Ligand recognition and G-protein coupling of trace amine receptor TAAR1.

Trace-amine-associated receptors (TAARs), a group of biogenic amine receptors, have essential roles in neurological and metabolic homeostasis1. They recognize diverse endogenous trace amines and subsequently activate a range of G-protein-subtype signalling pathways2,3. Notably, TAAR1 has emerged as a promising therapeutic target for treating psychiatric disorders4,5. However, the molecular mechanisms underlying its ability to recognize different ligands remain largely unclear. Here we present nine cryo-electron microscopy structures, with eight showing human and mouse TAAR1 in a complex with an array of ligands, including the endogenous 3-iodothyronamine, two antipsychotic agents, the psychoactive drug amphetamine and two identified catecholamine agonists, and one showing 5-HT1AR in a complex with an antipsychotic agent. These structures reveal a rigid consensus binding motif in TAAR1 that binds to endogenous trace amine stimuli and two extended binding pockets that accommodate diverse chemotypes. Combined with mutational analysis, functional assays and molecular dynamic simulations, we elucidate the structural basis of drug polypharmacology and identify the species-specific differences between human and mouse TAAR1. Our study provides insights into the mechanism of ligand recognition and G-protein selectivity by TAAR1, which may help in the discovery of ligands or therapeutic strategies for neurological and metabolic disorders.

Effect of M2-macrophage treated lymphatic endothelial cells on angiogenesis that promoted osteointegration.

Early vascularization plays an essential role during the whole process in bone regeneration because of the function of secreting cytokines, transporting nutrients and metabolic wastes. As the preliminary basis of bone repair, angiogenesis is regulated by immune cells represented by macrophages to a great extent. However, with the discovery of the endolymphatic circulation system inside bone tissue, the role of vascularization became complicated and confusing. Herein, we developed a macrophage/lymphatic endothelial cells (LECs)/human umbilical vein endothelial cells (HUVECs) co-culture system to evaluate the effect of macrophage treated lymphatic endothelial cells on angiogenesis in vitro and in vivo. In this study, we collected the medium from macrophage (CM) for LECs culture. We found that CM2 could promote the expression of LECs markers and migration ability, which indicated the enhanced lymphogenesis. In addition, the medium from LECs was collected for culturing HUVECs. The CM2-treated LECs showed superior angiogenesis property including the migration capacity and expression of angiogenetic markers, which suggested the superior vascularization. Rat femoral condyle defect model was applied to confirm the hypothesis in vivo. Generally, M2-macrophage treated LECs showed prominent angiogenetic potential coupling with osteogenesis.

Integrin αV mediated activation of myofibroblast via mechanoparacrine of transforming growth factor ß1 in promoting fibrous scar formation after myocardial infarction.

BACKGROUND: Myocardial infarction (MI) dramatically changes the mechanical stress, which is intensified by the fibrotic remodeling. Integrins, especially the αV subunit, mediate mechanical signal and mechanoparacrine of transforming growth factor ß1 (TGF-ß1) in various organ fibrosis by activating CFs into myofibroblasts (MFBs). We investigated a possible role of integrin αV mediated mechanoparacrine of TGF-ß1 in MFBs activation for fibrous reparation in mice with MI. METHODS: Heart samples from MI, sham, or MI plus cilengitide (14 mg/kg, specific integrin αV inhibitor) treated mice, underwent functional and morphological assessments by echocardiography, and histochemistry on 7, 14 and 28 days post-surgery. The mechanical and ultrastructural changes of the fibrous scar were further evaluated by atomic mechanics microscope (AFM), immunofluorescence, second harmonic generation (SHG) imaging, polarized light and scanning electron microscope, respectively. Hydroxyproline assay was used for total collagen content, and western blot for protein expression profile examination. Fibroblast bioactivities, including cell shape, number, Smad2/3 signal and expression of extracellular matrix (ECM) related proteins, were further evaluated by microscopic observation and immunofluorescence in polyacrylamide (PA) hydrogel with adjustable stiffness, which was re-explored in fibroblast cultured on stiff matrix after silencing of integrin αV. The content of total and free TGF-ß1 was tested by enzyme-linked immunosorbent assay (ELISA) in both infarcted tissue and cell samples. RESULT: Increased stiffness with heterogeneity synchronized with integrin αV and alpha smooth muscle actin (α-SMA) positive MFBs accumulation in those less mature fibrous areas. Cilengitide abruptly reduced collagen content and disrupted collagen alignment, which also decreased TGF-ß1 bioavailability, Smad2/3 phosphorylation, and α-SMA expression in the fibrous area. Accordingly, fibroblast on stiff but not soft matrix exhibited obvious MFB phenotype, as evidenced by enlarged cell, hyperproliferation, well-developed α-SMA fibers, and elevated ECM related proteins, while silencing of integrin αV almost abolished this switch via attenuating paracrine of TGF-ß1 and nuclear translocation of Smad2/3. CONCLUSION: This study illustrated that increased tissue stiffness activates CFs into MFBs by integrin αV mediated mechanoparacrine of TGF-ß1, especially in immature scar area, which ultimately promotes fibrous scar maturation.

Preparation and Functionalization of Mono- and Polyfluoroepoxides via Fluoroalkylation of Carbonyl Electrophiles.

We outline a new synthetic method to prepare mono- and polyfluoroepoxides from a diverse pool of electrophiles (ketones, acyl chlorides, esters) and fluoroalkyl anion equivalents. The initially formed α-fluoro alkoxides undergo subsequent intramolecular ring closure when heated. We demonstrated the versatility of the method through the isolation of 16 mono- and polyfluoroepoxide products. These compounds provide unique entry points for further diversification via either fluoride migration coupled with ring opening, or defluorinative functionalization reactions, the latter of which can be used as a late-stage method to install select bioactive moieties. The reaction sequences described herein provide a pathway to functionalize the commonly observed products formed from 1,2-addition into carbonyl electrophiles.

Simple Approach toward N-Heterocyclic Carbene-Protected Gold Nanoclusters.

Little advance has been made toward developing alternative bottom-up synthetic strategies for N-heterocyclic carbene (NHC)-stabilized gold nanoclusters, although this unique class of nanomaterials has exhibited exciting properties. We report in this work a simple and straightforward approach toward NHC-ligated gold nanoclusters by using imidazolium salts rather than free carbenes or NHC-coordinated gold complexes (NHC-Au-X, X is counterions) as precursors. Illustrated here is a one-pot and one-step preparation of an NHC-stabilized Au13Br4 cluster that features a distinct molecular formula, surface motifs, and assembling modes via chemical reduction of dpaAu, NaOMe, and FNHCBn·HBr by NaBH4 (Hdpa is dipyridylamine; FNHCBn·HBr is 1,3-dibenzyl-5,6-difluoro-1H-benzo[d]imidazole-3-ium bromide). In situ UV-vis and NMR studies have elucidated the base-assisted formation of NHCs from imidazolium salts for the protection of the metal core. This work not only reports a new NHC-ligated superatom that completes the Au13 library, thus facilitating structure-property studies, but also opens the door to explore underlying analogues in a facile and reasonable way.

One-step preparation of Pt/Ag nanoclusters for CO2 transformation.

Structurally precise metal nanoclusters with a facile synthetic process and high catalytic performance have been long pursued. These atomically precise nanocatalysts are regarded as model systems to study structure-performance relationships, surface coordination chemistry, and the reaction mechanism of heterogeneous metal catalysts. Nevertheless, the research on silver-based nanoclusters for driving chemical transformations is sluggish in comparison to gold counterparts. Herein, we report the one-step synthesis of Pt/Ag alloy nanoclusters of [PtAg9(C18H12Br3P)7Cl3](C18H12Br3P), which are highly active in catalysing cycloaddition reactions of CO2 and epoxides. The cluster was obtained in a rather simple way with the reduction of silver and platinum salts in the presence of ligands in one pot. The molecular structure of the titled cluster describes the protection of the Pt-centred Ag9 crown by the shell of phosphine ligands and halides. Its electronic structure, as revealed by density function theoretical calculations, adopts a superatomic geometry with 1S21P6 configuration. Interestingly, the cluster displays high activity in the formation of cyclic carbonates from CO2 under mind conditions.

Clinicopathological characteristics of rectal multiple neuroendocrine neoplasms and literature review.

BACKGROUND: There are only a few epidemiological reports available for reference. The clinicopathological features are not clear, so there is no consensus on treating rectal multiple neuroendocrine neoplasms. This study aims to summarize the clinicopathological characteristics and preliminarily discuss the clinical diagnosis and treatment of rectal multiple neuroendocrine neoplasms. METHODS: This study retrospectively analyzed rectal neuroendocrine neoplasm patients diagnosed and treated at the Fourth Hospital of Hebei Medical University from February 2007 to May 2021. The clinicopathological characteristics of rectal multiple neuroendocrine neoplasms were summarized and analyzed in combination with 14 studies on rectal multiple neuroendocrine neoplasms. RESULTS: The incidence of RM-NENs accounted for 3.8% of all R-NENs in this study. The number of tumors varied to some extent, the size of tumors was basically no more than 10 mm, and there were more G1 grade tumors. In the analysis of 46 cases with known lymph node metastasis, the difference in lymph node metastasis rate between the number of tumors < 8 and ≥ 8 was statistically significant (p = 0.002). CONCLUSIONS: The incidence of rectal multiple neuroendocrine neoplasms accounted for 3.8% of all rectal neuroendocrine neoplasms. For rectal multiple neuroendocrine neoplasms, the lymph node metastasis rate was higher when the number of tumors was ≥ 8. The influence of the number of tumors on lymph node metastasis should be considered in the selection of treatment.

Salvia plebeia R.Br. and Rosmarinic Acid Attenuate Dexamethasone-Induced Muscle Atrophy in C2C12 Myotubes.

Skeletal muscle atrophy occurs when protein degradation exceeds protein synthesis and is associated with increased circulating glucocorticoid levels. Salvia plebeia R.Br. (SPR) has been used as herbal remedy for a variety of inflammatory diseases and has various biological actions such as antioxidant and anti-inflammatory activities. However, there are no reports on the effects of SPR and its bioactive components on muscle atrophy. Herein, we investigated the anti-atrophic effect of SPR and rosmarinic acid (RosA), a major compound of SPR, on dexamethasone (DEX)-induced skeletal muscle atrophy in C2C12 myotubes. Myotubes were treated with 10 µM DEX in the presence or absence of SPR or RosA at different concentrations for 24 h and subjected to immunocytochemistry, western blot, and measurements of ROS and ATP levels. SPR and RosA increased viability and inhibited protein degradation in DEX-treated C2C12 myotubes. In addition, RosA promoted the Akt/p70S6K/mTOR pathway and reduced ROS production, and apoptosis. Furthermore, the treatment of RosA significantly recovered SOD activity, autophagy activity, mitochondrial contents, and APT levels in DEX-treated myotubes. These findings suggest that SPR and RosA may provide protective effects against DEX-induced muscle atrophy and have promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy.

Escaping speed of bacteria from confinement.

Microswimmers such as bacteria exhibit large speed fluctuation when exploring their living environment. Here, we show that the bacterium Escherichia coli with a wide range of length speeds up beyond its free-swimming speed when passing through narrow and short confinement. The speedup is observed in two modes: for short bacteria with L <20 µm, the maximum speed occurs when the cell body leaves the confinement, but a flagellar bundle is still confined. For longer bacteria (L ≥ 20 µm), the maximum speed occurs when the middle of the cell, where the maximum number of flagellar bundles locate, is confined. The two speed-up modes are explained by a vanishing body drag and an increased flagella drag-a universal property of an "ideal swimmer." The spatial variance of speed can be quantitatively explained by a simple model based on the resistance matrix of a partially confined bacterium. The speed change depends on the distribution of motors, and the latter is confirmed by fluorescent imaging of flagellar hooks. By measuring the duration of slowdown and speedup, we find that the effective chemotaxis is biased in filamentous bacteria, which might benefit their survival. The experimental setup can be useful to study the motion of microswimmers near surfaces with different surface chemistry.

Chinese abnormal compound heterozygote spinocerebellar ataxia type 8: a case report.

CASE REPORTS: An elderly Chinese male patient was diagnosed with compound heterozygous spinocerebellar ataxia type 8; molecular diagnosis found that the (CTA)n(CTG)n repeat unit of his ATXN8/ATXN8OS gene was 134/93. The patient has a 6-year medical history, mainly manifested by ataxia, dysarthria, abnormal eye movements, and pyramidal signs. Magnetic resonance imaging (MRI) showed no obvious abnormalities in the medulla oblongata and cervical spinal cord except for cerebellar atrophy and sulci enlargement. There are heterozygous SCA8 individuals among his family members, but there are significant differences in their onset age and clinical manifestations. DISCUSSION AND CONCLUSION: This case reminds us that (CTA)n(CTG)n repeats are very prone to dynamic mutations in intergenerational inheritance, and the ATXN8/ATXN8OS gene penetrance is different in different SCA8 individuals, which suggests that genetic detection is of great importance.

Wetting Dynamics of a Lipid Monolayer.

Direct measurement and control of the dynamic wetting properties of a lipid-coated water-air interface over a wide range of surface tension variations have many important applications. However, the wetting dynamics of the interface near its partial-to-complete wetting transition has not been fully understood. Here, we report a systematic study of the wetting dynamics of a lipid-coated water-air interface around a thin glass fiber of diameter 1-5 µm and length 100-300 µm. The glass fiber is glued onto the front end of a rectangular cantilever to form a "long-needle" atomic-force-microscope probe. Three surface modifications are applied to the glass fiber to change its wetting properties from hydrophilic to hydrophobic. A monolayer of phospholipid dipalmitoylphosphatidylcholine (DPPC) is deposited on the water-air interface in a homemade Langmuir-Blodgett trough, and the surface tension γL of the DPPC-coated water-air interface is varied in the range of 2.5 ≲ γL ≲ 72 mN/m. From the measured hysteresis loop of the capillary force for the three coated fiber surfaces with varying γL, we observe a sharp transition from partial to complete wetting when γL is reduced to a critical value (γL)c. The obtained values of (γL)c are 27 ± 1 mN/m for a DPPC-coated fiber surface and 23 ± 1 mN/m for an trichloro(1H,1H,2H,2H-perfluorooctyl) silane (FTS)-coated surface. Below (γL)c, the contact angle θ0 of the liquid interface is found to be zero for both hydrophobic fiber surfaces and the corresponding spreading parameter S becomes positive. For the FTS-coated fiber surface, the height of capillary rise exhibits a jump when γL is reduced to (γL)c, which indicates that a rapidly advancing liquid film is formed on the fiber surface when the partial-to-complete wetting transition takes place. Our experiment thus establishes a quantitative method by which many other liquid interfaces coated with polymers, surfactants, and biomolecules (such as proteins and lipids) may be characterized dynamically.

Symmetric shear banding and swarming vortices in bacterial superfluids.

Bacterial suspensions-a premier example of active fluids-show an unusual response to shear stresses. Instead of increasing the viscosity of the suspending fluid, the emergent collective motions of swimming bacteria can turn a suspension into a superfluid with zero apparent viscosity. Although the existence of active superfluids has been demonstrated in bulk rheological measurements, the microscopic origin and dynamics of such an exotic phase have not been experimentally probed. Here, using high-speed confocal rheometry, we study the dynamics of concentrated bacterial suspensions under simple planar shear. We find that bacterial superfluids under shear exhibit unusual symmetric shear bands, defying the conventional wisdom on shear banding of complex fluids, where the formation of steady shear bands necessarily breaks the symmetry of unsheared samples. We propose a simple hydrodynamic model based on the local stress balance and the ergodic sampling of nonequilibrium shear configurations, which quantitatively describes the observed symmetric shear-banding structure. The model also successfully predicts various interesting features of swarming vortices in stationary bacterial suspensions. Our study provides insights into the physical properties of collective swarming in active fluids and illustrates their profound influences on transport processes.

Magnesium promotes bone formation and angiogenesis by enhancing MC3T3-E1 secretion of PDGF-BB.

Although magnesium and its alloys are candidates for orthopedic implants, they can effectively promote osteogenesis and angiogenesis. However, due to the degradability of magnesium, different concentrations of magnesium ions have different effects on cells, which affects the safety of magnesium implants. The cellular and molecular mechanisms by which magnesium promotes osteogenesis and angiogenesis are still unclear, which further affects its clinical use. In this study, HUVECs were treated with different concentrations of magnesium ions, and the concentration between 1 and 5 mM, especially 5 mM, was most suitable for cultivation of HUVECs. Using gene sequencing, RT-PCR, ELISA and Western blot analysis, we found that magnesium can promote MC3T3-E1 expression and secretion of PDGF-BB. Then, osteogenesis-related tests and angiogenesis-related tests found that magnesium promotes the secretion of PDGF-BB by MC3T3-E1 not only to improve the osteogenic differentiation ability of osteoblasts but also to effectively promote the angiogenic ability of HUVECs.

Comparative effectiveness of PEEK rods versus titanium alloy rods in cervical fusion in a new sheep model.

BACKGROUND: Pedicle screw and rod instrumentation based on titanium can produce satisfying strength and stiffness for spinal fusion. However, excessive stiffness produced by titanium rods may cause stress shielding. Thus, polyetheretherketone (PEEK) rods with a low modulus of elasticity were introduced as substitutes for titanium rods. The purpose of this paper is to compare the effectiveness of PEEK rods versus titanium alloy rods in anterior spinal fusion with a new sheep model. METHODS: Sheep models of anterior-posterior cervical fusion were innovatively adopted in our study. Twenty-four sheep were randomly divided into a control group and a treatment group that received anterior-posterior cervical fixation with titanium rods or PEEK rods, respectively. Then, surgical segments were harvested and assessed by X-ray, micro-CT and histological examination to evaluate the efficiency of bone fusion. RESULTS: No complications related to fixation were found during the research process. The results of the X-ray showed a stronger spinal fusion in the PEEK rod groups than in the titanium rod group at 12 weeks postoperatively, and both groups underwent bone fusion at 24 weeks postoperatively. The results of micro-CT showed that fixation with PEEK rods achieved better bone ingrowth at an early postoperative stage (12 weeks) compared to fixation with titanium rods (bone volume fraction (BVF): 20.26 ± 4.36% vs 14.48 ± 3.49%, p < 0.05). The same trend was detected in the histological analysis, where the mineralized bone fraction in the experiment group (21.01 ± 3.48%) was significantly higher than that in the control group (16.73 ± 2.95%). In addition, better osseointegration was found in the experiment group at the early postoperative stage at 12 weeks (bone apposition (BA): 16.22 ± 3.24% vs 11.67 ± 3.63%, p < 0.05). However, there were no significant differences at 24 weeks postoperatively. CONCLUSION: PEEK rods can be used safely in a sheep model of anterior-posterior cervical fixation. Compared to traditional titanium rods, earlier and more evident bone fusion was found in the PEEK rods group. These slides can be retrieved under Electronic Supplementary Material.

Microstructure, mechanical properties, and in vitro behavior of biodegradable Zn-1Mg-0.1Ca and Zn-1Mg-0.5Ca.

In the present study, the microstructure, mechanical properties, corrosion behavior, wettability, haemocompatibility, and cytocompatibility of the as-cast and as-rolled biodegradable Zn-1Mg-0.1Ca and Zn-1Mg-0.5Ca have been systematically investigated to evaluate their feasibility as potential biodegradable materials. The results demonstrated that the Zn-1Mg-0.1Ca have significantly improved mechanical properties, with the yield strength (YS), ultimate tensile strength (UTS), and elongation of as-rolled Zn-1Mg-0.1Ca are (209.04 ± 28.31) MPa, (331.51 ± 40.06) MPa, and (35.43 ± 3.53)%, respectively. Wettability test results demonstrated that the Zn-1Mg-0.1Ca and Zn-1Mg-0.5Ca have hydrophilic surfaces that can enhance cell responses and tissue-implant interactions. The haemocompatibility evaluation showed that the hemolysis ratio of Zn-1Mg-0.1Ca have a low hemolysis ratio of 0.6%; the platelets remain sphere morphology and are not activated. High cell viability indicates the cytocompatibility of the as-rolled Zn-1Mg-0.1Ca alloy. The Zn-1Mg-0.1Ca alloy can be considered as new suitable biodegradable Zn-based alloys for further biomedical applications.

[Cloning and expression of SmDXS2 gene in Swertia mussotii].

1-deoxy-D-xylulose-5-phosphate synthase2(DXS2) is the first key enzyme of the MEP pathway,which plays an important role in terpene biosynthesis of plants. According to the data of Swertia mussotii transcriptome, DXS2 gene(Gen Bank number MH535905) was cloned and named as Sm DXS2. The bioinformatics results showed that Sm DXS2 has no intron,with a 2 145 bp open reading frame encoding a polypeptide of 714 amino acids. They are belonging to 20 kinds of amino acids,and the most abundant amino acids include Ala,Gly and Trp. The predicted protein molecular weight was 76. 91 k Da and its theoretical isoelectric point(p I) was6. 5,which belonging to a hydrophilic protein. α-Helix and loop were the major motifs of predicted secondary structure of DXS2. The three function domains are TPP＿superfamily,Transket＿pyr＿ superfamily and Transketolase＿C superfamily,respectively. The Sm DXS2 protein shared high identity with other DXS2 proteins of plants. Phylogenetic analysis showed that Sm DXS2 protein is grouped with the gentian DXS2 protein. The recombinant protein of Sm DXS2 gene in Escherichia coli was approximately 92. 00 k Da(containing sumo-His tag protein 13 k Da),which was consistent with the anticipated size.This work will provide a foundation for further functional research of Sm DXS2 protein and increasing the product of iridoid compound by genetic engineering in S. mussotii.

1,2-(Bis)trifluoromethylation of Alkynes: A One-Step Reaction to Install an Underutilized Functional Group.

Modifying the electronic properties of olefins is the quintessential approach to tuning alkene reactivity. In this context, the exploration of trifluoromethyl groups as divergent electronic modifiers has not been considered. In this work, we describe a copper-mediated 1,2-(bis)trifluoromethylation of acetylenes to create E-hexafluorobutenes (E-HFBs) under blue light in a single step. The reaction proceeds with high yield and E/Z selectivity. Since the alkyne captures two trifluoromethyl groups from each molecule of bpyCu(CF3 )3 , mechanistic studies were conducted to illuminate the role of the reactants. Interestingly, E-HFBs exhibit remarkable stability to standard olefin functionalization reactions in spite of the pendant trifluoromethyl groups. This finding has significant implications for medicine, agroscience, and materials.

Aqueous Benzylic C-H Trifluoromethylation for Late-Stage Functionalization.

The installation of trifluoromethyl groups has become an essential step across a number of industries such as agrochemicals, drug discovery, and materials. Consequently, the rapid introduction of this critical functional group in a predictable fashion would benefit current practitioners in those fields. This communication describes a mild trifluoromethylation of benzylic C-H bonds with high selectivity for the least hindered hydrogen atom. The reaction provides monotrifluoromethylation and proceeds in an environmentally friendly acetone/water solvent system. The method can be used to install benzylic trifluoromethyl groups on highly functionalized drug molecules.

Crystallographic features of poly(vinylidene fluoride) film upon an attractive substrate of KBr.

Among all the polymorphs of poly(vinylidene fluoride) (PVDF), the polar γ-form possesses the highest melting point and electrical breakdown strength as well as the strongest solvent and irradiation resistance, which are beneficial for the durability of PVDF products. Since the γ-form is neither kinetically favorable nor the most thermodynamically stable, it is still difficult to attain the exclusive γ-polymorph, particularly in the case of neat PVDF. In this study, the melt isothermal crystallization of PVDF films was carried out between two KBr wafers. Owing to the characteristics of KBr wafer, including no IR absorbance and high optical transmittance, the crystallographic features originating from the KBr substrate can be conveniently elucidated through the in situ inspected techniques of FTIR and PLM. The KBr wafers significantly accelerated the crystallization kinetics of α-crystals, and then readily triggered the solid-state α- to γ-transformation of the pre-formed α-spherulites, resulting in a 10 µm-thick, neat PVDF film with an absolute crystallinity of 35% and a relative γ fraction as high as 94%. When the film thickness was increased to 40 µm, the crystallization rate of the α-form was still rapid, but the solid-state transformation was not appreciable. These interesting crystallographic phenomena are attributed to the existence of ion-dipole interaction between the -CF2 or -CH2 of PVDF chains and the surface of KBr wafer. Unlike most traditional substrate-dominated crystallizations that prevail in a surface epitaxy manner, in which the target films are of ultra-thin thickness (of the order of 10 nm), the ion-dipole interaction promotes the effective thickness to a ten micron level, which enables its production and application at scalable level. Moreover, the triggering of α- to γ-transformation via external fields could be an alternative for achieving the γ-dominant PVDF products, particularly when the introduction of external additives is prohibited.

Silver-mediated oxidative aliphatic C-H trifluoromethylthiolation.

The first example of a practical and direct trifluoromethylthiolation reaction of unactivated aliphatic CH bonds employs a silver-based reagent. The reaction is operationally simple, scalable, and proceeds under aqueous conditions in air. Furthermore, its broad scope and good functional-group compatibility were demonstrated by applying this method to the selective trifluoromethylthiolation of natural products and natural-product derivatives.