Search

Prized for their ability to generate chemical complexity rapidly, catalytic carbon-hydrogen (C-H) activation and functionalization reactions have enabled a paradigm shift in the standard logic of synthetic chemistry. Directing group strategies have been used extensively in C-H activation reactions to control regio- and enantioselectivity with transition metal catalysts. However, current methods rely heavily on coordination with nitrogen and/or oxygen atoms in molecules and have therefore been found to exhibit limited generality in asymmetric syntheses. Here, we report enantioselective C-H activation with unsaturated hydrocarbons directed by phosphorus centres to rapidly construct libraries of axially chiral phosphines through dynamic kinetic resolution. High reactivity and enantioselectivity are derived from modular assembly of an iridium catalyst with an endogenous phosphorus atom and an exogenous chiral phosphorus ligand, as confirmed by detailed experimental and computational studies. This reaction mode significantly expands the pool of enantiomerically enriched functional phosphines, some of which have shown excellent efficiency for asymmetric catalysis.

A novel synthesis of aryl-substituted, enantioenriched fulvenes from an oxidative Heck cascade and rearrangement of a carboxy-substituted spiro[4.4]nonatriene is disclosed. Mechanistic investigations with density functional theory (DFT) calculations and empirical results support the net transformation occurring through a novel Pd(ii)-mediated 1,5-vinyl shift from a vinyl-palladium intermediate that terminates with protodepalladation. This spiro-to-fused bicycle conversion tolerates a range of electron-rich and deficient arylboronic acids to give a range of mono- and diaryl substituted annulated fulvenes in moderate to good yields and enantiomeric ratios. Overall, this work connects two classes of molecules with a rich history in physical organic chemistry.

The development of advanced nuclear energy systems imposes stringent requirements on the service stability of nuclear materials under extreme environments characterized by multiple stressors. Continuous silicon-carbide-fiber-reinforced silicon carbide (SiCf/SiC) ceramic matrix composites possess advantages such as low density, excellent high-temperature mechanical properties,corrosion resistance, and irradiation tolerance. Furthermore, SiCf/SiC composites demonstrate a pseudo-ductile fracture behavior under external forces, positioning them as highly promising structural materials for advanced nuclear energy systems. This study systematically summarizes the fundamental research framework on nuclear-grade SiCf/SiC composites at the material, component,and service performance levels. It also analyzes the developmental trends in this field among traditional nuclear powerhouses such as the United States, France, and Japan, as well as in other emerging nuclear energy countries and China. Furthermore, the study identifies existing issues and challenges faced by China’s nuclear-grade SiCf/SiC sector in terms of raw materials, data accumulation,and patent standards, and proposes targeted measures and suggestions: (1) strengthening the research and development of material preparation technologies, (2) developing a new paradigm of research and development, (3) reinforcing the industry-universityresearch-application cooperation, and (4) enhancing international exchanges on the basis of maintaining independence. The aim of the study is to provide guidance and reference for the research directions and policy-making in China’s nuclear-grade SiCf/SiC sector.

Lignin valorization is being intensely pursued via tandem catalytic depolymerization and biological funneling to produce single products. In many lignin depolymerization processes, aromatic dimers and oligomers linked by carbon-carbon bonds remain intact, necessitating the development of enzymes capable of cleaving these compounds to monomers. Recently, the catabolism of erythro-1,2-diguaiacylpropane-1,3-diol (erythro-DGPD), a ring-opened lignin-derived β-1 dimer, was reported in Novosphingobium aromaticivorans. The first enzyme in this pathway, LdpA (formerly LsdE), is a member of the nuclear transport factor 2 (NTF-2)-like structural superfamily that converts erythro-DGPD to lignostilbene through a heretofore unknown mechanism. In this study, we performed biochemical, structural, and mechanistic characterization of the N. aromaticivorans LdpA and another homolog identified in Sphingobium sp. SYK-6, for which activity was confirmed in vivo. For both enzymes, we first demonstrated that formaldehyde is the C1 reaction product, and we further demonstrated that both enantiomers of erythro-DGPD were transformed simultaneously, suggesting that LdpA, while diastereomerically specific, lacks enantioselectivity. We also show that LdpA is subject to a severe competitive product inhibition by lignostilbene. Three-dimensional structures of LdpA were determined using X-ray crystallography, including substrate-bound complexes, revealing several residues that were shown to be catalytically essential. We used density functional theory to validate a proposed mechanism that proceeds via dehydroxylation and formation of a quinone methide intermediate that serves as an electron sink for the ensuing deformylation. Overall, this study expands the range of chemistry catalyzed by the NTF-2-like protein family to a prevalent lignin dimer through a cofactorless deformylation reaction.

Direct molecular editing of heteroarene carbon-hydrogen (C-H) bonds through consecutive selective C-H functionalization has the potential to grant rapid access into diverse chemical spaces, which is a valuable but often challenging venture to achieve in medicinal chemistry1. In contrast to electronically biased heterocyclic C-H bonds2-9, remote benzocyclic C-H bonds on bicyclic aza-arenes are especially difficult to differentiate because of the lack of intrinsic steric/electronic biases10-12. Here we report two conceptually distinct directing templates that enable the modular differentiation and functionalization of adjacent remote (C6 versus C7) and positionally similar (C3 versus C7) positions on bicyclic aza-arenes through careful modulation of distance, geometry and previously unconsidered chirality in template design. This strategy enables direct C-H olefination, alkynylation and allylation at adjacent C6 and C7 positions of quinolines in the presence of a competing C3 position that is spatially similar to C7. Notably, such site-selective, iterative and late-stage C-H editing of quinoline-containing pharmacophores can be performed in a modular fashion in different orders to suit bespoke synthetic applications. This Article, in combination with previously reported complementary methods, now fully establishes a unified late-stage molecular editing strategy to directly modify bicyclic aza-arenes at any given site in different orders.

Computations and experiments leading to new chiral phosphoric acids (CPAs) for epoxide thionations are reported. Density functional theory calculations reveal the mechanism and origin of the enantioselectivity of such CPA-catalyzed epoxide thionations. The calculated mechanistic information was used to design new efficient CPAs that were tested experimentally and found to be highly effective. Bulky ortho-substituents on the 3,3'-aryl groups of the CPA are important to restrict the position of the epoxide in the key transition states for the enantioselectivity-determining step. Larger para-substituents significantly improve the enantioselectivity of the reaction.

Objective To investigate the factors causing delays in seeking medical attention and its relationship with short-term prognosis in patient with acute ischemic stroke, and provide reference for the interventions on seeking timely medical attention. Methods Totally 131 patients with acute ischemic stroke who attended the hospital between September 2021 and August 2022 were included. The general information and clinical data of patients were retrospectively analyzed. According to the time to medical attention, those with time to medical attention more than 3. 5 h were included as the Delay group, and those with time to medical attention less than 3. 5 h were assigned to the Non-Delay group. Results There were 74 cases in the Non-Delay group and 57 cases in the Delay group. There was no significant difference in age, gender, marital status, education level, medical insurance, employment status, current place of residence, distance to hospital, type of hospital attention, place of disease onset, time to medical attention, time of disease onset, symptoms, type of disease onset, medical history and NIHSS score at hospital admission between two groups (P＞0. 05). The type of symptom identification and NIHSS score at 14th day of hospital admission in the Non-Delay group was lower than that in the Delay group(P＜0. 05). Conclusion There is a relationship between delays in seeking medical attention and type of symptom identification, which may affect the short-term prognosis in patient with acute ischemic stroke. It is required to enhance the public health education about identification of stroke signs. (目的 调查分析急性缺血性脑卒中患者院前延迟就医的原因与短期预后的相关性, 为制定促使患者院前及时就医的干预措施而提供科学依据。方法 纳入2021年9月—2022年8月就诊于医院急诊科的131例急性缺血性脑卒中患者作为研究对象。采用统一的自制调查表记录患者一般信息和临床资料。根据就诊时间, 将症状出现至就诊时间≥3. 5 h的患者设为院前延迟就医组, 时间＜3. 5h的患者设为及时就医组。采用单因素分析相关因素。结果 及时就医组患者74 例, 延迟就医组患者 57例。两组患者在年龄、性别、婚姻状况、文化程度、医疗保险、职业状态、现居住地、距离、就诊方式、发病地点、入院时间、发病时间、发病症状、发病模式、既往病史、入院时美国国立卫生研究院卒中量表(NIHSS)评分方面差异无统计学意义(P＞0. 05)。两组患者症状识别方式和发病第14天的NIHSS评分比较, 差异有统计学意义(P< 0. 05)。结论 急性缺血性脑卒中延迟就医原因与相关症状识别方式密切相关, 影响患者的短期预后, 应加强大众识别卒中相关症状的健康教育以促进患者及时就诊。)

Background Diabetes is one of the common diseases among inpatients in non-endocrinology department. Patients with diabetes require assistance from endocrinologists in their blood glucose management. Objective To investigate consultation of blood glucose management for inpatients with diabetes in non-endocrinology department and analyze the quality of consultation and the needs of patients. Methods The inpatients with diabetes in non-endocrinology department consulted by the endocrinologists in West China Hospital, Sichuan University from January 1, 2013 to May 23, 2019 were selected and reviewed. The consultation and medical record information was recorded and organized. The recommended medications for the patients were analyzed to determine the potential contraindications according to drug instructions. Results During the study period, we identified 145 428 inpatients with diabetes in non-endocrinology department, 24 499 of them had 31 369 consultations from endocrinologists (0.17 consultations/inpatients), and 20 486 of them had 24 343 consultations for blood glucose management (0.17 consultations/inpatients). The top three departments with the most blood glucose management consultations per patient were neurology (0.30 consultations/inpatients), respiratory medicine (0.25 consultations/inpatients), and cardiology (0.18 consultations/inpatients). There were 18 306 blood glucose management consultations (16 269 inpatients) with complete suggestions, and the most commonly recommended hypoglycemic regimen was the combination of insulin with a meal and basal insulin, accounting for 32.34% (5 921/18 306). Among the all consultations, 1.16% (212/18 306) patients' hypoglycemic regimens had drug contraindications. Conclusion A large number of inpatients with diabetes in non-endocrinology department need specialized blood glucose management. The overall quality of the consultation for blood glucose management is relatively high but far from meeting the management requirements.

Diabetes is a disease frequently encountered in hospitals in China. Good glycemic management can improve clinical outcomes and shorten the length of stay of diabetic patients, enhance healthcare efficiency and save medical resources. To provide a reference for clinical glycemic management and associated research, we reviewed relevant literature, then summarized the characteristics and applicable settings of different blood glucose management modes, and detailed the advantages and limitations of three major glycemic management models, including general-specialist consultation, hospital-wide glycemic management program, and smart decision support system for blood glucose management. With the support of information technology, different glycemic management modes will contribute to the continuous improvement of efficiency and quality of hospital care.

Heteroarenes containing carbon-silicon (C-Si) bonds are important building blocks that play an important role in the construction of natural products, pharmaceuticals, and organic materials. In this context, the C-H silylation of heteroarenes is a topic of intense interest. Indole C-H silylation can preferentially occur at the nucleophilic C3 and C2 position (pyrrole core), while accessing the C4-C7 positions (benzene core) of the indole remains highly challenging. Here, we show a general strategy for the regioselective C7-H silylation of indole derivatives. Mainly, the regioselectivity is determined by strong coordination of the palladium catalyst with phosphorus (III) directing group. Using this expedient synthetic strategy, the diverse C7-silylated indoles are synthesized effectively which exhibits the broad functional group compatibility. Moreover, this protocol also been extended to other heteroarenes such as carbazoles. The obtained silylated indoles have been employed in various transformations to enable the corresponding differently functionalized indole derivatives. Significantly, a cyclopalladated intermediate is successfully synthesized to test the hypothesis about the P(III)-directed C-H metalation event. A series of mechanistic experiments and density functional theory (M06-2X) calculations has shown the preferred pathway of this directed C-H silylation process.

Site-selective functionalization of C-H bonds will ultimately afford chemists transformative tools for editing and constructing complex molecular architectures. Towards this goal, it is essential to develop strategies to activate C-H bonds that are distal from a functional group. In this context, distinguishing remote C-H bonds on adjacent carbon atoms is an extraordinary challenge due to the lack of electronic or steric bias between the two positions. Herein, we report the design of a catalytic system leveraging a remote directing template and a transient norbornene mediator to selectively activate a previously inaccessible remote C-H bond that is one bond further away. The generality of this approach has been demonstrated with a range of heterocycles, including a complex anti-leukaemia agent and hydrocinnamic acid substrates.

A simple and efficient nitrile-directed meta-C-H olefination, acetoxylation, and iodination of biaryl compounds is reported. Compared to the previous approach of installing a complex U-shaped template to achieve a molecular U-turn and assemble the large-sized cyclophane transition state for the remote C-H activation, a synthetically useful phenyl nitrile functional group could also direct remote meta-C-H activation. This reaction provides a useful method for the modification of biaryl compounds because the nitrile group can be readily converted to amines, acids, amides, or other heterocycles. Notably, the remote meta-selectivity of biphenylnitriles could not be expected from previous results with a macrocyclophane nitrile template. DFT computational studies show that a ligand-containing Pd-Ag heterodimeric transition state (TS) favors the desired remote meta-selectivity. Control experiments demonstrate the directing effect of the nitrile group and exclude the possibility of non-directed meta-C-H activation. Substituted 2-pyridone ligands were found to be key in assisting the cleavage of the meta-C-H bond in the concerted metalation-deprotonation (CMD) process.

In this paper, the research progress of ammonium bisulfate (ABS) volatilization in coal-fired power plants the SCR denitrification process was reviewed. Combination with self-made experiments, SEM, flue gas analyzer and TG-DTG curves of ABS and ion chromatography. The volatilization and condensation characteristics of ABS were investigated carefully. Results show that as the temperature increased by 50 oC, the ABS/AS volatilization rate increased by an order of magnitude. The decomposition process of ABS should have a two-step reaction. The reaction in the initial volatiliza-tion stage is ABS dehydration turned into (NH4)2S2O7. The reaction in the rapid volat-ilization stage is (NH4)2S2O7 decomposed into NH3, N2, SO2 and H2O. There is an inter-section in the reaction temperature range (especially 300 oC) between the two-step re-action. This research provides an experimental basis for temperature control of ABS to avoid air pre-heater fouling.

A cornerstone of modern synthetic chemistry rests on the ability to manipulate the reactivity of a carbon center by rendering it either electrophilic or nucleophilic. However, accessing a similar reactivity spectrum with boron-based reagents has been significantly more challenging. While classical nucleophilic carbon-based reagents normally do not require steric protection, readily accessible, unprotected boron-based nucleophiles have not yet been realized. Herein, we demonstrate that the bench stable closo-hexaborate cluster anion can engage in a nucleophilic substitution reaction with a wide array of organic and main group electrophiles. The resulting molecules containing B‒C bonds can be further converted to tricoordinate boron species widely used in organic synthesis.

In the early screening of ophthalmic diseases, diabetes, heart disease and other diseases, automatic mon-itoring of fundus capillaries occupies an important position. To solve the deficiency of blood vessel segmentation caused by the imprecise expression of capillary features, this paper proposes a multi-block residual neural network model (MbResU-Net) which uses the encoding-decoding network structure. In order to reduce the information loss caused by the semantic gap between network encoder and decoder, the model uses a nonlinear network structure instead of shortcut connections to be embedded in the network. In order to obtain the detailed features of fundus blood vessels, MbResU-Net connects three U-shaped networks in a residual block, and then extracts as much as possible low-level features of the fundus tube on the premise of avoiding information loss. To ensure the seg-mentation quality, with the proper pre-processing images to the network, it designs a cross-entropy loss function incorporating the cost matrix to train the network parameters. This paper compares MbResU-Net and the existing fundus blood vessel segmentation algorithms on the DRIVE and CHASE DB1 color fundus image datasets. Exper-iments show that MbResU-Net is superior to existing methods in Sen, ACC and AUC. The Sen is 0.7987 and 0.7972, ACC is 0.9648 and 0.9726 and AUC is 0.9791 and 0.9824. Experiments prove the effectiveness and robustness of the model in the segmentation of complex curvature and small blood vessels.