Profilin1 Regulates Trophoblast Invasion and Macrophage Differentiation.

Unexplained recurrent spontaneous abortion (URSA) has been associated with the dysfunction of trophoblasts and decidual macrophages. Current evidence suggests that profilin1 (PFN1) plays an important role in many biological processes. However, little is known about whether PFN1 is related to URSA. Herein, the location of PFN1 was detected by immunohistochemistry, and the level of PFN1 was detected by quantitative real-time PCR, Western blot analysis, and immunohistochemistry. The proliferation of trophoblasts was detected by CCK8 and 5-ethynyl-2'-deoxyuridine assays, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays were used to detect apoptosis of trophoblasts. The migration and invasion ability of trophoblasts was assessed by using the wound-healing test and transwell test. Polarization of macrophages was detected in macrophages cultured in trophoblast conditioned medium. PFN1 expression was observed in cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts and was decreased in the villous tissue of patients with URSA. The migration and invasion ability and cell viability of trophoblastic cell lines that underwent PFN1 knockdown significantly decreased, and apoptosis increased. Opposite findings were observed after the overexpression of PFN1 in trophoblastic cells. In addition, PFN1 could regulate trophoblast function through phosphatidylinositol 3-kinase/AKT signal transduction rather than mitogen-activated protein kinase signaling pathways. Finally, knockdown of PFN1 in trophoblasts promoted tumor necrosis factor-α secretion to induce macrophage polarization to M1 phenotype, mediated by the NF-κB signaling pathway. These findings indicate that PFN1 has a broad therapeutic potential for patients with URSA.

Sub-pm linewidth, high pulse energy, high beam quality microsecond-pulse Ti:sapphire laser at 766.699†nm.

In this letter, a sub-pm linewidth, high pulse energy and high beam quality microsecond-pulse 766.699 nm Ti:sapphire laser pumped by a frequency-doubled Nd:YAG laser is demonstrated. At an incident pump energy of 824 mJ, the maximum output energy of 132.5 mJ at 766.699 nm with linewidth of 0.66 pm and a pulse width of 100 µs is achieved at a repetition rate of 5 Hz. To the best of our knowledge, this is the highest pulse energy at 766.699 nm with pulse width of hundred micro-seconds for a Ti:sapphire laser. The beam quality factor M2 is measured to be 1.21. It could be precisely tuned from 766.623 to 766.755 nm with a tuning resolution of 0.8 pm. The wavelength stability is measured to be less than ±0.7 pm over 30 min. The sub-pm linewidth, high pulse energy and high beam quality Ti:sapphire laser at 766.699 nm can be used to create a polychromatic laser guide star together with a home-made 589 nm laser in the mesospheric sodium and potassium layer for the tip-tilt correction resulting in the near-diffraction limited imagery on a large telescope.

Pterostilbene ameliorates oxidative damage and ferroptosis in human ovarian granulosa cells by regulating the Nrf2/HO-1 pathway.

The survival of ovarian granulosa cells is of great significance to the physiological maintenance of the ovary. Oxidative damage to the ovarian granulosa cells can lead to various diseases related to ovarian dysfunction. Pterostilbene exerts many pharmacological effects, such as anti-inflammatory and cardiovascular protective effects. Moreover, pterostilbene was shown to have antioxidant properties. This study aimed to investigate the effect and underlying mechanism of pterostilbene on oxidative damage in ovarian granulosa cells. Ovarian granulosa cell (OGC) lines COV434 and KGN were exposed to H2O2 to establish an oxidative damage model. After treatment with different concentrations of H2O2 or pterostilbene, the cell viability, mitochondrial membrane potential, oxidative stress, and iron levels were detected, and the expression of ferroptosis-related and Nrf2/HO-1 signaling pathway-related proteins were evaluated. Pterostilbene treatment could effectively improve cell viability, reduce oxidative stress, and inhibit ferroptosis stimulated by H2O2. More importantly, pterostilbene could up-regulate Nrf2 transcription by stimulating histone acetylation, and inhibition of Nrf2 signaling could reverse the therapeutic effect of pterostilbene. In conclusion, this research shows that pterostilbene protects human OGCs from oxidative stress and ferroptosis through the Nrf2/HO-1 pathway.

Electrochemical selenium-catalyzed para-amination of N-aryloxyamides: access to polysubstituted aminophenols.

Aminophenols are a class of important compounds with various pharmacological activities such as anticancer, anti-inflammatory, antimalarial, and antibacterial activities. Herein, we introduce a mild and efficient electrochemical selenium-catalyzed strategy to synthesize polysubstituted aminophenols. High atom efficiency and transition metal-free and oxidant-free conditions are the striking features of this protocol. By merging electrochemical and organoselenium-catalyzed processes, the intramolecular rearrangement of N-aryloxyamides produces para-amination products at room temperature in a simple undivided cell.

Histone deacetylase 6 promotes skin wound healing by regulating fibroblast migration and differentiation in aged mice.

Skin wound healing tends to slow down with aging, which is detrimental to both minor wound recovery in daily life and the recovery after surgery. The aim of current study was to explore the effect of histone deacetylase 6 (HDAC6) on wound healing during aging. Cultured human dermal fibroblasts (HDFs) and mouse full-thickness skin wound model were used to explore the functional changes of replicative senescent dermal fibroblasts and the effect of aging on skin wound healing. Scratch wound healing assay revealed significantly decreased migration speed of senescent HDFs, and BrdU incorporation assay indicated their considerably retardant proliferation. The protein expression levels of collagen and HDAC6 were significantly decreased in both senescent HDFs and skin tissues from aged mice. HDAC6 activity inhibition with highly selective inhibitor tubastatin A (TsA) or HDAC6 knockdown with siRNA decreased the migration speed of HDFs and considerably suppressed fibroblast differentiation induced by transforming growth factor-ß1 (TGF-ß1), which suggests the involvement of HDAC6 in regulating fundamental physiological activities of dermal fibroblasts. In vivo full-thickness skin wound healing was significantly delayed in young HDAC6 knockout mice when compared with young wild type mice. In addition, the wound healing was significantly slower in aged wild type mice than that in young wild type mice, and became even worse in aged HDAC6 knockout aged mice. Compared to the aged wild type mice, aged HDAC6 knockout mice exhibited delayed angiogenesis, reduced collagen synthesis, and decreased collagen deposition in skin wounds. Together, these results suggest that delayed skin wound healing in aged mice is associated with impaired fibroblast function. Adequate expression and activity of HDAC6 are required for fibroblasts migration and differentiation.

Photon Momentum Transfer in Single-Photon Double Ionization of Helium.

We theoretically and experimentally investigate the photon momentum transfer in single-photon double ionization of helium at various large photon energies. We find that the forward shifts of the momenta along the light propagation of the two photoelectrons are roughly proportional to their fraction of the excess energy. The mean value of the forward momentum is about 8/5 of the electron energy divided by the speed of light. This holds for fast and slow electrons despite the fact that the energy sharing is highly asymmetric and the slow electron is known to be ejected by secondary processes of shake off and knockout rather than directly taking its energy from the photon. The biggest deviations from this rule are found for the region of equal energy sharing where the quasifree mechanism dominates double ionization.

Proposal for Measuring Electron Displacement Induced by a Short Laser Pulse.

In laser-matter interaction, most previous studies have focused on the change of the electron momentum induced by the external fields. Here, we theoretically investigate the electron displacement induced by an ultrashort pulse, whose precise waveform is hard to determine experimentally. We propose and numerically demonstrate a scheme to accurately measure the electron displacement using a ruler formed by the interfering spirals in the photoelectron momentum distribution generated by two oppositely circularly polarized pulses. The scheme is robust against the focusing volume effects and the jitter of the carrier envelope phase of the two circular pulses. The ability to measure the electron displacement by an arbitrary pulse may pave the way to quantitative control of the charge migration in matter on the scale of Ångström.

Antimicrobial Secondary Metabolites from the Seawater-Derived Fungus Aspergillus sydowii SW9.

Marine-derived fungi are considered to be valuable producers of bioactive secondary metabolites used as lead compounds with medicinal importance. In this study, chemical investigation of the seawater-derived fungus Aspergillus sydowii SW9 led to the isolation and identification of one new quinazolinone alkaloid, 2-(4-hydroxybenzyl)-4-(3-acetyl)quinazolin-one (1), one new aromatic bisabolene-type sesquiterpenoid, (2) and one new chorismic acid analogue (3), as well as two known alkaloids (compounds 4 and 5). Their structures were determined by extensive 1D/2D NMR and mass spectrometric data, and the absolute configurations of 2 and 3 were assigned by the analysis of ECD spectra aided by quantum chemical computations. Compounds 1, 2, and 4 exhibited selective inhibitory activities against the human pathogenic bacteria Escherichia coli, Staphylococcus aureus, S. epidermidis, and Streptococcus pneumoniae, with MIC values ranging from 2.0 to 16 µg/mL.

[Research advance in chemical compounds,pharmacological action and clinical application of Dengzhan Shengmai Capsules].

Dengzhan Shengmai Capsules( DZSMC),a well-known traditional Chinese medicine( TCM) formula,is comprised of the main drug of Erigeron breviscapus,and supplemented with Panax ginseng,Ophiopogon japonicus and Schisandra chinensis,with functions of supplementing Qi and nourishing Yin,promoting blood circulation and strengthening brain. DZSMC is the only Chinese patent drug with A-level evidence-based medicine in secondary prevention for stroke and ranks first among TCMs for neurological treatment. Modern studies indicate that the chemical constituents of DZSMC mainly include flavonoids,phenolic acids,lignans,saponins and so on. Pharmacological experimental studies have shown that DZSMC has such pharmacological effects as anti-oxidation,anti-inflammatory and anti-myocardial ischemia. DZSMC is mainly used in the convalescent care of ischemic cardiovascular and cerebrovascular diseases,and is often used in combination with various conventional therapeutic drugs to exert clinical efficacy through brain protection,neuroprotection,etc.,and improve clinical symptoms in patients. In this review,according to domestic and international related literature combined with research results obtained by our project,the research advances in the chemical constituents,pharmacological effects and clinical application of DZSMC have been systematically reviewed and summarized,providing reference and support for further study and secondary development of the formula.

Evaluation of medical record quality and communication skills among pediatric interns after standardized parent training history-taking in China.

OBJECTIVE: The effect of using standardized parent training history-taking on the quality of medical records and communication skills among pediatric interns was determined. METHODS: Fifth-year interns who were undertaking a pediatric clinical practice rotation were randomized to intervention and control groups. All of the pediatric interns received history-taking training by lecture and bedside teaching. The pediatric interns in the intervention group also received standardized parent history-taking training. The following two outcome measures were used: the scores of medical records, which were written by the pediatric interns after history-taking from real parents of pediatric patients; and the communication assessment tool (CAT) assessed by real parents. RESULTS: The general information, history of present illness (HPI), past medical history, personal history, family history, diagnosis, diagnostic analysis, and differential diagnosis scores in the intervention group were significantly higher than the control group (p < 0.05). Assessment of the CAT indicated that the real parents were more satisfied with the pediatric interns in the intervention group. CONCLUSIONS: Standardized parent training history-taking is effective in improving the quality of medical records by pediatric interns. Standardized parent training history-taking is a superior teaching tool for clinical reasoning ability, as well as communication skills in clinical pediatric practice.

Plaque distribution of low-grade basilar artery atherosclerosis and its clinical relevance.

BACKGROUND: The underlying pathophysiology of BA distribution is unclear and intriguing. Using high-resolution magnetic resonance imaging (HR-MRI), we sought to explore the plaque distribution of low-grade basilar artery (BA) atherosclerosis and its clinical relevance. METHODS: We retrospectively analyzed the imaging and clinical data of 61 patients with low-grade atherosclerotic BA stenosis (<50%). On HR-MRI, the plaques were categorized based on the involvement of the ventral, dorsal, or lateral sides of BA wall. A culprit plaque was defined if it was on the same slice or neighboring slices of symptomatic pontine infarcts and played a probable causal role (dorsal plaques with median pontine infarcts or lateral plaques with ipsilateral pontine infarcts). The relationships between plaque distribution and clinical presentations were analyzed. RESULTS: Twenty-five symptomatic and thirty-six asymptomatic BAs with 752 HR-MRI image slices were studied. The average length of BA atherosclerosis plaques was 12.16 ± 5.61mm (10.30 ± 6.44mm in symptomatic and 13.46 ± 7.03mm in asymptomatic patients, p = 0.079). The plaque distribution was similar at ventral (29.0%), dorsal (37.6%) and lateral walls (33.1%). The BA plaques in symptomatic patients were more frequently located at the dorsal (42.5%) and lateral (41.2%) walls than at the ventral walls (16.1%; P < 0.05). Compared with symptomatic patients, asymptomatic patients more likely had their plaques distributed at the ventral walls (P = 0.022). Culprit plaques were observed in 85.0% (17/20) pontine infarcts in symptomatic patients and only 14.3% (2/14) silent pontine infarcts in asymptomatic patients (p < 0.001). CONCLUSIONS: Low-grade BA atherosclerosis has a long distribution and evenly involves ventral, dorsal and lateral walls. The plaques at dorsal and lateral walls are associated with symptomatic pontine infarcts but not with silent infarcts.

Roles of Mitogen-Activating Protein Kinase Kinase Kinase Kinase-3 (MAP4K3) in Preterm Skeletal Muscle Satellite Cell Myogenesis and Mammalian Target of Rapamycin Complex 1 (mTORC1) Activation Regulation.

BACKGROUND Preterm skeletal muscle genesis is a paradigm for myogenesis. The role of mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3) in preterm skeletal muscle satellite cells myogenesis or its relationship to mammalian target of rapamycin complex 1 (mTORC1) activity have not been previously elaborated. MATERIAL AND METHODS Small interfering RNA (siRNA) interference technology was used to inhibit MAP4K3 expression. Leucine stimulation experiments were performed following MAP4K3-siRNA interference. The differentiation of primary preterm skeletal muscle satellite cells was observed after siRNA-MAP4K3 interference. Western blot analysis was used to determine the expression of MAP4K3, MyHC, MyoD, myogenin, p-mTOR, and p-S6K1. The immunofluorescence fusion index of MyHC and myogenin were detected. MAP4K3 effects on preterm rat satellite cells differentiation and its relationship to mTORC1 activity are reported. RESULTS MAP4K3 siRNA knockdown inhibited myotube formation and both MyoD and myogenin expression in primary preterm rat skeletal muscle satellite cells, but MAP4K3 siRNA had no effect on the activity of mTORC1. In primary preterm rat skeletal muscle satellite cells, MAP4K3 knockdown resulted in significantly weaker, but not entirely blunted, leucine-induced mTORC1 signaling. CONCLUSIONS MAP4K3 positively regulates preterm skeletal muscle satellite cell myogenesis, but may not regulate mTORC1 activity. MAP4K3 may play a role in mTORC1 full activation in response to leucine.

[Idiopathic teratozoospermia is not correlated with c.144delC polymorphism in the AURKC gene in Sichuan].

OBJECTIVE: To investigate the association of a very common mutation of c.144delC in the aurora kinase C (AURKC) gene with idiopathic teratozoospermia in Chinese infertile men in Sichuan. METHODS: Using polymerase chain reaction (PCR) and next-generation sequencing, we analyzed the correlation between c.144delC polymorphism of the AURKC gene and male infertility in 98 idiopathic teratozoospermia patients in comparison with 162 normal fertile men. RESULTS: Neither c.144delC mutation nor other meaningful mutations were detected in the AURKC gene in the 98 idiopathic teratozoospermia patients or the 162 normal controls. CONCLUSIONS: Teratozoospermia is not correlated with c.144delC mutation in the AURKC gene in the men of the Sichuan area. Therefore, large-scale genotyping of the AURKC gene may not be necessary clinically among Chinese patients with idiopathic teratozoospermia.

Expression of angiogenesis regulatory proteins and epithelial-mesenchymal transition factors in platelets of the breast cancer patients.

Platelets play a role in tumor angiogenesis and growth and are the main transporters of several angiogenesis regulators. Here, we aimed to determine the levels of angiogenesis regulators and epithelial-mesenchymal transition factors sequestered by circulating platelets in breast cancer patients and age-matched healthy controls. Platelet pellets (PP) and platelet-poor plasma (PPP) were collected by routine protocols. Vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), thrombospondin-1 (TSP-1), platelet factor 4 (PF4), and transforming growth factor-ß1 (TGF-ß1) were measured by enzyme-linked immunosorbent assay. Angiogenesis-associated expression of VEGF (2.1 pg/10(6) platelets versus 0.9 pg/10(6) platelets, P < 0.001), PF4 (21.2 ng/10(6) platelets versus 10.2 ng/10(6) platelets, P < 0.001), PDGF-BB (42.9 pg/10(6) platelets versus 19.1 pg/10(6) platelets, P < 0.001), and TGF-ß1 (15.3 ng/10(6) platelets versus 4.3 ng/10(6) platelets, P < 0.001) differed in the PP samples of cancer and control subjects. In addition, protein concentrations were associated with clinical characteristics (P < 0.05). Circulating platelets in breast cancer sequester higher levels of PF4, VEGF, PDGF-BB, and TGF-ß1, suggesting a possible target for early diagnosis. VEGF, PDGF, and TGF-ß1 concentrations in platelets may be associated with prognosis.

[Effects of extensively hydrolyzed protein formula on feeding and growth in preterm infants: a multicenter controlled clinical study].

OBJECTIVE: To study the effects of extensively hydrolyzed protein formula (eHF) on the feeding and growth in preterm infants through a multicenter controlled clinical study. METHODS: Preterm infants admitted to eight upper first-class hospitals in China between February 2012 and December 2013 were randomly selected. They were divided into two observation groups and two control groups. The first observation group consisted of preterm infants with a gestational age of <32 weeks, who were fed with eHF for 10-14 days after birth and then with standard preterm formula (SPF) until discharge. The second observation group consisted of preterm infants with a gestational age of 32-34 weeks, who were fed with SPF after birth, but were switched to eHF (7-14 days) if suffering feeding intolerance at 6-8 days after birth. The two control groups with corresponding gestational ages kept to be fed with SPF after birth. Clinical data were recorded to compare feeding condition, physical growth, blood biochemical indices, and major complications between different groups. RESULTS: A total of 328 preterm infants were enrolled. Preterm infants with a gestational age of <32 weeks in the observation group had a significantly shorter meconium evacuation time than in the corresponding control group (P<0.05). They also had significantly lower levels of serum total bilirubin at weeks 1 and 2 after birth compared with the control group (P<0.05). The observation group needed more time in reaching enteral nutrition (EN) basic energy uptake of 50 kcal/(kg·d), partial parenteral nutrition (PPN), hospitalization, and corrected gestational age at discharge compared with the controlled infants (P<0.05). There was no difference in the incidence of extrauterine growth retardation (EUGR) at discharge between the two groups (P>0.05). Preterm infants with a gestational age of 32-34 weeks in the observation group had significantly lower serum total bilirubin levels at 2 weeks after birth compared with the corresponding control group (P<0.05). They required more time in achieving EN basic energy and PPN than in the control group (P<0.05). There was no difference in the incidence of EUGR at discharge between the two groups (P>0.05). CONCLUSIONS: For preterm infants, eHF can improve gastrointestinal motility, accelerate bilirubin metabolism and excretion and does not increase the incidence of EUGR.

A Data Driven Strategy and Case Study for Implementation of Singlicate Analysis in Ligand Binding Assays Used for PK Quantitation.

Duplicate analysis has been a conventional practice in the industry for ligand-binding assays (LBA), particularly for plate-based platforms like Enzyme-linked immunosorbent assay (ELISA) and Meso Scale Discovery (MSD) assays. Recent whitepapers and guidance have opened a door to exploring the implementation of single-well (singlicate) analysis approach for LBAs. Although the bioanalytical industry has actively investigated the suitability of singlicate analysis, applications in supporting regulated LBA bioanalysis are limited. The primary reason for this limitation is the absence of appropriate strategy to facilitate the transition from duplicate to singlicate analysis. In this paper we present the first case study with our data-driven approach to implement singlicate analysis in a clinical pharmacokinetics (PK) plate based LBA assay with ISR data. The central aspect of this strategy is a head-to-head comparison with Precision and Accuracy assessment in both duplicate and singlicate formats as the initial stage of assay validation. Subsequently, statistical analysis is conducted to evaluate method variability in both precision and accuracy. The results of our study indicated that there was no impactful difference between duplicate vs singlicate, affirming the suitability of singlicate analysis for the remaining steps of PK assay validation. The validation results obtained through singlicate analysis demonstrated acceptable assay performance characteristics across all validation parameters, aligning with regulatory guidance. The validated PK assay in singlicate has been employed to support a Phase I study. The appropriateness of singlicate analyses is further supported by initial Incurred Sample Reanalysis (ISR) data in which 90.1% of ISR samples fall within the acceptable criteria.

The microbiome compositional and functional differences between rectal mucosa and feces.

In recent years, most studies on the gut microbiome have primarily focused on feces samples, leaving the microbial communities in the intestinal mucosa relatively unexplored. To address this gap, our study employed shotgun metagenomics to analyze the microbial compositions in normal rectal mucosa and matched feces from 20 patients with colonic polyps. Our findings revealed a pronounced distinction of the microbial communities between these two sample sets. Compared with feces, the mucosal microbiome contains fewer genera, with Burkholderia being the most discriminating genus between feces and mucosa, highlighting its significant influence on the mucosa. Furthermore, based on the microbial classification and KEGG Orthology (KO) annotation results, we explored the association between rectal mucosal microbiota and factors such as age, gender, BMI, and polyp risk level. Notably, we identified novel biomarkers for these phenotypes, such as Clostridium ramosum and Enterobacter cloacae in age. The mucosal microbiota showed an enrichment of KO pathways related to sugar transport and short chain fatty acid metabolism. Our comprehensive approach not only bridges the knowledge gap regarding the microbial community in the rectal mucosa but also underscores the complexity and specificity of microbial interactions within the human gut, particularly in the Chinese population. IMPORTANCE: This study presents a system-level map of the differences between feces and rectal mucosal microbial communities in samples with colorectal cancer risk. It reveals the unique microecological characteristics of rectal mucosa and its potential influence on health. Additionally, it provides novel insights into the role of the gut microbiome in the pathogenesis of colorectal cancer and paves the way for the development of new prevention and treatment strategies.

DNA adductomics aided rapid screening of genotoxic impurities using nucleosides and 3D bioprinted human liver organoids.

Current genotoxicity assessment methods are mainly employed to verify the genotoxic safety of drugs, but do not allow for rapid screening of specific genotoxic impurities (GTIs). In this study, a new approach for the recognition of GTIs has been proposed. It is to expose the complex samples to an in vitro nucleoside incubation model, and then draw complete DNA adduct profiles to infer the structures of potential genotoxic impurities (PGIs). Subsequently, the genotoxicity is confirmed in human by 3D bioprinted human liver organoids. To verify the feasibility of the approach, lansoprazole chloride compound (Lanchlor), a PGI during the synthesis of lansoprazole, was selected as the model drug. After confirming genotoxicity by Comet assay, it was exposed to different models to map and compare the DNA adduct profiles by LC-MS/MS. The results showed Lanchlor could generate diverse DNA adducts, revealing firstly its genotoxicity at molecular mechanism of action. Furthermore, the largest variety and content of DNA adducts were observed in the nucleoside incubation model, while the human liver organoids exhibited similar results with rats. The results showed that the combination of DNA adductomics and 3D bioprinted organoids were useful for the rapid screening of GTIs.

Electrochemical Oxidative Difunctionalization of Diazo Compounds with Diselenides and Nucleophiles.

An electrochemical oxidative difunctionalization of diazo compounds with diselenides and nucleophiles has been developed. This innovative approach yields a diverse array of selenium-containing pyrazole esters and alkoxy esters, overcoming the limitations of traditional synthesis methods. Remarkably, various nucleophiles, including acids, alcohols, and pyrazoles, can be seamlessly incorporated. Notably, this protocol boasts high atom efficiency, excellent functional group tolerance, and good efficiency and operates under transition metal- and oxidant-free conditions, distinguishing it in the field.

Dearomative Cyclization/Spirocyclization via Electrochemical Reductive Hydroarylation of Nonactivated Arenes.

An electrochemical cyclization/spirocyclization hydroarylation via reductive dearomatization of a series of nonactivated arenes including N-substituted indoles, indole-3-carboxamide derivatives, and iodo-substituted benzamides is described. This protocol boasts high atom efficiency, broad substrate applicability, and excellent selectivity. Utilizing a simple undivided cell, various nonactivated arenes undergo cyclization/spirocyclization through the intramolecular addition of aryl radicals to an aromatic ring, yielding 50 indolines, spirocyclizative hydroarylation products, and phenanthridinones.