The intermolecular three-component alkene vicinal dicarbofunctionalization (DCF) reaction allows installation of two different carbon fragments. Despite extensive investigation into its ionic ...chemistry, the enantioseletive radical-mediated versions of DCF reactions remain largely unexplored. Herein, we report an intermolecular, enantioselective three-component radical vicinal dicarbofunctionalization reaction of olefins enabled by merger of radical addition and cross-coupling using photoredox and copper dual catalysis. Key to the success of this protocol relies on chemoselective addition of acyl and cyanoalkyl radicals, generated in situ from the redox-active oxime esters by a photocatalytic N-centered iminyl radical-triggered C-C bond cleavage event, onto the alkenes to form new carbon radicals. Single electron metalation of such newly formed carbon radicals to TMSCN-derived L1Cu(II)(CN)
complex leads to asymmetric cross-coupling. This three-component process proceeds under mild conditions, and tolerates a diverse range of functionalities and synthetic handles, leading to valuable optically active β-cyano ketones and alkyldinitriles, respectively, in a highly enantioselective manner (>60 examples, up to 97% ee).
Conjugated microporous polymers are a new class of porous materials with an extended π-conjugation in an amorphous organic framework. Owing to the wide-ranging flexibility in the choice and design of ...components and the available control of pore parameters, these polymers can be tailored for use in various applications, such as gas storage, electronics and catalysis. Here we report a class of cobalt/aluminium-coordinated conjugated microporous polymers that exhibit outstanding CO2 capture and conversion performance at atmospheric pressure and room temperature. These polymers can store CO2 with adsorption capacities comparable to metal-organic frameworks. The cobalt-coordinated conjugated microporous polymers can also simultaneously function as heterogeneous catalysts for the reaction of CO2 and propylene oxide at atmospheric pressure and room temperature, wherein the polymers demonstrate better efficiency than a homogeneous salen-cobalt catalyst. By combining the functions of gas storage and catalysts, this strategy provides a direction for cost-effective CO2 reduction processes.
The construction of carbon–heteroatom bonds is one of the most active areas of research in organic chemistry because the function of organic molecules is often derived from the presence of ...heteroatoms. Although considerable advances have recently been achieved in radical-involved catalytic asymmetric C–N bond formation, there has been little progress in the corresponding C–O bond-forming processes. Here, we describe a photoinduced copper-catalyzed cross-coupling of readily available oxime esters and 1,3-dienes to generate diversely substituted allylic esters with high regio- and enantioselectivity (>75 examples; up to 95% ee). The reaction proceeds at room temperature under excitation by purple light-emitting diodes (LEDs) and features the use of a single, earth-abundant copper-based chiral catalyst as both the photoredox catalyst for radical generation and the source of asymmetric induction in C–O coupling. Combined experimental and density functional theory (DFT) computational studies suggest the formation of π-allylcopper complexes from redox-active oxime esters as bifunctional reagents and 1,3-dienes through a radical–polar crossover process.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
A unified approach to four different (atisine, ajaconine, denudatine, and hetidine) diterpenoid alkaloid skeletons was developed and applied to the total synthesis of the natural products ...dihydroajaconine (2, atisine type) and gymnandine (4, denudatine type). The synthesis features a biogenetically inspired strategy that relies on C−H oxidation, aza‐pinacol coupling, and aza‐Prins cyclization as key steps.
Worthy cores: A unified synthetic approach to four types of diterpenoid alkaloids with cagelike structures was developed on the basis of biogenetically inspired C−H oxidation, aza‐pinacol coupling, and aza‐Prins cyclization reactions (see scheme). Compounds synthesized with the four target core structures included the natural products dihydroajaconine and gymnandine.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Photodegradation may be the most important elimination process for cephalosporin antibiotics in surface water. Cefazolin (CFZ) and cephapirin (CFP) underwent mainly direct photolysis (t1/2 = 0.7, 3.9 ...h), while cephalexin (CFX) and cephradine (CFD) were mainly transformed by indirect photolysis, which during the process a bicarbonate-enhanced nitrate system contributed most to the loss rate of CFX, CFD, and cefotaxime (CTX) (t1/2 = 4.5, 5.3, and 1.3 h, respectively). Laboratory data suggested that bicarbonate enhanced the phototransformation of CFD and CFX in natural water environments. When used together, NO3 –, HCO3 –, and DOM closely simulated the photolysis behavior in the Jingmei River and were the strongest determinants in the fate of cephalosporins. TOC and byproducts were investigated and identified. Direct photolysis led to decarboxylation of CFD, CFX, and CFP. Transformation only (no mineralization) of all cephalosporins was observed through direct photolysis; byproducts were found to be even less photolabile and more toxic (via the Microtox test). CFZ exhibited the strongest acute toxicity after just a few hours, which may be largely attributed to its 5-methyl-1,3,4-thiadiazole-2-thiol moiety. Many pharmaceuticals were previously known to undergo direct sunlight photolysis and transformation in surface waters; however, the synergistic increase in toxicity caused by this cocktail (via pharmaceutical photobyproducts) cannot be ignored and warrants future research attention.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Background and Aims
DNA damage‐induced NF‐κB activation is a major obstacle to effective antitumour chemotherapy. Long noncoding RNAs (lncRNAs) that regulate chemoresistance of cancer cells remain ...largely unknown. This study aimed to characterize the lncRNAs that may affect chemotherapy sensitivity.
Approach and Results
We found that lncRNA PDIA3P1 (protein disulfide isomerase family A member 3 pseudogene 1) was up‐regulated in multiple cancer types and following treatment with DNA‐damaging chemotherapeutic agents, like doxorubicin (Dox). Higher PDIA3P1 level was associated with poorer recurrence‐free survival of human hepatocellular carcinoma (HCC). Both gain‐of‐function and loss‐of‐function studies revealed that PDIA3P1 protected cancer cells from Dox‐induced apoptosis and allowed tumor xenografts to grow faster and to be more resistant to Dox treatment. Mechanistically, miR‐125a/b and miR‐124 suppressed the expression of tumor necrosis factor receptor‐associated factor 6 (TRAF6), but PDIA3P1 bound to miR‐125a/b/miR‐124 and relieved their repression on TRAF6, leading to activation of the nuclear factor kappa B (NF‐κB) pathway. Consistently, the effect of PDIA3P1 inhibition in promoting Dox‐triggered apoptosis was antagonized by silencing the inhibitor of κBα (IκBα) or overexpressing TRAF6. Administration of BAY 11‐7085, an NF‐κB inhibitor attenuated PDIA3P1‐induced resistance to Dox treatment in mouse xenografts. Moreover, up‐regulation of PDIA3P1 was significantly correlated with elevation of TRAF6, phosphorylated p65, or NF‐κB downstream anti‐apoptosis genes in human HCC tissues. These data indicate that enhanced PDIA3P1 expression may confer chemoresistance by acting as a microRNA sponge to increase TRAF6 expression and augment NF‐κB signaling. Subsequent investigations into the mechanisms of PDIA3P1 up‐regulation revealed that human homologue of mRNA transport mutant 4 (hMTR4), which promotes RNA degradation, could bind to PDIA3P1, and this interaction was disrupted by Dox treatment. Overexpression of hMTR4 attenuated Dox‐induced elevation of PDIA3P1, whereas silencing hMTR4 increased PDIA3P1 level, suggesting that Dox may up‐regulate PDIA3P1 by abrogating the hMTR4‐mediated PDIA3P1 degradation.
Conclusion
There exists a hMTR4‐PDIA3P1‐miR‐125/124‐TRAF6 regulatory axis that regulates NF‐κB signaling and chemoresistance, which may be exploited for anticancer therapy.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
TiO
2
and g-C
3
N
4
samples were successfully prepared by simple one-step hydrothermal method and calcination method, respectively. Then, g-C
3
N
4
@TiO
2
hollow microspheres were prepared by simple ...water bath evaporation method. This work mainly studies the photocatalytic performance of a series of g-C
3
N
4
composite TiO
2
hollow microspheres with different contents. In the experiment, the amount of g-C
3
N
4
was adjusted to obtain the highest photocatalytic activity. Therefore, finding the most suitable amount of g-C
3
N
4
has become the main task of this work. By degrading the catalytic effect of Rhodamine B (RhB) solution, the photocatalytic performance of a series of samples was compared. Finally, it was discovered that when the weight ratio of g-C
3
N
4
to TiO
2
was 15%, the photocatalytic effect of the sample prepared in this way was the best and the sample was recorded as 15% g-C
3
N
4
@TiO
2
composite. The heterostructure of TiO
2
and g-C
3
N
4
was constructed through the synergistic effect, achieving excellent photocatalytic performance to a certain extent. Therefore, the degradation rate of 15% g-C
3
N
4
@TiO
2
composite material is 90.8% within 90 min of UV–visible light irradiation. We further used SEM, TEM, XRD, FT-IR spectroscopy, DRS, XPS and other test methods to characterize the composition, morphology and chemical properties of the composite material.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived ...from marigold flowers, exhibits a spectrum of biological activities including anti‐inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC‐derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)‐induced lipid accumulation and the upregulation of adipose differentiation‐associated protein Plin2 in a dose‐ and time‐responsive manner. We elucidated that Scu effectively diminishes OA‐provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B‐II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA‐induced decrement of LC3B‐II levels in the presence of bafilomycin‐a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross‐sectional area, wall‐to‐lumen ratio and serum total cholesterol levels in comparison to the high‐fat diet model group. Collectively, our findings suggest that Scu attenuates OA‐induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Primary familial brain calcification (PFBC) is a genetically heterogeneous disorder characterized by bilateral calcifications in the basal ganglia and other brain regions. The genetic basis of this ...disorder remains unknown in a significant portion of familial cases. Here, we reported a recessive causal gene, MYORG, for PFBC. Compound heterozygous or homozygous mutations of MYORG co-segregated completely with PFBC in six families, with logarithm of odds (LOD) score of 4.91 at the zero recombination fraction. In mice, Myorg mRNA was expressed specifically in S100β-positive astrocytes, and knockout of Myorg induced the formation of brain calcification at 9 months of age. Our findings provide strong evidence that loss-of-function mutations of MYORG cause brain calcification in humans and mice.
•MYORG is a major causal gene for autosomal recessive PFBC•Specific expression of MYORG suggests astrocyte involves in PFBC•Myorg knockout mice develops calcium deposits in the brain
Yao et al. provide evidence that MYORG is a major causal gene for autosomal recessive PFBC by a comprehensive strategy combining whole-exome sequencing analysis, Sanger sequencing, linkage analysis, RNA expression analysis, and a mouse model.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
High planting density is essential to increasing maize grain yield.However,single plants suffer from insufficient light under high planting density.Ammonium (NH4+) assimilation consumes less energy ...converted from radiation than nitrate (NO3-).It is hypothesized that a mixed NO3-/NH4+ supply is more important to improving plant growth and population productivity under high vs.low planting density.Maize plants were grown under hydroponic conditions at two planting densities (low density:208 plants m-2 and high density:667 plants m-2) and three nitrogen forms (nitrate only,75/25NO3-/NH4+ and ammonium only).A significant interaction effect was found between planting density and N form on plant biomass.Compared to nitrate only,75/25NO3-/NH4+ increased per-plant biomass by 44％ under low density,but by 81％ under high density.Treatment with 75/25NO3-/NH4+ increased plant ATP,photosynthetic rate,and carbon amount per plant by 31,7,and 44％ under low density,respectively,but by 51,23,and 95％ under high density.Accordingly,carbon level per plant under 75/25NO3-/NH4+ was improved,which increased leaf area,specific leaf weight and total root length,especially for high planting density,increased by 57,17 and 63％,respectively.Furthermore,under low density,75/25NO3-/NH4+ increased nitrogen uptake rate,while under high density,75/25NO3-/NH4+ increased nitrogen,phosphorus,copper and iron uptake rates.By increasing energy use efficiency,an optimum NO3-/NH4+ ratio can improve plant growth and nutrient uptake efficiency,especially under high planting density.In summary,an appropriate supply of NH4+ in addition to nitrate can greatly improve plant growth and promote population productivity of maize under high planting density,and therefore a mixed N form is recommended for high-yielding maize management in the field.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
