Stress Induces Dynamic, Cytotoxicity-Antagonizing TDP-43 Nuclear Bodies via Paraspeckle LncRNA NEAT1-Mediated Liquid-Liquid Phase Separation.

Despite the prominent role of TDP-43 in neurodegeneration, its physiological and pathological functions are not fully understood. Here, we report an unexpected role of TDP-43 in the formation of dynamic, reversible, liquid droplet-like nuclear bodies (NBs) in response to stress. Formation of NBs alleviates TDP-43-mediated cytotoxicity in mammalian cells and fly neurons. Super-resolution microscopy reveals distinct functions of the two RRMs in TDP-43 NB formation. TDP-43 NBs are partially colocalized with nuclear paraspeckles, whose scaffolding lncRNA NEAT1 is dramatically upregulated in stressed neurons. Moreover, increase of NEAT1 promotes TDP-43 liquid-liquid phase separation (LLPS) in vitro. Finally, we discover that the ALS-associated mutation D169G impairs the NEAT1-mediated TDP-43 LLPS and NB assembly, causing excessive cytoplasmic translocation of TDP-43 to form stress granules, which become phosphorylated TDP-43 cytoplasmic foci upon prolonged stress. Together, our findings suggest a stress-mitigating role and mechanism of TDP-43 NBs, whose dysfunction may be involved in ALS pathogenesis.

A case of visual impairment due to HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation in childhood acute myeloid leukemia-M2 subtype.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a crucial treatment option for children with M2 subtype acute myeloid leukemia (AML). Human herpesvirus 6 (HHV-6) encephalitis following transplantation is a rare postoperative complication, with a poor prognosis and a high fatality rate in allo-HSCT recipients. In this report, a juvenile patient with AMLwas successfully treated after developing visual impairment as a result of HHV-6B encephalitis during allo-HSCT therapy. HHV-6 encephalitis-associated visual impairment after transplantation is rare, and clinical diagnosis and treatment are challenging, requiring more attention in the future.

Parental expressions of love in Chinese American immigrant families: Implications for children's attachment security.

Harlow's seminal work on the nature of attachment focused on the importance of warm, responsive, and loving relationships in children's healthy development. While the need for love and care is arguably universal, the ways in which these emotions are expressed can vary across cultural contexts. We examined how Chinese American parents' expressions of love were associated with children's attachment security. A total of 110 Chinese American immigrant parent-child dyads (children 7-11 years old, 49% girls) participated in 3-min conversations in which parents were instructed to communicate love and care. Proposition-level analyses in speech (total 8825 propositions) identified three types of affection: training (guan and chiao shun); relational affection (qin); and validation (acceptance and encouragement of child's own expression of emotion, thoughts, and behaviors). Higher training was observed in parents with lower American orientation and lower income. Higher relational affection was observed in parents with lower income. Higher validation was observed in parents with higher income. Using path analyses, training and validation were found to be positively associated with children's attachment security beyond parenting styles. Effects of parents' relational affection were moderated by children's American orientation. Results demonstrate how immigrant parents draw on multiple cultural scripts to express love and care. These findings expand traditional concepts of parental love in immigrant families and illustrate how bicultural expressions of love can shape attachment security in middle childhood. A video abstract of this article can be viewed at https://youtu.be/HqUfIDxkFsE RESEARCH HIGHLIGHTS: Analyses of parent-child discussions identified three parental affection styles (i.e., training, relational affection, and validation) as expressions of love and care in Chinese American immigrant families. Training and validation were positively associated with children's attachment security. Relational affection was associated with lower attachment security for children with higher American cultural orientation, suggesting the effects of parent-child expressions of love are shaped by acculturation.

The scoring system combined with radiomics and imaging features in predicting the malignant potential of incidental indeterminate small (<20 mm) solid pulmonary nodules.

OBJECTIVE: Develop a practical scoring system based on radiomics and imaging features, for predicting the malignant potential of incidental indeterminate small solid pulmonary nodules (IISSPNs) smaller than 20 mm. METHODS: A total of 360 patients with malignant IISSPNs (n = 213) and benign IISSPNs (n = 147) confirmed after surgery were retrospectively analyzed. The whole cohort was randomly divided into training and validation groups at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) algorithm was used to debase the dimensions of radiomics features. Multivariate logistic analysis was performed to establish models. The receiver operating characteristic (ROC) curve, area under the curve (AUC), 95% confidence interval (CI), sensitivity and specificity of each model were recorded. Scoring system based on odds ratio was developed. RESULTS: Three radiomics features were selected for further model establishment. After multivariate logistic analysis, the combined model including Mean, age, emphysema, lobulated and size, reached highest AUC of 0.877 (95%CI: 0.830-0.915), accuracy rate of 83.3%, sensitivity of 85.3% and specificity of 80.2% in the training group, followed by radiomics model (AUC: 0.804) and imaging model (AUC: 0.773). A scoring system with a cutoff value greater than 4 points was developed. If the score was larger than 8 points, the possibility of diagnosing malignant IISSPNs could reach at least 92.7%. CONCLUSION: The combined model demonstrated good diagnostic performance in predicting the malignant potential of IISSPNs. A perfect accuracy rate of 100% can be achieved with a score exceeding 12 points in the user-friendly scoring system.

Lipid nephrotoxicity mediated by HIF-1α activation accelerates tubular injury in diabetic nephropathy.

This study is intended to explore the effect of hypoxia-inducible factor-1α (HIF-1α) activation on lipid accumulation in the diabetic kidney. A type 1 diabetic rat model was established by STZ intraperitoneal injection. Cobalt chloride (CoCl2) and YC-1 were used as the HIF-1α activator and antagonist, respectively. CoCl2 treatment significantly increased HIF-1α expression, accelerated lipid deposition, and accelerated tubular injury in diabetic kidneys. In vitro, CoCl2 effectively stabilized HIF-1α and increased its transportation from the cytoplasm to the nucleus, which was accompanied by significantly increased lipid accumulation in HK-2 cells. Furthermore, results obtained in vivo showed that HIF-1α protein expression in the renal tubules of diabetic rats was significantly downregulated by YC-1 treatment. Meanwhile, lipid accumulation in the tubules of the DM + YC-1 group was markedly decreased in comparison to the DM + DMSO group. Accordingly, PAS staining revealed that the pathological injury caused to the tubular epithelial cells was alleviated by YC-1 treatment. Furthermore, the blood glucose level, urine albumin creatinine ratio, and NAG creatinine ratio in the DM + YC-1 group were significantly decreased compared to the DM + DMSO group. Moreover, the protein expression levels of transforming growth factor ß1 (TGF-ß1) and connective tissue growth factor (CTGF) in diabetic kidneys were decreased by YC-1 treatment. Our findings demonstrate that the activation of HIF-1α contributed to interstitial injury in a rat model of diabetic nephropathy and that the underlying mechanism involved the induction of lipid accumulation.

Remarkable Second Harmonic Generation Response in (C5H6NO)+(CH3SO3)-: Unraveling the Role of Hydrogen Bond in Thermal Driven Nonlinear Optical Switch.

Heat-activated second harmonic generation (SHG) switching materials are gaining interest for their ability to switch between SHG on and off states, offering potential in optoelectronic applications. The novel nonlinear optical (NLO) switch, (C5H6NO)+(CH3SO3)- (4-hydroxypyridinium methylsulfonate, 4HPMS), is a near-room-temperature thermal driven material with a strong SHG response (3.3 × KDP), making it one of the most potent heat-stimulated NLO switches. It offers excellent contrast of 13 and a high laser-induced damage threshold (2.5 × KDP), with reversibility > 5 cycles. At 73 °C, 4HPMS transitions from the noncentrosymmetric Pna21 room temperature phase (RTP) to the centrosymmetric P21/c phase, caused by the rotation of the (C5H6NO)+ and (CH3SO3)- due to partially thermal breaking of intermolecular hydrogen bonds. The reverse phase change exhibits a large 50 °C thermal hysteresis. Density functional theory (DFT) calculations show that (C5H6NO)+ primarily dictates both the SHG coefficient (dij) and birefringence (▵n(Zeiss) = 0.216 vs ▵n(cal.) = 0.202 at 546 nm; Δn(Immersion) = 0.210 vs ▵n(cal.) = 0.198 at 589.3 nm), while the band gap (Eg) is influenced synergistically by (C5H6NO)+ and (CH3SO3)-. Additionally, 4HPMS-RTP also exhibits mechanochromism upon grinding as well as an aggregation-enhanced emission in a mixture of acetone and water.

Microglia in epilepsy.

Epilepsy is one of most common chronic neurological disorders, and the antiseizure medications developed by targeting neurocentric mechanisms have not effectively reduced the proportion of patients with drug-resistant epilepsy. Further exploration of the cellular or molecular mechanism of epilepsy is expected to provide new options for treatment. Recently, more and more researches focus on brain network components other than neurons, among which microglia have attracted much attention for their diverse biological functions. As the resident immune cells of the central nervous system, microglia have highly plastic transcription, morphology and functional characteristics, which can change dynamically in a context-dependent manner during the progression of epilepsy. In the pathogenesis of epilepsy, highly reactive microglia interact with other components in the epileptogenic network by performing crucial functions such as secretion of soluble factors and phagocytosis, thus continuously reshaping the landscape of the epileptic brain microenvironment. Indeed, microglia appear to be both pro-epileptic and anti-epileptic under the different spatiotemporal contexts of disease, rendering interventions targeting microglia biologically complex and challenging. This comprehensive review critically summarizes the pathophysiological role of microglia in epileptic brain homeostasis alterations and explores potential therapeutic or modulatory targets for epilepsy targeting microglia.

Whole-Genome Resequencing of Worldwide Wild and Domestic Sheep Elucidates Genetic Diversity, Introgression, and Agronomically Important Loci.

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.

Initiation and duration of folic acid supplementation in preventing congenital malformations.

BACKGROUND: Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. METHODS: A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. RESULTS: Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44-1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21-1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08-5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33-0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36-0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. CONCLUSIONS: The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. TRIAL REGISTRATION: Chictr.org.cn identifier: ChiCTR-SOC-17010976.

Wrinkle-bioinspired silver nanowire surface enhanced Raman scattering sensors for pesticide molecule detection.

We demonstrate wrinkle-bioinspired flexible SERS sensor covered by silver nanowire (AgNWs) network for the detection of pesticide molecules. Compared with the silver film deposition substrates, the wrinkle-bioinspired AgNWs SERS substrates show stronger SERS effect, which were attributed to the electromagnetic field enhancement posed by the relatively high density "hot spots" of AgNWs. In order to investigate the adsorption performance of wrinkle-bioinspired flexible sensors, we measured the corresponding contact angles of AgNWs on the substrate surfaces before and after plasma treatment and found that the AgNWs treated with plasma are more hydrophilic than that without plasma treatment. Additionally, the wrinkle-bioinspired SERS sensors show different SERS activities under different tensile strain, and the 10-6 mol/L concentration of Rhodamine dye (R6G) molecules can be detected by portable Raman spectra, reducing greatly detection cost. The surface plasmon resonance of AgNWs is induced by adjusting the deformation of AgNWs substrate, enhancing the SERS signal. This reliability of wrinkle-bioinspired SERS sensors is further verified by in situ detection of pesticide molecules.

Cereal intake and mortality in older Chinese: a 15-year follow-up of a prospective cohort study.

PURPOSE: We examined the association between whole grain and refined grain intake with all-cause, cancer and cardiovascular disease (CVD) mortality using the data from the Guangzhou Biobank Cohort Study. METHODS: 19,597 participants aged 50+ years were recruited from 2003 to 2006 and followed-up until April 2021. Multivariable Cox regression was used to calculate hazard radios (HRs) and 95% confidence intervals (CIs). Substitution analysis was used to replace a serving (50 g/day) of whole grain with a serving of refined grain. RESULTS: During 286,821 person-years of follow-up, 4385 deaths occurred, including 1450 from cancer, 1678 from CVD and 1257 from other causes. Compared with never whole grain intake, the highest intake category of whole grain (> 300 g/week) was associated with lower risk of all-cause (HR 0.90, 95% CI 0.82-0.98) and CVD mortality (HR 0.85, 0.74-0.98). Compared with the low-intake category of refined grain (< 500 g/day), the highest intake category (> 900 g/week) was associated with a lower risk of cancer mortality (HR 0.76, 0.62-0.95), but a higher risk of CVD mortality (HR 1.25, 1.03-1.51). No significant associations were found between whole grain intake and cancer mortality nor refined grain and all-cause mortality. The HRs of all-cause, cancer and CVD mortality substituting a serving of whole grain for refined grain were 0.96 (0.94-0.99), 1.01 (0.99-1.02) and 0.95 (0.90-0.99), respectively. CONCLUSION: We have first shown that in older Chinese, whole grain intake was associated with lower risk of all-cause and CVD mortality. Our results suggest that intake of whole grain of at least 300 g/week and refined grain of ≤ 900 g/day might be suitable for older Asian. Substituting 50 g/day of whole grain for refined grain was associated with a 4-5% lower risk of all-cause and CVD mortality.

Maternal traditional Chinese medicine exposure and risk of congenital malformations: a multicenter prospective cohort study.

INTRODUCTION: The potential teratogenic risk of traditional Chinese medicine (TCM) is of widespread concern; however, related evidence is largely absent in humans. This study aimed to compare the prevalence of congenital malformations between pregnant women with and without TCM exposure. MATERIAL AND METHODS: This was a multicenter prospective cohort study of 17 713 women who participated in a survey on periconceptional TCM exposure. Primary outcome was congenital malformations diagnosed from a survey conducted on the day 42 after delivery. RESULTS: A total of 16 751 pregnant women with 273 congenital malformations were included in the analysis. Fetuses exposed to TCM had an increased risk of congenital malformations compared to those without exposure (odds ratio [OR] 2.10; 95% confidence interval [CI] 1.09-4.02) after controlling for potential confounders. There were significant associations with congenital malformations in women with early pregnant exposure (OR 2.04, 95% CI 1.00-4.20) and for those who received ≥2 TCM formulas (OR 5.84, 95% CI 1.44-23.65). Pre-pregnancy TCM exposure was significantly associated with an increased risk of congenital heart defects (OR 12.69; 95% CI 3.01-53.51). CONCLUSIONS: Periconceptional TCM exposure is associated with an increased risk of congenital malformation. This effect was cumulative and sensitive to periconceptional age. Therefore, TCM deserves more attention and should be used cautiously for pregnant women and those trying to become pregnant.

Inhibition of the MEK/ERK pathway suppresses immune overactivation and mitigates TDP-43 toxicity in a Drosophila model of ALS.

TDP-43 is an important DNA/RNA-binding protein that is associated with age-related neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD); however, its pathomechanism is not fully understood. In a transgenic RNAi screen using Drosophila as a model, we uncovered that knockdown (KD) of Dsor1 (the Drosophila MAPK kinase dMEK) suppressed TDP-43 toxicity without altering TDP-43 phosphorylation or protein levels. Further investigation revealed that the Dsor1 downstream gene rl (dERK) was abnormally upregulated in TDP-43 flies, and neuronal overexpression of dERK induced profound upregulation of antimicrobial peptides (AMPs). We also detected a robust immune overactivation in TDP-43 flies, which could be suppressed by downregulation of the MEK/ERK pathway in TDP-43 fly neurons. Furthermore, neuronal KD of abnormally increased AMPs improved the motor function of TDP-43 flies. On the other hand, neuronal KD of Dnr1, a negative regulator of the Drosophila immune deficiency (IMD) pathway, activated the innate immunity and boosted AMP expression independent of the regulation by the MEK/ERK pathway, which diminished the mitigating effect of RNAi-dMEK on TDP-43 toxicity. Finally, we showed that an FDA-approved MEK inhibitor trametinib markedly suppressed immune overactivation, alleviated motor deficits and prolonged the lifespan of TDP-43 flies, but did not exhibit a lifespan-extending effect in Alzheimer disease (AD) or spinocerebellar ataxia type 3 (SCA3) fly models. Together, our findings suggest an important role of abnormal elevation of the MEK/ERK signaling and innate immunity in TDP-43 pathogenesis and propose trametinib as a potential therapeutic agent for ALS and other TDP-43-related diseases.

Photoredox-Catalyzed Acyl Lactonization of Alkenes with Aldehydes: Synthesis of Acyl Lactones.

An acyl lactonization of alkenes with aldehydes under visible-light photoredox catalysis is described. With the protocol, a broad scope of alkenoic acids and aldehydes could be compatible and good functional group tolerance is obtained. A series of acyl lactones are obtained with isolated yields ranging from 50-95%. Mechanistic studies revealed that the transformation should proceed via a radical chain process.

Isolation, synthesis and bioactivity evaluation of isoquinoline alkaloids from Corydalis hendersonii Hemsl. against gastric cancer in vitro and in vivo.

Isoquinoline alkaloid displays significant anti-gastric cancer effects due to its unique structure, which is attracting more and more attention for the development of anti-gastric cancer drugs. In this study, we explore the active components against gastric cancer from the Tibetan Medicine Corydalis hendersonii Hemsl, which is rich in isoquinoline alkaloids. 14 compounds including 2 previously undescribed natural products were obtained. Interestingly, an new active compound displays potent anti-gastric cancer activity. After accomplishing the total syntheses of the active compound and its derivatives, the anti-gastric cancer activity of the active compound was further investigated. In vitro experiments revealed that the active compound significantly attenuated the proliferative capacity, caused G2/M phase arrest, inhibited the cell migration and invasion, and induced cell apoptosis. Mechanistically, the active compound could increase the Bax/Bcl-2 ratio, elevate cytochrome c in the cytosol, and activate caspase-9/3, along with inactivating the upstream PI3K/Akt/mTOR signaling pathway. In addition, the active compound could also cause gastric cancer cell death by inhibiting topoisomerase I activity. More importantly, the anti-gastric cancer activity of the active compound was confirmed in MGC-803 xenograft nude mice in vivo. This work not only promotes the exploitation of Corydalis hendersonii Hemsl., but also provides some experience for discovering new entities from natural sources.

A comparison of three preoperative nutritional assessment methods for predicting ovarian cancer patient prognosis: which is better?

BACKGROUND: The study aimed to compare the predictive values of three widely used nutritional assessment methods, body mass index (BMI), Nutritional Risk Screening 2002 (NRS 2002), and the prognostic nutritional index (PNI), for different clinical prognostic indicators of ovarian cancer patients. METHODS: Patients diagnosed with ovarian cancer treated in our hospital between January 2017 and March 2019 were retrospectively included. The three nutritional assessment methods were assessed, and multivariable analysis was conducted to explore predictive factors for clinical prognoses. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUROC) were generated to evaluate the discriminative abilities of the three nutritional assessment tools. RESULTS: A total of 442 patients were recruited. Multivariable analysis revealed that the PNI value predicted 1-year death and 1-year recurrence and that both the NRS 2002 score and the PNI value predicted 30-day readmission (P < 0.05). For PNI, AUROCs were 0.834 for predicting 1-year death and 0.719 for 1-year recurrence prediction; for NRS, the AUROC was 0.820 2002 for predicting 30-day readmission. The optimal cutoff values that maximized the prognostic prediction ability were PNI values of 47.75 g/L and 50.40 g/L for 1-year death and 1-year recurrence, respectively, and an NRS 2002 score of 3 points for 30-day readmission following discharge. CONCLUSION: For ovarian cancer patients, the PNI is better at predicting 1-year death and 30-day readmission after discharge, and the NRS 2002 is superior for predicting 1-year recurrence.

Discovery of NLO Semiorganic (C5H6ON)+(H2PO4)-: Dipole Moment Modulation and Superior Synergy in Solar-Blind UV Region.

We herein report a novel semiorganic NLO material, (C5H6ON)+(H2PO4)-, 4HPP, showing promising excellent properties in the important solar-blind UV region where LAP and its deuterated form DLAP are the only commercialized semiorganic materials. For the first time, the 4-hydroxypyridine (4HP+, (C5H6ON)+) cation is identified as NLO active and how to eliminate the dipole-dipole interaction to avoid the unwanted center-symmetry-trap caused by the polar-induced susceptibility is well demonstrated. Remarkably, 4HPP exhibits competitive and even better properties compared with LAP that include better thermal stability (decomposition at 166 vs 112 °C of LAP); wider transparency range (0.26-1.50 µm); very strong SHG response (3 × KDP); a suitable large birefringence (Δncal = 0.25 vs 0.075 of LAP); and a high laser-induced damage threshold (2.2 × KDP). First-principles calculations show that the π-conjugated organic (4HP)+ cation governs the optical anisotropy, whereas the synergy of the organic and inorganic moieties dominates the SHG process. Our discovery points out a new path for the rational design of high performance semiorganic materials that require an acentric structure.

Direct Access to α,ß-Unsaturated Ketones via Rh/MgCl2-Mediated Acylation of Vinylsilanes.

We report herein the facile and practical construction of α,ß-unsaturated ketones via rhodium-catalyzed direct acylation of vinylsilanes with readily available and abundant carboxylic acids. This protocol features access to a diverse array of synthetically useful functionalities with moderate to excellent yields. More importantly, the late-stage functionalization of pharmaceuticals was also realized with synthetically useful yield.

Copper-Catalyzed Intermolecular C(sp2)-H Amination with Electrophilic O-Benzoyl Hydroxylamines.

A copper-catalyzed intermolecular electrophilic amination of benzamides with O-benzoyl hydroxylamines was achieved with the assistance of an 8-aminoquinolyl group. With this protocol, good compatibility was observed for a variety of aryl amides and heteroaryl amides, and excellent tolerance with various functional groups was achieved. Significantly, the monoaminated product was overwhelmingly delivered under the simple reaction conditions. Preliminary mechanistic investigations suggested that a radical pathway should be excluded and C-H activation be potentially the rate-determining step.

Visible-Light Photoredox-Catalyzed Sulfonyl Lactonization of Alkenoic Acids with Sulfonyl Chlorides for Sulfonyl Lactone Synthesis.

A visible-light photoredox-catalyzed sulfonyl lactonization of unsaturated carboxylic acids with sulfonyl chlorides is described. This reaction features good functional group tolerance and a broad substrate scope, providing a simple and efficient protocol to access a wide range of sulfonyl lactones in high to excellent yields. Preliminary mechanistic investigations suggested that a free-radical pathway should be involved in the process.