Emerging evidence indicates that microRNAs (miRNAs) have important roles in regulating osteogenic differentiation and bone formation. Thus far, no study has established the pathophysiological role for miRNAs identified in human osteoporotic bone specimens. Here we found that elevated miR-214 levels correlated with a lower degree of bone formation in bone specimens from aged patients with fractures. We also found that osteoblast-specific manipulation of miR-214 levels by miR-214 antagomir treatment in miR-214 transgenic, ovariectomized, or hindlimb-unloaded mice revealed an inhibitory role of miR-214 in regulating bone formation. Further, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-214 and decreased by agomir-214, and miR-214 directly targeted ATF4 to inhibit osteoblast activity. These data suggest that miR-214 has a crucial role in suppressing bone formation and that miR-214 inhibition in osteoblasts may be a potential anabolic strategy for ameliorating osteoporosis.

The development of mild and general methods for C-S bond formation has received significant attention because the C-S bond is indispensable in many important biological and pharmaceutical compounds. Early examples for the synthesis of C-S bonds are generally limited to the condensation reaction between a metal thiolate and an organic halide. Recent chemical approaches for C-S bond formation, based upon direct C-H bond functionalization and decarboxylative reactions, not only provide new insights into the mechanistic understanding of C-S coupling reactions but also allow the synthesis of sulfur-containing compounds from more effective synthetic routes with high atom economy. This review intends to explore recent advances in C-S bond formation via C-H functionalization and decarboxylation, and the growing opportunities they present to the construction of complex chemical scaffolds for applications encompassing natural product synthesis, synthetic methodology development, and functional materials as well as nanotechnology.

Lipid nanoparticles (LNPs) are effective vehicles to deliver mRNA vaccines and therapeutics. It has been challenging to assess mRNA packaging characteristics in LNPs, including payload distribution and capacity, which are critical to understanding structure-property-function relationships for further carrier development. Here, we report a method based on the multi-laser cylindrical illumination confocal spectroscopy (CICS) technique to examine mRNA and lipid contents in LNP formulations at the single-nanoparticle level. By differentiating unencapsulated mRNAs, empty LNPs and mRNA-loaded LNPs via coincidence analysis of fluorescent tags on different LNP components, and quantitatively resolving single-mRNA fluorescence, we reveal that a commonly referenced benchmark formulation using DLin-MC3 as the ionizable lipid contains mostly 2 mRNAs per loaded LNP with a presence of 40%–80% empty LNPs depending on the assembly conditions. Systematic analysis of different formulations with control variables reveals a kinetically controlled assembly mechanism that governs the payload distribution and capacity in LNPs. These results form the foundation for a holistic understanding of the molecular assembly of mRNA LNPs.

Without the need for organohalide precursors, the convenient and general synthesis of aryl (or diaryl) sulfides can be achieved by using aryl carboxylic acids and thiols or disulfides for decarboxylative C-S cross-coupling catalyzed by a bimetallic system (see scheme).

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In recent years, the catalytic enantioselective reactions of p-QMs have drawn much attention, because of their distinctive reactivities. As such, a variety of chiral catalytic systems have been developed. This Focus Review describes the reactions of p-QMs according to the chiral catalyst system used, with the aim of provide the first complete picture of the exciting developments in this field. Special emphasis is placed on recent work regarding their reaction mechanisms.

The first example of nickel(II)-catalyzed site-selective C-H bond trifluoromethylation of arylamine in water is established. In this transformation, a coordinating activation strategy is performed by the utilization of picolinamide as a directing group, and target products are obtained in moderate to good yields. In addition, the catalyst-in-water system can be reutilized eight times with a slight loss of catalytic activity and applied in the green, concise synthesis of acid red 266. Furthermore, a series of control experiments verify that a single-electron transfer mechanism is responsible for this reaction.

The 4-quinolones and their analogs are a heterogeneous group of biologically active compounds that have evolved in modern days to provide utilities at the forefront of antibiotic research. They have been used to combat Gram-negative or Gram-positive bacteria, suppress tumor growth, and treat many serious infections. These antimicrobial agents have also been used to promote apoptosis and DNA repair for the treatment of cancer. This review summarizes the experimental progress made in the synthetic development of various catalytic routes to preparing 4-quinolones and their analogs; discusses our current understanding of the reaction mechanisms involving biocatalytic synthesis, general catalytic synthesis, and asymmetric synthesis; and finally presents the future prospects of the emerging field.