Regiodivergent alkene functionalization that produces either regioisomer starting from the same raw materials is desirable. Herein, we report a nickel‐catalyzed switchable site‐selective alkene ...hydroalkylation. The selection of reaction temperatures leads to protocols that provide regiodivergent hydroalkylated products starting from a single alkene substrate. This protocol allows the convenient synthesis of α‐ and β‐branched protected amines, both of which are important to the fields of pharmaceutical chemistry and biochemistry. In addition, enantioenriched β‐branched alkylamines can be accessed in a catalytic asymmetric variant. Preliminary mechanistic studies indicate that the formation of a more stable nickelacycle provides the driving force of migration. The thermodynamic and kinetic properties of different reduction elimination intermediates are responsible for the switchable site‐selectivity.
A nickel‐catalyzed switchable site‐selective alkene hydroalkylation was developed. The selection of reaction temperatures led to protocols that provide regiodivergent hydroalkylated products starting from a single alkene substrate.
Intravesical administration of first‐line drugs has shown failure in the treatment of bladder cancer owing to the poor tumor retention time of chemotherapeutics. Herein, we report an intracellular ...hydrolytic condensation (IHC) system to construct long‐term retentive nano‐drug depots in situ, wherein sustained drug release results in highly efficient suppression of bladder cancer. Briefly, the designed doxorubicin (Dox)‐silane conjugates self‐assemble into silane‐based prodrug nanoparticles, which condense into silicon particle‐based nano‐drug depots inside tumor cells. Significantly, we demonstrate that the IHC system possesses highly potent antitumor efficacy, which leads to the regression and eradication of large established tumors and simultaneously extends the overall survival of air pouch bladder cancer mice compared with that of mice treated with Dox. The concept of intracellular hydrolytic condensation can be extended via conjugating other chemotherapeutic drugs, which may facilitate rational design of novel nanomedicines for augmentation of chemotherapy.
An intracellular hydrolytic condensation (IHC) system to construct long‐term retentive nano‐drug depots in situ is presented. Based on silicon particles, the nano‐drug depots are capable of sustained drug release, which results in highly efficient suppression of bladder cancer.
Summary
Crop production is facing unprecedented challenges. Despite the fact that the food supply has significantly increased over the past half‐century, ~8.9 and 14.3% people are still suffering ...from hunger and malnutrition, respectively. Agricultural environments are continuously threatened by a booming world population, a shortage of arable land, and rapid changes in climate. To ensure food and ecosystem security, there is a need to design future crops for sustainable agriculture development by maximizing net production and minimalizing undesirable effects on the environment. The future crops design projects, recently launched by the National Natural Science Foundation of China and Chinese Academy of Sciences (CAS), aim to develop a roadmap for rapid design of customized future crops using cutting‐edge technologies in the Breeding 4.0 era. In this perspective, we first introduce the background and missions of these projects. We then outline strategies to design future crops, such as improvement of current well‐cultivated crops, de novo domestication of wild species and redomestication of current cultivated crops. We further discuss how these ambitious goals can be achieved by the recent development of new integrative omics tools, advanced genome‐editing tools and synthetic biology approaches. Finally, we summarize related opportunities and challenges in these projects.
Significance Statement
To ensure food and ecosystem security, there is a need to design future crops for sustainable agriculture development by maximizing net production and minimalizing undesirable effects on the environment. The future crops design projects, recently launched by the National Natural Science Foundation of China and Chinese Academy of Sciences (CAS), aim to develop a roadmap for rapid design of customized future crops using cutting‐edge technologies in the Breeding 4.0 era.
Recognizing and controlling the structure–activity relationships of single‐atom catalysts (SACs) is vital for manipulating their catalytic properties for various practical applications. Herein, Fe ...SACs supported on nitrogen‐doped carbon (SA‐Fe/CN) are reported, which show high catalytic reactivity (97% degradation of bisphenol A in only 5 min), high stability (80% of reactivity maintained after five runs), and wide pH suitability (working pH range 3–11) toward Fenton‐like reactions. The roles of different N species in these reactions are further explored, both experimentally and theoretically. It is discovered that graphitic N is an adsorptive site for the target molecule, pyrrolic N coordinates with Fe(III) and plays a dominant role in the reaction, and pyridinic N, coordinated with Fe(II), is only a minor contributor to the reactivity of SA‐Fe/CN. Density functional theory (DFT) calculations reveal that a lower d‐band center location of pyrrolic‐type Fe sites leads to the easy generation of Fe‐oxo intermediates, and thus, excellent catalytic properties.
Single‐atom Fe catalysts with different types of nitrogen species are synthesized by controlling the pyrolyzing temperature using a hard‐template strategy. Different roles of the nitrogen species in Fenton‐like reactions are revealed. Graphitic N can adsorb the target molecule, pyrrolic N plays an essential role, and pyridinic N has little role in the reactivity of Fe single‐atom catalysts supported on nitrogen‐doped carbon.
Osteoarthritis (OA) is a chronic disease pathologically characterized by articular cartilage degeneration and damage. Currently, studies have found that circular RNA (circRNA) is involved in ...intracellular RNA regulating network and is closely related to the occurrence and development of diseases, therefore it may become a new biological marker and therapeutic target. After stimulating chondrocytes with interleukin‐1 beta (IL‐1β), hsa_circ_0005105 expression was significantly upregulated, while miR‐26a expression was significantly inhibited. Hsa_circ_0005105 did not influence miR‐26a expression but inhibited its transcriptional activity so as to upregulate the expression of its target NAMPT. Studies further indicated that hsa_circ_0005105 can inhibit the expression of type II collagen and aggrecan, promote the expression of MMP‐13 and ADAMTS‐4, and the generation of PGE2, IL‐6, and IL‐8, but the linear sequence of hsa_circ_0005105 cannot. MiR‐26a has the opposite effect, and hsa_circ_0005105 can antagonize the function of miR‐26a. When NAMPT expression was downregulated, the above function of hsa_circ_0005105 was significantly weakened. Therefore, hsa_circ_0005105 can promote extracellular matrix (ECM) degradation by regulating the expression of miR‐26a target NAMPT. These findings will provide new targets for treatment and prevention of OA and other orthopedic diseases.
The realization of porous materials for highly selective separation of acetylene (C2H2) from various other gases (e.g., carbon dioxide and ethylene) by adsorption is of prime importance but ...challenging in the petrochemical industry. Herein, a chemically stable Hofmann‐type metal−organic framework (MOF), Co(pyz)Ni(CN)4 (termed as ZJU‐74a), that features sandwich‐like binding sites for benchmark C2H2 capture and separation is reported. Gas sorption isotherms reveal that ZJU‐74a exhibits by far the record C2H2 capture capacity (49 cm3 g−1 at 0.01 bar and 296 K) and thus ultrahigh selectivity for C2H2/CO2 (36.5), C2H2/C2H4 (24.2), and C2H2/CH4 (1312.9) separation at ambient conditions, respectively, of which the C2H2/CO2 selectivity is the highest among all the robust MOFs reported so far. Theoretical calculations indicate that the oppositely adjacent nickel(II) centers together with cyanide groups from different layers in ZJU‐74a can construct a sandwich‐type adsorption site to offer dually strong and cooperative interactions for the C2H2 molecule, thus leading to its ultrahigh C2H2 capture capacity and selectivities. The exceptional separation performance of ZJU‐74a is confirmed by both simulated and experimental breakthrough curves for 50/50 (v/v) C2H2/CO2, 1/99 C2H2/C2H4, and 50/50 C2H2/CH4 mixtures under ambient conditions.
A chemically stable Hofmann‐type metal−organic framework is realized for benchmark acetylene capture capacity and separation, mainly attributed to the unique sandwich‐like binding environments constructed by the oppositely adjacent open metal centers and cyanide groups from the two different Ni(CN)42− building units, thus affording a record‐high acetylene uptake at 0.01 bar and very high selectivities for acetylene‐related separation applications.
Cisplatin is a clinically advanced and highly effective anticancer drug used in the treatment of a wide variety of malignancies, such as head and neck, lung, testis, ovary, breast cancer, etc. ...However, it has only a limited use in clinical practice due to its severe adverse effects, particularly nephrotoxicity; 20%-35% of patients develop acute kidney injury (AKI) after cisplatin administration. The nephrotoxic effect of cisplatin is cumulative and dose dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI result in impaired renal tubular function and acute renal failure, chronic kidney disease, uremia, and hypertensive nephropathy. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, apoptosis, oxidative stress, inflammation, and vascular injury in the kidneys. At present, there are no effective drugs or methods for cisplatin-induced kidney injury. Recent in vitro and in vivo studies show that numerous natural products (flavonoids, saponins, alkaloids, polysaccharide, phenylpropanoids, etc.) have specific antioxidant, anti-inflammatory, and anti-apoptotic properties that regulate the pathways associated with cisplatin-induced kidney damage. In this review we describe the molecular mechanisms of cisplatin-induced nephrotoxicity and summarize recent findings in the field of natural products that undermine these mechanisms to protect against cisplatin-induced kidney damage and provide potential strategies for AKI treatment.
Cyclopropene hydrofunctionalization has been a promising strategy for accessing multi‐substituted cyclopropanes; however, cyclopropene hydroalkylation remains underdeveloped. Herein, we report a ...low‐valent CoH‐catalyzed facial‐selective cyclopropene hydroalkylation to access multi‐substituted cyclopropanes. This reaction exhibits a broad substrate scope of alkyl halides and cyclopropenes and tolerates many functional groups. Moderate‐to‐good facial‐selectivity is obtained without any directing groups. Mechanism studies provide evidence that alkyl radicals are generated from alkyl halides and irreversible CoH insertion is responsible for the facial‐selectivity. Our preliminary exploration demonstrates that asymmetric cyclopropene hydroalkylation can be realized without conspicuous auxiliary groups.
Low‐valent CoH‐catalyzed facial‐selective cyclopropene hydroalkylation has been reported. The reaction works in the absence of any additional directing groups.
The use of simple and easily available feedstock to quickly and efficiently obtain compounds with complex molecular structures through the transition-metal-catalyzed construction of C(sp
3
)-C bonds ...has important significance. As traditional C(sp
3
)-C coupling reagents, alkylmetallic reagents often have limitations such as air and moisture sensitivity and difficulties in storage. Nickel-catalyzed reductive olefin hydrocarbonation reactions use alkenes to replace organometallic reagents, reduce the synthesis steps, improve the functional group compatibility, and expand the substrate scope This minireview discusses important progress in the hydroalkylation and hydroarylation of electronically unbiased alkenes in recent years and describes the key mechanism and applications.
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