Synergistic assessment of multi-scenario urban waterlogging through data-driven decoupling analysis in high-density urban areas: A case study in Shenzhen, China.

Extreme meteorological events and rapid urbanization have led to serious urban flooding problems. Characterizing spatial variations in flooding susceptibility and elucidating its driving factors are essential for preventing damages from urban pluvial flooding. However, conventional methods, limited by spatial heterogeneity and the intricate mechanisms of urban flooding, frequently demonstrated a deficiency in precision when assessing flooding susceptibility in dense urban areas. Therefore, this study proposed a novel framework for an integrated assessment of urban flood susceptibility, based on a comprehensive cascade modeling chain consisting of XGBoost, SHapley Additive exPlanations (SHAP), and Partial Dependence Plots (PDP) in combination with K-means. It aimed to recognize the specific influence of urban morphology and the spatial patterns of flooding risk agglomeration under different rainfall scenarios in high-density urban areas. The XGBoost model demonstrated enhanced accuracy and robustness relative to other three benchmark models: RF, SVR, and BPDNN. This superiority was effectively validated during both training and independent testing in Shenzhen. The results indicated that urban 3D morphology characteristics were the dominant factors for waterlogging magnitude, which occupied 46.02 % of relative contribution. Through PDP analysis, multi-staged trends highlighted critical thresholds and interactions between significant indicators like building congestion degree (BCD) and floor area ratio (FAR). Specifically, optimal intervals like BCD between 0 and 0.075 coupled with FAR values between 0.5 and 1 have the potential to substantially mitigate flooding risks. These findings emphasize the need for strategic building configuration within urban planning frameworks. In terms of the spatial-temporal assessment, a significant aggregation effect of high-risk areas that prone to prolonged duration or high-intensity rainfall scenarios emerged in the old urban districts. The approach in the present study provides quantitative insights into waterlogging adaptation strategies for sustainable urban planning and design.

Characterization of the Metabolites of Neonicotinoid Insecticide Imidaclothiz in Mice.

As a member of the neonicotinoid group, imidaclothiz has garnered increasing attention due to its possible health risks. This study investigated the metabolism and distribution of imidaclothiz in mice. Seven imidaclothiz metabolites were found, four of which are known, and three are unknown. The metabolic reactions observed were hydroxylation, nitrate ester hydrolysis, methylation, urea formation, and reduction to NO. Precise quantification revealed that after 2 h of oral administration, imidaclothiz rapidly dispersed into various organs and tissues, peaking at 4 h, and was then swiftly eliminated. No propensity for accumulation in the body, particularly in the liver, was observed. Toxicity data from the T.E.S.T prediction indicated that imidaclothiz had moderate toxicity to rats, and a majority of its metabolites were more toxic than the parent compound. These findings complement the existing knowledge of the imidaclothiz environmental fate in mammals and offer a reference point for its application in agriculture and industry.

Framework nucleic acid-based nanoparticles enhance temozolomide sensitivity in glioblastoma.

O6-methylguanine DNA methyltransferase (MGMT) is a crucial determinant of temozolomide (TMZ) sensitivity in patients with glioblastoma (GBM). The therapeutic potential of small interfering RNA (siRNA) targeting MGMT to enhance TMZ sensitivity has been hampered by serum nuclease degradation, off-target effects, poor accumulation at tumor sites, and low circulation in blood stream. In this study, we developed a framework nucleic acid-based nanoparticles (FNN), which is constructed from a six-helix DNA bundle, to encapsulate and protect siMGMT for improving TMZ sensitivity in GBM treatment. For better blood-brain barrier (BBB) penetration and GBM targeting, we conjugated Angiopep-2 (ANG) targeting modules to each end of the FNN. Nucleolin (NCL)-responsive locks were engineered along the sides of the six-helix DNA bundle, which safeguard siMGMT before tumor entry. Upon interaction with tumor-overexpressed NCL, these locks unlock, exposing siMGMT, this allows for effective suppression of MGMT, resulting in a significant improvement of TMZ therapeutic efficacy in GBM. This innovative strategy has the potential to transform the current treatment landscape for GBM.

Inhibitory effects of chlorophyll pigments on the bioaccessibility of ß-carotene: Influence of chlorophyll structure and oil matrix.

Chlorophylls and ß-carotene are fat-soluble phytochemicals in daily diets, while their bioaccessibility interaction remains unknown. Eight dietary chlorophylls and their derivatives (chlorophyll a, chlorophyll b, pheophytin a, pheophytin b, chlorophyllide a, chlorophyllide b, pheophorbide a, pheophorbide b) were combined with ß-carotene in six different oil matrices (corn oil, coconut oil, medium-chain triglycerides, peanut oil, olive oil and fish oil) and were subjected to in vitro digestion. Generally, chlorophylls significantly decreased ß-carotene bioaccessibility by competitive incorporation into micelles. Dephytylated chlorophylls had a greater inhibitory effect on the micellarization and bioaccessibility of ß-carotene compared to phytylated chlorophylls. In their co-digestion system, olive oil group exhibited the smallest particle size and biggest zeta potential in both digesta and micelles. For chlorophylls, the phytol group and their levels are key factors, which was also buttressed by the mice model where additional supplementation of pheophorbide a significantly hindered the accumulation of ß-carotene and retinoids compounds.

Histone H3K9 Lactylation Confers Temozolomide Resistance in Glioblastoma via LUC7L2-Mediated MLH1 Intron Retention.

Temozolomide (TMZ) resistance remains the major obstacle in the treatment of glioblastoma (GBM). Lactylation is a novel post-translational modification that is involved in various tumors. However, whether lactylation plays a role in GBM TMZ resistance remains unclear. Here it is found that histone H3K9 lactylation (H3K9la) confers TMZ resistance in GBM via LUC7L2-mediated intron 7 retention of MLH1. Mechanistically, lactylation is upregulated in recurrent GBM tissues and TMZ-resistant cells, and is mainly concentrated in histone H3K9. Combined multi-omics analysis, including CUT&Tag, SLAM-seq, and RNA-seq, reveals that H3K9 lactylation is significantly enriched in the LUC7L2 promoter and activates LUC7L2 transcription to promote its expression. LUC7L2 mediates intron 7 retention of MLH1 to reduce MLH1 expression, and thereby inhibit mismatch repair (MMR), ultimately leading to GBM TMZ resistance. Of note, it is identified that a clinical anti-epileptic drug, stiripentol, which can cross the blood-brain barrier and inhibit lactate dehydrogenase A/B (LDHA/B) activity, acts as a lactylation inhibitor and renders GBM cells more sensitive to TMZ in vitro and in vivo. These findings not only shed light on the mechanism of lactylation in GBM TMZ resistance but also provide a potential combined therapeutic strategy for clinical GBM treatment.

Natural product Kaji-ichigoside F1 exhibits rapid antidepression via activating the AMPA-BDNF-mTOR pathway and inhibiting the NMDAR-CaMKIIα pathway.

BACKGROUND: Depression is a common and recurrent neuropsychiatric disorder. Recent studies have shown that the N-methyl-d-aspartate (NMDA) receptor (NMDAR) is involved in the pathophysiology of depression. Previous studies have found that Kaji-ichigoside F1 (KF1) has a protective effect against NMDA-induced neurotoxicity. However, the antidepressant mechanism of KF1 has not been confirmed yet. PURPOSE: In the present study, we aimed to evaluate the rapid antidepressant activity of KF1 and explore the underlying mechanism. STUDY DESIGN: First, we explored the effect of KF1 on NMDA-induced hippocampal neurons and the underlying mechanism. Second, depression was induced in C57BL/6 mice via chronic unpredictable mild stress (CUMS), and the immediate and persistent depression-like behavior was evaluated using the forced swimming test (FST) after a single administration of KF1. Third, the contributions of NMDA signaling to the antidepressant effect of KF1 were investigated using pharmacological interventions. Fourth, CUMS mice were treated with KF1 for 21 days, and then their depression-like behaviors and the underlying mechanism were further explored. METHODS: The FST was used to evaluate immediate and persistent depression-like behavior after a single administration of KF1 with or without NMDA pretreatment. The effect of KF1 on depressive-like behavior was investigated in CUMS mice by treating them with KF1 once daily for 21 days through the sucrose preference test, FST, open field test, and tail suspension test. Then, the effects of KF1 on the morphology and molecular and functional phenotypes of primary neuronal cells and hippocampus of mice were investigated by hematoxylin-eosin staining, Nissl staining, propidium iodide staining, TUNEL staining, Ca2+ imaging, JC-1 staining, ELISA, immunofluorescence analysis, RT-PCR, and Western blot. RESULTS: KF1 could effectively improve cellular viability, reduce apoptosis, inhibit the release of LDH and Ca2+, and increase the mitochondrial membrane potential and the number of dendritic spines numbers in hippocampal neurons. Moreover, behavioral tests showed that KF1 exerted acute and sustained antidepressant-like effects by reducing Glu-levels and ameliorating neuronal damage in the hippocampus. Additionally, in vivo and in vitro experiments revealed that PSD95, Syn1, α-amino-3­hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and brain-derived neurotrophic factor (BDNF) were upregulated at the protein level, and BDNF and AMPA were upregulated at the mRNA level. NR1 and NR2A showed the opposite trend. CONCLUSION: These results confirm that KF1 exerts rapid antidepressant effects mainly by activating the AMPA-BDNF-mTOR pathway and inhibiting the NMDAR-CaMKIIα pathway. This study serves as a new reference for discovering rapid antidepressants.

Structural and functional insight into the interaction of Clostridioides difficile toxin B and FZD7.

The G protein-coupled receptors of the Frizzled (FZD) family, in particular FZD1,2,7, are receptors that are exploited by Clostridioides difficile toxin B (TcdB), the major virulence factor responsible for pathogenesis associated with Clostridioides difficile infection. We employ a live-cell assay examining the affinity between full-length FZDs and TcdB. Moreover, we present cryoelectron microscopy structures of TcdB alone and in complex with full-length FZD7, which reveal that large structural rearrangements of the combined repetitive polypeptide domain are required for interaction with FZDs and other TcdB receptors, constituting a first step for receptor recognition. Furthermore, we show that bezlotoxumab, an FDA-approved monoclonal antibody to treat Clostridioides difficile infection, favors the apo-TcdB structure and thus disrupts binding with FZD7. The dynamic transition between the two conformations of TcdB also governs the stability of the pore-forming region. Thus, our work provides structural and functional insight into how conformational dynamics of TcdB determine receptor binding.

Changes in toxicity after mixing imidacloprid and cadmium: enhanced, diminished, or both? From a perspective of oxidative stress, lipid metabolism, and amino acid metabolism in mice.

Imidacloprid (IMI) and cadmium (Cd) are pollutants of concern in the environment. Although investigations about their combined toxicity to organisms such as earthworms, aquatic worms, Daphnia magna, and zebrafish have been carried out, their combined toxicity to mammals remains unknow. In this study, twenty-four 8-week-old mice were arbitrarily separated into 4 groups: CK (control group), IMI (15 mg/kg bw/day, 1/10 LD50), Cd (15 mg/kg bw/day, 1/10 LD50), and IMI + Cd (15 mg/kg bw/day IMI + 15 mg/kg bw/d Cd) and the combined toxic effects of IMI and Cd were examined with biochemical (oxidative stress testing) and omics approaches (metabolomics and lipidomics). The results revealed changes in each treatment group in terms of oxidative stress, abnormalities in lipid metabolism, and disturbances in amino acid metabolism. Co-administration had antagonistic effects on MDA accumulation and lipid metabolism disorders while acting synergistically on changes in SOD and GSH-Px activities. It is worth noting that after analysis, the changes caused by mixed administration in vivo were closer to those caused by IMI administration alone. This study provides new insights into the combined toxicity of neonicotinoids and heavy metals, which is helpful for relevant environmental governance and further investigations about their impacts on human health and the environment.

Chemical Tagging of Bioactive Amides by Cooperative Catalysis: Applications in the Syntheses of Drug Conjugates.

We disclose a practical catalytic method for arming bioactive amide-based natural products and other small-molecule drugs with various functional handles for the synthesis of drug conjugates. We demonstrate that a set of readily available Sc-based Lewis acids and N-based Brønsted bases can function cooperatively to deprotonate amide N-H bonds in polyfunctional drug molecules. An aza-Michael reaction between the resulting amidate and α,ß-unsaturated compounds produces an array of drug analogues that are equipped with an alkyne, azide, maleimide, tetrazine, or diazirine moiety under redox and pH-neutral conditions. The utility of this chemical tagging strategy is showcased through the production of drug conjugates by the click reaction between the alkyne-tagged drug derivatives and an azide-containing green fluorescent protein, nanobody, or antibody.

Profile of Human Milk Phospholipids at Different Lactation Stages with UPLC/Q-TOF-MS: Characterization, Distribution, and Differences.

Human milk phospholipids are important for the regular growth and development of infants. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) was employed to qualitatively and quantitatively analyze 277 phospholipid molecular species in 112 human milk samples to obtain a detailed profile of human milk phospholipids along the lactation stage. MS/MS fragmentation patterns of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine were characterized in detail. Phosphatidylcholine is the most dominant group, followed by sphingomyelin. PC(18:0/18:2), SM(d18:1/24:1), PE(18:0/18:0), PS(18:0/20:4), and PI(18:0/18:2) showed the highest average concentration among all of the phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol molecular species, respectively. The fatty acids attached to the phospholipid molecules were mainly palmitic, stearic, oleic, and linoleic acids, and the plasmalogens decreased along the lactation stage. The increase of sphingomyelins and phosphatidylethanolamines and the decrease of phosphatidylcholines are the key changes from colostrum to transitional milk; the increase of lysophosphatidylcholines and lysophosphatidylethanolamines and the continuous decrease of phosphatidylcholines are the vital changes from transitional milk to mature milk.

A Survey of the Landscape Visibility Analysis Tools and Technical Improvements.

Visual perception of the urban landscape in a city is complex and dynamic, and it is largely influenced by human vision and the dynamic spatial layout of the attractions. In return, landscape visibility not only affects how people interact with the environment but also promotes regional values and urban resilience. The development of visibility has evolved, and the digital landscape visibility analysis method allows urban researchers to redefine visible space and better quantify human perceptions and observations of the landscape space. In this paper, we first reviewed and compared the theoretical results and measurement tools for spatial visual perception and compared the value of the analytical methods and tools for landscape visualization in multiple dimensions on the principal of urban planning (e.g., complex environment, computational scalability, and interactive intervention between computation and built environment). We found that most of the research was examined in a static environment using simple viewpoints, which can hardly explain the actual complexity and dynamic superposition of the landscape perceptual effect in an urban environment. Thus, those methods cannot effectively solve actual urban planning issues. Aiming at this demand, we proposed a workflow optimization and developed a responsive cross-scale and multilandscape object 3D visibility analysis method, forming our analysis model for testing on the study case. By combining the multilandscape batch scanning method with a refined voxel model, it can be adapted for large-scale complex dynamic urban visual problems. As a result, we obtained accurate spatial visibility calculations that can be conducted across scales from the macro to micro, with large external mountain landscapes and small internal open spaces. Our verified approach not only has a good performance in the analysis of complex visibility problems (e.g., we defined the two most influential spatial variables to maintain good street-based landscape visibility) but also the high efficiency of spatial interventions (e.g., where the four recommended interventions were the most valuable), realizing the improvement of intelligent landscape evaluations and interventions for urban spatial quality and resilience.

Efficacy and safety of 188Re-HEDP in lung cancer patients with bone metastases: a randomized, multicenter, multiple-dose phase IIa study.

PURPOSE: To investigate the pain-relieving effect and safety of three different doses of 188Re-hydroxyethylidine diphosphonate (HEDP) in patients with lung cancer and bone metastases. METHODS: For this randomised, phase 2 and multicenter trial, we enrolled patients with lung carcinoma and multifocal bone metastases and excluded patients who had received bisphosphonates or external-beam radiotherapy within the previous 4 weeks. Fifty-four patients were randomized to receive a single injection of 188Re-HEDP, at doses of 30, 40 or 50 MBq/kg (interval, 12 weeks). Patients were followed-up by assessment of numerical rating scale (NRS) score, global quality of life (QOL) score and adverse events (AEs). ANOVA analysis, Chi-Squared test and LSD-t test were used in this study. RESULTS: Significantly decreased NRS scores relative to baseline were observed in 40 MBq/kg group (Week 0 vs. Week 12: 6.0 ± 1.4 vs. 4.8 ± 2.5, P = 0.033) and 50 MBq/kg group (Week 0 vs. Week 12: 5.5 ± 1.5 vs. 4.5 ± 2.9, P = 0.046). Significant change of global QOL score from baseline was observed in 40 MBq/kg group at week 8 (global QOL score: P = 0.024, pain score: P = 0.041) and 50 MBq/kg group (pain score: P = 0.021) at week 12. No patients withdrew trial because of AEs in three groups. CONCLUSIONS: 188Re-HEDP at dose of 40 and 50 MBq/kg was generally effective to alleviate pain and improve QOL in lung cancer patients with painful bone metastases. 188Re-HEDP was safe and well-tolerated.

Enantioselective Synthesis of N-Alkylamines through ß-Amino C-H Functionalization Promoted by Cooperative Actions of B(C6F5)3 and a Chiral Lewis Acid Co-Catalyst.

We disclose a catalytic method for ß-C(sp3)-H functionalization of N-alkylamines for the synthesis of enantiomerically enriched ß-substituted amines, entities prevalent in pharmaceutical compounds and used to generate different families of chiral catalysts. We demonstrate that a catalyst system comprising of seemingly competitive Lewis acids, B(C6F5)3, and a chiral Mg- or Sc-based complex, promotes the highly enantioselective union of N-alkylamines and α,ß-unsaturated compounds. An array of δ-amino carbonyl compounds was synthesized under redox-neutral conditions by enantioselective reaction of a N-alkylamine-derived enamine and an electrophile activated by the chiral Lewis acid co-catalyst. The utility of the approach is highlighted by late-stage ß-C-H functionalization of bioactive amines. Investigations in regard to the mechanistic nuances of the catalytic processes are described.

Ring-opening iodination and bromination of unstrained cycloalkanols through ß-scission of alkoxy radicals.

Ring-opening iodination or bromination of unstrained cycloalkanols with NaI or NaBr and PhI(OAc)2 under visible light irradiation is developed. In this protocol the concentration of I2 is modulated through the generation of triiodide (I3-), thus significantly avoiding undesired side reactions. The reaction is under mild conditions and has a wide substrate scope, thus providing a practically useful method for accessing ω-iodo or ω-bromoketones.

Phase I clinical study with different doses of 99mTc-TRODAT-1 in healthy adults.

OBJECTIVES: To study the pharmacokinetics, biodistribution, and injection doses of 99mTc-TRODAT-1 in healthy adults. METHODS: Thirty healthy individuals comprising 15 females and 15 males were randomly divided into three groups and the injection doses of 99mTc-TRODAT-1 of group 1, 2, and 3 were 370 MBq, 740 MBq, and 1110 MBq, respectively. Assessments of subjective symptoms and tests were performed before and after injection. Blood and urine collections and whole-body planar imaging were analyzed at various time points. Bilateral brain striatal SPECT images obtained at 3.5 h PI were assessed visually and semiquantitatively. RESULTS: No serious adverse events or deaths were observed in our study. The pharmacokinetic analysis showed that 99mTc-TRODAT-1 was eliminated rapidly from the circulation, with just about 4% of the injected dose remaining in blood at 1 h post-injection. The mean cumulative urinary excretion over 24 h was just 2.96 ± 0.96%ID. The time-activity curve demonstrated that the radioactivity was mainly in liver and abdomen. The highest absorbed dose was in the dose-limiting organ, liver (20.88 ± 4.45 × 10-3 mSv/MBq). The average effective dose was 5.22 ± 1.05 × 10-3 mSv/MBq. The clarity of striatal images assessed visually in group 1 was worse than that in group 2 and 3. The semiquantitative analysis showed that there were no differences in striatum/cerebellum between the three groups (group 1: 1.77 ± 0.11, group 2: 1.62 ± 0.14, and group 3: 1.75 ± 0.20; P = 0.088). CONCLUSIONS: 99mTc-TRODAT-1 was safe to use in humans and showed the status of dopaminergic neurons specifically and clearly. The injection dose we suggested was 740 MBq.

Correction to: A phase 2, open-label, multi-center study to evaluate the efficacy and safety of 99mTc-TRODAT-1 SPECT to detect Parkinson's disease.

The corresponding author of the article would like to remove "Jian Wang" in the author group.

A phase 2, open-label, multi-center study to evaluate the efficacy and safety of 99mTc-TRODAT-1 SPECT to detect Parkinson's disease.

OBJECTIVES: To assess the efficacy and safety of 99mTc-TRODAT-1 SPECT in diagnosing Parkinson's disease (PD). METHODS: 99mTc-TRODAT-1 SPECT imaging was performed in 34 healthy controls and 96 PD patients 2.5 h later after injection. The striatal image was evaluated visually and semi-quantitively. Sensitivity and specificity of 99mTc-TRODAT-1 SPECT were analyzed according to Hoehn and Yahr scale (HYS). Based on HYS, the PD patients were divided into mild (HYS 1-2) and moderate (HYS 3-5) groups. The uptake ratios of striatum (ST) and cerebellum (CB) in contralateral, ipsilateral and bilateral striatum in different groups were calculated and analyzed. The safety was assessed. RESULTS: The sensitivity and specificity of 99mTc-TRODAT-1 SPECT to discriminate PD patients from healthy subjects were 98.96% and 94.12% and it has perfect agreement with HYS (κ = 0.94, p < 0.001). The sensitivity to diagnose mild and moderate PD was 43.42% and 95% separately. The uptake ratio in PD patients was significantly lower than that in healthy controls (1.37 ± 0.13 vs 1.68 ± 0.18, p < 0.001). And the uptake ratio in contralateral side was markedly reduced in unilateral PD patients as compared with the ipsilateral side (1.50 ± 0.20 vs 1.46 ± 0.21, p < 0.001). The striatal uptakes in affected striatum and bilateral striatum were reduced with increasing disease severity between healthy control versus mild stage versus moderate stage in the affected striatum and bilateral striatum in PD patients. No serious adverse events or death was observed after injecting 99mTc-TRODAT-1. CONCLUSION: We demonstrated that 99mTc-TRODAT-1 was a safety radiotracer which can be used in clinic to diagnose PD using SPECT.

Evaluation of 99mTC-ECD SPECT/CT brain Imaging with NeuroGam analysis in Moyamoya disease after surgical revascularization.

To evaluate the clinical value of NeuroGam software in assessing the brain foci perfusion changes by TC-ECD single photon emission computed tomography/computed tomography (SPECT/CT) brain imaging in patients with Moyamoya Disease (MMD).Seventy-two patients with MMD who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass combined with encephalo-duro-myo-synangiosis (EDMS) surgical revascularization were included. Baseline and follow-up TC-ECD SPECT/CT brain scans were performed on all patients at least twice before and after operation. Pre- and post-SPECT dicom images were reoriented into Talairach space using NeuroGam Software package. Additional visual analysis was performed. Differences mean pixel value between pre- and post- operation brain perfusion were assessed with paired t test and McNemar test.Significant differences in the number of hypoperfusion foci were found between visual assessment and NeuroGam aided assessment. More hypoperfusion foci were found by NeuroGam software aided assessment in the frontal, parietal, temporal, occipital lobe, thalamus, basal ganglia and cerebellum before and after surgery (P < .0001). According to NeuroGam software assessment, the perfusion of frontal, parietal, temporal lobe, anterior and middle cerebral regions on the operative side significantly improved before and after surgery (t = -3.734, t = -3.935, t = -5.099, t = -4.006, t = -5.170, all P < .001). However, no significant differences were found in the occipital lobe (t = -1.962, P = .054), thalamus (t = 1.362, P = .177), basal ganglia (t = -2.394, P = .019), and cerebellum (t = 1.383, P = .171) before and after surgery.The NeuroGam software provides a quantitative approach for monitoring surgical effect of MMD in a variable time (3-12 months after surgery). It could discover the perfusion changes that are neglected in conventional visual assessment.

Visible-Light-Promoted Ring-Opening Alkynylation, Alkenylation, and Allylation of Cyclic Hemiacetals through ß-Scission of Alkoxy Radicals.

The alkoxy radicals that are derived from cyclic hemiacetals have been generated through the visible-light-promoted reaction of the corresponding N-alkoxyphthalimides with Hantzsch ester as the reductant. The alkoxy radicals subsequently undergo ß-scission of the C-C bond to generate carbon-centered radicals, which are trapped by alkynyl-, alkenyl-, or allylsulfones.

Enantioselective iridium-catalyzed carbonyl isoprenylation via alcohol-mediated hydrogen transfer.

Highly enantioselective iridium catalyzed carbonyl (2-vinyl)allylation or "isoprenylation" is achieved via hydrogen auto-transfer or 2-propanol-mediated reductive coupling from primary alcohol or aldehyde reactants, respectively. Using this method, asymmetric total syntheses of the terpenoid natural products (+)-ipsenol and (+)-ipsdienol were achieved.