Engineering "three-in-one" fluorescent nanozyme of Ce-Au NCs for on-site visual detection of Hg2.

Hg2+ contamination poses a serious threat to the environment and human health. Although gold nanoclusters (Au NCs) have been utilized as fluorescence probes or colorimetric nanozymes for performing Hg2+ assays by using a single method, designing multifunctional nanoclusters as fluorescent nanozyme remains challenging. Herein, Ce-aggregated gold nanoclusters (Ce-Au NCs) were reported with "three in one" functions to generate strong fluorescence, excellent peroxidase-like activity, and the highly specific recognition of Hg2+ via its metallophilic interaction. A portable fluorescence and colorimetric dual-mode sensing device based on Ce-Au NCs was developed for on-site visual analysis of Hg2+. In the presence of Hg2+, fluorescence was effectively quenched and the paper-based chips gradually darkened from green till they became completely absent, while peroxidase-like activity was significantly enhanced. Two independent signals were captured by one identification unit, which provided self-validation to improve reliability and accuracy. Therefore, this work presents a simple synthesis of a multifunctional fluorescent nanozyme, and the developed portable device for on-site visual detection has considerable potential for application in the rapid on-site analysis of heavy metal ions in the environment.

Drinking contexts, coping motive, simultaneous cannabis use, and high-intensity drinking among adults in the United States.

AIMS: High-intensity drinking (HID), extreme drinking considerably above the level of heavy episodic drinking (HED), is associated with long-term health and social consequences. There is limited understanding of HID beyond young adulthood. This study aims to identify concurrent risk factors for HID, comparing age differences among all adults. METHODS: Multinomial logistic and linear regression modeling was performed using a nationally-representative sample of adults (analytic n = 7956) from the 2015 and 2020 National Alcohol Surveys. The outcomes were any HID of 8-11 drinks and 12+ drinks for men, and 8+ drinks for women, and corresponding frequencies. Concurrent risk factors included coping motive, sensation seeking, simultaneous use of alcohol and cannabis (SAC), and drinking at a bar or party. Analyses were stratified by age (18-29 vs. older) and sex. RESULTS: For younger men, sensation-seeking was significantly associated with HID (vs. no HED) at both levels and frequency of HID 8-11 drinks, while drinking to cope was only significant for 12+ drinks. For older men, drinking to cope was a consistent predictor for both HID level and its frequency, but sensation-seeking was not significant. Both coping and sensation-seeking were significantly associated with any HID for all women, while coping was significant for HID frequency for younger women. Frequent drinking at bars and parties were associated with greater odds of HID for all adults. With HED as referent, similar patterns of (though fewer significant) associations were observed. CONCLUSIONS: Younger and older adults share similar risk factors for HID, with coping more consistent for older men.

Protective effects of ethnic enclaves: Testing pathways to alcohol use and use disorders in Mexican American young adults.

Ethnic enclave residence is associated with decreased risk for drinking and related problems, but less is known about the mechanisms that explain this association. Informed by theories of social control, we used a multilevel framework to examine whether negative attitudes toward drinking mediated associations between ethnic enclave residence (i.e., neighborhood linguistic isolation) and alcohol outcomes among Mexican American young adults (N = 628) in Southern California. Model 1 assessed mediation effects in the pathways from linguistic isolation to current drinking and alcohol use disorder (AUD). Model 2 adjusted for parental drinking attitudes and neighborhood alcohol availability. There were differential associations by gender in direct effects of linguistic isolation and negative drinking attitudes on both drinking and AUD. Among women only, linguistic isolation was related to greater abstinence and decreased AUD after accounting for social control proxies of parent attitudes and alcohol availability. Young adults' own drinking attitudes did not mediate relationships between linguistic isolation and alcohol outcomes. This study offers evidence on the importance of disaggregating Hispanic national groups by gender to uncover social mechanisms within ethnic enclave settings for tailored supports in reducing risk of drinking and alcohol-related harms.

Drinking patterns among US men and women: Racial and ethnic differences from adolescence to early midlife.

BACKGROUND: Drinking patterns among young adult men and women in the United States have been understudied, especially among racial and ethnic groups such as Asian Americans and Hispanics. Because alcohol-related racial and ethnic health disparities persist or increase in midlife, identifying peak ages of hazardous drinking could help to reduce disparities. METHODS: We used the National Longitudinal Study of Adolescent to Adult Health to examine: (1) past 12-month heavy episodic drinking (HED) and total alcohol volume consumption among non-Hispanic White (NHW), Black, Hispanic, and Asian men and women from ages 12 through 41, and (2) age-varying associations of race and ethnicity with drinking. Hispanic and Asian ethnic groups were disaggregated by historical drinking patterns. Time-varying effect models accounted for major demographic confounders. RESULTS: NHW men and women experienced elevated drinking rates in their early 20s, with a second elevation in their 30s. Black men and women did not have elevated drinking until their 30s. Among Hispanic men and women, peak drinking periods varied by gender and subgroup drinking pattern. Peak HED and total consumption emerged in the early 30s for Asian men, while peak HED occurred in the early 20s for Asian women. Drinking at certain ages for some racial and ethnic minoritized men and women did not differ from that in their NHW counterparts. CONCLUSIONS: Age periods during which subgroups in the U.S. population experience elevated alcohol consumption vary by ethnicity and gender. Recognition of these group differences could enhance our understanding of intervention timing.

Distinct expression patterns of Hedgehog signaling components in mouse gustatory system during postnatal tongue development and adult homeostasis.

The Hedgehog (HH) pathway regulates embryonic development of anterior tongue taste fungiform papilla (FP) and the posterior circumvallate (CVP) and foliate (FOP) taste papillae. HH signaling also mediates taste organ maintenance and regeneration in adults. However, there are knowledge gaps in HH pathway component expression during postnatal taste organ differentiation and maturation. Importantly, the HH transcriptional effectors GLI1, GLI2 and GLI3 have not been investigated in early postnatal stages; the HH receptors PTCH1, GAS1, CDON and HHIP, required to either drive HH pathway activation or antagonism, also remain unexplored. Using lacZ reporter mouse models, we mapped expression of the HH ligand SHH, HH receptors, and GLI transcription factors in FP, CVP and FOP in early and late postnatal and adult stages. In adults we also studied the soft palate, and the geniculate and trigeminal ganglia, which extend afferent fibers to the anterior tongue. Shh and Gas1 are the only components that were consistently expressed within taste buds of all three papillae and the soft palate. In the first postnatal week, we observed broad expression of HH signaling components in FP and adjacent, non-taste filiform (FILIF) papillae in epithelium or stroma and tongue muscles. Notably, we observed elimination of Gli1 in FILIF and Gas1 in muscles, and downregulation of Ptch1 in lingual epithelium and of Cdon, Gas1 and Hhip in stroma from late postnatal stages. Further, HH receptor expression patterns in CVP and FOP epithelium differed from anterior FP. Among all the components, only known positive regulators of HH signaling, SHH, Ptch1, Gli1 and Gli2, were expressed in the ganglia. Our studies emphasize differential regulation of HH signaling in distinct postnatal developmental periods and in anterior versus posterior taste organs, and lay the foundation for functional studies to understand the roles of numerous HH signaling components in postnatal tongue development.

When the Going Gets Tough: Multimorbidity and Heavy and Binge Drinking Among Adults.

INTRODUCTION: Multimorbidity, the presence of two or more long-term health conditions in the same individual, is an emerging epidemic associated with increased morbidity and mortality. Continued drinking concurrent with alcohol-related chronic conditions, particularly with multimorbidity, is likely to further elevate health risk. This study aimed to examine the associations of multimorbidity among diabetes, hypertension, heart disease, and cancer with drinking, and moderation of these associations by age. METHODS: Logistic regression modeling was performed in 2023 using a nationally representative sample of U.S. adults from the 2015-19 National Survey on Drug Use and Health. Multimorbidity was assessed using (1) a count of these conditions and (2) disease-specific categories. The outcomes were past month heavy drinking (7+/14+ drinks weekly) and binge drinking (4+/5+ drinks per occasion) for women and men. RESULTS: A pattern of reduced odds for drinking outcomes associated with a greater degree of multimorbidity was found. This pattern was more apparent in models using the continuous measure of multimorbidity than in those using the categorical measure, and more consistent for binge drinking than for heavy drinking and for women than for men. Significant age interactions were found: the log odds of heavy drinking and binge drinking for both men and women decreased as the number of conditions increased, and more steeply for those ages 50+ than the younger. The log odds of heavy drinking varied little among men under age 50 regardless of multimorbidity. CONCLUSIONS: Alcohol interventions to reduce drinking with multimorbidity, particularly among heavy-drinking men under age 50, are warranted.

Hierarchically porous MOF@COF structures with ultrafast gas diffusion rate for C2H6/C2H4 separation.

For ethylene purification, C2H6-selective metal-organic frameworks (MOFs) show great potential to directly produce polymer-grade C2H4 from C2H6/C2H4 mixtures. Most C2H6-traping MOFs are ultra-microporous structures so as to strengthen multiple supramolecular interactions with C2H6. However, the narrowed pore channels of C2H6-traping MOFs cause large guest diffusion barriers, greatly hampering their practical applications. Herein, we present a feasible strategy by precisely constructing hierarchically porous MOF@COF core-shell structures to address this issue. Additional mesoporous diffusion channels were incorporated between MOF crystals through the construction of the COF shell, thereby enhancing the gas adsorption kinetics. Notably, designing a core-shell MOF@COF structure with an optimal coating amount of mesoporous COF shell will further improve the gas diffusion rate. Breakthrough experiments reveal that the tailored MOF@COF composites can effectively achieve C2H6/C2H4 separation and maintain its separation performance over five continuous measurement cycles. This investigation opens up a new avenue to solve the diffusion/transfer issues and provides more opportunities and potentials for MOF@COF composites in practical separation applications.

Epidemiological characteristics and antibody kinetics of elderly population with booster vaccination following both Omicron BA.5 and XBB waves in China.

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.

Opening and Constructing Stable Lithium-ion Channels within Polymer Electrolytes.

Lithium-ion batteries play an integral role in various aspects of daily life, yet there is a pressing need to enhance their safety and cycling stability. In this study, we have successfully developed a highly secure and flexible solid-state polymer electrolyte (SPE) through the in situ polymerization of allyl acetoacetate (AAA) monomers. This SPE constructed an efficient Li+ transport channel inside and effectively improved the solid-solid interface contact of solid-state batteries to reduce interfacial impedance. Furthermore, it exhibited excellent thermal stability, an ionic conductivity of 3.82×10-4 S cm-1 at room temperature (RT), and a Li+ transport number (tLi+) of 0.66. The numerous oxygen vacancies on layered inorganic SiO2 created an excellent environment for TFSI- immobilization. Free Li+ migrated rapidly at the C=O equivalence site with the poly(allyl acetoacetate) (PAAA) matrix. Consequently, when cycled at 0.5C and RT, it displayed an initial discharge specific capacity of 140.6 mAh g-1 with a discharge specific capacity retention rate of 70 % even after 500 cycles. Similarly, when cycled at a higher rate of 5C, it demonstrated an initial discharge specific capacity of 132.3 mAh g-1 while maintaining excellent cycling stability.

Lavender essential oil alleviates depressive-like behavior in alcohol-withdrawn rats: Insights from gut metabolites and hippocampal transcriptome analysis.

Lavender, an aromatic plant with a history dating back to ancient Egypt and Greece, is consumed because of its diverse pharmacological properties, including sedation, sleep aid, and antidepressant effects. However, the mechanisms underlying these antidepressant properties remain unclear. In this study, we explored the impact of lavender essential oil (LEO) inhalation on the diversity of gut microbiota, metabolites, and differential gene expression in the hippocampus of alcohol-withdrawn depressive rats. Additionally, we examined alterations in the hippocampal transient receptor potential (TRP) channel-mediated inflammatory regulation within the brain-gut axis of depressive rats. The results demonstrated a significant decrease in sucrose preference, diminished activity in the central zone of the open field test, and prolonged immobility time in the forced swim test in alcohol-withdrawn depressive rats, indicating the amelioration of depressive states following lavender essential oil inhalation. 16 S rDNA sequencing analysis revealed a significant reduction in Bacteroidota and Muribaculaceae in the gut of alcohol-withdrawn depressive rats, whereas lavender essential oil significantly increased the relative abundance of Muribaculaceae and other bacterial species. Metabolomic analysis identified 646 distinct metabolites as highly correlated biomarkers between the model and lavender essential oil groups. Furthermore, lavender essential oil inhalation significantly attenuated hippocampal inflammatory factors IL-2, IL-6, IL-1ß, and TNF-α. This study identified elevated expression of Trpv4 and Calml4 in the hippocampal region of alcohol-withdrawn depressed rats and showed that lavender essential oil inhalation regulated aberrantly expressed genes. Our research suggests that lavender essential oil downregulates Trpv4, modulates inflammatory factors, and alleviates depressive-like behavior in alcohol withdrawal rats.

Lesions of the lateral habenula excite dopamine neurons in the ventral tegmental area and serotonin neurons in the dorsal raphe nuclei in hemiparkinsonian rats.

The lateral habenula (LHb) projects to the ventral tegmental area (VTA) and dorsal raphe nuclei (DRN) that deliver dopamine (DA) and serotonin (5-HT) to cortical and limbic regions such as the medial prefrontal cortex (mPFC), hippocampus and basolateral amygdala (BLA). Dysfunctions of VTA-related mesocorticolimbic dopaminergic and DRN-related serotonergic systems contribute to non-motor symptoms in Parkinson's disease (PD). However, how the LHb affects the VTA and DRN in PD remains unclear. Here, we used electrophysiological and neurochemical approaches to explore the effects of LHb lesions on the firing activity of VTA and DRN neurons, as well as the levels of DA and 5-HT in related brain regions in unilateral 6-hydroxydopamie (6-OHDA)-induced PD rats. We found that compared to sham lesions, lesions of the LHb increased the firing rate of DA neurons in the VTA and 5-HT neurons in the DRN, but decreased the firing rate of GABAergic neurons in the same nucleus. In addition, lesions of the LHb increased the levels of DA and 5-HT in the mPFC, ventral hippocampus and BLA compared to sham lesions. These findings suggest that lesions of the LHb enhance the activity of mesocorticolimbic dopaminergic and serotonergic systems in PD.

Long-term trends in beverage-specific drinking in the National Alcohol Surveys: Differences by sex, age, and race and ethnicity.

BACKGROUND: Despite substantial declines in underage drinking and binge drinking, alcohol consumption has increased in the past 30 years. This study examined how beverage-specific drinking patterns varied by sex, age, and race and ethnicity from 1979 to 2020. METHODS: Secondary data analysis was conducted on pooled data from the National Alcohol Survey series from 1979 to 2020 of a sample of U.S. adults ages 18 years or older. Total and beverage-specific volume were calculated from graduated frequency questions on reported beverage type, which included beer, wine, and spirits. Sex-stratified analyses focused on descriptive trends of each alcohol measure over time and by age and race and ethnicity. Time-varying effect models were also conducted to identify subgroups at higher risk for increased consumption over time. RESULTS: Women's drinking increased, with alcohol volume rising substantially from 2000 to 2020; the largest increase was among women 30 and older. Men's alcohol volume also rose over this period but remained below the levels of 1979 and 1984, with older adults increasing their consumption those 18-29 decreased their drinking. Beverage-specific trends showed some similarities by gender: in 2020, wine volume was at its highest level for both women and men, while spirits volume also was at its highest level for men and in women was tied with the 1979 peak in spirits consumption. Increases were also found among Black men and women and Latina women from 2000 to 2020. CONCLUSIONS: Given the increases in alcohol volume, particularly among women and older age groups, alcohol policy, interventions, and education should consider ways to reduce harms associated with alcohol use among these groups. Continued monitoring of beverage-specific drinking patterns is needed to track policy-relevant changes.

Hydrophobic functionalization of a metal-organic framework as an ammonia visual sensing material under high humidity conditions.

Since exhaled ammonia (NH3) is one of the metabolic markers of liver and kidney diseases, ammonia visual sensing materials in humid environments have received extensive attention and investigation. Herein, through a tailor-made pore environment provided by metal-organic framework (MOF) materials (CH3-Cu(BDC)), we achieved NH3 anti-interference sensing with apparent color changing under humid conditions. With methyl (CH3-) functionalization, CH3-Cu(BDC) demonstrated a strong response for trace ammonia and showed high selectivity under a humid environment. Grand canonical Monte Carlo (GCMC) simulations indicated that CH3-Cu(BDC) showed stronger attraction towards NH3 molecules than H2O. Benefiting from the target changing coordination environment, CH3-Cu(BDC) showed a rapid response and simple analysis properties for patients' exhaled air. The strategy used in this study not only provides a demonstration case for NH3 colorimetric sensing with high humidity and anti-interference but also introduces a new method for painless and quick exhaled breath analysis for diagnosis of patients with kidney and liver diseases.

Alcohol Consumption Questionnaire: Scale development in a sample of Mexican American young adults and association with ADH7.

BACKGROUND: To understand why some individuals who develop alcohol use disorders (AUD) first begin to drink heavily, a number of scales have been developed that index aspects of alcohol craving and restraint from drinking. We developed a new measure called the Alcohol Consumption Questionnaire (ACQ), based in part on items modified from scales used to index binge eating because there are data to suggest that binge eating and binge drinking may share common antecedents. We present an initial validity study using data from a sample of Mexican Americans. METHODS: Data were from 699 Mexican American young adults in San Diego County, CA. A subsample (n=60) had short-term test-retest data. Factor analysis and reliability assessment guided item reduction. Item response theory (IRT) analyses quantified item severity and identified questions with differential item functioning (DIF). Logistic regression assessed associations of mean scale scores with AUD, adjusting for key demographics, alcohol expectancies and subjective response to alcohol. We also examined associations with a protective genetic variant downstream from the alcohol dehydrogenase 7 gene (ADH7). RESULTS: The scale was reduced from 20 to 14 questions, which can be summarized by a single overall score (Cronbach's alpha=0.896) or by two sub-scores (Consumption: 12 items, Cronbach's alpha=0.896; Enjoyment: 2 items, Cronbach's alpha=0.780). Test-retest reliability was very high (0.80-0.98) in this sample. The overall ACQ score and each subdomain score were strongly associated with AUD (ORs= 5.95 mild; 11.41 moderate; 48.56 severe) and family history of AUD. Respondents with the protective genetic variant had significantly lower overall ACQ scores (p<.001). CONCLUSION: The ACQ is a novel measure of alcohol consumption with strong relationships with both the AUD phenotype and ADH7 gene variants in a sample of Mexican American young adults.

Chiral Phosphine Ligands of COAP and SKP Switched Regiodivergent Asymmetric Allylic Alkylation of MBH Adducts.

The palladium-catalyzed highly regioselective asymmetric allylic alkylation of 3'-indolyl-3-oxindole derivatives with Morita-Baylis-Hillman (MBH) carbonates was developed to facilely construct chiral 3,3'-bisindole derivatives under mild reaction conditions. The regioselectivity (α/γ) of MBH carbonates was efficiently switched in the presence of chiral oxalamide phosphine or spiroketal-based diphosphine/Pd(0) complexes as a chiral catalyst. A series of multifunctional 3,3'-bisindole derivatives with all-carbon quaternary stereogenic centers were obtained in high yields with good to excellent enantio-, diastereo-, and regioselectivity. The present process is endowed with some salient features such as broad substrate scope, N-protecting group-free, excellent stereoselectivity, as well as adjustable regioselectivity.

Seaweed-inspired underwater anti-oil-fouling and anti-fogging coating with mechanical durability.

Ecofriendly fabrication of anti-oil-fouling materials is of interest. Surfaces with underwater superoleophobicity have been fabricated which exhibit limited mechanical durability and water resistance. In this study, we report on a bioinspired bilayer design of a transparent anti-oil-fouling coating. Seaweed surfaces show anti-oil-fouling in the sea due to its high surface hydration ability. Mussels can adhere tightly onto a surface with good stability in the sea by virtue of its levodopa-containing secretions. The surface layer was fabricated using a crosslinked combination of carboxymethyl cellulose (CMC) and sodium alginate (AlgS) inspired by seaweed, with the addition of calcium ions. Polydopamine (PDA), a derivative of levodopa, was used as the underlayer to enhance bonding strength and water resistance. Oil that adhered to the coated surface was spontaneously detached upon immersion in water. The mechanism underlying this anti-oil-fouling effect was elucidated using Gibbs free energy theory. The coating exhibited mechanical durability and water resistance. The coating is transparent and preserves the original color of the substrate. The coated glass showed stable anti-fogging and anti-frost performance. These coatings hold promise for a wide range of anti-oil-fouling applications.

Loading of AuNCs with AIE effect onto cerium-based MOFs to boost fluorescence for sensitive detection of Hg2.

Ligand-protected gold nanoclusters (AuNCs) have become promising nanomaterials in fluorescence (FL) methods for mercury ions (Hg2+) monitoring, but low FL efficiency hinders their widespread application. Herein, AuNCs/cerium-based metal-organic frameworks (AuNCs/Ce-MOFs) were prepared by loading 6-aza-2-thiothymine-protected AuNCs (ATT-AuNCs) with aggregation-induced emission (AIE) effect on the surface of Ce-MOFs by electrostatic attraction. This strategy improved the FL intensity of AuNCs through two aspects: (i) the AIE effect of ATT-AuNCs and (ii) the confinement effect of Ce-MOFs, which improved the restriction of intramolecular motion (RIM) of ATT-AuNCs. In addition, Ce-MOFs could adsorb and aggregate Hg2+ during detection, which might increase the local concentration. Therefore, based on the high FL signal of AuNCs/Ce-MOFs and enriched Hg2+, sensitive detection of Hg2+ could be achieved. More importantly, the strong specific recognition between AuNCs and Hg2+ could guarantee selectivity. The developed FL sensor exhibited superior detection performances with a wide linear range of 0.2-500 ng mL-1 and a low detection limit of 0.067 ng mL-1. Furthermore, the FL sensor used for sensitive and selective detection of Hg2+ in real samples, and the results agreed well with the standard method. In summary, this work proposed an effective and generalized strategy for improving the FL efficiency of AuNCs, which would greatly facilitate their application in pollutant monitoring.

Synaptic cell-adhesion molecule latrophilin-2 is differentially directed to dendritic domains of hippocampal neurons.

Hippocampal pyramidal cells possess elaborate dendritic arbors with distinct domains that are targeted with input-specific synaptic sites. This synaptic arrangement is facilitated by synaptic cell-adhesion molecules that act as recognition elements to connect presynaptic and postsynaptic neurons. In this study, we investigate the organization of the synaptic recognition molecule latrophilin-2 at the surface of pyramidal neurons classified by spatial positioning and action potential firing patterns. Surveying two hippocampal neurons that highly express latrophilin-2, late-bursting CA1 pyramidal cells and early-bursting subiculum pyramidal cells, we found the molecule to be differentially positioned on their respective dendritic compartments. Investigating this latrophilin-2 positioning at the synaptic level, we found that the molecule is not present within either the pre- or postsynaptic terminal but rather is tightly coupled to synapses at a perisynaptic location. Together these findings indicate that hippocampal latrophilin-2 distribution patterning is cell-type specific, and requires multiple postsynaptic neurons for its synaptic localization.

Atroposelective Synthesis of Axially Chiral Diaryl Ethers by N-Heterocyclic-Carbene-Catalyzed Sequentially Desymmetric/Kinetic Resolution Process.

We describe herein an N-heterocyclic-carbene-catalyzed atroposelective synthesis of axially chiral diaryl ethers. Through a sequentially enantioselective desymmetric process and a kinetic resolution process, the products could be constructed in good yields with excellent enantiopurities. Both alcohols and phenols were compatible with this catalytic system. The axially chiral carboxylic acids derived from the esters were proven to be potential chiral ligands for asymmetric synthesis, for example, Rh(III)-catalyzed enantioselective C-H functionalization.

Targeting the Nrf2-dependent mechanism of b-Ecdysterone in attenuating the motor dysfunction in the MPTP/Pro-induced Parkinson's disease mice model.

Oxidative stress is a pivotal stimulating factor in neurocyte apoptosis and has been involved in the pathogenesis of Parkinson's disease (PD). In this study, we have demonstrated that the improvement in the motor disorder of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/Pro-induced mice caused by b-Ecdysterone (b-Ecd) treatment is due to its antioxidant properties. Using open field, rotarod, and pole climbing tests, we have found that b-Ecd alleviates motor disorder in MPTP/Pro-induced mice and ultimately reduces the impairment of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra (SN). Notably, these effects of b-Ecd were not observed in Nrf2-KO mice. In addition, b-Ecd significantly reduced the formation of ROS and the level of MDA, blocked the increase of LPO, and partially reversed the GSH/GSSG ratio in MPTP/Pro-induced WT mice; however, these results were also not observed in MPTP/Pro-induced Nrf2-KO mice. Mechanistically, b-Ecd enhanced the expression levels of heme oxygenase 1 (HO-1) and GCLc, but not NQO1 (NAD(P)H quinone dehydrogenase 1) and GCLm expression. Interestingly, b-Ecd failed to increase the protein and mRNA levels of HO-1 and GCLc in Nrf2-KO mice, suggesting that b-Ecd attenuates oxidative stress through an Nrf2-dependent mechanism. Furthermore, b-Ecd promoted the expressions of PI3K/Akt phosphorylation (activity) and GSK-3b phosphorylation (inactivity). Conversely, administration of b-Ecd markedly decreased Fyn phosphorylation levels. Collectively, our findings suggest that b-Ecd focuses on Nrf2 in reducing MPTP/Pro-induced oxidative stress and subsequent motor deficits by inhibiting its nuclear export through PI3K/Akt/GSK-3b/Fyn pathway regulation. These further indicate that b-Ecd may be an absorbing therapeutic agent for PD.