Emerging roles of nerve-bone axis in modulating skeletal system.

Over the past decades, emerging evidence in the literature has demonstrated that the innervation of bone is a crucial modulator for skeletal physiology and pathophysiology. The nerve-bone axis sparked extensive preclinical and clinical investigations aimed at elucidating the contribution of nerve-bone crosstalks to skeleton metabolism, homeostasis, and injury repair through the perspective of skeletal neurobiology. To date, peripheral nerves have been widely reported to mediate bone growth and development and fracture healing via the secretion of neurotransmitters, neuropeptides, axon guidance factors, and neurotrophins. Relevant studies have further identified several critical neural pathways that stimulate profound alterations in bone cell biology, revealing a complex interplay between the skeleton and nerve systems. In addition, inspired by nerve-bone crosstalk, novel drug delivery systems and bioactive materials have been developed to emulate and facilitate the process of natural bone repair through neuromodulation, eventually boosting osteogenesis for ideal skeletal tissue regeneration. Overall, this work aims to review the novel research findings that contribute to deepening the current understanding of the nerve-bone axis, bringing forth some schemas that can be translated into the clinical scenario to highlight the critical roles of neuromodulation in the skeletal system.

HIF-1α inhibition in macrophages preserves acute liver failure by reducing IL-1ß production.

The development of acute liver failure (ALF) is dependent on its local inducer. Inflammation is a high-frequency and critical factor that accelerates hepatocyte death and liver failure. In response to injury stress, the expression of the transcription factor hypoxia-inducible factor-1α (HIF-1α) in macrophages is promoted by both oxygen-dependent and oxygen-independent mechanisms, thus promoting the expression and secretion of the cytokine interleukin-1ß (IL-1ß). IL-1ß further induces hepatocyte apoptosis or necrosis by signaling through the receptor (IL-1R) on hepatocyte. HIF-1α knockout in macrophages or IL-1R knockout in hepatocytes protects against liver failure. However, whether HIF-1α inhibition in macrophages has a protective role in ALF is unclear. In this study, we revealed that the small molecule HIF-1α inhibitor PX-478 inhibits the expression and secretion of IL-1ß, but not tumor necrosis factor α (TNFα), in bone marrow-derived macrophages (BMDMs). PX-478 pretreatment alleviates liver injury in LPS/D-GalN-induced ALF mice by decreasing the hepatic inflammatory response. In addition, preventive or therapeutic administration of PX-478 combined with TNFα neutralizing antibody markedly improved LPS/D-GalN-induced ALF. Taken together, our data suggest that PX-478 administration leads to HIF-1α inhibition and decreased IL-1ß secretion in macrophages, which represents a promising therapeutic strategy for inflammation-induced ALF.

Recognizing Functional Groups of MES/APG Mixed Surfactants for Enhanced Solubilization toward Benzo[a]pyrene.

Benzo[a]pyrene is difficult to remove from soil due to its high octanol/water partition coefficient. The use of mixed surfactants can increase solubility but with the risk of secondary soil contamination, and the compounding mechanism is still unclear. This study introduced a new approach using environmentally friendly fatty acid methyl ester sulfonate (MES) and alkyl polyglucoside (APG) to solubilize benzo[a]pyrene. The best result was obtained when the ratio of MES/APG was 7:1 under 6 g/L total concentration, with an apparent solubility (Sw) of 8.58 mg/L and a molar solubilization ratio (MSR) of 1.31 for benzo[a]pyrene, which is comparable to that of Tween 80 (MSR, 0.95). The mechanism indicates that the hydroxyl groups (-OH) in APG form "O-H···OSO2-" hydrogen bonding with the sulfonic acid group (-SO3-) of MES, which reduces the electrostatic repulsion between MES molecules, thus facilitating the formation of large and stable micelles. Moreover, the strong solubilizing effect on benzo[a]pyrene should be ascribed to the low polarity of ester groups (-COOCH3) in MES. Functional groups capable of forming hydrogen bonds and having low polarity are responsible for the enhanced solubilization of benzo[a]pyrene. This understanding helps choose suitable surfactants for the remediation of PAH-contaminated soils.

Health risk assessment of heavy metal(loid)s in road dust via dermal exposure pathway from a low latitude plateau provincial capital city: The importance of toxicological verification.

The human health risk assessment through the dermal exposure of metal (loid)s in dust from low latitude and high geological background plateau cities was largely unknown. In this study, the road dust samples were harvested from a typical low-latitude plateau provincial capital city Kunming, Southwest China. The total concentration and dermal bioaccessibility of heavy metal (loid)s in road dust were determined, and their health risks as well as cytotoxicity on human skin keratinocytes were also assessed. The average concentrations of As (28.5 mg/kg), Cd (2.65 mg/kg), Mn (671 mg/kg), and Zn (511 mg/kg) exceeded the soil background values. Arsenic had the highest bioaccessibility after 2 h (3.79%), 8 h (4.24%), and 24 h (16.6%) extraction. The dermal pathway when bioaccessibility is considered has a higher hazard quotient than the conventional method using total metal(loid)s in the dust. In addition, toxicological verification suggested that the dust extracts suppressed the cell viability, increased the reactive oxygen species (ROS) level and DNA damage, and eventually activated the mitochondria-mediated apoptosis pathway, evidenced by the upregulation of Caspase-3/9, Bax, and Bak-1. Cadmium was positively correlated with the mRNA expression of Bax. Taken together, our data indicated that both dermal bioaccessibility and cytotoxicity should be considered for accurate human skin health risk assessment of heavy metal(loid)s in road dust, which may provide new insight for accurate human health risk assessment and environmental management.

Metabolic Regulation of Gene Expression by Histone Lysine ß-Hydroxybutyrylation.

Here we report the identification and verification of a ß-hydroxybutyrate-derived protein modification, lysine ß-hydroxybutyrylation (Kbhb), as a new type of histone mark. Histone Kbhb marks are dramatically induced in response to elevated ß-hydroxybutyrate levels in cultured cells and in livers from mice subjected to prolonged fasting or streptozotocin-induced diabetic ketoacidosis. In total, we identified 44 histone Kbhb sites, a figure comparable to the known number of histone acetylation sites. By ChIP-seq and RNA-seq analysis, we demonstrate that histone Kbhb is a mark enriched in active gene promoters and that the increased H3K9bhb levels that occur during starvation are associated with genes upregulated in starvation-responsive metabolic pathways. Histone ß-hydroxybutyrylation thus represents a new epigenetic regulatory mark that couples metabolism to gene expression, offering a new avenue to study chromatin regulation and diverse functions of ß-hydroxybutyrate in the context of important human pathophysiological states, including diabetes, epilepsy, and neoplasia.

The establishment of diseased human whole organ model by normothermic machine perfusion technique: Principle of concept.

BACKGROUND: The global incidence of liver diseases is rising, yet there remains a dearth of precise research models to mimic these diseases. The use of normothermic machine perfusion (NMP) to study diseased livers recovered from liver transplantation (LT) recipients presents a promising avenue. Accordingly, we have developed a machine perfusion system tailored specifically for the human whole diseased livers and present our experience from the NMP of diseased livers. METHODS: Six diseased livers recovered from LT recipients with different diagnoses were collected. The diseased livers were connected to the machine perfusion system that circulated tailored perfusate, providing oxygen and nutrients. The pressure and flow of the system were recorded, and blood gas analysis and laboratory tests of perfusate and bile were examined to analyze the function of the diseased livers. Liver tissues before and after NMP were collected for histological analysis. RESULTS: Experiments showed that the system maintained the diseased livers in a physiological state, ensuring stable hemodynamics and a suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory tests demonstrated a restoration and sustenance of metabolism with minimal damage. Notably, a majority of the diseased livers exhibited bile production continuously, signifying their vivid functional integrity. The pathological characteristics remained stable before and after NMP. CONCLUSION: We successfully established the machine perfusion system tailored specifically for diseased human whole livers. Through the application of this system, we have developed a novel in vitro model that faithfully recapitulates the main features of human liver disease. This model holds immense promise as an advanced disease modeling platform, offering profound insights into liver diseases and potential implications for research and therapeutic development.

The Relationship between Different Delivery Timing and the Outcome of Premature Rupture of Membranes in Primiparous Women.

Objective: To investigate the relationship between different delivery timing and the outcome of premature rupture of membranes (PROM) in primiparous women. Methods: Within the context of exploring optimal delivery strategies for managing PROM, we conducted a retrospective study at Shijiazhuang Fourth Hospital. From May 2019 to May 2022, a total of 400 single pregnant women with premature rupture of membranes (PROM) at different gestational weeks (28-36 weeks) were enrolled. This study aims to understand the impact of delivery timing on pregnancy outcomes more clearly. Pregnant women were divided into two distinct groups based on gestational weeks: Group A (28 to 33 weeks, n=192) and Group B (34 to 36 weeks, n=208). The clinical data of pregnant women were analyzed retrospectively, and the methods of delivery, maternal and infant pregnancy outcomes, and factors affecting delivery outcomes were compared in different groups. Results: Compared with the delivery methods of the two groups, the proportion of vaginal delivery in group A (69.27%) was significantly higher than that in group B (49.04%). The proportion of assisted vaginal delivery and cesarean section (13.54% and 17.19%) was significantly lower than that in group B (18.75% and 32.21%) (P < .001). There was no difference in neonatal death outcomes between the two groups (P > .297). The incidence of chorioamnionitis, postpartum hemorrhage, and puerperal infection in group A (25.00%), (19.27%) and (11.46%) was significantly higher than that in group B (6.25%), (5.29%) and (2.40%), respectively. The incidence rates of neonatal asphyxia, neonatal respiratory distress syndrome (NRDS), and hypoxic-ischemic encephalopathy (HIE) in group A were 9.38%, 7.29%, and 6.77%, which were significantly higher than those in group B (1.92%, 0.48% and 0.48%) (P = .001). There was no difference in neonatal death outcomes at different delivery times (P = .259). The incidence rates of amniotic infection, postpartum hemorrhage, and puerperal infection were (3.98%), (7.39%) and (3.41%), which were significantly lower than those of pregnant women from PROM to delivery time ≥48 h (24.11%), (15.63%) and (9.38%). The incidence rates of neonatal asphyxia, NRDS, and HIE were (1.14%), (1.14%) and (2.27%) in neonates from PROM to delivery time < 48 h, significantly lower than those in neonates from PROM to delivery time ≥48 h (8.93%), (5.80%), and (4.46%) (P < .001). Logistic regression analysis showed that the older the gestational week was the protective factor for amniotic space infection, postpartum hemorrhage, puerperal infection, neonatal asphyxia, NRDS, and HIE. Late delivery time was an independent risk factor for amniotic cavity infection(P < .001), postpartum hemorrhage(P = .014), puerperal infection(P = .023), neonatal asphyxia(P = .004), and NRDS (P = .028). Conclusion: In pregnant women with PROM who are not at full term, a greater gestational week is associated with a lower rate of adverse delivery outcomes. In contrast, a longer time interval between membrane rupture and delivery is associated with a higher rate of adverse delivery outcomes.

Organophosphorus Flame Retardant TPP-Induced Human Corneal Epithelial Cell Apoptosis through Caspase-Dependent Mitochondrial Pathway.

A widely used organophosphate flame retardant (OPFR), triphenyl phosphate (TPP), is frequently detected in various environmental media and humans. However, there is little known on the human corneal epithelium of health risk when exposed to TPP. In this study, human normal corneal epithelial cells (HCECs) were used to investigate the cell viability, morphology, apoptosis, and mitochondrial membrane potential after they were exposed to TPP, as well as their underlying molecular mechanisms. We found that TPP decreased cell viability in a concentration-dependent manner, with a half maximal inhibitory concentration (IC50) of 220 µM. Furthermore, TPP significantly induced HCEC apoptosis, decreased mitochondrial membrane potential in a dose-dependent manner, and changed the mRNA levels of the apoptosis biomarker genes (Cyt c, Caspase-9, Caspase-3, Bcl-2, and Bax). The results showed that TPP induced cytotoxicity in HCECs, eventually leading to apoptosis and changes in mitochondrial membrane potential. In addition, the caspase-dependent mitochondrial pathways may be involved in TPP-induced HCEC apoptosis. This study provides a reference for the human corneal toxicity of TPP, indicating that the risks of OPFR to human health cannot be ignored.

Genetically encoded protein sensors for metal ion detection in biological systems: a review and bibliometric analysis.

Metal ions are indispensable elements in living organisms and are associated with regulating various biological processes. An imbalance in metal ion content can lead to disorders in normal physiological functions of the human body and cause various diseases. Genetically encoded fluorescent protein sensors have the advantages of low biotoxicity, high specificity, and a long imaging time in vivo and have become a powerful tool to visualize or quantify the concentration level of biomolecules in vivo and in vitro, temporal and spatial distribution, and life activity process. This review analyzes the development status and current research hotspots in the field of genetically encoded fluorescent protein sensors by bibliometric analysis. Based on the results of bibliometric analysis, the research progress of genetically encoded fluorescent protein sensors for metal ion detection is reviewed, and the construction strategies, physicochemical properties, and applications of such sensors in biological imaging are summarized.

A review of the current research on in vivo and in vitro detection for alpha-synuclein: a biomarker of Parkinson's disease.

Parkinson's disease is a health-threatening neurodegenerative disease of the elderly with clinical manifestations of motor and non-motor deficits such as tremor palsy and loss of smell. Alpha-synuclein (α-Syn) is the pathological basis of PD, it can abnormally aggregate into insoluble forms such as oligomers, fibrils, and plaques, causing degeneration of nigrostriatal dopaminergic neurons in the substantia nigra in the patient's brain and the formation of Lewy bodies (LBs) and Lewy neuritis (LN) inclusions. As a result, achieving α-Syn aggregate detection in the early stages of PD can effectively stop or delay the progression of the disease. In this paper, we provide a brief overview and analysis of the molecular structures and α-Syn in vivo and in vitro detection methods, such as mass spectrometry, antigen-antibody recognition, electrochemical sensors, and imaging techniques, intending to provide more technological support for detecting α-Syn early in the disease and intervening in the progression of Parkinson's disease.

Enantiomeric pairs of macrocyclic acylphloroglucinols from Syzygium szemaoense.

Two enantiomeric pairs of macrocyclic acylphloroglucinols (1a/1b and 2a/2b) with an unprecedented carbon skeleton featuring a bicyclo[12.3.1]octadecane core, together with an undescribed biogenetically related long-chain acylphloroglucinol (3), were isolated from Syzygium szemaoense. Their structures were fully established by spectroscopic method, X-ray crystallographic analysis, and ECD calculation. Compounds 1b and 2a/2b exhibited inhibition against death-associated protein kinase-related apoptosis inducing protein kinase 2 (DRAK2) and ATP citrate lyase (ACLY), respectively.

Leukoencephalopathy with calcifications and cysts: A case report with literature review.

Leukoencephalopathy with calcifications and cysts (LCC; OMIM #614561) is a rare disease and at present there are less than 100 cases reported worldwide. Mutations in the SNORD118 gene is now known to be the cause of LCC. We present a case who was heterozygous for the n.70G>A and n.6C>T sequence variants of the SNORD118 gene, variants which to date have not been described. Compared with the cases that we reviewed, our patient had the second longest time to diagnosis (age 56) from onset of symptoms 40 years prior. Moreover, his cousin's family has a high prevalence of epilepsy. This paper reviewed all published reports to date that had descriptive cases involving LCC as well as testing for the SNORD118 gene. Since 1996 only 85 patients have been described in 59 case reports. In this review, we summarize their clinical features, especially central nervous system symptoms, treatment, pathology, and gene testing results.

Base-Promoted Intramolecular Addition of Vinyl Cyclopropanecarboxamides to Access Conformationally Restricted Aza[3.1.0]bicycles.

3-Azabicyclo[3.1.0]hexanes are common structural components in natural products and bioactive compounds. Traditionally, the metal-mediated cyclopropanation domino reaction of chain enzymes is the most commonly used strategy for the construction of this type of aza[3.1.0]bicycle derivative. In this study, a base-promoted intramolecular addition of alkenes used to deliver conformationally restricted highly substituted aza[3.1.0]bicycles is reported. This reaction was tailor-made for saturated aza[3.1.0] bicycle-containing fused bicyclic compounds that may be applied in the development of concise and divergent total syntheses of bioactive compounds.

Sustained silence of tiny signet ring cell carcinoma.

A 47-year-old man developed recurrent bloating. First gastroscopy showed there was a fading lesion about 0.5cm in size near the anterior wall of the large curve of the junction of the gastric antrum and the edge was red, and the biopsy pathology showed signet ring cell carcinoma (SRC). Subsequently, he went to other hospital for endoscopic submucosal dissection (ESD). However, postoperative pathology indicated inflammation. After 6 months, gastroscopy showed that the lesion size was similar to that of the first time, the fading was obvious, and no redness was observed. Another year later, the lesion size was not significantly changed from these before. Weak amplification of Narrow Band Imaging (NBI) showed slight dilatation of the glandular duct, mainly fading, no redness, and the biopsy was still SRC. Finally, he received a second ESD, and the postoperative pathology was consistent with that of our results.

Punicalagin attenuates ventricular remodeling after acute myocardial infarction via regulating the NLRP3/caspase-1 pathway.

CONTEXT: Punicalagin has myocardial protection; the mechanism of punicalagin on ventricular remodeling (VR) after acute myocardial infarction (AMI) remains unclear. OBJECTIVE: These studies explore the role and mechanism of punicalagin in preventing and treating VR after AMI. MATERIALS AND METHODS: Molecular docking was used to predict the targets of punicalagin. After 2 weeks of AMI model, the SD rats were randomly divided into model, and punicalagin (200, 400 mg/kg, gavage) groups for 4 weeks. Thoracotomy with perforation but no ligature was performed on rats in control group. The protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and GSDMD-N, the mRNA expression of NLRP3, caspase-1, GSDMD, interleukin-1ß (IL-1ß) and IL-18 were evaluated. RESULTS: Punicalagin had binding activities with NLRP3 (Vina score, -5.8), caspase-1 (Vina score, -6.7), and GSDMD (Vina score, -6.7). Punicalagin could improve cardiac function, alleviate cardiac pathological changes, minimize the excessive accumulation of collagen in the left ventricular myocardium (p < 0.01), and inhibit cardiomyocyte apoptosis (p < 0.01). Furthermore, punicalagin could inhibit the overexpression of NLRP3, caspase-1, and GSDMD via immunohistochemistry (p < 0.01). Punicalagin inhibited the protein levels of NLRP3, caspase-1, ASC, GSDMD, and GSDMD-N (p < 0.05, p < 0.01). Punicalagin reduced the mRNA expression of NLRP3, caspase-1, GSDMD, IL-1ß and IL-18 (p < 0.05, p < 0.01). CONCLUSIONS: Punicalagin may provide a useful treatment for the future myocardial protection.

Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/reperfusion-induced acute kidney injury via mitochondrial dysfunction.

Kidney tubular epithelial cells are high energy-consuming epithelial cells that depend mainly on fatty acid oxidation for an energy supply. AMP-activated protein kinase (AMPK) is a key regulator of energy production in most cells, but the function of AMPK in tubular epithelial cells in acute kidney disease is unclear. Here, we found a rapid decrease in Thr172-AMPKα phosphorylation after ischemia/reperfusion in both in vivo and in vitro models. Mice with kidney tubular epithelial cell-specific AMPKα deletion exhibited exacerbated kidney impairment and apoptosis of tubular epithelial cells after ischemia/reperfusion. AMPKα deficiency was accompanied by the accumulation of lipid droplets in the kidney tubules and the elevation of ceramides and free fatty acid levels following ischemia/reperfusion injury. Mechanistically, ischemia/reperfusion triggered ceramide production and activated protein phosphatase PP2A, which dephosphorylated Thr172-AMPKα. Decreased AMPK activity repressed serine/threonine kinase ULK1-mediated autophagy and impeded clearance of the dysfunctional mitochondria. Targeting the PP2A-AMPK axis by the allosteric AMPK activator C24 restored fatty acid oxidation and reduced tubular cell apoptosis during ischemia/reperfusion-induced injury, by antagonizing PP2A dephosphorylation and promoting the mitophagy process. Thus, our study reveals that AMPKα plays an important role in protecting against tubular epithelial cell injury in ischemia/reperfusion-induced acute kidney injury. Hence, activation of AMPK could be a potential therapeutic strategy for acute kidney injury treatment.

Activating Adenosine Monophosphate-Activated Protein Kinase Mediates Fibroblast Growth Factor 1 Protection From Nonalcoholic Fatty Liver Disease in Mice.

BACKGROUND AND AIMS: Fibroblast growth factor (FGF) 1 demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. This study investigated the therapeutic activity and mechanism of a nonmitogenic FGF1 variant carrying 3 substitutions of heparin-binding sites (FGF1△HBS ) against NAFLD. APPROACH AND RESULTS: FGF1△HBS administration was effective in 9-month-old diabetic mice carrying a homozygous mutation in the leptin receptor gene (db/db) with NAFLD; liver weight, lipid deposition, and inflammation declined and liver injury decreased. FGF1△HBS reduced oxidative stress by stimulating nuclear translocation of nuclear erythroid 2 p45-related factor 2 (Nrf2) and elevation of antioxidant protein expression. FGF1△HBS also inhibited activity and/or expression of lipogenic genes, coincident with phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its substrates. Mechanistic studies on palmitate exposed hepatic cells demonstrated that NAFLD-like oxidative damage and lipid accumulation could be reversed by FGF1△HBS . In palmitate-treated hepatic cells, small interfering RNA (siRNA) knockdown of Nrf2 abolished only FGF1△HBS antioxidative actions but not improvement of lipid metabolism. In contrast, AMPK inhibition by pharmacological agent or siRNA abolished FGF1△HBS benefits on both oxidative stress and lipid metabolism that were FGF receptor (FGFR) 4 dependent. Further support of these in vitro findings is that liver-specific AMPK knockout abolished therapeutic effects of FGF1△HBS against high-fat/high-sucrose diet-induced hepatic steatosis. Moreover, FGF1△HBS improved high-fat/high-cholesterol diet-induced steatohepatitis and fibrosis in apolipoprotein E knockout mice. CONCLUSIONS: These findings indicate that FGF1△HBS is effective for preventing and reversing liver steatosis and steatohepatitis and acts by activation of AMPK through hepatocyte FGFR4.

Rhodomeroterpene alleviates macrophage infiltration and the inflammatory response in renal tissue to improve acute kidney injury.

Inflammation is broadly recognized as an important factor in the pathogenesis of acute kidney injury (AKI), but pharmacological approaches to alleviate inflammation in AKI have not been proved successful in clinical trials. Macrophage infiltration into renal tissue promotes inflammatory responses that contribute to the pathogenesis of AKI. Suppression of renal tissue inflammatory responses is postulated to improve renal injury of patients and animals. Rhodomeroterpene (RMT) is a novel meroterpenoid isolated from the Rhododendron genus that was shown to exert anti-inflammatory action in vivo or in vitro in this study. We investigated the treatment effects of RMT on LPS-induced sepsis and two different AKI models. The results showed that pretreatment with RMT (30 mg kg-1  d-1 , ip, for 3 days) significantly inhibited acute inflammatory responses in LPS-induced septic mice. In both renal ischemia-reperfusion injury (I/R) and sepsis-induced AKI models, RMT (30 mg kg-1  d-1 , ip, for 3 days) ameliorated renal function and injury and alleviated inflammation by reducing the infiltration of immune cells, including macrophages and neutrophils. Furthermore, our study demonstrated that RMT inhibits inflammatory responses in macrophages. The anti-inflammatory effects of RMT may be due to the inactivation of the IKK/NF-κB and PI3K/PDK1/Akt inflammatory signaling pathways in macrophages. Collectively, our findings indicate that RMT ameliorates renal injury and alleviates the renal inflammatory state in different AKI models, suggesting that RMT may be a potential agent for the treatment of AKI.

Radical Esterification of Unactivated Alkenes Using Formate as Carbonyl Source.

In recent years, methyl formate has received considerable attention as an ideal and green C1 building block to synthesize carboxylic esters. However, examples of a one-step route to esters with one-carbon elongation using methyl formate as a source of methoxycarbonyl radical are still rare. Herein, we present peroxide-induced radical carbonylation of N-(2-methylallyl)benzamides with methyl formate as the precursor of methoxycarbonyl radical and RuCl3 as catalyst, affording a series of biologically valuable 4-[(methoxycarbonyl)methyl]-3,4-dihydroisoquinolinones with good tolerance and insensitivity to moisture in one pot under simple and mild conditions.

Rh(III)-Catalyzed Oxidative Domino C-H/N-H Annulation: Diarylureas as Arylamine Donors for the Assembly of Indolo[2,1-a]isoquinolines.

An efficient and convenient Rh(III)-catalyzed double aryl C(sp2)-H bond and N-H activation and annulation reaction is reported for the synthesis of indolo[2,1-a]isoquinolines in the presence of the Cu(OAc)2 oxidant under heating conditions. Distinct from previous works with other arylamine donors, one molecule of 1,3-diarylurea can serve as a precursor of two molecules of arylamine in the reaction with diaryl-substituted alkynes.