E3 ubiquitin ligase UBR5 promotes gemcitabine resistance in pancreatic cancer by inducing O-GlcNAcylation-mediated EMT via destabilization of OGA.

Pancreatic cancer (PC) is among the deadliest malignancies, with an extremely poor diagnosis and prognosis. Gemcitabine (GEM) remains the first-line drug for treating PC; however, only a small percentage of patients benefit from current immunotherapies or targeted therapies. Resistance to GEM is prevalent and affects long-term survival. We found that ubiquitin-protein ligase E3 module N-recognition 5 (UBR5) is a therapeutic target against GEM resistance. UBR5 was markedly upregulated in clinical GEM-resistant PC samples and GEM-resistant PC cells. UBR5 knockdown markedly increased GEM sensitivity in GEM-resistant PC cell lines. UBR5-mediated GEM resistance was accompanied by activation of epithelial-mesenchymal transition (EMT) and could be mitigated by inhibiting EMT. Further analysis revealed that UBR5 promoted GEM resistance in PC cells by enhancing O-GlcNAcylation-mediated EMT. In addition, UBR5 knockdown resulted in increased O-GlcNAase (OGA) levels, an essential negatively regulated enzyme in the O-GlcNAcylation process. We identified a negative association between OGA and UBR5 levels, which further supported the hypothesis that O-GlcNAcylation-mediated GEM resistance induced by UBR5 is OGA-dependent in PC cells. Mechanistic studies revealed that UBR5 acts as an E3 ubiquitin ligase of OGA and regulates O-GlcNAcylation by binding and modulating OGA, facilitating its degradation and ubiquitination. Additionally, high-throughput compound library screening using three-dimensional protein structure analysis and drug screening identified a Food and Drug Administration drug, Y-39983 dihydrochloride, as a potent GEM sensitiser and UBR5 inhibitor. The combination of Y-39983 dihydrochloride and GEM attenuated tumour growth in a mouse xenograft tumour model. Collectively, these data demonstrated that UBR5 plays a pivotal role in the sensitisation of PC to GEM and provides a potential therapeutic strategy to overcome GEM resistance.

Asperustins A-J: Austocystins with Immunosuppressive and Cytotoxic Activities from Aspergillus ustus NRRL 5856.

Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1″-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.

Suppressed Magnitude of Spectral Diffusion in Cube-Shaped CdSe/CdS Core/Shell Nanocrystals with Exceedingly Stable Photoluminescence.

Colloidal semiconductor nanocrystals are promising candidates for quantum light sources, yet their application has been impeded by photoluminescence instability due to blinking and spectral diffusion. This study introduces a new category of cube-shaped CdSe/CdS core/shell nanocrystals with exceptionally stable photoluminescence characteristics. Under continuous excitation, the emissive quantum state remained consistent without alterations of the charge state for 4000 s, and the average photon energy variation stayed within the bounds of spectral resolution throughout this extended duration. Systematic examination of single-nanocrystal photoluminescence, upon variation of the core and shell dimensions, revealed that a thicker CdS shell and increased core edge length significantly curtail spectral diffusion, considering that the nanocrystals possess well-controlled CdSe-CdS and facet-ligand interfaces. This study advances the optimization of colloidal semiconductor nanocrystals as high-performance quantum light sources.

Construction of catalase@hollow silica nanosphere: Catalase with immobilized but not rigid state for improving catalytic performances.

Enzyme immobilization usually make use of nanomaterials to hold up biocatalysis stability in various unamiable reaction conditions, but also lead large discount on enzyme activity. Thus, there are abundant researches focus on how to deal with the relation of enzyme molecules and supports. In this work, a new state of highly active enzymes has been established through facile and novel in situ immobilization and soft template removal method to construct enzyme contained hollow silica nanosphere (catalase@HSN) biocatalysts where enzymes in the cavity exhibit "immobilized but not rigid state". The obtained catalase@HSN was characterized by transmission electron microscopy, scanning electron microscopy and confocal laser scanning microscopy et al. Catalase@HSN exhibits excellent activity (about 80 % activity recovery rate) and stability suffers from extreme pH, temperature, and organic solvents. Moreover, the reusability and storage stability of catalase@HSN also are satisfactory. This proposed strategy provides a facile method for preparing biocatalysts under mild conditions, facilitating the applications of immobilized enzyme in the fields of real biocatalytic industry with high apparent activity and passable stability.

A follow-up study on factors affecting the recovery of patients with hypothyroidism in different selenium environments.

BACKGROUND: Hypothyroidism is a major manifestation of autoimmune thyroid diseases (AITD). We previously reported that a low selenium (Se) status was linked to an elevated prevalence of thyroid diseases. We hypothesized that Se status may also influence the restoration of thyroid function. Thus, this study aimed to investigate the factors affecting the recovery of thyroid function in patients with (sub-)clinical hypothyroidism, with a specific focus on Se status. METHODS: We conducted a 6-year prospective cohort study comparing two counties with different Se concentrations. Demographic and disease data were collected from 1,190 individuals (549 Se-adequate and 641 Se-deficient) who completed a follow-up study in 2019. In addition, urinary iodine (I) levels, thyroid function, and serum and nail Se levels were measured. Logistic regression was used to investigate the relationship between Se deficiency and recovery of thyroid function. RESULTS: Sex and smoking status was similar between the two counties studied. Thyroid function recovery rate was significantly higher in Se-deficient counties (46.0% vs. 30.6%, P = 0.008). In the multivariate analysis, our results show that female sex (odds ratio [OR] (95% confidence interval [CI]) = 1.875 (1.080-3.257), P = 0.026] and increasing age [OR (95%CI) = 1.028(1.007-1.049), P = 0.009] were associated with the recovery rate. Additionally, our study revealed that while Se status was significant in the univariate analysis, this association appeared to disappear in the multivariate analysis. CONCLUSIONS: Female sex and increasing age have unfavorable effects on the recovery of thyroid function in patients over 30 years of age with (sub-) clinical hypothyroidism.

Chaepseubakerins A-J, ten undescribed cytotoxic [11]-chaetoglobosins from an endophytic fungus Pseudeurotium bakeri.

Ten previously unreported [11]-chaetoglobosins, chaepseubakerins A-J (1-10), were characterized from the solid rice-based culture of Pseudeurotium bakeri P1-1-1, an endophyte harbored in the roots of Macrocoma tenue subsp. sullivantii Vitt. (Orthotrichaceae). Their structures were determined by spectroscopic analysis, single-crystal X-ray diffraction (Cu Kα radiation), and chemical methods. Chaepseubakerin A (1) exhibited significant cytotoxic effects against seven human cancer cell lines, A549, A427, HCT116, HT-29, HeLa, HepG2, and MCF-7, with IC50 values of 2.9, 3.0, 4.0, 4.4, 7.1, 6.7, and 8.9 µM, respectively. Mechanistically, 1 induced G2/M cell cycle arrest and apoptosis in A549, Hela, and HCT116 cells in a dose dependent manner.

Unraveling Mechanisms of Highly Efficient Yet Stable Electrochemiluminescence from Quantum Dots.

With CdSe/CdS/ZnS core/shell/shell quantum dots (QDs) as the model system, time- and potential-resolved spectroelectrochemical measurements are successfully applied for studying the general mechanisms and kinetics of electrochemiluminescence (ECL) generation. The rate constant of electron injection from the cathode into a QD to form a negatively charged QD (QD-) increases monotonically from -0.88 V to -1.2 V (vs Ag/AgCl). Mainly due to the deep LUMO of the QDs, the resulting QD- as the key intermediate for ECL generation is structurally stable and possesses very slow spontaneous deionization channels. The latter (the main non-ECL channels) are usually 3-4 orders of magnitude slower than the rate constant of the successive hole injection from an active co-reactant into a QD-. The kinetic studies quantify the internal ECL quantum yield of ideal QD ECL emitters to be nearly identical to that of photoluminescence, which is near unity for the current system. Identification of the key intermediate, discovery of the related elementary steps, and determination of all rate constants not only establish a general framework for understanding ECL generation but also offer basic design rules for ECL emitters.

Band-Edge Energy Levels of Dynamic Excitons in Cube-Shaped CdSe/CdS Core/Shell Nanocrystals.

An electron-hole pair in a cube-shaped CdSe/CdS core/shell nanocrystal exists in the form of dynamic excitons across the strongly and weakly confined regimes under ambient temperatures. Photochemical doping is applied to distinguish the band-edge electron and hole levels, confirming an effective mass model with universal constants. Reduction of the optical bandgap upon epitaxy of the CdS shells is caused by lowering the band-edge electron level and barely affecting the band-edge hole level. Similar shifts of the electron levels, yet retaining the hole levels, can switch the order in energy of the three lowest-energy transitions. Thermal distribution of 1-4 electrons among the two thermally accessible electron levels follows number-counting statistics, instead of Fermi-Dirac distribution.

Surface Sites and Ligation in Amine-capped CdSe Nanocrystals.

Converting colloidal nanocrystals (NCs) into devices for various applications is facilitated by designing and controlling their surface properties. One key strategy for tailoring surface properties is thus to choose tailored surface ligands. In that context, amines have been universally used, with the goal to improve NCs synthesis, processing and performances. However, understanding the nature of surface sites in amine-capped NCs remains challenging, due to the complex surface compositions as well as surface ligands dynamic. Here, we investigate both surface sites and amine ligation in CdSe NCs by combining advanced NMR spectroscopy and computational modelling. Notably, dynamic nuclear polarization (DNP) enhanced 113 Cd and 77 Se 1D NMR helps to identify both bulk and surface sites of NCs, while 113 Cd 2D NMR spectroscopy enables to resolve amines terminated sites on both Se-rich and nonpolar surfaces. In addition to directly bonding to surface sites, amines are shown to also interact through hydrogen-bonding with absorbed water as revealed by 15 N NMR, augmented with computations. The characterization methodology developed for this work provides unique molecular-level insight into the surface sites of a range of amine-capped CdSe NCs, and paves the way to identify structure-function relationships and rational approaches towards colloidal NCs with tailored properties.

Selective Formation of Monodisperse Right Trigonal-Bipyramidal and Cube-Shaped CdSe Nanocrystals: Stacking Faults and Facet-Ligand Pairing.

Formation of monodisperse right trigonal-bipyramidal (rTriBP) and cube-shaped CdSe nanocrystals─both being encased with six (100) facets─is found to be dictated by type of stacking faults along the (111) direction of the zinc-blende structure and an ideal facet-ligand pairing for the (100) facets. During growth with little kinetic overdriving, seeds with single twin boundary (TB) and single intrinsic stacking fault (ISF) grow into rTriBP and cube-shaped nanocrystals, respectively, through two consecutive stages. During the facet-formation stage, each seed would grow rapidly into the smallest faceted one to contain the ∼3 nm seed, with cube-shaped ones growing much faster than rTriBP ones because of the stacking-fault-dependent seed location in the final faceted nanocrystals. In the following facet-growth stage, cube-shaped nanocrystals also grow faster, presumably due to the highly reactive stacking fault edges. Consistent with this hypothesis, growth of rTriBP nanocrystals can become faster than that of cube-shaped ones by intentionally introducing additional intrinsic stacking fault(s) in the seeds. Cube-shaped and rTriBP CdSe nanocrystals exhibit distinctive optical properties, representing two classes of optical materials.

Oncogenic KRASG12D Reprograms Lipid Metabolism by Upregulating SLC25A1 to Drive Pancreatic Tumorigenesis.

Pancreatic cancer is a highly lethal disease with obesity as one of the risk factors. Oncogenic KRAS mutations are prevalent in pancreatic cancer and can rewire lipid metabolism by altering fatty acid (FA) uptake, FA oxidation (FAO), and lipogenesis. Identification of the underlying mechanisms could lead to improved therapeutic strategies for treating KRAS-mutant pancreatic cancer. Here, we observed that KRASG12D upregulated the expression of SLC25A1, a citrate transporter that is a key metabolic switch to mediate FAO, fatty acid synthesis, glycolysis, and gluconeogenesis. In genetically engineered mouse models and human pancreatic cancer cells, KRASG12D induced SLC25A1 upregulation via GLI1, which directly stimulated SLC25A1 transcription by binding its promoter. The enhanced expression of SLC25A1 increased levels of cytosolic citrate, FAs, and key enzymes in lipid metabolism. In addition, a high-fat diet (HFD) further stimulated the KRASG12D-GLI1-SLC25A1 axis and the associated increase in citrate and FAs. Pharmacologic inhibition of SLC25A1 and upstream GLI1 significantly suppressed pancreatic tumorigenesis in KrasG12D/+ mice on a HFD. These results reveal a KRASG12D-GLI1-SLC25A1 regulatory axis, with SLC25A1 as an important node that regulates lipid metabolism during pancreatic tumorigenesis, thus indicating an intervention strategy for oncogenic KRAS-driven pancreatic cancer. SIGNIFICANCE: Upregulation of SLC25A1 induced by KRASG12D-GLI1 signaling rewires lipid metabolism and is exacerbated by HFD to drive the development of pancreatic cancer, representing a targetable metabolic axis to suppress pancreatic tumorigenesis.

Isomeric eremophilane lactones from the whole plant of Parasenecio albus and their cytotoxic and immunosuppressive activities.

Ten previously unreported eremophilane lactones (parasalbolides A-J), including three pairs of C-10 epimers (parasalbolides A and G, B and H, and F and I, respectively), were isolated and identified from the whole plant of Parasenecio albus. Their structures were established on the basis of the HRESIMS and NMR spectroscopic analyses, combined with the comparison of the ECD spectra. The absolute configuration of parasalbolide A was confirmed by single-crystal X-ray diffraction using Cu Kα radiation. Parasalbolides A-J represent the first examples of 1,2,10-trioxygenated eremophila-7(11),8-dien-12,8-olides. The cytotoxic and immunosuppressive activities of selected isolates were evaluated and the (10S)-eremophilane lactones (parasalbolides A, B, and F) showed more potent activities than the (10R)-ones (parasalbolides G, H, and I).

Chlorogenic Acid Ameliorates Post-Infectious Irritable Bowel Syndrome by Regulating Extracellular Vesicles of Gut Microbes.

Post-infectious irritable bowel syndrome (PI-IBS) occurs after acute infectious diarrhea, and dysbiosis can be involved in its pathogenesis. Here, the role of chlorogenic acid (CGA) is investigated, a natural compound with several pharmacological properties, in alleviating PI-IBS in rats. It is elucidated that the gut microbiota plays a key role in PI-IBS pathogenesis and that rectal administration of CGA alleviated PI-IBS by modulating the gut microbiota and its metabolites. CGA supplementation significantly increased fecal Bacteroides acidifaciens abundance and glycine levels. Glycine structurally altered B. acidifaciens extracellular vesicles (EVs) and enriched functional proteins in the EVs; glycine-induced EVs alleviated PI-IBS by reducing inflammation and hypersensitivity of the intestinal viscera and maintaining mucosal barrier function. Moreover, B. acidifaciens EVs are enriched in the brain tissue. Thus, CGA mediates the mitigation of PI-IBS through the gut microbiota and its metabolites. This study proposes a novel mechanism of signal exchange between the gut microenvironment and the host.

Toward Surface Chemistry of Semiconductor Nanocrystals at an Atomic-Molecular Level.

ConspectusProperties of colloidal semiconductor nanocrystals with a single-crystalline structure are largely dominated by their surface structure at an atomic-molecular level, which is not well understood and controlled, due to a lack of experimental tools. However, if viewing the nanocrystal surface as three relatively independent spatial zones (i.e., crystal facets, inorganic-ligands interface, and ligands monolayer), we may approach an atomic-molecular level by coupling advanced experimental techniques and theoretical calculations.Semiconductor nanocrystals of interest are mainly based on compound semiconductors and mostly in two (or related) crystal structures, namely zinc-blende and wurtzite, which results in a small group of common low-index crystal facets. These low-index facets, from a surface-chemistry perspective, can be further classified into polar and nonpolar ones. Albeit far from being successful, the controlled formation of either polar or nonpolar facets is available for cadmium chalcogenide nanocrystals. Such facet-controlled systems offer a reliable basis for studying the inorganic-ligands interface. For convenience, here facet-controlled nanocrystals refer to a special class of shape-controlled ones, in which shape control is at an atomic level, instead of those with poorly defined facets (e.g., typical spheroids, nanorods, etc).Experimental and theoretical results reveal that type and bonding mode of surface ligands on nanocrystals is facet-specific and often beyond Green's classification (X-type, Z-type, and L-type). For instance, alkylamines bond strongly to the anion-terminated (0001) wurtzite facet in the form of ammonium ions, with three hydrogens of an ammonium ion bonding to three adjacent surface anion sites. With theoretically assessable experimental data, facet-ligands pairing can be identified using density functional theory (DFT) calculations. To make the pairing meaningful, possible forms of all potential ligands in the system need to be examined systematically, revealing the advantage of simple solution systems.Unlike the other two spatial zones, the ligands monolayer is disordered and dynamic at an atomic level. Thus, an understanding of the ligands monolayer on a molecular scale is sufficient for many cases. For colloidal nanocrystals stably coordinated with surface ligands, their solution properties are dictated by the ligands monolayer. Experimental and theoretical results reveal that solubility of a nanocrystal-ligands complex is an interplay between the intramolecular entropy of the ligands monolayer and intermolecular interactions of the ligands/nanocrystals. By introducing entropic ligands, solubility of nanocrystal-ligands complexes can be universally boosted by several orders of magnitude, i.e., up to >1 g/mL in typical organic solvents. Molecular environment in the pseudophase surrounding each nanocrystal plays a critical role in its chemical, photochemical, and photophysical properties.For some cases, such as the synthesis of high-quality nanocrystals, all three spatial zones of the nanocrystal surface must be taken into account. By optimizing nanocrystal surface at an atomic-molecular level, semiconductor nanocrystals with monodisperse size and facet structure become available recently through either direct synthesis or afterward facet reconstruction, implying full realization of their size-dependent properties.

Peniandrastins A-H: Andrastin-type meroterpenoids with immunosuppressive activity from a Penicillium sp.

Eight unreported andrastin-type meroterpenoids, namely peniandrastins A-H (1-8), along with six known analogues (9-14), were isolated from the fermentation of a soil-derived fungus Penicillium sp.sb62. Their structures with absolute configurations were elucidated by detailed analyses of the spectroscopic data and single-crystal X-ray diffraction. Compounds 1-4 belong to a rare class of 21-nor-andrastin meroterpenoids, of which 1 bears a 10-hydroperoxyl group, and 2 and 3 feature a 6/6/6/5/5 and a 6/6/6/5/6 pentacyclic systems, respectively. Compounds 5-8 are C25 andrastin-type meroterpenoids, wherein 5 features an unprecedented cyclopentan-1-keton-3-hemiacetal moiety. Additionally, the absolute configuration of compound 9 was corroborated by single-crystal X-ray crystallography for the first time. All isolates were evaluated for their immunosuppressive activities. As a result, compounds 1, 3, 4, 7-9 and 12-14 inhibited concanavalin A-induced T cell proliferation with IC50 values ranging from 7.49 to 36.52 µM, and 1-4, 6-9 and 12-14 inhibited lipopolysaccharide-induced B cell proliferation with IC50 values ranging from 6.73 to 26.27 µM. The preliminary structure-activity relationships (SARs) of those isolates were also discussed.

Hot-Electron-Induced Photochemical Properties of CdSe/ZnSe Core/Shell Quantum Dots under an Ambient Environment.

Using CdSe/ZnSe core-shell quantum dots (QDs) as a model, we systematically investigate the photochemical properties of QDs with the ZnSe shells under an ambient environment, which show almost opposite responses to either oxygen or water in comparison with CdSe/CdS core/shell QDs. While the ZnSe shells provide an efficient potential barrier for photoinduced electron transfer from the core to the surface-adsorbed oxygen, they also act as a stepping stone for hot-electron transfer directly from the ZnSe shells to oxygen. The latter process is so effective and competes favorably with ultrafast relaxation of hot electrons from the ZnSe shells to the core QDs, which can completely quench the photoluminescence (PL) with saturated adsorption of oxygen (1 bar) and initiate oxidation of the surface anion sites. Water can slowly eliminate the excess hole to neutralize the positively charged QDs, partially canceling the photochemical effects of oxygen. Alkylphosphines─through two distinctive reaction pathways with oxygen─stop the photochemical effects of oxygen and completely recover PL. With limited thickness (around two monolayers), the ZnS outer shells substantially slow down photochemical effects on CdSe/ZnSe/ZnS core/shell/shell QDs but cannot fully stop PL quenching by oxygen.

The ubiquitin-like protein FAT10 in hepatocellular carcinoma cells limits the efficacy of anti-VEGF therapy by accelerating VEGF-independent angiogenesis.

INTRODUCTION: The efficacy of anti-vascular endothelial growth factor (VEGF) therapy is limited. However, the key factors involved in limiting the efficacy of anti-VEGF therapy and the underlying mechanisms remain unclear. OBJECTIVES: To investigate the effects and mechanisms of human leukocyte antigen F locus-adjacent transcript 10 (FAT10), a ubiquitin-like protein, in limiting the efficacy of anti-VEGF therapy in hepatocellular carcinoma (HCC) cells. METHODS: FAT10 was knocked out in HCC cells using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 technology. Bevacizumab (BV), an anti-VEGF monoclonal antibody, was used to evaluate the efficacy of anti-VEGF therapy in vivo. Mechanisms of FAT10 action were assessed by RNA sequencing, glutathione S-transferase pulldown assays and in vivo ubiquitination assays. RESULTS: FAT10 accelerated VEGF-independent angiogenesis in HCC cells which limited BV efficacy and BV-aggravated hypoxia and inflammation promoted FAT10 expression. FAT10 overexpression increased levels of proteins involved in several signaling pathways in HCC cells, resulting in upregulation of VEGF and multiple non-VEGF proangiogenic factors. Upregulation of multiple FAT10-mediated non-VEGF signals compensated for the inhibition of VEGF signaling by BV, enhancing VEGF-independent angiogenesis and promoting HCC growth. CONCLUSIONS: Our preclinical findings identify FAT10 in HCC cells as a key factor limiting the efficacy of anti-VEGF therapy and elucidate its underlying mechanisms. This study provides new mechanistic insights into the development of antiangiogenic therapies.

Reversible Facet Reconstruction of CdSe/CdS Core/Shell Nanocrystals by Facet-Ligand Pairing.

Synthesis of colloidal semiconductor nanocrystals with defined facet structures is challenging, though such nanocrystals are essential for fully realizing their size-dependent optical and optoelectronic properties. Here, for the mostly developed colloidal wurtzite CdSe/CdS core/shell nanocrystals, facet reconstruction is investigated under typical synthetic conditions, excluding nucleation, growth, and interparticle ripening. Within the reaction time window, two reproducible sets of facets─each with a specific group of low-index facets─can be reversibly reconstructed by switching the ligand system, indicating thermodynamic stability of each set. With a unique <0001> axis, atomic structures of the low-index facets of wurtzite nanocrystals are diverse. Experimental and theoretical studies reveal that each facet in a given set is paired with a common ligand in the solution, namely, either fatty amine and/or cadmium alkanoate. The robust bonding modes of ligands are found to be strongly facet-dependent and often unconventional, instead of following Green's classification. Results suggest that facet-controlled nanocrystals can be synthesized by optimal facet-ligand pairing either in synthesis or after-synthesis reconstruction, implying semiconductor nanocrystal formation with size-dependent properties down to an atomic level.

Peniandranoids A-E: Meroterpenoids with Antiviral and Immunosuppressive Activity from a Penicillium sp.

Peniandranoids A-E (1-5), five new meroterpenoids, together with three known analogues (6-8), were isolated from the fermentation of a soil-derived fungus, Penicillium sp.sb62. Their structures including absolute configurations were determined by extensive spectroscopic analysis, and the absolute configurations of compounds 1 and 5 were further elucidated by single-crystal X-ray diffraction. Peniandranoids A-E belong to a rare class of andrastin-type meroterpenoids incorporating an extra polyketide unit (a C10 polyketide unit for 1 and 2, a C9 polyketide unit for 3 and 4, and a furancarboxylic acid unit for 5). Compounds 1 and 6 exhibited favorable inhibitory activities against influenza virus A (H1N1) with EC50 values of 19 and 14 µg/mL, respectively. Compounds 3-8 exhibited potent immunosuppressive activities against concanavalin A-induced T cell proliferation with EC50 values ranging from 4.3 to 27 µM and lipopolysaccharide-induced B cell proliferation with EC50 values ranging from 7.5 to 23 µM, respectively.

Visible-light induced three-component reaction for α-aminobutyronitrile synthesis by C-C bond formation using quantum dots as photocatalysts.

We describe a three-component reaction of malononitrile, benzaldehyde and N,N-dimethylaniline using aluminium doped CdSeS/CdZnSeS(Al)/ZnS quantum dots (QDs) as visible light catalysts to synthesize α-aminobutyrilitriles at room temperature and under mild conditions. The reactions exhibit high functional group tolerance, and the well dispersed quantum dot catalysts are highly efficient with a turnover number (TON) greater than 1.1 × 103 and can be recycled at least three times without significant loss of catalytic activity.