OsFTL12, a member of FT-like family, modulates the heading date and plant architecture by florigen repression complex in rice.

FLOWERING LOCUS T (FT), a florigen in Arabidopsis, plays critical roles in floral transition. Among 13 FT-like members in rice, OsFTL2 (Hd3a) and OsFTL3 (RFT1), two rice homologues of FT, have been well characterized to act as florigens to induce flowering under short-day (SD) and long-day (LD) conditions, respectively, but the functions of other rice FT-like members remain largely unclear. Here, we show that OsFTL12 plays an antagonistic function against Hd3a and RFT1 to modulate the heading date and plant architecture in rice. Unlike Hd3a and RFT1, OsFTL12 is not regulated by daylength and highly expressed in both SD and LD conditions, and delays the heading date under either SD or LD conditions. We further demonstrate that OsFTL12 interacts with GF14b and OsFD1, two key components of the florigen activation complex (FAC), to form the florigen repression complex (FRC) by competing with Hd3a for binding GF14b. Notably, OsFTL12-FRC can bind to the promoters of the floral identity genes OsMADS14 and OsMADS15 and suppress their expression. The osmads14 osmads15 double mutants could not develop panicles and showed erect leaves. Taken together, our results reveal that different FT-like members can fine-tune heading date and plant architecture by regulating the balance of FAC and FRC in rice.

The Rice Circadian Clock Regulates Tiller Growth and Panicle Development Through Strigolactone Signaling and Sugar Sensing.

Circadian clocks regulate growth and development in plants and animals, but the role of circadian regulation in crop production is poorly understood. Rice (Oryza sativa) grain yield is largely determined by tillering, which is mediated by physiological and genetic factors. Here we report a regulatory loop that involves the circadian clock, sugar, and strigolactone (SL) pathway to regulate rice tiller-bud and panicle development. Rice CIRCADIAN CLOCK ASSOCIATED1 (OsCCA1) positively regulates expression of TEOSINTE BRANCHED1 (OsTB1, also known as FC1), DWARF14 (D14), and IDEAL PLANT ARCHITECTURE1 (IPA1, also known as OsSPL14) to repress tiller-bud outgrowth. Downregulating and overexpressing OsCCA1 increases and reduces tiller numbers, respectively, whereas manipulating PSEUDORESPONSE REGULATOR1 (OsPPR1) expression results in the opposite effects. OsCCA1 also regulates IPA1 expression to mediate panicle and grain development. Genetic analyses using double mutants and overexpression in the mutants show that OsTB1, D14, and IPA1 act downstream of OsCCA1 Sugars repress OsCCA1 expression in roots and tiller buds to promote tiller-bud outgrowth. The circadian clock integrates sugar responses and the SL pathway to regulate tiller and panicle development, providing insights into improving plant architecture and yield in rice and other cereal crops.

Fluoride enrichment mechanisms and related health risks of groundwater in the transition zone of geomorphic units, northern China.

Although groundwater is the primary drinking water source in northern of China, little is known about generation mechanisms and related health risks of high fluoride groundwater at the geomorphic transition zones. Thus, 419 groundwater samples were collected from Zhangjiakou region, where is a typically geomorphic transition zone of the North China Plain and the Inner Mongolia Plateau, to conduct the hydrochemical analysis, geochemical modeling, multivariate statistical analysis, and health risks assessment. From the results, F- concentration in groundwater had a range of 0.05-9.71 mg L-1. About 37.1% and 26.2% of groundwater samples from Bashang region (BSR) and Baxia region (BXR), respectively, were over the 1.50 mg L-1, which were mainly distributed in the groundwater flow retardation area and/or evaporation discharge area. Thermodynamic simulations demonstrated that F-bearing minerals dissolution and Ca2+/Mg2+ removal via calcite/dolomite precipitation primarily governed high-F- groundwater formation in the whole study area. Competitive adsorption, evaporation, evaporites dissolution and salt-effect also affected F- enrichment in BSR. Desorption in alkaline environment, ion exchange and human activities played a vital role in F- enrichment at BXR. The multivariate statistical analysis revealed that the origin of F- contamination was geogenic in BSR; whereas, it was geogenic and anthropogenic in BXR. Besides, more than 71.8%, 51.0%, 36.1% and 25.5% of the study area exceeded the acceptable level (health index>1) for infants, children, adult males, and females, respectively. The health risks for different groups of people varied significantly and ranked: infants > children > males > females, suggesting that younger people were more susceptible to fluoride contamination. Meanwhile, females were more resistant to fluoride contamination than males. These findings are vital to providing insights on high-F- groundwater formation, investigate the situation of health risks, and conduct the integrated management for high fluoride groundwater in geomorphic transition zones at northern China.

[Effects of different drying methods on ginsenosides based on UHPLC-Q-Exactive Orbitrap MS technique].

The present study quickly identified the ginsenosides in fresh Panax ginseng and specified the effects of different drying methods(50 ℃-drying, 80 ℃-drying, and-70 ℃ freeze-drying) on ginsenosides.Three P.ginseng products by different drying methods were prepared, and the UHPLC-Q-Exactive Orbitrap high-resolution liquid mass spectrometry(MS) technique was applied to perform gradient elution using water-acetonitrile as the mobile phase, and the data collected in the negative ion mode were analyzed using X Calibur 2.2.The results showed that 57 saponins were identified from fresh P.ginseng.As revealed by the comparison with the fresh P.ginseng, in terms of the loss of ginsenosides, the dried products were ranked as the dried product at 50 ℃, freeze-dried products at-70 ℃, and the dried product at 80 ℃ in the ascending order.This study elucidated the effects of different drying methods on the types and relative content of ginsenosides, which can provide references for the processing of P.ginseng in the producing areas.

Human health risk assessment of groundwater nitrate at a two geomorphic units transition zone in northern China.

To assess groundwater nitrate contamination and its human health risks, 489 unconfined groundwater samples were collected and analyzed from Zhangjiakou, northern China. The spatial distribution of principle hydrogeochemical results showed that the average concentrations of ions in descend order was HCO3-, SO42-, Na+, Ca2+, Cl-, NO3-, Mg2+ and K+, among which the NO3- concentrations were between 0.25 and 536.73 mg/L with an average of 29.72 mg/L. In total, 167 out of 489 samples (~ 34%) exceeded the recommended concentration of 20 mg/L in Quality Standard for Groundwater of China. The high NO3- concentration groundwater mainly located in the northern part and near the boundary of the two geomorphic units. As revealed by statistical analysis, the groundwater chemistry was more significantly affected by anthropogenic sources than by the geogenic sources. Moreover, human health risks of groundwater nitrate through oral and dermal exposure pathways were assessed by model, the results showed that about 60%, 50%, 32% and 26% of the area exceeded the acceptable level (total health index>1) for infants, children, adult males and females, respectively. The health risks for different groups of people varied significantly, ranked: infants> children> adult males>adult females, suggesting that younger people are more susceptible to nitrate contamination, while females are more resistant to nitrate contamination than males. To ensure the drinking water safety in Zhangjiakou and its downstream areas, proper management and treatment of groundwater will be necessary to avoid the health risks associated with nitrate contamination.

Preparation of a novel chloromethylated polystyrene-2-mercapto-1,3,4-thiadiazole chelating resin and its adsorption properties and mechanism for separation and recovery of Hg(II) from aqueous solutions.

With an efficient methodology, a novel chloromethylated polystyrene-g-2-mercapto-1,3,4-thiadiazole chelating resin (MTR resin) was prepared via a one-step reaction. The structure of MTR resin was characterized by elements analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Meanwhile, the adsorption properties of the resin for Hg(II) were investigated by batch and column experiments. The results showed that the resin possessed much better adsorption capability for Hg(II) than for other metal ions. The statically and the dynamic saturated adsorption capacities were 343.8 mg/g and 475.1 mg/g. The adsorption kinetic and equilibrium data were well fitted to the second-order model and the Langmuir isotherm model, respectively. Desorption of mercury from the resin can be achieved using 30 mL of 2 mol/L HCl-5% thiourea solution with a desorption ratio of 92.3%. Compared with other absorbents, MTR resin was greatly conserve natural resources and reduce the cost.

Internal blood lead exposure levels in permanent residents of Jiangxi Province and its effects on routine hematological and biochemical indices.

Background: Lead exposure levels are closely linked to human health and can cause damage to multiple organ systems, including the blood system and liver. However, due to insufficient evidence, the effects of lead exposure on hematological and biochemical indices have not been fully established. Objective: This study aims to explore the blood lead levels of permanent residents in Jiangxi Province and analyze the factors affecting blood lead levels and the impact of blood lead levels on hematological and biochemical indices. Methods: We conducted a cross-sectional study including questionnaires, health examinations, and blood sample examinations on 720 randomly selected permanent residents (3-79 years) in Jiangxi Province in 2018. The blood lead levels were measured using inductively coupled plasma mass spectrometry. Routine hematological and biochemical tests were determined by qualified medical institutions using automated hematology analyzers and biochemistry analyzers. Results: The geometric mean of blood lead concentration in permanent residents of Jiangxi Province was 20.45 µg/L. Gender, age, annual household income, smoking, and hypertension were the influencing factors for blood lead levels. For each 1 µg/L increase in blood lead, the risks of elevated red blood cell count (from low to high), platelet volume distribution width, alkaline phosphatase (from low to high), and cholesterol increased by 2.4, 1.6, 3.6, and 2.3%, respectively, whereas the risks of elevation of direct bilirubin and total bilirubin both decreased by 1.7%. Conclusion: The blood lead level in permanent residents of Jiangxi Province is higher than the national average. Higher blood lead levels were found in men than in women; blood lead levels were positively correlated with age but negatively correlated with annual household income; smoking and hypertension are risk factors for elevated blood lead; and blood lead levels affect routine hematological and biochemical markers such as red blood cell count, platelet volume distribution width, direct bilirubin, total bilirubin, alkaline phosphatase, and cholesterol.

A high-sensitivity flexible bionic tentacle sensor for multidimensional force sensing and autonomous obstacle avoidance applications.

Bionic tentacle sensors are important in various fields, including obstacle avoidance, human‒machine interfaces, and soft robotics. However, most traditional tentacle sensors are based on rigid substrates, resulting in difficulty in detecting multidirectional forces originating from the external environment, which limits their application in complex environments. Herein, we proposed a high-sensitivity flexible bionic tentacle sensors (FBTSs). Specifically, the FBTS featured an ultrahigh sensitivity of 37.6 N-1 and an ultralow detection limit of 2.4 mN, which benefited from the design of a whisker-like signal amplifier and crossbeam architecture. Moreover, the FBTS exhibited favorable linearity (R2 = 0.98) and remarkable durability (more than 5000 cycles). This was determined according to the improvement in the uniformity of the sensing layer through a high-shear dispersion process. In addition, the FBTS could accurately distinguish the direction of external stimuli, resulting in the FBTS achieving roughness recognition, wind speed detection and autonomous obstacle avoidance. In particular, the ability of autonomous obstacle avoidance was suitably demonstrated by leading a bionic rat through a maze with the FBTS. Notably, the proposed FBTS could be widely applied in tactile sensing, orientation perception, and obstacle avoidance.

Flexible wide-range multidimensional force sensors inspired by bones embedded in muscle.

Flexible sensors have been widely studied for use in motion monitoring, human‒machine interactions (HMIs), personalized medicine, and soft intelligent robots. However, their practical application is limited by their low output performance, narrow measuring range, and unidirectional force detection. Here, to achieve flexibility and high performance simultaneously, we developed a flexible wide-range multidimensional force sensor (FWMFS) similar to bones embedded in muscle structures. The adjustable magnetic field endows the FWMFS with multidimensional perception for detecting forces in different directions. The multilayer stacked coils significantly improved the output from the µV to the mV level while ensuring FWMFS miniaturization. The optimized FWMFS exhibited a high voltage sensitivity of 0.227 mV/N (0.5-8.4 N) and 0.047 mV/N (8.4-60 N) in response to normal forces ranging from 0.5 N to 60 N and could detect lateral forces ranging from 0.2-1.1 N and voltage sensitivities of 1.039 mV/N (0.2-0.5 N) and 0.194 mV/N (0.5-1.1 N). In terms of normal force measurements, the FWMFS can monitor finger pressure and sliding trajectories in response to finger taps, as well as measure plantar pressure for assessing human movement. The plantar pressure signals of five human movements collected by the FWMFS were analyzed using the k-nearest neighbors classification algorithm, which achieved a recognition accuracy of 92%. Additionally, an artificial intelligence biometric authentication system is being developed that classifies and recognizes user passwords. Based on the lateral force measurement ability of the FWMFS, the direction of ball movement can be distinguished, and communication systems such as Morse Code can be expanded. This research has significant potential in intelligent sensing and personalized spatial recognition.

Cucumber mosaic virus suppressor 2b binds to AGO4-related small RNAs and impairs AGO4 activities.

Cucumber mosaic virus suppressor 2b (CMV2b) is a nuclear viral suppressor that interferes with local and systemic silencing and inhibits AGO1 slicer activity. CMV2b-mediated transgene hypomethylation and its localization in Cajal bodies suggests a role of CMV2b in RNA-directed DNA methylation (RdDM). However, its direct involvement in RdDM, or its binding with small RNAs (sRNAs) in vivo is not yet established. Here, we show that CMV2b binds both microRNAs (miRNAs) and small interfering RNAs (siRNAs) in vivo. sRNA sequencing data from the CMV2b immunocomplex revealed its preferential binding with 24-nt repeat-associated siRNAs. We provide evidence that CMV2b also has direct interaction with the AGO4 protein by recognizing its PAZ and PIWI domains. Subsequent analysis of AGO4 functions revealed that CMV2b reduced AGO4 slicer activity and the methylation of several loci, accompanied by the augmented accumulation of 24-nt siRNAs in Arabidopsis inflorescences. Intriguingly, CMV2b also regulated an AGO4-related epiallele independently of its catalytic potential, which further reinforces the repressive effects of CMV2b on AGO4 activity. Collectively, our results demonstrate that CMV2b can counteract AGO4-related functions. We propose that by adopting novel counter-host defense strategies against AGO1 and AGO4 proteins, CMV creates a favorable cellular niche for its proliferation.

Rice yellow stunt rhabdovirus protein 6 suppresses systemic RNA silencing by blocking RDR6-mediated secondary siRNA synthesis.

The P6 protein of Rice yellow stunt rhabdovirus (RYSV) is a virion structural protein that can be phosphorylated in vitro. However its exact function remains elusive. We found that P6 enhanced the virulence of Potato virus X (PVX) in Nicotiana benthamiana and N. tabacum plants, suggesting that it might function as a suppressor of RNA silencing. We examined the mechanism of P6-mediated silencing suppression by transiently expressing P6 in both N. benthamiana leaves and rice protoplasts. Our results showed that P6 could repress the production of secondary siRNAs and inhibit systemic green fluorescent protein RNA silencing but did not interfere with local RNA silencing in N. benthamiana plants or in rice protoplasts. Intriguingly, P6 and RDR6 had overlapping subcellular localization and P6 bound both rice and Arabidopsis RDR6 in vivo. Furthermore, transgenic rice plants expressing P6 showed enhanced susceptibility to infection by Rice stripe virus. Hence, we propose that P6 is part of the RYSV's counter-defense machinery against the plant RNA silencing system and plays a role mainly in affecting RDR6-mediated secondary siRNA synthesis. Our work provides a new perspective on how a plant-infecting nucleorhabdovirus may counteract host RNA silencing-mediated antiviral defense.

Enantioselective copper-catalyzed intramolecular phenolic O-H bond insertion: synthesis of chiral 2-carboxy dihydrobenzofurans, dihydrobenzopyrans, and tetrahydrobenzooxepines.

Efficient: A copper-catalyzed enantioselective intramolecular insertion of carbenoids into phenolic O-H bonds has been developed. This method can be used for the synthesis of the title compounds in high yields and excellent enantioselectivities under mild and neutral conditions. NaBAr(F)=sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate.

Association between multiple metal(loid)s exposure and renal function: a cross-sectional study from southeastern China.

In the real world, humans are exposed to multiple metal(loid)s (designated hereafter metals) that contain essential metals as well as toxic metals. Exposure to the metal mixture was assumed to be associated with renal function impairment; however, there is no consensus on available studies. Therefore, we here explored the association between multiple metals exposure and indicators of renal function in the general population from southeastern China. A total of 11 metals with 6 human essential metals and 5 toxic metals were determined in the selected 720 subjects. In addition, serum uric acid (SUA), serum creatinine (SCR), and the estimated glomerular filtration rate (eGFR) were measured or calculated as indicators of renal function. Using multiple flexible statistical models of generalized linear model, elastic net regression, and Bayesian kernel machine regression, the joint as well as the individual effect of metals within the mixture, and the interactions between metals were explored. When exposed to the metal mixture, the statistically non-significantly increased SUA, the significantly increased SCR, and the significantly declined eGFR were observed. In addition, the declined renal function may be primarily attributed to lead (Pb), arsenic (As), and nickel (Ni) exposure. Finally, interactions, such as the synergistic effect between Pb and Mo on SUA, whereas the antagonistic effect between Ni and Cd on SCR and eGFR were identified. Our finding suggests that combined exposure to multiple metals would impair renal function. Therefore, reducing exposure to toxic heavy metals of Pb, As, and Cd and limiting exposure to the human essential metal of Ni would protect renal function.

Association Between Multiple Metal(loid)s Exposure and Blood Lipid Levels: Evidence from a Cross-Sectional Study of Southeastern China.

Exposure to essential and toxic metals occurs simultaneously as a mixture in real-life. However, there is no consensus regarding the effects of co-exposure to multiple metal(loid)s (designated hereafter metals) on blood lipid levels. Thus, blood concentrations of six human essential metals and five toxic metals in 720 general populations from southeastern China were simultaneously determined as a measure of exposure. In addition, quantile g-computation, Bayesian kernel machine regression, elastic net regression, and generalized linear model were used to investigate both the joint and individual effects of exposure to this metal mixture on human blood lipid levels. The significant positive joint effect of exposure to this metal mixture on serum total cholesterol (TC) levels, rather than on serum triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, Castelli risk index I, Castelli risk index II, atherogenic coefficient, and non-HDL-C levels, was found. In addition, the positive effect may be primarily driven by selenium (Se), lead (Pb), and mercury (Hg) exposure. In addition, on the effect of TC levels, the synergistic effect between Pb and Hg and the antagonistic effect between Se and Pb were identified. Our finding suggests that combined exposure to this metal mixture may affect human blood lipid levels. Therefore, reducing exposure to heavy metals, such as Pb and Hg, should be a priority for the general population. In addition, Se supplementation should also be considered with caution.

Targeting a gene regulatory element enhances rice grain yield by decoupling panicle number and size.

Crop genetic improvement requires balancing complex tradeoffs caused by gene pleiotropy and linkage drags, as exemplified by IPA1 (Ideal Plant Architecture 1), a typical pleiotropic gene in rice that increases grains per panicle but reduces tillers. In this study, we identified a 54-base pair cis-regulatory region in IPA1 via a tiling-deletion-based CRISPR-Cas9 screen that, when deleted, resolves the tradeoff between grains per panicle and tiller number, leading to substantially enhanced grain yield per plant. Mechanistic studies revealed that the deleted fragment is a target site for the transcription factor An-1 to repress IPA1 expression in panicles and roots. Targeting gene regulatory regions should help dissect tradeoff effects and provide a rich source of targets for breeding complementary beneficial traits.

OsMPK4 promotes phosphorylation and degradation of IPA1 in response to salt stress to confer salt tolerance in rice.

Salt stress adversely affects plant growth, development, and crop yield. Rice (Oryza sativa L.) is one of the most salt-sensitive cereal crops, especially at the early seedling stage. Mitogen-activated protein kinase (MAPK/MPK) cascades have been shown to play critical roles in salt response in Arabidopsis. However, the roles of the MPK cascade signaling in rice salt response and substrates of OsMPK remain largely unknown. Here, we report that the salt-induced OsMPK4-Ideal Plant Architecture 1 (IPA1) signaling pathway regulates the salt tolerance in rice. Under salt stress, OsMPK4 could interact with IPA1 and phosphorylate IPA1 at Thr180, leading to degradation of IPA1. Genetic evidence shows that IPA1 is a negative regulator of salt tolerance in rice, whereas OsMPK4 promotes salt response in an IPA1-dependent manner. Taken together, our results uncover an OsMPK4-IPA1 signal cascade that modulates the salt stress response in rice and sheds new light on the breeding of salt-tolerant rice varieties.

Chilling-induced phosphorylation of IPA1 by OsSAPK6 activates chilling tolerance responses in rice.

Chilling is a major abiotic stress harming rice development and productivity. The C-REPEAT BINDING FACTOR (CBF)-dependent transcriptional regulatory pathway plays a central role in cold stress and acclimation in Arabidopsis. In rice, several genes have been reported in conferring chilling tolerance, however, the chilling signaling in rice remains largely unknown. Here, we report the chilling-induced OSMOTIC STRESS/ABA-ACTIVATED PROTEIN KINASE 6 (OsSAPK6)-IDEAL PLANT ARCHITECTURE 1 (IPA1)-OsCBF3 signal pathway in rice. Under chilling stress, OsSAPK6 could phosphorylate IPA1 and increase its stability. In turn, IPA1 could directly bind to the GTAC motif on the OsCBF3 promoter to elevate its expression. Genetic evidence showed that OsSAPK6, IPA1 and OsCBF3 were all positive regulators of rice chilling tolerance. The function of OsSAPK6 in chilling tolerance depended on IPA1, and overexpression of OsCBF3 could rescue the chilling-sensitive phenotype of ipa1 loss-of-function mutant. Moreover, the natural gain-of-function allele ipa1-2D could simultaneously enhance seedling chilling tolerance and increase grain yield. Taken together, our results revealed a chilling-induced OsSAPK6-IPA1-OsCBF signal cascade in rice, which shed new lights on chilling stress-tolerant rice breeding.

Critical role of SIRT1 upregulation on the protective effect of lncRNA ANRIL against hypoxia/reoxygenation injury in H9c2 cardiomyocytes.

Dysregulation of long non­coding RNA (IncRNA) antisense non­coding RNA in the INK4 locus (ANRIL) is associated with the risk of myocardial infarction (MI). Therefore, the present study aimed to determine the mechanisms underlying this association, which is currently poorly understood, to the best of our knowledge. The current study used an in vitro myocardial ischemia and reperfusion (MI/R) model, in which H9c2 cardiomyocytes were exposed to hypoxia/reoxygenation (H/R), which demonstrated that ANRIL expression was downregulated and that ANRIL positively regulated sirtuin 1 (SIRT1) expression following H/R injury. Subsequently, it was demonstrated that ANRIL upregulated SIRT1 expression by sponging microRNA­181a (miR­181a). In addition, ANRIL overexpression reduced lactate dehydrogenase release and apoptosis of H9c2 cardiomyocytes exposed to H/R, indicating that ANRIL prevented H/R­induced cardiomyocyte injury. Moreover, both miR­181a overexpression and SIRT1 knockdown significantly decreased the protective effects of ANRIL on H/R­induced cardiomyocyte injury, thus demonstrating that SIRT1 upregulation via sponging miR­181a is a critical mechanism that mediates the function of ANRIL. These results provided a novel mechanistic insight into the role of ANRIL in H/R­injured cardiomyocytes and suggested that the ANRIL/miR­181a/SIRT1 axis may be a therapeutic target for reducing MI/R injury.

GABAB1e promotes the malignancy of human cancer cells by targeting the tyrosine phosphatase PTPN12.

Neurotransmitter receptors are involved in cancer progression. Among them, the heterodimeric GABAB receptor, activated by the main inhibitory neurotransmitter GABA, is composed of the transmembrane GABAB1 and GABAB2 subunits. The oncogenic role of the isoform GABAB1e (GB1e) containing only the extracellular domain of GABAB1 remains unclear. We revealed that GB1e is largely expressed in human breast cancer (BrCa) cell lines as well as in BrCa tissues where it is upregulated. Moreover, GB1e promoted the malignancy of BrCa cells both in vitro and in vivo. We propose that GB1e favors EGFR signaling by interacting with PTPN12 to disrupt the interaction between EGFR and PTPN12, and phosphorylation of Y230 and Y404 on GB1e is required in this process. Our data highlight that the GABBR1 gene through the expression of the GB1e isoform might play an important oncogenic role in BrCa and that GB1e is of interest for the treatment of some cancers.

Enantioselective copper-catalyzed intramolecular O-H insertion: an efficient approach to chiral 2-carboxy cyclic ethers.

A copper-catalyzed asymmetric intramolecular O-H insertion of ω-hydroxy-α-diazoesters has been accomplished by using chiral spiro bisoxazoline ligands. This highly enantioselective intramolecular O-H insertion reaction provides an efficient approach to a variety of synthetically important chiral 2-carboxy cyclic ethers with different ring sizes as well as substitution patterns.