Association of long-term triglyceride-glucose index patterns with the incidence of chronic kidney disease among non-diabetic population: evidence from a functional community cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and previous studies have confirmed the association of TyG index with incident chronic kidney disease (CKD). However, the impact of longitudinal patterns of TyG index on CKD risk among non-diabetic population is still unknown. Therefore, this study aimed to investigate the association of longitudinal patterns of TyG index with incident CKD among non-diabetic population. METHODS: A total of 5484 non-diabetic participants who underwent one health examination per year from 2015 to 2017 were included in this prospective study. TyG index variability and cumulative TyG index were calculated to assess the longitudinal patterns of TyG index. Cox proportional hazard models were performed to estimate the association of TyG index variability or cumulative TyG index with incident CKD. RESULTS: During a median of 3.82 years follow-up, 879 participants developed CKD. Compared with participants in the lowest quartile, the hazard ratio (HR) and 95% confidence interval (CI) of incident CKD were 1.772 (95% CI: 1.453, 2.162) for the highest TyG index variability quartile and 2.091 (95% CI: 1.646, 2.655) for the highest cumulative TyG index quartile in the fully adjusted models. The best discrimination and reclassification improvement were observed after adding baseline TyG, TyG index variability and cumulative TyG index to the clinical risk model for CKD. CONCLUSIONS: Both TyG index variability and cumulative TyG index can independently predict incident CKD among non-diabetic population. Monitoring longitudinal patterns of TyG index may assist with prediction and prevention of incident CKD.

Genome-Wide Mapping of Plasma IgG N-Glycan Quantitative Trait Loci Identifies a Potentially Causal Association between IgG N-Glycans and Rheumatoid Arthritis.

Observational studies highlight associations of IgG N-glycosylation with rheumatoid arthritis (RA); however, the causality between these conditions remains to be determined. Standard and multivariable two-sample Mendelian randomization (MR) analyses integrating a summary genome-wide association study for RA and IgG N-glycan quantitative trait loci (IgG N-glycan-QTL) data were performed to explore the potentially causal associations of IgG N-glycosylation with RA. After correcting for multiple testing (p < 2 × 10-3), the standard MR analysis based on the inverse-variance weighted method showed a significant association of genetically instrumented IgG N-glycan (GP4) with RA (odds ratioGP4 = 0.906, 95% confidence interval = 0.857-0.958, p = 5.246 × 10-4). In addition, we identified seven significant associations of genetically instrumented IgG N-glycans with RA by multivariable MR analysis (p < 2 × 10-3). Results were broadly consistent in sensitivity analyses using MR_Lasso, MR_weighted median, MR_Egger regression, and leave-one-out analysis with different instruments (all p values <0.05). There was limited evidence of pleiotropy bias (all p values > 0.05). In conclusion, our MR analysis incorporating genome-wide association studies and IgG N-glycan-QTL data revealed that IgG N-glycans were potentially causally associated with RA. Our findings shed light on the role of IgG N-glycosylation in the development of RA. Future studies are needed to validate our findings and to explore the underlying physiological mechanisms in the etiology of RA.

Age and sex differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction.

BACKGROUND: The effects of air pollution on endothelial function remain unclear across populations. We aimed to use brachial artery flow-mediated dilatation (FMD) to identify demographic differences in the effects of air pollution exposure on endothelial dysfunction. METHODS: We measured FMD in 850 participants from October 2016 to January 2020. Location-specific concentrations of fine particulate matter < 2.5 µm aerodynamic diameter (PM2.5), inhalable particulate matter < 10 µm aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) measured by fixed ambient air monitoring stations were collected for short- and long-term exposure assessment. Multiple linear regression models and restricted cubic splines were used to assess the associations before and after stratification by age and sex. RESULTS: This study eventually included 828 participants [551 (66.5%) younger than 65 years and 553 (66.8%) men]. Each 10 µg/m3 increase in 7-day exposure to PM2.5 and PM10 was significantly linearly associated with a 0.07% (ß = -0.07, 95% CI: -0.13 to -0.004) and 0.05% (ß = -0.05, 95% CI: -0.10 to -0.004) decrease in FMD in the fully adjusted model. After full adjustment, long-term exposure to all air pollutants was significantly associated with impaired FMD. Each 10 µg/m3 increase in long-term exposure to PM2.5 and PM10 was significantly associated with a -0.18% (95% CI: -0.34 to -0.03) and - 0.23% (95% CI: -0.40 to -0.06) change in FMD, respectively. After stratification, the associations of lower FMD with long-term exposure to PM2.5, PM10, SO2, NO2, and CO significantly persisted in men and participants younger than 65 years instead of women or older participants. For short-term exposure, we observed differences consistent with long-term exposure and a stronger effect of 7-day exposure to SO2 in men due to a significant interaction effect. CONCLUSION: Short- and long-term exposure to different air pollutants are strongly associated with decreased endothelial function, and susceptibility to air pollution varies significantly with age and sex.

Association between systemic immune inflammatory/inflammatory response index and hypertension: A cohort study of functional community.

BACKGROUND AND AIMS: In prospective studies, there is limited evidence of the association between inflammation and hypertension. We aimed to explore the relationship between systemic immune inflammatory index (SII)/systemic inflammatory response index (SIRI) and hypertension in a prospective cohort study to identify the best inflammatory cell markers that predict hypertension. METHODS AND RESULTS: This study was conducted in a functional community cohort in Beijing. In 2015, a total of 6003 individuals without hypertension were recruited and followed up until 2021. Using a restriction cubic spline with baseline SII/SIRI as a continuous variable, the dose-response relationship between hypertension and SII/SIRI was explored. Logistic regression was used to analyze the correlation between hypertension and SII/SIRI trajectory groups. At a mean follow-up of 6 years, 970 participants developed hypertension. SII showed a significant nonlinear dose-response relationship with hypertension (P < 0.05). Higher SII/SIRI was associated with an increased risk of hypertension (SII: RR = 1.003, 95%CI: 1.001-1.004; SIRI: RR = 1.228, 95%CI: 1.015-1.486). Both SII and SIRI were more predictive in males than females (SII: 0.698 vs. 0.695; SIRI: 0.686 vs. 0.678). CONCLUSION: Both systemic immune inflammatory index (SII) and systemic inflammatory response Index (SIRI) independently increased the risk of hypertension, and both were effective inflammatory cell indicators that predict the risk of hypertension.

Controlling desertification brings positive socioeconomic benefits beyond regional environmental improvement: Evidence from China's Gonghe Basin.

Large-scale desertification combatting programs (DCPs) are crucial tools for addressing climate change and improving the ecological environment. Despite existing research having predominantly focused on assessing the ecological benefits of DCPs, the understanding of their impacts on surrounding socioeconomic aspects remains limited, particularly at the household level. To comprehensively evaluate the returns of DCPs, this study chose the representative desertification control area of the Gonghe Basin on the Qinghai-Tibet Plateau as the research region and identified the dual benefits in terms of ecological environment and socioeconomic gains. Firstly, two essential ecosystem services, carbon sequestration (CS) and wind erosion prevention (WEP), were assessed using the MODIS NPP dataset and the RWEQ model from 2001 to 2021. Household surveys were conducted in 36 villages across 14 townships within the Gonghe Basin to gain a deeper understanding of the residents' socioeconomic conditions. Through regression analysis, the study assessed the impact of DCPs on the regional ecological environment and household socioeconomic status. The research findings revealed significant improvements in CS and WEP across a significant portion of the study area from 2001 to 2021. Upon analyzing data from 401 household questionnaires, it was generally perceived by residents in the Gonghe Basin that the implementation of DCPs led to environmental improvements and increased their income levels. Further regression analysis revealed a significant impact of both natural factors and the extent of resident participation in the projects on the ecological environment surrounding the villages and on household socioeconomic aspects. With increased resident engagement in the projects, the likelihood of increased household income and life satisfaction was higher. The diverse array of DCPs implemented in the Gonghe Basin not only improved the regional ecological environment but also stimulated socioeconomic development. In future projects, it is imperative to consider regional characteristics, align ecological effects, ensure the sustainability of livelihoods, and maximize the role of social capital.

Association of variability in metabolic parameters with the incidence of type 2 diabetes: evidence from a functional community cohort.

BACKGROUND: To investigate the association of variability in metabolic parameters such as total cholesterol concentrations (TC), uric acid (UA), body mass index (BMI), visceral adiposity index (VAI) and systolic blood pressure (SBP) with incident type 2 diabetes (T2D) and whether variability in these metabolic parameters has additive effects on the risk of T2D. METHODS: Based on the Beijing Functional Community Cohort, 4392 participants who underwent three health examinations (2015, 2016, and 2017) were followed up for incident T2D until the end of 2021. Variability in metabolic parameters from three health examinations were assessed using the coefficient of variation, standard deviation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability index. Participants were grouped according to the number of high-variability metabolic parameters. Cox proportional hazards models were performed to assess the hazard ratio (HR) and 95% confidence interval (CI) for incident T2D. RESULTS: During a median follow-up of 3.91 years, 249 cases of incident T2D were identified. High variability in TC, BMI, VAI and SBP was significantly associated with higher risks of incident T2D. As for UA, significant multiplicative interaction was found between variability in UA and variability in other four metabolic parameters for incident T2D. The risk of T2D significantly increased with the increasing numbers of high-variability metabolic parameters. Compared with the group with low variability for 5 parameters, the HR (95% CI) for participants with 1-2, 3, 4-5 high-variability metabolic parameters were 1.488 (1.051, 2.107), 2.036 (1.286, 3.222) and 3.017 (1.549, 5.877), respectively. Similar results were obtained in various sensitivity analyses. CONCLUSIONS: High variability of TC, BMI, VAI and SBP were independent predictors of incident T2D, respectively. There was a graded association between the number of high-variability metabolic parameters and incident T2D.

Plaque modification and stabilization after drug-coated balloon angioplasty for intracranial atherosclerotic lesions.

OBJECTIVES: A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). We aimed to evaluate changes of vessel wall features of ICAD lesions after DCB treatment by using vessel wall MRI (VWMRI). METHODS: We retrospectively included patients with symptomatic ICAD who underwent DCB angioplasty alone. The incidences of stenosis of the lumen area, vessel wall thickening, hyperintense plaques, and prominent wall enhancement were compared between the baseline and follow-up VWMRI. RESULTS: There were 29 ICAD lesions from 29 patients, of which 22 were stenosis and 7 were occlusion. The median interval between DCB treatment and follow-up VWMRI was 4.1 [3.3, 6.7] months. After DCB treatment, follow-up VWMRI showed a significant decrease in the stenosis degree of the lumen area (83% [71%, 96%] vs 15% [3%, 41%], p < 0.001). Thirty-eight percent (11/29) of the patients observed normal appearance of the target vessel wall on follow-up VWMRI. In the stenosis group, the prevalence of hyperintense plaques decreased from 66.7% (14/21) at baseline to 23.8% (5/21) at follow-up, and prominent wall enhancement decreased from 66.7% (14/21) at baseline to 19.0%(4/21) at follow-up. The incidence of hyperintense plaques (p = 0.028) and vessel wall thickening (p = 0.018) tended to decrease with follow-up time. Although not significant (p = 0.106), a similar trend was observed between the incidence of prominent wall enhancement and follow-up time. CONCLUSION: Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions. KEY POINTS: • A drug-coated balloon (DCB) has potential applications in the treatment of intracranial atherosclerotic disease (ICAD). • Vascular healing with plaque modification and stabilization occurred following DCB treatment of ICAD lesions.

Estrogen receptor alpha-mediated mitochondrial damage in intrahepatic bile duct epithelial cells leading to the pathogenesis of primary biliary cholangitis.

This study investigated the effects of estrogen and estrogen receptor alpha (ERα) on the pathogenesis of primary biliary cholangitis (PBC) in human intrahepatic bile duct epithelial cells (HiBECs). The researchers measured serum levels of ERα, oxidative stress indicators, and cytokines in PBC patients and healthy controls. They examined the expression of ERα, pyruvate dehydrogenase complex E2-component (PDC-E2), and apoptosis-related proteins in the small bile ducts. In vitro experiments with HiBECs showed that estrogen had a dual effect on cell viability, increasing it at low concentrations but reducing it at higher concentrations. ERα activation led to mitochondrial damage, apoptosis, and upregulation of ERα and PDC-E2 expression. These findings suggest that the high expression of ERα in the bile ducts contributes to mitochondrial damage, inflammation, and apoptosis in PBC. The study highlights ERα as a potential target for understanding and treating estrogen-mediated PBC pathogenesis.

Gender-specific predictive ability for the risk of hypertension incidence related to baseline level or trajectories of adiposity indices: a cohort study of functional community.

BACKGROUND: Early prevention of hypertension is important for global cardiovascular disease morbidity and mortality. This study aims to explore better predictors for hypertension incidence related to baseline level or trajectories of adiposity indices, as well as the gender-specific effect. METHODS: 6085 subjects from a functional community cohort in urban Beijing participated in our study. Restricted cubic splines were used to estimate nonlinear associations of body mass index (BMI) and waist-to-height ratio (WHtR) as continuous variable with risk of hypertension. Stepwise logistic regression model was performed to estimate the relative risks (RRs) of adiposity indices and metabolic status, adjusted for covariates. Nomogram models and receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive power of BMI trajectory groups and WHtR trajectory groups on hypertension incidence. Further, all analysis were performed by gender. RESULTS: The risk of hypertension incidence was related to BMI trajectory groups (persistent overweight: RR = 1.88, 95% CI: 1.48-2.37; persistent obesity: RR = 2.79, 95% CI: 2.18-3.56; persistent the highest: RR = 4.30, 95% CI: 3.20-5.78) and WHtR trajectory groups (persistent medium: RR = 2.69, 95% CI: 2.07-3.50; persistent high: RR = 3.85, 95% CI: 2.92-5.09; increasing to higher: RR = 7.00, 95% CI: 4.96-9.89). In total population, BMI trajectories and WHtR trajectories showed similar ability to predict the risk of hypertension incidence with AUC 0.723 and 0.726, respectively. After stratified by gender, both BMI trajectories and WHtR trajectories showed higher power in female than male (BMI trajectories: 0.762 vs. 0.661; WHtR trajectories: 0.768 vs. 0.661). CONCLUSIONS: BMI and WHtR trajectories have higher predictive power for hypertension incidence compared to baseline data. Females are more vulnerable to obesity than males.

Organization of the parallel antennal-lobe tracts in the moth.

The olfactory pathways of the insect brain have been studied comprehensively for more than 40 years, yet the last decade has included a particularly large accumulation of new information relating to this system's structure. In moths, sharp intracellular recording and staining has been used to elucidate the anatomy and physiology of output neurons from the primary olfactory center, the antennal lobe. This review concentrates on the connection patterns characterizing these projection neurons, which follow six separate antennal-lobe tracts. In addition to highlighting the connections between functionally distinct glomerular clusters and higher-order olfactory neuropils, we discuss how parallel tracts in the male convey distinct features of the social signals released by conspecific and heterospecific females. Finally, we consider the current state of knowledge regarding olfactory processing in the moth's protocerebrum and make suggestions as to how the information concerning antennal-lobe output may be used to design future studies.

Detection and analysis of long noncoding RNA expression profiles related to epithelial-mesenchymal transition in keloids.

BACKGROUND: The role of epithelial-mesenchymal transition (EMT) in the pathogenesis of keloids is currently raising increasing attention. Long noncoding RNAs (lncRNAs) govern a variety of biological processes, such as EMT, and their dysregulation is involved in many diseases including keloid disease. The aim of this study was to identify differentially expressed EMT-related lncRNAs in keloid tissues versus normal tissues and to interpret their functions. RESULTS: Eleven lncRNAs and 16 mRNAs associated with EMT were identified to have differential expression between keloid and normal skin tissues (fold change > 1.5, P < 0.05). Gene Ontology (GO) analysis showed that these differentially expressed mRNAs functioned in the extracellular matrix, protein binding, the positive regulation of cellular processes, the Set1C/COMPASS complex and histone acetyltransferase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these mRNAs are involved in pathways in cancer. The lncRNA, XLOC_000587 may promote cell proliferation and migration by enhancing the expression of ENAH, while AF268386 may facilitate the invasive growth of keloids by upregulating DDR2. CONCLUSIONS: We characterized the differential expression profiles of EMT-related lncRNAs and mRNAs in keloids, which may contribute to preventing the occurrence and development of keloids by targeting the corresponding signaling pathways. These lncRNAs and mRNAs may provide biomarkers for keloid diagnosis and serve as potential targets for the treatment of this disease.

L-Cysteine attenuates osteopontin-mediated neuroinflammation following hypoxia-ischemia insult in neonatal mice by inducing S-sulfhydration of Stat3.

We previously show that L-Cysteine administration significantly suppresses hypoxia-ischemia (HI)-induced neuroinflammation in neonatal mice through releasing H2S. In this study we conducted proteomics analysis to explore the potential biomarkers or molecular therapeutic targets associated with anti-inflammatory effect of L-Cysteine in neonatal mice following HI insult. HI brain injury was induced in postnatal day 7 (P7) neonatal mice. The pups were administered L-Cysteine (5 mg/kg) at 24, 48, and 72 h post-HI. By conducting TMT-based proteomics analysis, we confirmed that osteopontin (OPN) was the most upregulated protein in ipsilateral cortex 72 h following HI insult. Moreover, OPN was expressed in CD11b+/CD45low cells and infiltrating CD11b+/CD45high cells after HI exposure. Intracerebroventricular injection of OPN antibody blocked OPN expression, significantly attenuated brain damage, reduced pro-inflammatory cytokine levels and suppressed cerebral recruitment of CD11b+/CD45high immune cells following HI insult. L-Cysteine administration reduced OPN expression in CD11b+/CD45high immune cells, concomitant with improving the behavior in Y-maze test and suppressing cerebral recruitment of CD11b+/CD45high immune cells post-HI insult. Moreover, L-Cysteine administration suppressed the Stat3 activation by inducing S-sulfhydration of Stat3. Intracerebroventricular injection of Stat3 siRNA not only decreased OPN expression, but also reversed HI brain damage. Our data demonstrate that L-Cysteine administration effectively attenuates the OPN-mediated neuroinflammation by inducing S-sulfhydration of Stat3, which contributes to its anti-inflammatory effect following HI insult in neonatal mice. Blocking OPN expression may serve as a new target for therapeutic intervention for perinatal HI brain injury.

Association between insulin resistance and incidence of carotid atherosclerotic plaque: A cohort study.

BACKGROUND AND AIMS: There is limited evidence on the association between insulin resistance (IR) and carotid plaque was reported in prospective study. We aimed to exploit the relationship between IR and carotid plaque in a prospective cohort study. METHODS AND RESULTS: The study was performed in a functional community cohort in urban Beijing. In 2015, a total of 7061 individuals without intima-media thickness (IMT) thickening and carotid artery plaque were recruited and followed up until 2019. Restricted cubic spline was conducted to exploit the dose-response relationship between carotid plaque and baseline HOMA-IR or TyG index as continuous variables. Logistic regression was used to analyze the associations between carotid plaque and HOMA-IR or TyG index. During the average 4 years follow-up, 589 subjects developed carotid plaque. Both HOMA-IR and TyG index showed significant linear dose-response relationship on carotid plaque (p < 0.001). The RRs (95%CI) for subjects with baseline HOMA-IR in quartile 2, quartile 3 and quartile 4 were 1.52 (1.14-2.04), 1.86 (1.40-2.46), and 2.55 (1.94-3.35) compared to quartile 1, respectively. Compared to the first quartile of TyG, the RRs (95%CI) for subjects in quartile 2, quartile 3 and quartile 4 were 1.43 (1.08-1.90), 1.59 (1.20-2.12), and 1.69 (1.26-2.25), respectively. In total population, the predictive ability of HOMA-IR for carotid plaque was significantly better than that of TyG index (p = 0.025). CONCLUSION: IR is an independent risk factor of carotid plaque. Both HOMA-IR and TyG has significant predictive ability for carotid plaque.

Liquiritigenin protects against myocardial ischemic by inhibiting oxidative stress, apoptosis, and L-type Ca2+ channels.

Liquiritigenin (Lq) offers cytoprotective effects against various cardiac injuries, but its beneficial effects on myocardial ischemic (MI) injury and the related mechanisms remain unclear. In the in vivo study, an animal model of MI was induced by intraperitoneal injection of isoproterenol (Iso, 85 mg/kg). ECG, heart rate, serum levels of CK and CK-MB, histopathological changes, and reactive oxygen species (ROS) levels were all measured. In vitro, H9c2 cells were divided into four groups and treated for 24 hr with liquiritigenin (30 µmol/L and 100 µmol/L) followed with CoCl2 (800 µmol/L) for another 24 hr. Cell viability, apoptosis, mitochondrial membrane potential, and intracellular Ca2+ concentration ([Ca2+ ]i ) were then assessed. The L-type Ca2+ current (ICa-L ) was detected using a patch clamp technique on isolated rat ventricular myocytes. The myocyte contraction and Ca2+ transients were measured using an IonOptix detection system. The remarkable cardiac injury and generation of intracellular ROS induced by Iso were alleviated via treatment with Lq. CoCl2 administration induced cell apoptosis, mitochondrial dysfunction, and Ca2+ overload in H9c2; Lq reduces these deleterious effects of CoCl2 . Meanwhile, Lq blocked ICa-L in a dose-dependent manner. The half-maximal inhibitory concentration of Lq was 110.87 µmol/L. Lq reversibly reduced the amplitude of cell contraction as well as the Ca2+ transients. The results show that Lq protects against MI injury by antioxidation, antiapoptosis, counteraction mitochondrial dysfunction, and inhibition of ICa-L , thus damping intracellular Ca2+ .

The tradeoffs between food supply and demand from the perspective of ecosystem service flows: A case study in the Pearl River Delta, China.

Ecosystem service flows are a research topic of significant interest, and exploring this topic may mitigate the shortcomings related to the spatial mismatches between supply and demand in the current ecosystem services studies. The Pearl River Delta (PRD) experiences a serious spatial mismatch in ecosystem services in particular the food supply, between the supply areas (hilly areas) and demand areas (central areas). Therefore, this study focused on the PRD as a case study to analyze change trends of food supply-demand ratio (FSDR) at city level, and depict the spatial flow path within and between cities from the perspective of ecosystem service flow with different threshold distance, using an enhanced two-step floating catchment area accessibility method. The results showed that the food demand significantly exceeded the supply, the budget was 3.58 million tons and FSDR was 0.49 in 2015. There were large discrepancies in the FSDR at the city level before and after when considering the ecosystem service flows. The FSDR of cities in the central areas increased 0.1%-30%, due to the ecosystem service flow from the low hilly areas. As delivery distances increased, the size of food flow decreased within cities and increased among cities. This led to a significant decline in the population living in severe undersupplied areas (FSDR＜0.1) and oversupplied areas (FSDR＞1), and an increase in undersupplied areas (0.1＜FSDR＜0.9). Our findings indicate that local governments would benefit from enhancing connections between supply and demand areas to meet the food demand of big cities. This study offers a comprehensive and realistic understanding of the physical situation of ecosystem service consumption by human beings, and provides decision-making information for optimize land use allocation.

Multicolor Emissive Phosphorescent Iridium(III) Complexes Containing L-Alanine Ligands: Photophysical and Electrochemical Properties, DFT Calculations, and Selective Recognition of Cu(II) Ions.

Three novel Ir(III) complexes, (ppy)2Ir(L-alanine) (Ir1) (ppy = 2-phenylpyridine), (F4ppy)2Ir(L-alanine) (Ir2) (F4ppy = 2-(4-fluorophenyl)pyridine), and (F2,4,5ppy)2Ir(L-alanine) (Ir3) (F2,4,5ppy = 2-(2,4,5-trifluorophenyl)pyridine), based on simple L-alanine as ancillary ligands were synthesized and investigated. Due to the introduction of fluorine substituents on the cyclometalated ligands, complexes Ir1-Ir3 exhibited yellow to sky-blue emissions (λem = 464-509 nm) in acetonitrile solution. The photoluminescence quantum yields (PLQYs) of Ir1-Ir3 ranged from 0.48-0.69, of which Ir3 with sky-blue luminescence had the highest PLQY of 0.69. The electrochemical study and density functional theory (DFT) calculations show that the highest occupied molecular orbital (HOMOs) energy of Ir1-Ir3 are stabilized by the introduction of fluorine substituents on the cyclometalated ligands, while L-alanine ancillary ligand has little contribution to HOMOs and lowest unoccupied molecular orbitals (LUMOs). Moreover, Ir1-Ir3 presented an excellent response to Cu2+ with a high selectivity, strong anti-interference ability, and short response time. Such a detection was based on significant phosphorescence quenching of their emissions, showing the potential application in chemosensors for Cu2+.

Sexual Incentive Motivation and Copulatory Behavior in Male Rats Treated With the Adrenergic α2-Adrenoceptor Agonists Tasipimidine and Fadolmidine: Implications for Treatment of Premature Ejaculation.

BACKGROUND: Premature ejaculation is the most common sexual dysfunction in young men, and it often leads to reduced relationship satisfaction and quality of life. AIM: To determine the role of central and peripheral α2-adrenoceptors in the control of ejaculation and sexual incentive motivation in rats. METHODS: Sexual incentive motivation was studied in a large arena in which a male subject could choose between approaching and remaining close to a sexually receptive female or another male. Sexual behavior was studied in standard observation cages in which a male was allowed to freely interact with a receptive female for 30 minutes. Two highly selective agonists at the α2-adrenoceptors, tasipimidine and fadolmidine, were administered before the tests. Low peripheral doses of fadolmidine have been reported to have effects mainly outside of the central nervous system, whereas at large doses also the central effects are evident. OUTCOMES: The time spent close to the receptive female in relation to the time spent with the male and measures of ambulatory activity were obtained from the test for sexual incentive motivation, while the habitual parameters of sexual behavior were recorded with the copulation test. RESULTS: Tasipimidine prolonged ejaculation latency and the interintromission interval at the dose of 200 µg/kg when data from fast-ejaculating rats were used. No other sexual parameter was modified. A dose of 100 µg/kg was ineffective. There was no consistent effect on sexual incentive motivation, although modest sedation was observed. Fadolmidine, a drug that does not easily penetrate the blood-brain barrier, had no effect on sexual incentive motivation at any of the doses used (3, 30, and 100 µg/kg). The largest dose had clear sedative effects. The lower doses had no systematic effect on sexual behavior, not even when only fast or very fast ejaculating males were analyzed. CLINICAL TRANSLATION: The findings are relevant to the search for treatments for premature ejaculation that are specific enough to selectively delay ejaculation. STRENGTHS & LIMITATIONS: The procedures used here are standard in the field and yield the most reliable data. Whether the effects observed in male rats are directly transferrable to men can only be determined through clinical studies. CONCLUSION: The observation that drugs acting at central but not peripheral α2-adrenoceptors prolong ejaculation latency without affecting any other parameter of sexual behavior or sexual incentive motivation suggests that this kind of drug may be suitable for treating premature ejaculation. Jyrki L., Elisa V.-A., Xi C., et al. Sexual Incentive Motivation and Copulatory Behavior in Male Rats Treated With the Adrenergic α2-Adrenoceptor Agonists Tasipimidine and Fadolmidine: Implications for Treatment of Premature Ejaculation. J Sex Med 2021;18:1677-1689.

Gender differences in risk factors for high plasma homocysteine levels based on a retrospective checkup cohort using a generalized estimating equation analysis.

BACKGROUND: Hyperhomocysteinemia (HHcy) is associated with various health problems, but less is known about the gender differences in risk factors for high plasma homocysteine (Hcy) levels. METHODS: In this study, a retrospective study was carried out on 14,911 participants (7838 males and 7073 females) aged 16-102 years who underwent routine checkups between January 2012 and December 2017 in the Health Management Department of Xuanwu Hospital, China. Anthropometric measurements, including body mass index (BMI) and waist-to-hip ratio, were collected. Fasting blood samples were collected to measure the biochemical indexes. The outcome variable was Hcy level, and a generalized estimating equation (GEE) analysis was used to identify the associations of interest based on gender. RESULTS: Males exhibited increased Hcy levels (16.37 ± 9.66 vs 11.22 ± 4.76 µmol/L) and prevalence of HHcy (37.0% vs 11.3%) compared with females. Hcy levels and HHcy prevalence increased with age in both genders, except for the 16- to 29-year-old group. GEE analysis indicated that irrespective of gender, aspartate aminotransferase, creatinine, uric acid, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were positively correlated with Hcy levels, and alanine aminotransferase, total cholesterol and glucose were negatively correlated with Hcy levels. However, age, BMI and triglycerides (TGs) were positively correlated with Hcy levels exclusively in females. CONCLUSIONS: Gender differences in risk factors for high plasma Hcy levels were noted. Although common correlational factors existed in both genders, age, BMI and TGs were independent risk factors for Hcy levels specifically in females.

The effectiveness of different down-regulating protocols on in vitro fertilization-embryo transfer in endometriosis: a meta-analysis.

BACKGROUND: To investigate the effectiveness of the GnRH-a ultra-long protocol, GnRH-a long protocol, and GnRH-a short protocol used in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with endometriosis. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, Elsevier Science Direct, OA Library, Google Scholar, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, China Science and Technology Journal database, and the China Biology Medicine disc for randomized controlled trials (RCTs) and observational studies (non-RCTs) to evaluate the efficacy of the GnRH-a ultra-long protocol, GnRH-a long protocol, and GnRH-a short protocol in IVF-ET in infertile patients with endometriosis. RESULTS: A total of 21 studies in compliance with the standard literature were included, and RCT and non-RCT studies were analyzed separately. This meta-analysis showed that the GnRH-a ultra-long protocol could improve the clinical pregnancy rate of infertile patients in RCT studies, especially in patients with stages III-IV endometriosis (RR = 2.04, 95% CI: 1.37~3.04, P < 0.05). However, subgroup analysis found the different down-regulation protocols provided no significant difference in improving clinical outcomes in patients with endometriosis in the non-RCT studies. CONCLUSION: This study suggests that the GnRH-a ultra-long protocol can improve the clinical pregnancy rate of the patients with stages III-IV endometriosis in RCT studies. Although it is generally believed that the results of RCT are more reliable, the conclusions of the non-RCT studies cannot be easily neglect, which let us draw conclusions more cautious.

Safranal, an active constituent of saffron, ameliorates myocardial ischemia via reduction of oxidative stress and regulation of Ca2+ homeostasis.

Safranal (SFR) is the major constituent of saffron. The purpose of this study was to observe the effect of SFR on myocardial ischemia induced by isoprenaline (ISO) and to explore its possible mechanism. The myocardial ischemia rat model was established by subcutaneous injection of ISO (85 mg/kg/d) on the 8th and 9th day of the experiment. Serum creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured, as were changes in calcium concentration, reactive oxygen species (ROS) and cardiac morphology of the myocardial tissue. The effects of SFR on cell contraction, Ca2+ transient and L-type Ca2+ current (ICa-L) in isolated rat myocardial cells were measured using the Ion Optix detection system and the whole-cell patch-clamp technique. SFR can decrease the activity of serum CK, LDH and MDA, and increase the activity of serum SOD, reduce intracellular calcium concentration and the manufacture of ROS. In addition, SFR can improve changes in heart morphology. SFR can significantly inhibit contraction, Ca2+ transients and ICa-L in isolated ventricular myocytes. SFR has a cardioprotective role in ISO-induced MI rats, and the underling mechanism is related to the inhibition of oxidative stress, myocardial contractility, ICa-L and the regulation of Ca2+ homeostasis.