A hybrid palladium catalyst assembled from a chiral phosphoric acid (CPA) and thioamide enables a highly efficient and enantioselective β‐C(sp3)−H functionalization of thioamides (up to 99 % yield, ...97 % ee). A kinetic resolution of unsymmetrical thioamides by intermolecular C(sp3)−H arylation can be achieved with high s‐factors. Mechanistic investigations have revealed that stereocontrol is achieved by embedding the substrate in a robust chiral cavity defined by the bulky CPA and a neutral thioamide ligand.
Bulk up: A Pd‐catalyzed enantioselective β‐C(sp3)−H functionalization of thioamides has been developed using a chiral phosphoric acid (CPA) as the chiral auxiliary. Mass spectrometry studies and DFT analysis elucidate the role of the bulky CPA and the assistance of the thioamide ligand, which define a robust chiral cavity for achieving a high level of stereocontrol.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
2-(2-Phenylethyl)chromones (PECs) are the principal constituents contributing to the distinctive fragrance of agarwood. How PECs are biosynthesized is currently unknown. In this work, we describe a ...diarylpentanoid-producing polyketide synthase (PECPS) identified from Aquilaria sinensis. Through biotransformation experiments using fluorine-labeled substrate, transient expression of PECPS in Nicotiana benthamiana, and knockdown of PECPS expression in A. sinensis calli, we demonstrate that the C
-C
-C
scaffold of diarylpentanoid is the common precursor of PECs, and PECPS plays a crucial role in PECs biosynthesis. Crystal structure (1.98 Å) analyses and site-directed mutagenesis reveal that, due to its small active site cavity (247 Å
), PECPS employs a one-pot formation mechanism including a "diketide-CoA intermediate-released" step for the formation of the C
-C
-C
scaffold. The identification of PECPS, the pivotal enzyme of PECs biosynthesis, provides insight into not only the feasibility of overproduction of pharmaceutically important PECs using metabolic engineering approaches, but also further exploration of how agarwood is formed.
The iron content can be used as a proxy for the intensity of weathering and pedogenesis, which reflect long‐term climate cycles and short‐term climate fluctuations and events. In this study, a ...typical loess–palaeosol sequence for 19.85 m in thickness deposited since 423 ka BP in northeastern China was investigated, and its iron pools were determined. The results reveal that with increasing depth, the abundances of different forms of iron are consistent with the changes in the magnetic susceptibility. Iron (Fe) in all forms is more abundant in the palaeosol than in the loess. The silicate‐bound Fe pool (Fer = Fet − Fed) accounts for 60.4% of the total Fe (Fet), indicating weak pedogenesis. The Fe in the crystalline oxides (Fec = Fed − Feo) is predominantly free Fe (Fed), with a crystallinity Fey = (Fed − Feo) × 100 / Fed of as high as 97.2%. The coefficients of variation of the different forms of iron associated with the soil depth are as follows: Fec > Fed > poorly crystalline Fe (Feo) > Fer > Fet. The distribution of the forms of Fe throughout the profile is a clear indicator of the pedogenesis. The Fed, Fec, and Fe freeness (freeness = Fed × 100 / Fet) correlate with the magnetic susceptibility. The neoformation of iron (Fe) oxides was closely related to the degree of pedogenesis. More crystalline Fe oxides were found in the soil layers corresponding to warm interglacial periods. We detected variations in the abundance of the Fe pools for characterizing climate fluctuations that occurred in a short period of time. In this study, we demonstrated that when used in combination with dating techniques, morphological development indices, and magnetic susceptibility, the measurement of soil Fe pools can be extremely useful for tracing the iron evolution in the Earth's critical zone and reconstructing past climatic events in loess–palaeosol sequences.
Loess–paleosol sequences display records of past climate events. Neoformation of iron oxides was closely related to pedogenesis degree. More crystalline Fe oxides were found in soils corresponding to warm interglacial periods. We detected many variations in abundance of Fe pools characterizing climate fluctuations that occurred in a short period of time. We demonstrated that measurements of Fe pools with dating techniques, morphological development indices, and magnetic susceptibility can be useful for tracing iron evolution in the Earth's critical zone.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
ABSTRACT We report Shanghai Tian Ma Radio Telescope (TMRT) detections of several long carbon-chain molecules in the C and Ku bands, including HC3N, HC5N, HC7N, HC9N, C3S, C6H, and C8H toward the ...starless cloud Serpens South 1a. We detected some transitions (HC9N J = 13-12, F = 12-11, and F = 14-13; H13CCCN J = 2-1, F = 1-0, and F = 1-1; HC13CCN J = 2-1, F = 2-2, F = 1-0, and F = 1-1; HCC13CN J = 2-1, F = 1-0, and F = 1-1) and resolved some hyperfine components (HC5N J = 6-5, F = 5-4; H13CCCN J = 2-1, F = 2-1) for the first time in the interstellar medium. The column densities of these carbon-chain molecules in the range 1012-1013 cm−2 are comparable to two carbon-chain molecule rich sources, TMC-1 and Lupus-1A. The abundance ratios are 1.00:(1.11 0.15):(1.47 0.18) for H13CCCN:HC13CCN:HCC13CN. This result implies that the 13C isotope is also concentrated in the carbon atom adjacent to the nitrogen atom in HC3N in Serpens South 1a, which is similar to TMC-1. The HC3N/H13CCCN ratio of 78 9, the HC3N/HC13CCN ratio of 70 8, and the HC3N/HCC13CN ratio of 53 4 are also comparable to those in TMC-1. Serpens South 1a proves to be a suitable testing ground for understanding carbon-chain chemistry.
An unusual hybrid palladium catalyst containing an anionic chiral Co
complex and a chiral phosphoramidite ligand shows a high capacity for catalyzing asymmetric thioamide-directed C(sp
)-H arylation ...and delivers excellent yield and enantioselectivity (up to 99 % yield, 99 % ee). Significant synergy between the chiral ligand and the anion in terms of stereochemical control was observed. Mechanistic investigations have revealed both the nature of the C-H activation and the origin of the enantioselectivity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Mechanistic studies are of great importance for the understanding, optimization, and design of chemical reactions, especially catalysis. In recent years, the combination of mass spectrometry and ...computational chemistry has been proven to be powerful and effective for the exploration of reaction mechanisms. The former provides information of possible reaction intermediates, which are difficult to obtain using other experimental methods, while the latter gives detailed structural information of reaction intermediates and explores reaction energy profiles. This review covers applications of the combined method and highlights its strengths in mechanistic studies. Representative works are discussed to demonstrate the complementarity and synergy of mass spectrometry and computational chemistry. Some challenges in mechanistic studies with these tools and their possible solutions, as well as the trend for future developments are also discussed.
The combination of mass spectrometry and computational chemistry has been proven to be powerful for exploring reaction mechanisms. The former provides information of reaction intermediates, while the latter gives detailed reaction energy profiles.
According to the 2012 statistics of the International Agency for Research on Cancer (IARC), gastric cancer is the fifth most common malignancy, and the third leading cause of cancer-related deaths ...worldwide. Conventional chemotherapy and radiation have shown limited efficacy for advanced gastric cancer, showing an overall survival (OS) rate of ~10 months. Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is the first approved molecularly targeted agent for HER2-overexpressing gastric cancer, which was found to prolong the OS and the progression-free survival (PFS) of patients. However, HER2 overexpression is present only in a minority of patients with gastric cancer. Hence, other targeted agents are urgently needed. Ramucirumab, a novel human IgG1 monoclonal antibody that selectively targets the extracellular domain of VEGF receptor 2 (VEGFR2), is regarded as a new standard second-line treatment for patients with advanced gastric cancer. The combination of two or more targeted agents directed against two different molecular targets may improve the survival of patients with advanced gastric cancer. Although great efforts have been made, the effect of targeted therapy for gastric cancer is limited. One key reason is that participants in clinical trials for new targeted agents were not selected by detection of the targeted molecule. Here, we review clinical trials related to molecular targets such as anti-epidermal growth factor receptor signaling including anti-HER2 and anti-EGFR1, anti-VEGF signaling, anti-mammalian target of rapamycin (mTOR), tyrosine kinase inhibitors (TKIs) and anti-MET.
In utero exposure to phthalates may have adverse effects on pregnant women and their offsprings. Therefore, the exposure level of these substances among individuals, particularly among sensitive ...population, is of concern. The objective of the present study is to characterize urinary concentrations of phthalate metabolites at multiple time points during pregnancy in Chinese women. A total of 3455 pregnant women were included from Ma'anshan Birth Cohort in China. Spot urine samples in the morning (8:00–10:00) and questionnaires were obtained at three separate visits (approximately in 10, 26, and 34 gestational weeks). Seven phthalate metabolites from urine samples were analyzed, including monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), mono benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Geometric means of concentrations were ranged from 0.05 to 41.0ng/mL for all the metabolites mentioned above. No individual exposure level was above the 95th percentiles for all the seven phthalates. On the three separate visits, 0.5%, 0.9% and 1.2% of the participants had coexposure to above the 75th percentiles for all metabolites. Taken these visits together, a total of 29 urine samples had concentrations above the 95th percentiles, while 3.0%–5.6% of urine levels were above 75th percentiles for at least one specific phthalate metabolite. We observed moderate intraclass correlation coefficients (ICCs) ranging from 0.44 to 0.56 for MBzP, MEHP and MEP, and lower ICCs, from 0.28 to 0.32, for MMP, MBP, MEOHP and MEHHP. Sampling season was associated with concentrations of all phthalate metabolites, showing heavier exposure was more likely to occur during summer. In summary, phthalate exposure is prevalent in Chinese pregnant women. However, throughout pregnancy coexposure to multiple phthalates at the upper percentile of exposure is infrequent. Mild to moderate temporal stability indicates that a single measurement in spot urine collected in the morning (8:00–10:00) seems not enough to describe throughout pregnancy phthalate exposure. Urinary levels vary by sampling seasons, which should be taken into consideration in future analyses.
The unadjusted and creatinine-adjusted concentrations of urinary phthalate metabolites. Display omitted
•Phthalate exposure is prevalent in Chinese pregnant women.•Coexposure to multiple phthalates at high-doses is infrequent among Chinese pregnant women.•Throughout pregnancy exposure to one specific phthalate at high-dose is infrequent.•Exposure to phthalates during pregnancy is mild to moderate temporal stability.•Urinary levels of all the phthalate metabolites vary by sampling seasons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Tripartite motif-containing proteins (TRIMs), exhibiting ubiquitin E3 ligase activity, are involved in regulation of not only autophagy and apoptosis but also pyrotosis and antiviral immune responses ...of host cells. TRIMs play important roles in modulating signaling pathways of antiviral immune responses
type I interferon, NF-κB, Janus kinase/signal transducer and activator of transcription (JAK/STAT), and Nrf2. However, viruses are able to antagonize TRIM activity or evenly utilize TRIMs for viral replication. This communication presents the current understanding of TRIMs exploited by viruses to evade host immune response.
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