Herein, we disclose a highly efficient cobalt-catalyzed cross-electrophile alkynylation of a broad range of unactivated chlorosilanes with alkynyl sulfides as a stable and practical alkynyl ...electrophiles. Strategically, employing easily synthesized alkynyl sulfides as alkynyl precursors allows access to various alkynylsilanes in good to excellent yields. Notably, this method avoids the utilization of strong bases, noble metal catalysts, high temperature and forcing reaction conditions, thus presenting apparent advantages, such as broad substrate scope (72 examples, up to 97% yield), high Csp-S chemo-selectivity and excellent functional group compatibility (Ar-X, X = Cl, Br, I, OTf, OTs). Moreover, the utilities of this method are also illustrated by downstream transformations and late-stage modification of structurally complex natural products and pharmaceuticals. Mechanistic studies elucidated that the cobalt catalyst initially reacted with alkynyl sulfides, and the activation of chlorosilanes occurred via an S
2 process instead of a radical pathway.
We monitored the gas hydrate through low‐field nuclear magnetic resonance measurement. An observed decrease of the relaxation time (T2) intensity corresponds to the formation process, whereas an ...increase of the intensity corresponds to the dissociation process. The right domain of the spectrum with T2 larger than 10 ms disappears gradually with the formation time, whereas the left domain with T2 smaller than 1 ms remains invariant, indicating the gas hydrate forms preferentially in larger pores. In addition, the right domain increases rapidly with the dissociation time, revealing that the gas hydrate preferentially decomposes in large pores. The spectrum distributions move toward the fast relaxation domain with the growth of gas hydrate, because the generated gas hydrate occupies the large pore and accelerate the relaxation rate. There is no obvious relationship between the gas hydrate saturation and the porosity, whereas the volume and preliminary dissociation ratio are strongly correlated with the porosity.
Key Points
An equipment to form the methane gas hydrate in porous rock is developed
Low‐field NMR responses of the gas hydrate bearing samples are measured and analyzed during the formation and dissociation processes
The formation and dissociate behaviors and habits for gas hydrate bearing samples are investigated
We developed a numerical simulation algorithm to explore the nuclear magnetic resonance (NMR) response of the porous media based on the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence and the Bloch ...equation. The evolution of the magnetization vector of two representative pores at different pulse properties, including the excitation angle, the refocusing angle, the phase angle, as well as the pulse duration are simulate to understand the NMR relaxation signals. The result showed that the normalized magnetization is symmetrical with the excitation angle and positive with the T2 spectrum's amplitude when the excitation angle is less than 90°. In additional, the refocusing angle has no clear influence on the NMR response. The phase angle of the excitation pulse is inversely correlated with the echo amplitude and can be neglected when the value is lower than 15°. The phase angle of the refocusing pulse causes the zig-zag phenomenon, but the response of the even echoes is not disturbed. Moreover, the influence of the pulse duration should not be neglected at higher values, particularly for the mesopore. The simulation results are helpful for the design and optimization of the pulse sequence, and the data manipulation of the measured signals.
•The magnetization evolution under the CPMG pulse sequence is established.•The NMR responses of reservoir rock is simulated and analyzed.•The influences of the pulse sequence properties on the NMR relaxations are investigated.
Natural gas hydrate is a kind of environmentally friendly unconventional energy with large reserves, which attract increasing attention in recent years. The microscopic pore structure and mineral ...composition of natural gas hydrate reservoir have a great influence on its seepage characteristics during exploitation. In this study, computed tomography and scanning electron microscope are used to obtain digital images of three clayey-silt natural gas hydrate reservoir samples in the Shenhu area of South China Sea, and then, the pore structure and the mineral composition of the samples are obtained after image processing. The result indicates that the clayey-silt samples show strong hydrophilic characteristics, small particles, good sorting properties, variable pore distribution, small average pore and throat radius, large porosity, and a large content of submicron pores. The mineral composition of the reservoir is mainly quartz and contains a certain amount of clay minerals, mainly illite, while the mineral composition of reservoir rich in microbial fossils is mainly carbonate. The results indicate that the pore structure and mineral composition of natural gas hydrate reservoirs in Shenhu area lay a foundation for the efficient development of the clayey-silt reservoir.
We aimed to compare the efficacy of chimeric antigen receptor T (CAR-T) cell therapy with that of autologous stem cell transplantation (auto-HSCT) in relapsed/refractory diffuse large B cell lymphoma ...(R/R DLBCL).
We searched eligible publications up to January 31st, 2022, in PubMed, Cochrane Library, Springer, and Scopus. A total of 16 publications with 3484 patients were independently evaluated and analyzed using STATA SE software.
Patients who underwent CAR-T cell therapy showed a better overall response rate (ORR) and partial response (PR) than those treated with auto-HSCT (CAR-T vs. auto-HSCT, ORR: 80% vs. 73%, HR:0.90,95%CI:0.76-1.07,
= 0.001; PR: 20% vs. 14%, HR:0.65,95%CI:0.62-0.68,
= 0.034). No significant difference was observed in 6-month overall survival (OS) (CAR-T vs. auto-HSCT, six-month OS: 81% vs. 84%, HR:1.23,95%CI:0.63-2.38,
= 0.299), while auto-HSCT showed a favorable 1 and 2-year OS (CAR-T vs. auto-HSCT, one-year OS: 64% vs. 73%, HR:2.42,95%CI:2.27-2.79, P < 0.001; two-year OS: 54% vs. 68%, HR:1.81,95%CI:1.78-1.97, P < 0.001). Auto-HSCT also had advantages in progression-free survival (PFS) (CAR-T vs. auto-HSCT, six-month PFS: 53% vs. 76%, HR:2.81,95%CI:2.53-3.11,
< 0.001; one-year PFS: 46% vs. 61%, HR:1.84,95%CI:1.72-1.97,
< 0.001; two-year PFS: 42% vs. 54%, HR:1.62,95%CI:1.53-1.71,
< 0.001). Subgroup analysis by age, prior lines of therapy, and ECOG scores was performed to compare the efficacy of both treatment modalities.
Although CAR-T cell therapy showed a beneficial ORR, auto-HSCT exhibited a better long-term treatment superiority in R/R DLBCL patients. Survival outcomes were consistent across different subgroups.
Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with a complicated prognosis. Even though various prognostic evaluations have been applied currently, they usually only ...use the clinical factors that overlook the molecular underlying DLBCL progression. Therefore, more accurate prognostic assessment needs further exploration. In the present study, we constructed a novel prognostic model based on microtubule associated genes (MAGs).
A total of 33 normal controls and 1360 DLBCL samples containing gene-expression from the Gene Expression Omnibus (GEO) database were included. Subsequently, the univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to select the best prognosis related genes into the MAGs model. To validate the model, Kaplan-Meier curve, and nomogram were analyzed.
A risk score model based on fourteen candidate MAGs (
) was established. The K-M curve presented that the high-risk patients had a significantly inferior overall survival (OS) time compared to low-risk patients in training and validation datasets. Furthermore, knocking-out
, a key gene belonging to the MAGs model, inhibited cell proliferation noticeably.
The novel MAGs prognostic model has a well predictive capability, which may as a supplement for the current assessments. Furthermore, candidate TMEM63A gene has therapeutic target potentially in DLBCL.
Langgu Depression is a mature oil and gas exploration area with complicated lithological and physical properties. The varying formation fluid, low-resistivity hydrocarbon-bearing reservoirs, and ...non-uniform logging series greatly increase the difficulty of gas reservoir identification. The Monte Carlo method is employed to simulate the neutron–gamma logging responses to gas saturation and the influential factors. According to the result, a new gas identification chart eliminating the influence of porosity and formation water salinity is proposed to identify gas reservoirs in the old wells. At the same time, a fluid factor extracted from array acoustic logging and core measurement data is sensitive to the development of gas-bearing layers and useful for the identification of gas reservoirs in the new wells with array acoustic logging. The field examples show that the new combined method greatly improves the ability to identify gas-bearing layers and works well in old well reexamination and new well interpretation.
Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangements (MLL-r) is an aggressive subtype of blood cancer with dismal prognosis, underscoring the urgent need for novel ...therapeutic strategies. E1A-binding protein (EP300) and CREB-binding protein (CREBBP) function as essential transcriptional coactivators and acetyltransferases, governing leukemogenesis through diverse mechanisms. Targeting EP300/CREBBP holds great promise for treating leukemia with some certain cytogenetic abnormalities. Here, we demonstrated that EP300 and CREBBP are core epigenetic regulators in the pathogenesis of MLL-r AML through assaying the transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Knocking-out EP300/CREBBP and inhibitor (A-485) treatment depressed the MLL-r cells proliferation, while the MLL wild-type cells remained uninfluenced. We found that the CDK4/RB/E2F axis was downregulated specifically in MLL-r AML cell after A-485 treatment by RNA-seq, western blot and cut-tag analyses. EP300/CREBBP inhibitor selectively exerted potent anti-leukemia activity through blocking the MLL-r-BET complex binding to H3K27Ac modification on critical genes loci, distinct from global histone acetylation. Collectively, our study identified EP300/CREBBP as a critical epigenetic driver of MLL-r leukemia and validated their therapeutic potential through targeting inhibition, offering a promising avenue for improving clinical outcomes in this aggressive leukemia.
A practical and efficient method to access polysubstituted aryl sulfides has been discovered via a Lewis acid-catalyzed reaction between alkynyl sulfide and 2-pyrone, involving a ...Diels–Alder/retro-Diels–Alder pathway. Alkynyl sulfide as an electron-rich dienophile and 2-pyrones as electron-poor dienes are conjunctively transformed into a series of polysubstituted aryl sulfides with broad functional group compatibility in good to excellent yields (40 examples, 43–88% yield). The robustness and practicality of the protocol has been demonstrated through gram-scale synthesis and the ease of transformation of the resulting products.
