotropoides Fr. Schmidt var. mandshuricum (Maxim.) Kitag. leaves grown under full and partial daylight conditions.

BACKGROUND: Asarum heterotropides Fr. Schmidt var. mandshuricum (Maxim.) Kitag. is an important medicinal and industrial plant, which is used in the treatment of various diseases. The main bioactive ingredient is the volatile oil having more than 82 identified components of which methyleugenol, safrole, myristicin, and toluene account for about 70% of the total volume. As a sciophyte plant, the amount of light it absorbs through leaves is an important factor for growth and metabolism. RESULTS: We grew Asarum plants under full, 50, 28, and 12% sunlight conditions to investigate the effect of different light irradiances on the four major volatile oil components. We employed de novo transcriptome sequencing to understand the transcriptional behavior of Asarum leaves regarding the biosynthetic pathways of the four volatile oil components, photosynthesis and biomass accumulation, and hormone signaling. Our results demonstrated that the increasing light conditions promoted higher percent of the four components. Under full sunlight conditions, cinnamyl alcohol dehydrogenase and cytochrome p450719As were upregulated and led the increased methyleugenol, safrole, and myristicin. The transcriptomic data also showed that Asarum leaves, under full sunlight conditions, adjust their photosynthesis-antenna proteins as a photoprotective response with the help of carotenoids. Plant hormone-signaling related genes were also differentially expressed between full sunlight and low light conditions. CONCLUSIONS: High light induces accumulation of major bioactive ingredients A. heterotropides volatile oil and this is ascribed to upregulation of key genes such as cinnamyl alcohol dehydrogenase and cytochrome p450719As. The transcriptome data presented here lays the foundation of further understanding of light responses in sciophytes and provides guidance for increasing bioactive molecules in Asarum.

Accurate Fluorescence Diagnosis of Cancer Based on Sequential Detection of Hydrogen Sulfide and pH.

Cancer ranks as a leading cause of death in every country of the world. However, if they are discovered early, a lot of cancers can be prevented or cured. Discovering and monitoring cancer markers are the main methods for early diagnosis of cancer. To date, many fluorescent probes designed and used for early cancer diagnosis can only react with a single marker, which always causes insufficient accuracy in complex systems. Herein, a novel near-infrared (NIR) fluorescent probe (CyO-DNP) for the sequential detection of H2S and H+ is synthesized. In this probe, a heptamethine dye is selected as the fluorophore and a 2,4-dinitrophenyl (DNP) ether is chosen as recognition group. In the presence of H2S, CyO-DNP is transformed into CyO, which exhibits an intense fluorescence at 663 nm. Then, H+ induces the protonation of CyO to obtain CyOH, and the final fluorescence emission at 793 nm significantly enhances. Owing to the low cytotoxicity and the NIR fluorescence emission, CyO-DNP can sequentially monitor endogenous H2S and H+ in cancer cells and image exogenous and endogenous H2S and H+ in mice. It is worth mentioning that CyO-DNP can effectively avoid the false positive signal caused by the liver and kidney and discriminate normal mice and tumor mice accurately. For all we know, CyO-DNP is the first fluorescent probe for early accurate diagnosis of cancer by sequentially detecting H2S and H+.

I2-Mediated Cross-Dehydrogenative Coupling and Amidation of 3-Aryl Benzofuranones with Aryl Amines for the Synthesis of 3,3-Diaryl Indolin-2-ones.

We have developed a protocol for efficient synthesis of indolin-2-ones from benzofuranones and aryl amines using iodine as a mediator. A diverse range of benzofuranones and aryl amines undergo cross-dehydrogenative coupling and amidation of 3-aryl benzofuranones for the cascade reaction to generate products in 24-93% yields. This reaction can be easily scaled-up to give an indolin-2-one in a gram scale. Further chemical manipulation of the products enabled useful transformations of the phenol ring including alkylation, arylation, etc.

Effects of non-viable Lactobacillus reuteri combining with 14-day standard triple therapy on Helicobacter pylori eradication: A randomized double-blind placebo-controlled trial.

BACKGROUND: Viable probiotics have shown effects on the eradication of Helicobacter pylori, but the role of non-viable probiotics in H. pylori eradication is unclear. This study aimed to evaluate the effects of non-viable Lactobacillus reuteri DSM17648 combining with 14-day standard triple therapy on H. pylori eradication. MATERIALS AND METHODS: Two hundred treatment-naive H. pylori-positive adult patients were randomized equally to receive non-viable L. reuteri DSM17648 (LR group) or placebo for 4 weeks, with the latter 2 weeks treated together with triple therapy. The Gastrointestinal Symptom Rating Scale (GSRS) was completed before and after treatment. Stool samples were collected for 16S rRNA gene sequencing at week0, week2, and week8. RESULTS: Eradication rates in the LR group and the placebo group were 81.8% and 83.7% in ITT analysis (p = 0.730), 86.2% and 87.2% in PP analysis (p = 0.830), respectively. After treatment, the mean GSRS score decreased significantly in the LR group as compared with the placebo group (1.9 ± 0.2 vs. 2.7 ± 0.3; p = 0.030). Significantly less patients in the LR group as compared with the placebo group reported abdominal distention (5.1% vs. 16.3%; p = 0.010) and diarrhea (11.1% vs. 23.5%; p = 0.022). The relative abundance of Proteobacteria phylum and Escherichia-Shigella genus in the placebo group was about 4.0-fold and 8.1-fold of that in the LR group at wk2, respectively. Significant changes of diversity and enhancements of Fusicatenibacter, Subdoligranulum, and Faecalibacterium were observed in the LR group compared with the placebo group. CONCLUSIONS: Supplementation of non-viable L. reuteri DSM17648 with triple therapy did not improve the eradication rate of H. pylori, but it helped to build up a beneficial microbial profile and reduced the frequencies of abdominal distention, diarrhea, and the GSRS score.