TMEM16A inhibits autophagy and promotes the invasion of hypopharyngeal squamous cell carcinoma through mTOR pathway.

Previous studies have indicated that transmembrane protein 16A (TMEM16A) plays a crucial role in the pathogenesis and progression of various tumors by influencing multiple signaling pathways. However, the role of TMEM16A in regulating autophagy via the mammalian target of rapamycin (mTOR) pathway and its impact on the development of hypopharyngeal squamous cell carcinoma (HSCC) remain unclear. Immunohistochemistry and western blotting were used to assess the expression of TMEM16A in HSCC tissues and metastatic lymph nodes. Manipulation of TMEM16A expression levels was achieved in the FaDu cell line through overexpression or knockdown, followed by assessment of its biological effects using cell colony formation, wound healing, transwell, and invasion assays. Additionally, apoptosis and autophagy-related proteins, as well as autophagosome formation, were evaluated through western blotting, transmission electron microscopy, and immunofluorescence following TMEM16A knockdown or overexpression in FaDu cells. Our study revealed significantly elevated levels of TMEM16A in both HSCC tissues and metastatic lymph nodes compared to normal tissues. In vitro experiments demonstrated that silencing TMEM16A led to a notable suppression of HSCC cell proliferation, invasion, and migration. Furthermore, TMEM16A silencing effectively inhibited tumor growth in xenografted mice. Subsequent investigations indicated that knockdown of TMEM16A in HSCC cells could suppress mTOR activation, thereby triggering autophagic cell death by upregulating sequestosome-1 (SQSTM1/P62) and microtubule-associated protein light chain 3 II (LC3II). This study highlights the crucial role of TMEM16A in modulating autophagy in HSCC, suggesting its potential as a therapeutic target for the treatment of this malignancy.

PmAGAMOUS recruits polycomb protein PmLHP1 to regulate single-pistil morphogenesis in Japanese apricot.

Japanese apricot (Prunus mume Sieb. et Zucc.) is a traditional fruit tree with a long history. Multiple pistils (MP) lead to the formation of multiple fruits, decreasing fruit quality and yield. In this study, the morphology of flowers was observed at 4 stages of pistil development: undifferentiated stage (S1), predifferentiation stage (S2), differentiation stage (S3), and late differentiation stage (S4). In S2 and S3, the expression of PmWUSCHEL (PmWUS) in the MP cultivar was significantly higher than that in the single-pistil (SP) cultivar, and the gene expression of its inhibitor, PmAGAMOUS (PmAG), also showed the same trend, indicating that other regulators participate in the regulation of PmWUS during this period. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) showed that PmAG could bind to the promoter and the locus of PmWUS, and H3K27me3 repressive marks were also detected at these sites. The SP cultivar exhibited an elevated level of DNA methylation in the promoter region of PmWUS, which partially overlapped with the region of histone methylation. This suggests that the regulation of PmWUS involves both transcription factors and epigenetic modifications. Also, the gene expression of Japanese apricot LIKE HETEROCHROMATIN PROTEIN (PmLHP1), an epigenetic regulator, in MP was significantly lower than that in SP in S2 to 3, contrary to the trend in expression of PmWUS. Our results showed that PmAG recruited sufficient PmLHP1 to maintain the level of H3K27me3 on PmWUS during the S2 of pistil development. This recruitment of PmLHP1 by PmAG inhibits the expression of PmWUS at the precise time, leading to the formation of 1 normal pistil primordium.

Circular RNA CircSLC22A23 Promotes Gastric Cancer Progression by Activating HNRNPU Expression.

BACKGROUND: Circular RNAs (CircRNAs) play essential roles in cancer occurrence as regulatory RNAs. However, circRNA-mediated regulation of gastric cancer (GC) remains poorly understood. AIM: The purpose of this study was to investigate the molecular mechanism of circSLC22A23 (hsa_circ_0075504) underlying GC occurrence. METHODS: CircSLC22A23 levels were first quantified by quantitative real-time reverse transcription-polymerase chain reaction in GC cell lines, 80 paired GC tissues and adjacent normal tissues, and 27 pairs of plasma samples from preoperative and postoperative patients with GC. Then circSLC22A23 was knocked-down with short hairpin RNA to analyze its oncogenic effects on the proliferation, migration, and invasion of GC cells. Finally, circRNA-binding proteins and their downstream target genes were identified by RNA pulldown, mass spectrometry, RNA immunoprecipitation, quantitative real-time reverse transcription-polymerase chain reaction, and Western blot assays. RESULTS: CircSLC22A23 was found to be highly expressed in GC cells, GC tissues, and plasma from GC patients. Knockdown of circSLC22A23 inhibited GC cell proliferation, migration and invasion. RNA pulldown and RNA immunoprecipitation assays verified the interaction between circSLC22A23 and heterogeneous nuclear ribonucleoprotein U (HNRNPU). Knockdown of circSLC22A23 decreased HNRNPU protein levels. Moreover, rescue assays showed that the tumor suppressive effect of circSLC22A23 knockdown was reversed by HNRNPU overexpression. Finally, epidermal growth factor receptor (EGFR) was found to be one of the downstream target genes of HNRNPU that was up regulated by circSLC22A23. CONCLUSION: CircSLC22A23 regulated the transcription of EGFR through activation of HNRNPU in GC cells, suggesting that circSLC22A23 may serve as a potential therapeutic target for the treatment of GC.

Analysis of abnormal expression of signaling pathways in PQ-induced acute lung injury in SD rats based on RNA-seq technology.

Background: Paraquat (PQ) plays an important role in agricultural production due to its highly effective herbicidal effect. However, it has led to multiple organ failure in those who have been poisoned, with damage most notable in the lungs and ultimately leading to death. Because of little research has been performed at the genetic level, and therefore, the specific genetic changes caused by PQ exposure are unclear.Methods: Paraquat poisoning model was constructed in Sprague Dawley (SD) rats, and SD rats were randomly divided into Control group, paraquat (PQ) poisoning group and Anthrahydroquinone-2,6-disulfonate (AH2QDS) treatment group. Then, the data was screened and quality controlled, compared with reference genes, optimized gene structure, enriched at the gene expression level, and finally, signal pathways with significantly different gene enrichment were screened.Results: This review reports on lung tissues from paraquat-intoxicated Sprague Dawley (SD) rats that were subjected to RNA-seq, the differentially expressed genes were mainly enriched in PI3K-AKT, cGMP-PKG, MAPK, Focal adhesion and other signaling pathways.Conclusion: The signaling pathways enriched with these differentially expressed genes are summarized, and the important mechanisms mediated through these pathways in acute lung injury during paraquat poisoning are outlined to identify important targets for AH2QDS treatment of acute lung injury due to paraquat exposure, information that will be used to support a subsequent in-depth study on the mechanism of PQ action.

Organo-Photocatalytic Anti-Markovnikov Hydroamidation of Alkenes with Sulfonyl Azides: A Combined Experimental and Computational Study.

The construction of C(sp3)-N bonds via direct N-centered radical addition with olefins under benign conditions is a desirable but challenging strategy. Herein, we describe an organo-photocatalytic approach to achieve anti-Markovnikov alkene hydroamidation with sulfonyl azides in a highly efficient manner under transition-metal-free and mild conditions. A broad range of substrates, including both activated and unactivated alkenes, are suitable for this protocol, providing a convenient and practical method to construct sulfonylamide derivatives. A synergistic experimental and computational mechanistic study suggests that the additive, Hantzsch ester (HE), might undergo a triplet-triplet energy transfer manner to achieve photosensitization by the organo-photocatalyst under visible light irradiation. Next, the resulted triplet excited state 3HE* could lead to a homolytic cleavage of C4-H bond, which triggers a straightforward H-atom transfer (HAT) style in converting sulfonyl azide to the corresponding key amidyl radical. Subsequently, the addition of the amidyl radical to alkene followed by HAT from p-toluenethiol could proceed to afford the desired anti-Markovnikov hydroamidation product. It is worth noting that mechanistic pathway bifurcation could be possible for this reaction. A feasible radical chain propagation mechanistic pathway is also proposed to rationalize the high efficiency of this reaction.

Copper-Catalyzed Radical Allene C(sp2 )-H Cyanation.

While the hydrogen atom abstraction (HAA) from C(sp3 )-H bond has been well explored, the radical-mediated chemo- and regio-selective functionalization of allenic C(sp2 )-H bond via direct HAA from C(sp2 )-H bond of allene remains an unsolved challenge in synthetic chemistry. This is primarily due to inherent challenges with addition of radical intermediates to allenes, regioselectivity of HAA process, instability of allenyl radical toward propargyl radical et al. Herein, we report a copper catalyzed allenic C(sp2 )-H cyanation of an array of tri- and di-substituted allenes with exceptional site-selectivity, while mono-substituted allene was successfully cyanated, albeit with a low yield. In the developed strategy, steric N-fluoro-N-alkylsulfonamide, serving as precursor of hydrogen atom abstractor, plays a crucial role in achieving the desired regioselectivity and avoiding addition of N-centered radical to allene.

Yeast: A platform for the production of L -tyrosine derivatives.

L -Tyrosine derivatives are widely applied in the pharmaceutical, food, and chemical industries. Their production is mainly confined to chemical synthesis and plant extract. Microorganisms, as cell factories, exhibit promising advantages for valuable chemical production to fulfill the increase in the demand of global markets. Yeast has been used to produce natural products owing to its robustness and genetic maneuverability. Focusing on the progress of yeast cell factories for the production of L -tyrosine derivatives, we summarized the emerging metabolic engineering approaches in building L -tyrosoine-overproducing yeast and constructing cell factories of three typical chemicals and their derivatives: tyrosol, p-coumaric acid, and L -DOPA. Finally, the challenges and opportunities of L -tyrosine derivatives production in yeast cell factories were also discussed.

Heat shock protein 90 inhibitors induce cell differentiation via the ubiquitin-dependent aurora kinase A degradation in a MPLW515L mouse model of primary myelofibrosis.

Primary myelofibrosis (PMF) is characterized by immature megakaryocytic hyperplasia, splenomegaly, extramedullary hematopoiesis and bone marrow fibrosis. Our preclinical study had demonstrated that aurora kinase A (AURKA) inhibitor MLN8237 reduced the mutation burden of PMF by inducing differentiation of immature megakaryocytes. However, it only slightly alleviated splenomegaly, reduced tissue fibrosis, and normalized megakaryocytes in PMF patients of the preliminary clinical study. So enhancing therapeutic efficacy of PMF is needed. In this study, we found that AURKA directly interacted with heat shock protein 90 (HSP90) and HSP90 inhibitors promoted the ubiquitin-dependent AURKA degradation. We demonstrated that HSP90 inhibitors 17-allylamino-17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), normalized peripheral blood counts, improved splenomegaly, attenuated extramedullary hematopoiesis, decreased tissue fibrosis and reduced mutant burden in a MPLW515L mouse model of PMF. Importantly, both 17-AAG and 17-DMAG treatment at effective doses in vivo did not influence on hematopoiesis in healthy mice. Collectively, the study demonstrates that HSP90 inhibitors induce cell differentiation via the ubiquitin-dependent AURKA and also are safe and effective for the treatment of a MPLW515L mouse model of PMF, which may provide a new strategy for PMF therapy. Further, we demonstrate that combined therapy shows superior activity in acute megakaryocytic leukemia mouse model than single therapy.

Merging Fluorine Incorporation and Functional Group Migration.

Fluorine incorporation by concomitant fluoroalkyl radical addition to alkene or alkyne and functional group migration (FGM) represents an ingenious and robust strategy for the synthesis of structurally diverse fluorinated compounds. This account gives an overview of related studies in our group, in which three main reaction modes are discussed: 1) radical fluoroalkylative difunctionalization of unactivated alkenes via intramolecular FGM; 2) alkene difunctionalization by docking-migration process using fluoroalkyl-containing bifunctional reagents; 3) incorporation of fluoroalkyl group into C(sp3 )-H bond via consecutive hydrogen atom transfer (HAT) and FGM. Relying on these methods, a variety of trifluoromethylation and di-/mono-fluoroalkylation reactions along with the migration of cyano, heteroaryl, oximino, formyl, alkynyl, and alkenyl groups have been accomplished under mild conditions.

Potent Half-Sandwich 16-/18-Electron Iridium(III) and Ruthenium(II) Anticancer Complexes with Readily Available Amine-Imine Ligands.

The synthesis and biological evaluation of stable 16-electron half-sandwich complexes have remained scarce. We herein present the different coordination modes (16-electron or 18-electron) between half-sandwich iridium(III) complexes and ruthenium(II) complexes derived from the same amine-imine ligands chelating hybrid sp3-N/sp2-N donors. The 16-electron iridium(III) and 18-electron ruthenium(II) complexes with different counteranions were obtained and identified by various techniques. The promising cytotoxicity of these complexes against A549 lung cancer cells, cisplatin-resistant A549/DPP cells, cervical carcinoma HeLa cells, and human hepatocellular liver carcinoma HepG2 cells was observed with IC50 values ranging from 5.4 to 16.3 µM. Moreover, these complexes showed a certain selectivity (selectivity index: 2.1-3.7) toward A549 cells and BEAS-2B normal cells. The variation of metal center, counteranion, 16/18-electron coordination mode, and ligand substituents showed little influence on the cytotoxicity and selectivity of these complexes. The mechanism of action study showed that these complexes could target mitochondria, induce the depolarization of the mitochondrial membrane, and promote the generation of intracellular reactive oxygen species (ROS). Further, the induction of cell apoptosis and the perturbation of the cell cycle in the G0/G1 phase were also observed for these complexes. Overall, it seems that the redox mechanism dominated the anticancer efficacy of these complexes.

Causal relationship between atrial fibrillation and stroke risk: a Mendelian randomization.

OBJECTIVES: This study aimed to investigate the causal relationship between Atrial Fibrillation (AF) and the risk of Stroke using a Mendelian randomization (MR) approach. METHODS: A two-sample MR analysis was conducted using publicly available genome-wide association study (GWAS) summary statistics data. In this analysis, genetic variants associated with AF were used as instrumental variables to estimate the causal effect. The inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were employed for estimation. Additionally, sensitivity analysis was performed using the leave-one-out method. RESULTS: The analysis included 87 single nucleotide polymorphisms (SNPs) associated with AF. The results from the IVW method indicated a positive association between genetic predisposition to AF and the risk of stroke (OR 1.002, 95 % CI 1.001-1.003, P < 0.001). The weighted median and MR-Egger methods showed consistent results (weighted median: OR 1.001, 95 % CI 1.000-1.002, P = 0.034; MR-Egger: OR 1.001, 95 % CI 1.000-1.003, P = 0.086). Sensitivity analysis demonstrated that no individual SNP significantly influenced the causal inference. CONCLUSIONS: This study provides evidence of a causal relationship between AF and an elevated risk of stroke. These findings emphasize the significance of managing AF in order to prevent and treat strokes. Additional research is required to better understand the underlying mechanisms of this causal association.

[Application and prospect of natural active ingredients of traditional Chinese medicine in immunological adjuvant for influenza vaccine].

Vaccination is an effective method for preventing influenza, and adjuvants can enhance the immune response intensity and persistence of influenza vaccines. However, there are currently shortcomings in clinical adjuvant approvals, ineffectiveness against weak antigens, and a tendency to cause headaches. Therefore, the development of safe and effective novel adjuvants for influenza vaccines is particularly important to enhance vaccine immunogenicity and safety. Given the wide range of sources, high safety, and biodegradability of traditional Chinese medicine(TCM), some studies have described it as a vaccine adjuvant. This article reviewed the current status and challenges of influenza vaccine adjuvants, summarized the types of TCM adjuvants, the safety and immunomodulatory effects of natural active ingredients from TCM combined with influenza vaccines, the role of TCM adjuvants in antigen storage, antigen presentation capability, immune cells and cytokines, and immune responses, and analyzed the advantages and disadvantages of TCM adjuvants compared with small molecule adjuvants, with the aim of promoting the clinical development and commercialization of TCM adjuvants for influenza vaccines.

Artificial Intelligence-Assisted Microcatheter Shaping for Intracranial Aneurysm Coiling: A Preliminary Study.

BACKGROUND: To evaluate the efficacy of artificial intelligence (AI) technology-assisted microcatheter shaping for coil embolization of intracranial aneurysms. METHODS: From June 2019 to May 2021, 30 aneurysms in 24 patients were treated with coiling embolization using computer software-assisted microcatheter shaping at our institution. All patients underwent digital subtraction angiography (DSA) before coiling embolization. After three-dimensional (3D) rotational angiography, digital imaging and communications in medicine (DICOM) data were extracted and imported into computer software based on an AI algorithm. 3D images of the parent artery and aneurysm were constructed with the software and data including the central axis of the parent artery, aneurysm location, aneurysm size, and 3D structure were automatically obtained. The optimal microcatheter path was calculated and the shape of the mandrel was automatically generated. Surgeons shaped the mandrel and microcatheter following the AI-generated template and completed the endovascular procedure. RESULTS: All patients successfully completed the endovascular procedure without perioperative complications. The microcatheters shaped as per the AI template accurately entered the aneurysm sacs in 1 attempt; 15 aneurysms required no microguidewire assistance in catheterizing the aneurysm sac and 15 did. The stability of the microcatheters during the procedures was satisfactory. No rebound incidence was observed and no reshaping was necessary. CONCLUSIONS: The AI-assisted microcatheter shaping technology provides a new method to generate the optimal shape for the mandrel and microcatheter during endovascular procedures. The technology facilitates microcatheter accuracy and stability during coiling embolization and provides technical support for surgeons.

The roles and mechanisms of circular RNAs related to mTOR in cancers.

BACKGROUND: Circular RNAs (circRNAs) are stable molecules with covalently closed structures that have an irreplaceable role in the occurrence, progression, and even treatment of plenty of cancers. Mammalian/mechanistic target of rapamycin (mTOR) is a key regulator in cancers and plays several biological functions, such as proliferation, migration, invasion, autophagy, and apoptosis. METHODS: All data were collected through PubMed and CNKI, using terms including "circRNA," "mTOR," "caner," "signaling pathway," "biomarker," "diagnosis," "treatment." Articles published in Chinese and English were included. RESULTS: In this review, the expression, function, and mechanism of circRNA-associated mTOR in cancers were described. CircRNA-associated-mTOR can regulate the progression and therapy of a variety of cancers in multiple signaling pathways, such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mTOR, mitogen-activated protein kinase (MAPK)/mTOR, and AMP-activated protein kinase (AMPK)/mTOR axis. These cancers including esophageal carcinoma (circLPAR3, ciRS-7), gastric cancer (circNRIP1, hsa_circ_0010882, hsa_circ_0000117, hsa_circ_0072309, and circST3GAL6), colorectal cancer (hsa_circ_0000392, hsa_circ_0084927, hsa_circ_0104631, and circFBXW7), liver cancer (circC16orf62, hsa_circ_100338, hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792, hsa_circ_0079299, and hsa_circ_0002130), pancreatic cancer (circ-IARS and circRHOBTB3), renal carcinoma (ciRS-7), bladder cancer (circUBE2K), prostate cancer (circMBOAT2 and circ-ITCH), ovarian cancer (circEEF2, circRAB11FIP1, circMYLK, and circTPCN), endometrial cancer (hsa_circ_0002577 and circWHSC1), lung cancer (circHIPK3, hsa_circ_0001666), thyroid cancer (hsa_circ_0007694 and hsa_circ_0008274), glioma (circGFRA1, circ-MAPK4, circPCMTD1, and hsa_circ_0037251), osteosarcoma (circTCF25), leukemia (circ-PRKDC), and breast cancer (hsa_circ_0000199, circUBAP2, and circWHSC1).

Application of covered stent graft in the treatment of complex carotid artery lesions: A single center experience.

PURPOSE: To assess the clinical efficiency and imaging outcome of applying covered stent grafts for the treatment of complex carotid artery lesions. METHOD: A total of 39 consecutive patients with carotid artery lesions treated with covered stent grafts at our institution from December 2016 to December 2019 were reviewed. Two kinds of stent including self-expandable covered stent (Viabahn; W. L. Gore & Associates) and balloon-expandable covered stent (Willis; Microport) were applied. The angiograms immediately after the procedure, perioperative complications, and follow-up outcomes were recorded. RESULT: Based on imaging features, 11 patients exhibited pseudoaneurysms, 23 patients had blood blister-like aneurysms (BBAs), and five patients were carotid cavernous fistulas. A total of 40 stent implantations were performed, including nine Viabahn stents and 31 Willis stents. Two patients received double implants of Willis stents. Stent failed to perform for one patient due to tortuous parent artery. The angiography reports immediately after the procedure showed that the lesions in 36 patients were completely occluded, whereas two patients had minimal endoleaks. With respect to the occurrence of procedural complications, an aneurysm ruptured during the procedure in one case, which resulted in CCF, and acute in-stent thrombosis occurred in another case. Clinical and angiographic follow-up (11.2±2.4 months) sessions were conducted for 38 patients and a complete lesion exclusion was achieved in 36 patients. The minimal endoleak persisted in one patient and another patient experienced recurrence with stent migration, leading to ipsilateral blepharoptosis. However, none of the patients developed hemorrhage or ischemia and in-stent stenosis was not observed. CONCLUSION: Covered stent grafts appear to be a safe and feasible for the treatment of complex carotid artery lesions. Despite the potential for stent delivery failure as well as endoleak and procedure-related complications, covered stent grafts should be considered when selecting the optimal treatment strategy.

Radical-mediated rearrangements: past, present, and future.

Rearrangement reactions, one of the most significant transformations in organic chemistry, play an irreplaceable role in improving synthetic efficiency and molecular complexity. Concomitant cleavage and reconstruction of chemical bonds can display the great artistry and the glamour of synthetic chemistry. Over the past century, ionic rearrangement reactions, in particular those involving cationic pathways, have represented most of the research. Alongside the renaissance of radical chemistry, radical-mediated rearrangements have recently seen a rapid increase of attention from the chemical community. Many new radical rearrangements that extensively reveal the migratory behaviour of functional groups have been unveiled in the last decade. This Review provides a comprehensive perspective on the area from the past to present achievements, and brings up the prospects that may inspire colleagues to develop more useful synthetic tools based on radical rearrangements.

Asymmetric Radical Cyclization of Alkenes by Stereospecific Homolytic Substitution of Sulfinamides.

We report a novel asymmetric radical cyclization of alkenes via stereospecific homolytic substitution of sulfinamides. This reaction produces a variety of cyclic sulfinamides with excellent stereocontrol. The protocol features broad functional group tolerance, high product diversity, and easy accessibility to feedstocks, and outlines a new pathway for the synthesis of chiral cyclic sulfinamides.

Radical-Mediated Remote Functional Group Migration.

Alkenes are ubiquitous in natural products and are extensively used as synthetic feedstocks in multiple fields including organic synthesis, medicinal chemistry, and materials science. Radical-mediated difunctionalization of alkenes provides a powerful tactic for alkene utilization. Despite the considerable progress made in the past several decades, state-of-the-art methods are highly dependent upon activated alkenes in which a proximal group with a π-electron system (e.g., aryl, carbonyl, and heteroatom) is requisite to stabilize the nascent alkyl radical intermediate via p-π conjugation or p orbitals of the heteroatom. In contrast, the transformation of unactivated alkenes, such as aliphatic alkenes, remains challenging.To overcome this obstacle, we have recently disclosed the strategy of intramolecular distal functional group migration (FGM), which has been efficiently applied in radical difunctionalization of unactivated alkenes. A portfolio of functional groups, such as cyano, heteroaryl, oximino, formyl, and alkynyl groups, showcase the excellent migratory aptitude. Mechanistically, after the addition of an extrinsic radical to the alkene, the newly formed active alkyl radical is rapidly captured by the intramolecular migratory group to generate a cyclic intermediate. Subsequent cleavage of the cyclic C-C bond of the intermediate leads to the functionalized product through the FGM process. Based on the strategy of FGM, a set of elusive difunctionalizations of unactivated alkenes have been accomplished (Part A).Alongside this research, an upgraded highly efficient synthetic strategy, "dock-migration," is created for intermolecular difunctionalization of alkenes. A diversity of sulfone-based dual-function reagents are developed. The intermolecular transformation is initiated by docking the dual-function reagent to the alkene, followed by intramolecular migration of the functional group. Compared to the original FGM protocol, the scope of alkenes is significantly extended from the strategically placed tertiary alcohol-substituted alkenes to general alkenes. Both activated and unactivated alkenes are well tolerated. By this approach, radical-mediated fluoroalkylheteroarylation, fluoroalkylalkynylation, and alkylation of alkenes have been achieved (Part B).Direct elaboration of C-H bonds into the targeted functional groups represents one of the most ideal and straightforward methods for molecular functionalization. The FGM strategy proves to be an ingenious tool for radical-mediated functionalization of remote unactivated C(sp3)-H bonds. Based on the FGM process, we have accomplished: (a) remote C(sp3)-H heteroarylation and cyanation of unprotected alcohols via the cascade of alkoxy radical-enabled hydrogen atom transfer (HAT) and intramolecular functional group (e.g., heteroaryl, cyano) migration, and (b) distal C(sp3)-H vinylation of propargylic alcohols through consecutive alkenyl radical-promoted HAT process and subsequent alkenyl migration (Part C).

Analytical Consideration for the Maximum Spreading Factor of Liquid Droplet Impact on a Smooth Solid Surface.

Based on the energy conservation approach, this study develops a universal model to predict the maximum spreading factor of liquid droplet impact on a smooth solid surface. Validated with the present simulations and experiments in the literature, this model effectively overcomes the limitation of previous models in the viscous regime and greatly reduces the computing errors from over 30% to below 6%. It is demonstrated that the underestimated maximum spreading factor by previous models results from the overestimation of viscous dissipation. By replacing the conventional model of spreading time, tm = 8D0/3U0, with a more precise one, tm = 1.47τiWe-0.44, the formulation to compute the viscous dissipation of entire spreading is improved. Finally, we examine the applicability of present model in the capillary regime and good performance is also shown.

Alkene Difunctionalization Triggered by a Stabilized Allenyl Radical: Concomitant Installation of Two Unsaturated C-C Bonds.

Radical-mediated difunctionalization of alkenes provides a promising approach to introduce one alkenyl or alkynyl group to target compounds. However, simultaneous installation of two unsaturated C-C bonds via alkene difunctionalization remains elusive, attributable to the high instability and transient lifetimes of alkenyl and alkynyl radicals. Herein, we report the photocatalytic 1,2-alkynylalkenylation and 1,2-enynylalkenylation of alkenes for the first time, triggered by the intermolecular addition of a stabilized allenyl radical to an alkene. A portfolio of strategically designed, easily accessible dual-function reagents are applied to a radical docking-migration cascade. The protocol has broad substrate scope and efficiently increases the degree of unsaturation.