Catalytic Asymmetric Reduction of α-Trifluoromethylated Imines with Catecholborane by BINOL-Derived Boro-phosphates.

A catalytic enantioselective reduction of α-trifluoromethylated imines by a BINOL-derived boro-phosphate employing catecholborane as hydride source has been developed. This method provides an efficient route to prepare synthetically useful chiral α-trifluoromethylated amines in high yields and with excellent enantioselectivities (up to 98% yield and 96% ee) under mild conditions.

Cascaded Multiresponsive Self-Assembled 19F MRI Nanoprobes with Redox-Triggered Activation and NIR-Induced Amplification.

Molecular probes featuring promising capabilities including specific targeting, high signal-to-noise ratio, and in situ visualization of deep tissues are in great demand for tumor diagnosis and therapy. 19F magnetic resonance imaging (MRI) techniques incorporating stimuli-responsive probes are anticipated to be highly beneficial for specific detection and imaging of tumors because of negligible background and deep tissue penetration. Herein, we report a cascaded multiresponsive self-assembled nanoprobe, which enables sequential redox-triggered and near-infrared (NIR) irradiation-induced 19F MR signal activation/amplification for sensing and imaging. Specifically, we designed and synthesized a cascaded multiresponsive 19F-bearing nanoprobe based on the self-assembly of amphiphilic redox-responsive 19F-containing polymers and NIR-absorbing indocyanine green (ICG) molecules. It could realize the activation of 19F signals in the reducing tumor microenvironment and subsequent signal amplification via the photothermal process. This stepwise two-stage activation/amplification of 19F signals was validated by 19F NMR and MRI both in vitro and in vivo. The multiresponsive 19F nanoprobes capable of cascaded 19F signal activation/amplification and photothermal effect exertion can provide accurate sensing and imaging of tumors.

Fluorinated Gadolinium Chelate-Grafted Nanoconjugates for Contrast-Enhanced T1-Weighted 1H and pH-Activatable 19F Dual-Modal MRI.

Magnetic resonance imaging (MRI) is one of the most popular imaging techniques, which offers an ionization-free noninvasive means for imaging deep tissues with high resolution. Conventional 1H MRI is well versed in providing detailed anatomical information but suffers from low contrast for tracking biomarkers because of the abundance of water in living bodies. 19F MRI with negligible endogenous background interference enables highly sensitive detection of biomolecular targets and has drawn extensive attention from the biomedical research community recently. However, this imaging technique only acquires the "hot spot" signals of exogenous 19F nucleus-containing imaging probes. 1H/19F MRI dual-modal imaging is expected to compensate for the limitations of either single-modal imaging and accomplish synergistic morphological and physiological imaging. Herein, we report a highly biocompatible nanoconjugate composed of pH-responsive 19F nucleus-bearing Gd3+ chelates, which enables significant contrast enhancement for T1-weighted 1H MRI and permits pH-responsive activation of 19F signals for 19F MRI, providing both clear anatomical details of living bodies and the biorelevant molecular information with low background interference. This nanoconjugate facilitates sensitive and accurate detection of tumors with contrast-enhanced T1-weighted 1H and pH-activatable 19F dual-modal imaging on a single MRI scanner.

Design and synthesis of new alkyl-based chiral phosphoric acid catalysts.

Using chiral BINOL-derived phosphoric acids (PA's) to activate substrates for enhanced reactivity is now regarded as a powerful strategy to control enantioselectivity in asymmetric synthesis. Generally, most substituents at the 3,3'-positions of BINOL PA's are aryl derivatives. These derivatives are pivotal in attaining high selectivity. PA's with alkyl substituents in these positions have rarely been reported. Herein, we introduced alkyl-based substituents at the 3,3'-position of PA's. These new potential catalysts, if applied in reactions, may allow altered noncovalent interactions (as opposed to the typical aryl substituents in these positions) with substrates used in chiral PA-catalyzed chemistry in the future.

A Self-Assembled Biocompatible Nanoplatform for Multimodal MR/Fluorescence Imaging Assisted Photothermal Therapy and Prognosis Analysis.

The need for better imaging assisted cancer therapy calls for new biocompatible agents with excellent imaging and therapeutic capabilities. This study successfully fabricates albumin-cooperated human serum albumin (HSA)-GGD-ICG nanoparticles (NPs), which are comprised of a magnetic resonance (MR) contrast agent, glycyrrhetinic-acid-modified gadolinium (III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (GGD), and a fluorescence (FL) dye, indocyanine green (ICG), for multimodal MR/FL imaging assisted cancer therapy. These HSA-GGD-ICG NPs with excellent biocompatibility are stable under physiological conditions, and exhibit enhanced T1 contrast capability and improved fluorescence imaging capacity. In vitro experiments reveal an apparent effect of the NPs in killing tumor cells under low laser irradiation, due to the enhanced photothermal conversion efficiency (≈85.1%). Importantly, multimodal MR/FL imaging clearly shows the in vivo behaviors and the efficiency of tumor accumulation of HSA-GGD-ICG NPs, as confirmed by a pharmacokinetic study. With the guidance of multimodal imaging, photothermal therapy is subsequently conducted, which demonstrates again high photothermal conversion capability for eliminating tumors without relapse. Notably, real-time monitoring of tumor ablation for prognosis and therapy evaluation is also achieved by MR imaging. This strategy of constructing nanoplatforms through albumin-mediated methods is both convenient and efficient, which would enlighten the design of multimodal imaging assisted cancer therapy for potential clinical translation.

Effects of duckweed (Spriodela polyrrhiza) remediation on the composition of dissolved organic matter in effluent of scale pig farms.

The swine effluent studied was collected from scale pig farms, located in Yujiang County of Jiangxi Province, China, and duckweed (Spriodela polyrrhiza) was selected to dispose the effluent. The purpose of this study was to elucidate the effects of duckweed growth on the dissolved organic matter composition in swine effluent. Throughout the experiment period, the concentrations of organic matter were determined regularly, and the excitation-emission matrix (3DEEM) spectroscopy was used to characterize the fluorescence component. Compared with no-duckweed treatments (controls), the specific ultra-violet absorbance at 254nm (SUVA254) was increased by a final average of 34.4% as the phytoremediation using duckweed, and the removal rate of DOC was increased by a final average of 28.0%. In swine effluent, four fluorescence components were identified, including two protein-like (tryptophan, tyrosine) and two humic-like (fulvic acids, humic acids) components. For all treatments, the concentrations of protein-like components decreased by a final average of 69.0%. As the growth of duckweed, the concentrations of humic-like components were increased by a final average of 123.5% than controls. Significant and positive correlations were observed between SUVA254 and humic-like components. Compared with the controls, the humification index (HIX) increased by a final average of 9.0% for duckweed treatments. Meanwhile, the duckweed growth leaded to a lower biological index (BIX) and a higher proportion of microbial-derived fulvic acids than controls. In conclusion, the duckweed remediation not only enhanced the removal rate of organic matter in swine effluent, but also increased the percent of humic substances.

[Characterizing Dissolved Organic Matter (DOM) in Wastewater from Scale Pig Farms Using Three-Dimensional Excitation-Emission Matrices (3DEEM].

The properties of material composition in swine wastewater are closely related to its potential environmental effects, and it could provide theoretical bases for formulating scientific resource management measures to study the composition of organic matter in wastewater. In the present study, swine wastewater was directly collected from waste-retention basins in various scale pig farms with a different farming scale (based on the annual pig slaughter), namely Cheng Lin (CL, 5 000), Wu Yang-gao (WYG, 2 000), Wan Gu (WG, 20 000), and Zhang Bang (ZB, 24 000), located in Yujiang County of Jiangxi Province. The main purpose of this study was to characterize dissolved organic matter (DOM) in swine wastewater using three-dimensional excitation-emission matrices (3DEEM) and parallel factor analysis (PARAFAC). Results of all samples examined showed, with respect to CL and WYG farm, chemical oxygen demand (COD), total nitrogen (TN), ammonium nitrogen (NH+4), and dissolved organic carbon (DOC) concentration in swine wastewater was significantly higher than WG and ZB farm. Three DOM components, including two protein-like components (C1, C2) and one humic-like component (C3), were identified in wastewater using 3DEEM and PARAFAC. Results of linear regression showed, the fluorescence intensity of C1 linked significantly with C2 (p<0.001) and C3 (p<0.001), respectively, suggesting a same source or similar variation trend existed possibly between different DOM components. Furthermore, consistent with the variation trend of nutrient concentration in wastewater, fluorescence intensity of each DOM component in CL and WYG farm was significantly higher than WG and ZB farm. The total contribution of C1 and C2 to DOM in swine wastewater was CL (89.7%), WG (77.5%), WYG (87.9%), and ZB (72.9%), respectively, and the percentage of C3 was CL (10.3%), WG (22.5%), WYG (12.1%), and ZB (27.1%), respectively. Thus, the percentage of two protein-like components was significantly higher than humic-like in swine wastewater. Meanwhile, the fluorescence indices FI370 and humification index (HIX) of WG and ZB farm were higher than CL and WYG. In addition, Pearson correlation analysis showed that the effects of environmental parameters on fluorescence indices were different, and COD and DOC concentrations were significantly correlated with the fluorescence intensities of DOM components in swine wastewater. In summary, to a certain degree, the nutrient levels affected formation of fluorescence characteristics and DOM compositions in swine wastewater between different scale pig farms.

[Structural Analysis of Organic Matter Composition in Piggery Wastewater during the Process of Organic Degradation Based on FTIR Spectroscopy].

More and more attentions were paid on the environmental pollutions of wastewater discharged from scale pig farms, and it could provide scientific bases for formulating reasonable pollution control measures to study the structural changes of organic matter composition in piggery wastewater. In the present study, a laboratory-scale incubation experiment was carried out with piggery wastewater collected from different scale pig farms, and a continuous sampling was conducted at a certain interval during the process of incubation experiment. The main purpose of this study was to elucidate the change of structural composition of dissolved organic matter (DOM) in piggery wastewater during the process of organic degradation. All dried and solid DOM samples were achieved using filtration and freeze-drying methods. Spectral analysis of all DOM samples was completed with the application of Fourier transform infrared (FTIR) spectrometer. Results of spectral analysis showed a similar DOM structural composition was observed in the wastewater derived from different scale pig farms, and was mainly comprised of lipids, proteins, fulvic acids, polysaccharides, and phenolic compounds. With the increase in the incubation days, the percent of functional groups, related to proteins, phenolic acids, and lipids, decreased gradually and kept stable eventually, while these functional groups, linked with fulvic acids and polysaccharides, showed a significant increase and leveled off at the end. Compared with primary samples, fulvic acids and polysaccharides were the predominant fractions of DOM at 20 days after organic degradation, indicating a higher aromatic degree of DOM. Meanwhile, the degradation rate of OH bonded by intermolecular H-bond of cellulose was faster than OH bonded by intra-molecular H-bond of cellulose, whereas the latter was more sensitive to microbial degradation. The degradation rate of phenolic hydroxyl C­O was the fastest, followed by aromatic COOH, carbohydrate C­O, and amide CO. Furthermore, the carbohydrate C­O was apt to be utilized preferentially by microorganisms. In sum, the structural change of various DOM in piggery wastewater was different during the process of organic degradation.

Effects of sitagliptin activation of the stromal cell-derived factor-1/CXC chemokine receptor 4 signaling pathway on the proliferation, apoptosis, inflammation, and osteogenic differentiation of human periodontal ligament stem cells induced by lipopolysaccharide.

OBJECTIVES: This study aimed to investigate the effects of sitagliptin on the proliferation, apoptosis, inflammation, and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in lipopolysaccharide (LPS)-induced inflammatory microenvironment and its molecular mechanism. METHODS: hPDLSCs were cultured in vitro and treated with different concentrations of sitagliptin to detect cell viability and subsequently determine the experimental concentration of sitagliptin. An hPDLSCs inflammation model was established after 24 h of stimulation with 1 µg/mL LPS and divided into blank, control, low-concentration sitagliptin (0.5 µmol/L), medium-concentration sitagliptin (1 µmol/L), and high-concentration sitagliptin (2 µmol/L), high-concentrationsitagliptin+stromal cell derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) pathway inhibitor (AMD3100) (2 µmol/L+10 µg/mL) groups. A cell-counting kit-8 was used to detect the proliferation activity of hPDLSCs after 24, 48, and 72 h culture. The apoptosis of hPDLSCs cultured for 72 h was detected by flow cytometry. After inducing osteogenic differentiation for 21 days, alizarin red staining was used to detect the osteogenic differentiation ability of hPDLSCs. The alkaline phosphatase (ALP) activity in hPDLSCs was determined using a kit. The levels of inflammatory factors [tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6] in the supernatant of hPDLSCs culture were detected by enzyme-linked immunosorbent assay. The mRNA expressions of osteogenic differentiation genes [Runt-associated transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN)], SDF-1 and CXCR4 in hPDLSCs were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Western blot analysis was used to determine SDF-1 and CXCR4 protein expression in hPDLSCs. RESULTS: Compared with the blank group, the proliferative activity, number of mineralized nodules, staining intensity, ALP activity, and RUNX2, OCN, OPN mRNA, SDF-1, and CXCR4 mRNA and protein expression levels of hPDLSCs in the control group significantly decreased. The apoptosis rate and levels of TNF-α, IL-1ß, and IL-6 significantly increased (P<0.05). Compared with the control group, the proliferative activity, number of mineralized nodule, staining intensity, ALP activity, and RUNX2, OCN, OPN mRNA, SDF-1, and CXCR4 mRNA and protein expression levels of hPDLSCs in low-, medium-, and high-concentration sitagliptin groups increased. The apoptosis rate and levels of TNF-α, IL-1ß, and IL-6 decreased (P<0.05). AMD3100 partially reversed the effect of high-concentration sitagliptin on LPS-induced hPDLSCs (P<0.05). CONCLUSIONS: Sitagliptin may promote the proliferation and osteogenic differentiation of hPDLSCs in LPS-induced inflammatory microenvironment by activating the SDF-1/CXCR4 signaling pathway. Furthermore, it inhibited the apoptosis and inflammatory response of hPDLSCs.

Whole-tumor histogram models based on quantitative maps from synthetic MRI for predicting axillary lymph node status in invasive ductal breast cancer.

PURPOSE: To investigate the potential of using histogram analysis of synthetic MRI (SyMRI) images before and after contrast enhancement to predict axillary lymph node (ALN) status in patients with invasive ductal carcinoma (IDC). METHODS: From January 2022 to October 2022, a total of 212 patients with IDC underwent breast MRI examination including SyMRI. Standard T2 weight images, DCE-MRI and quantitative maps of SyMRI were obtained. 13 features of the entire tumor were extracted from these quantitative maps, standard T2 weight images and DCE-MRI. Statistical analyses, including Student's t-test, Mann-Whiney U test, logistic regression, and receiver operating characteristic (ROC) curves, were used to evaluate the data. The mean values of SyMRI quantitative parameters derived from the conventional 2D region of interest (ROI) were also evaluated. RESULTS: The combined model based on T1-Gd quantitative map (energy, minimum, and variance) and clinical features (age and multifocality) achieved the best diagnostic performance in the prediction of ALN between N0 (with non-metastatic ALN) and N+ group (metastatic ALN ≥ 1) with the AUC of 0.879. Among individual quantitative maps and standard sequence-derived models, the synthetic T1-Gd model showed the best performance for the prediction of ALN between N0 and N+ groups (AUC = 0.823). Synthetic T2_entropy and PD-Gd_energy were useful for distinguishing N1 group (metastatic ALN ≥ 1 and ≤ 3) from the N2-3 group (metastatic ALN > 3) with an AUC of 0.722. CONCLUSIONS: Whole-tumor histogram features derived from quantitative parameters of SyMRI can serve as a complementary noninvasive method for preoperatively predicting ALN metastases.

Water-Soluble Chemically Precise Fluorinated Molecular Clusters for Interference-Free Multiplex 19F MRI in Living Mice.

Fluorine-19 magnetic resonance imaging (19F MRI) is gaining widespread interest from the fields of biomolecule detection, cell tracking, and diagnosis, benefiting from its negligible background, deep tissue penetration, and multispectral capacity. However, a wide range of 19F MRI probes are in great demand for the development of multispectral 19F MRI due to the limited number of high-performance 19F MRI probes. Herein, we report a type of water-soluble molecular 19F MRI nanoprobe by conjugating fluorine-containing moieties with a polyhedral oligomeric silsesquioxane (POSS) cluster for multispectral color-coded 19F MRI. These chemically precise fluorinated molecular clusters are of excellent aqueous solubility with relatively high 19F contents and of single 19F resonance frequency with suitable longitudinal and transverse relaxation times for high-performance 19F MRI. We construct three POSS-based molecular nanoprobes with distinct 19F chemical shifts at -71.91, -123.23, and -60.18 ppm and achieve interference-free multispectral color-coded 19F MRI of labeled cells in vitro and in vivo. Moreover, in vivo 19F MRI reveals that these molecular nanoprobes could selectively accumulate in tumors and undergo rapid renal clearance afterward, illustrating their favorable in vivo behavior for biomedical applications. This study provides an efficient strategy to expand the 19F probe libraries for multispectral 19F MRI in biomedical research.

Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica.

Long noncoding RNAs (lncRNAs) can regulate key genes and pathways in liver disease development. Moreover, macrophages are speculated to play an important role in regulating granulomatous inflammation during schistosomiasis. However, the role of lncRNAs in the formation of liver granulomas by influencing the polarization of macrophages in Schistosoma japonicum infection is unclear. Our study aimed to determine whether lncRNAs can play a role in S. japonicum-induced hepatic egg granulomas and elucidate their effect on macrophages. We established S. japonicum infection models and screened the target lncRNA Gm16685 highly expressed in schistosomiasis mice using high-throughput sequencing. Hematoxylin and eosin staining revealed that the knockdown of Gm16685 reduced the area of egg granulomas. Moreover, M1 macrophage factor genes were significantly downregulated in Gm16685 knockdown livers. Meanwhile, M2 macrophage factor genes were significantly upregulated, which was consistent with the protein detection results. Hepatocytes, hepatic stellate cells, and macrophages were isolated from mouse models infected with S. japonicum, with Gm16685 being significantly upregulated in macrophages. Moreover, the knockdown of Gm16685 in RAW264.7 cells revealed similar results to in liver tissue. RNA fluorescence in situ hybridization (FISH) and nucleocytoplasmic separation experiments revealed that Gm16685 was predominantly localized in the cytoplasm of cells. We found that miR-205-5p was upregulated after Gm16685 was knocked down. After overexpression of miR-205-5p, the expression of Gm16685 and inflammatory factors was significantly downregulated. These results indicate that Gm16685 can participate in the pathogenesis of hepatic disease in schistosomiasis and promote M1 macrophage polarization by regulating miR-205-5p. Thus, our study may provide a new target for schistosomiasis japonica treatment.

IL-37 alleviates liver granuloma caused by Schistosoma japonicum infection by inducing alternative macrophage activation.

BACKGROUND: Hepatic macrophages regulate liver granuloma formation and fibrosis caused by infection with Schistosoma japonicum, with the manner of regulation dependent on macrophage activation state. Interleukin (IL)-37 may have immunomodulatory effects on macrophages. However, whether IL-37 can affect liver granuloma formation and fibrosis by affecting the polarization of macrophages in S. japonicum infection remains unclear. The aim of this study was to investigate IL-37-affected macrophage polarization in liver granuloma formation and fibrosis in S. japonicum infection. METHODS: An enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of IL-37 in the serum of patients with acute S. japonicum infection and in the serum of healthy people. Recombinant IL-37 (rIL-37), CPP-IgG2Fc-IL-37 and no CPP-IgG2Fc-IL-37 proteins were injected into S. japonicum-infected mice every 3 days for a total of 6 times from day 24 post infection onwards. Subsequently, ELISA, quantitative reverse transcription-PCR, fluorescence-activated cell sorting and western blot were used to analyze whether IL-37 inhibits the formation of liver granulomas and the development of liver fibrosis by regulating the phenotypic transition of macrophages. Finally, the three IL-37 proteins and SIS3, a Smad3 inhibitor, were co-cultured in mouse peritoneal macrophages to explore the mechanism underlying the promotion of the polarization of M0 macrophages to the M2 phenotype by IL-37. RESULTS: Serum IL-37 levels were upregulated in schistosomiasis patients, and this increased level of IL-37 protein apparently alleviated the liver granuloma of mice in infection models. It also could induce liver and peritoneal macrophages to polarize to the M2 phenotype in S. japonicum-infected mice. The S. japonicum-infected mice injected with CPP-IgG2Fc-IL-37 group exhibited the most obvious improvement in inflammatory reaction against the liver granuloma. The number and ratio of M2 macrophages in the liver and peritoneal cavity were significantly higher in the three IL-37 protein groups, especially in the CPP-IgG2Fc-IL-37 group, compared to the controls. Similar results were also found regarding liver function damage. IL-37 induced macrophage M2 polarization by promoting AMP-activated protein kinase (AMPK) phosphorylation in vitro. Among all groups, the activation of AMPK was most significant in the CPP-IgG2Fc-IL-37 group, and it was found that SMAD3 could enhance the anti-inflammatory function of IL-37. CONCLUSIONS: The results show that IL-37 was able to promote the polarization of macrophages to the M2 phenotype, thereby inhibiting the development of schistosomiasis. In comparison to the rIL-37 protein, the CPP-IgG2Fc-IL-37 protein has the advantages of being effective in small doses and having fewer side effects and a better efficacy.

Expression and significance of mucin-4 and matrix metalloproteinase-7 in peri-implant disease.

OBJECTIVES: This study aims to detect the levels of mucin (MUC)-4, metalloproteinase (MMP)-7, and MMP-8 in peri-implant crevicular fluid (PICF) and investigate whether the novel combinations of MMP-7 and MUC-4 are effective markers of peri-implant diseases, particularly when used in the PICF of healthy individuals, to provide a theoretical basis for finding a novel reference index that can aid the diagnosis, evaluation, and treatment of peri-implant diseases. METHODS: A total of 63 subjects with 2-5 years of upper prosthesis loading were selected according to inclusion and exclusion criteria, composed of 24 controls and 39 patients with peri-implantitis (PI) group. MUC-4, MMP-7, and MMP-8 levels were detected through enzyme linked immunosorbent assay (ELISA). RESULTS: No significant differences in age, sex, and other parameters were found between the PI and control groups. The PI group had higher MMP-7 and MMP-8 expression levels (P<0.05) but lower MUC-4 level (P<0.001). Correlation analysis showed that MMP-7 was positively correlated with pocket probing depth (PPD) (r=0.451, P<0.001); MMP-8 was positively correlated with PPD, bleeding on probing (BOP), and gingival index (GI) (r=0.619, P<0.001; r=0.478, P<0.001; r=0.332, P=0.009). MUC-4 was negatively correlated with PPD, BOP, and GI (r=-0.492, P<0.001; r=-0.321, P=0.010; r=-0.396, P=0.001). MMP-7, MMP-8, and MUC-4 had certain diagnostic efficacy for PI. MMP-8 exhibited the best diagnostic efficacy for PI. When the cutoff value of MMP-8 was >21.21, the area under the curve (AUC) was 0.868, and the sensitivity and specificity for the diagnosis of PI were 0.96 and 0.68, respectively. The diagnostic efficacy of MMP-7 and MUC-4 parallel diagnostic models was higher than that of each factor, and the diagnostic sensitivity of the model for PI was 0.96, and the specificity was 0.56. CONCLUSIONS: Differences in MMP-7 and MUC-4 levels were found between the inflammation and control groups and may be diagnostic indicators for predicting PI; combinations of MMP-7 and MUC-4 had a good diagnostic value for inflammation.

Activatable 19 F MRI Nanoprobes for Visualization of Biological Targets in Living Subjects.

Visualization of biological targets such as crucial cells and biomolecules in living subjects is critical for the studies of important biological processes. Though 1 H magnetic resonance imaging (MRI) has demonstrated its power in offering detailed anatomical and pathological information, its capacity for in vivo tracking of biological targets is limited by the high biological background of 1 H. 19 F distinguishes itself from its competitors as an exceptional complement to 1 H in MRI through its high sensitivity, low biological background, and broad chemical shift range. The specificity and sensitivity of 19 F MRI can be further boosted with activatable nanoprobes. The advantages of 19 F MRI with activatable nanoprobes enable in vivo detection and imaging at the cellular or even molecular level in deep tissues, rendering this technique appealing as a potential solution for visualization of biological targets in living subjects. Here, recent progress over the past decades on activatable 19 F MRI nanoprobes made from three major 19 F-containing compounds, as well as present challenges and potential opportunities, are summarized to provide a panoramic prospective for the people who are interested in this emerging and exciting field.

Catalytic asymmetric Nakamura reaction by gold(I)/chiral N,N'-dioxide-indium(III) or nickel(II) synergistic catalysis.

Intermolecular addition of enols and enolates to unactivated alkynes was proved to be a simple and powerful method for carbon-carbon bond formation. Up to date, a catalytic asymmetric version of alkyne with 1,3-dicarbonyl compound has not been realized. Herein, we achieve the catalytic asymmetric intermolecular addition of 1,3-dicarbonyl compounds to unactivated 1-alkynes attributing to the synergistic activation of chiral N,N'-dioxide-indium(III) or nickel(II) Lewis acid and achiral gold(I) π-acid. A range of ß-ketoamides, ß-ketoesters and 1,3-diketones transform to the corresponding products with a tetra-substituted chiral center in good yields with good e.r. values. Besides, a possible catalytic cycle and a transition state model are proposed to illustrate the reaction process and the origin of chiral induction based on the experimental investigations.

Diastereo- and Enantioselective Synthesis of 3-Allyl-3-hydroxyoxindoles via Allylation of Isatins.

A highly diastereo- and enantioselective allylation of isatins with 3-substituted allylboronic compounds was achieved by the chiral N,N'-dioxide/Lu(OTf)3 complex. This approach provides an efficient route to useful enantioenriched 3-allyl-3-hydroxyoxindoles with adjacent tetrasubstituted tertiary or tetrasubstituted quaternary stereogenic centers. Density functional theory calculations were performed to understand the different diastereoselection between the background reaction and catalytic process. Moreover, allylation with potassium allyltrifluoroborate was accomplished by the chiral N,N'-dioxide/In(OTf)3 complex. The synthetic utility was demonstrated by further transformation of the product to a tetrahydrofuranyl oxindole derivative.

A Fluorinated Ionic Liquid-Based Activatable 19F MRI Platform Detects Biological Targets.

19F magnetic resonance imaging (19F MRI) is a promising technique for in vivo molecular imaging and clinical diagnosis, benefiting from its negligible background and unlimited tissue penetration depth. However, the development of 19F probes with good water solubility and versatile functions for bioresponsive and practical applications remains a challenge. Here, we report fluorinated ion liquids (ILs) as a new type of fluorine agents and build a fluorinated ionic liquid-based activatable 19F MRI platform (FILAMP), which relies on the phase transition of ILs. Upon exposure to environmental stimulation, coating polymer dissolves or degrades to release the fluorinated ILs payload, which rapidly enhances 19F signal. This "turn-on" response is verified by the successful detection of biological targets (for example, dysregulated pH and MMP overexpression) at the cellular level and in mice, demonstrating the potential of FILAMP as a robust activatable 19F probe for diagnosis and monitoring of biological and pathological processes.

Reversible redox-responsive 1H/19F MRI molecular probes.

Herein we report a pair of redox-responsive manganese complexes Mn(iii)/(ii)-N,N'-bis(2-hydroxy-4-trifluoromethylbenzyl)ethylenediamine-N,N'-diacetate (HTFBED, L1), which are water soluble and biologically interconvertible, as reversible redox-responsive probes in 1H/19F MRI for detecting and imaging biological redox species, offering a means to access valuable redox information associated with various diseases.