The genetic relationship between systemic lupus erythematosus and risk of primary ovarian failure from a mendelian randomization study.

Previous studies investigating the relationship between systemic lupus erythematosus (SLE) and primary ovarian failure (POF) generated conflicting results. To data, no mendelian randomization study has been applied to examine this association. In this study, genetic instruments for exposure (SLE) were selected from a GWAS study with 5201 cases and 9066 noncases. Outcome data for POF and three reproductive traits (age at menarche, age at menopause, and age at first live birth) were obtained from other eligible GWASs. To estimate causal association, the inverse-variance weighted (IVW) method (the main analyse), MR Egger test, weighted median, simple mode, and weighted mode were applied. Moreover, sensitivity analyses were conducted to ensure the robustness of the results. Estimated by the IVW method, SLE was suggested to be causally related to the risk of POF (OR = 1.166, 95% CI 1.055-1.289, P = 0.003) and delayed age at first live birth (OR = 1.006, 95% CI 1.002-1.010, P = 0.007), with no evidence of a causal association between SLE and age at menopause or menarche. The estimates were robust according to sensitivity analysis. In conclusion, the two-sample MR study supported a causal association between SLE and POF from a genetic aspect.

Photo-excited charge transfer from adamantane to electronic bound states in water.

Aqueous nanodiamonds illuminated by UV light produce free solvated electrons, which may drive high-energy reduction reactions in water. However, the influence of water conformations on the excited-state electron-transfer mechanism are still under debate. In this work, we offer a theoretical study of charge-transfer states in adamantane-water structures obtained by linear-response time-dependent density-functional theory. Small water clusters with broken hydrogen bonds are found to efficiently bind the electron from adamantane. A distinction is made with respect to the nature of the water clusters: some bind the electron in a water cavity, others along a strong permanent total dipole. These two types of bound states are more strongly binding, the higher their electron affinity and their positive electrostatic potential, the latter being dominated by the energy of the lowest unoccupied molecular orbital of the isolated water clusters. Structural sampling in a thermal equilibrium at room temperature via molecular dynamics snapshots confirms under which conditions the underlying waters clusters can occur and verifies that broken hydrogen bonds in the water network close to adamantane can create traps for the solvated electron.

An overview of CFTR mutation profiles and assisted reproductive technology outcomes in Chinese patients with congenital obstructive azoospermia.

PURPOSE: The cystic fibrosis transmembrane conductance regulator (CFTR) is the most common causative gene attributed to congenital obstructive azoospermia (OA). The aim of this study was to conduct an epidemiological survey of congenital OA patients, to screen for CFTR mutations, and to follow their pregnancy outcomes in assisted reproductive technology (ART). METHODS: This cohort study enrolled congenital OA patients undergoing ART and whole-exome sequencing from January 2018 to September 2023. Semen parameters, sex hormones, and seminal plasma biochemistry were evaluated. CFTR mutations identified in OA patients were analyzed. In addition, the laboratory outcomes, clinical outcomes, and neonatal outcomes were compared between OA patients carrying two CFTR mutations and the others after surgical sperm extraction-intracytoplasmic sperm injection (ICSI) treatment. RESULTS: A total of 76 patients with congenital OA were enrolled. CFTR mutations were identified in 35 (46.1%) congenital OA patients. A total of 60 CFTR mutation sites of 27 types were identified, and 10 of them were novel. The average frequency was 1.71 (60/35) per person. The most common mutation was c.1210-11T > G (25%, 15/60). After ICSI treatment, there were no statistically significant differences in laboratory outcomes, clinical outcomes, and neonatal outcomes between OA patients carrying two CFTR mutations (n = 25) and other OA patients (n = 51). CONCLUSION: Apart from the IVS9-5T mutation, the genetic mutation pattern of CFTR in Chinese OA patients is heterogeneous, which is significantly different from that of Caucasians. Although carrying two CFTR mutations or not had no effect on the pregnancy outcomes in OA patients after ICSI, genetic counseling is still recommended for such patients.

Ground and excited state charge transfer at aqueous nanodiamonds.

Nanodiamonds (NDs) are unique carbonaceous materials with exceptionally high stability, hardness, and notable electronic properties. Their applications in photocatalysis, biomedicine, and energy materials are usually carried out in aqueous environments, where they interact with aqueous adsorbates. Especially, electron density may rearrange from the diamond material toward oxidative adsorbates such as oxygen, which is known as charge transfer doping. In this article, we quantify the charge transfer doping for NDs with inhomogeneous surface coverings (hydroxyl, fluorine, and amorphous carbon), as well as NDs doped with heteroatoms (B, Si, N) using hybrid density functional theory (DFT) calculations. The transfer doping magnitude is largely determined by the NDs' highest occupied molecular orbital energies, which can in turn be modified by the surface covering and doping. However, local modifications of the ND structures do not have any local effects on the magnitude of the charge transfer. We furthermore analyze the impact of aqueous adsorbates on the excited states of an aqueous ND in the context of photocatalysis via time-dependent DFT. Here, we find that the excited electrons are biased to move in the direction of the respective oxidative adsorbate. Surprisingly, we find that also unreactive species such as nitrous oxide may attract the excited electrons, which is probably due to the positive partial charge that is induced by the local N 2 O solvation geometry.

Disruption of Histamine-H1R signaling exacerbates cardiac microthrombosis after periodontal disease via TLR4/NFκB-p65 pathway.

Periodontal disease is a chronic inflammatory disease that is highly correlated with cardiovascular disease(CVD). Histamine has been proven to participate in the pathophysiological processes of cardiovascular disease and oral inflammation. However, the role of histamine in the development of cardiac microthrombosis caused by periodontal disease has not been fully elucidated. We established a murine periodontal inflammation model by injecting lipopolysaccharide (LPS) or Porphyromonas gingivalis (P. gingivalis). In order to examine the effect of histamine/H1R signaling on cardiac injury after periodontal disease, we used histidine decarboxylase- knockout (HDC-/-) mice and histamine 1 receptor (H1R) antagonist. Our results demonstrated that LPS-induced periodontal inflammation significantly increased CD11b+Gr-1+ neutrophils in the peripheral blood and myocardial interstitium. Histamine deficiency resulted in further increases in P. gingivalis, neutrophils, inflammatory cytokines, and cardiac microthrombosis in the myocardium of HDC-/- mice compared to wild-type (WT) mice. Mechanistic analysis showed that blocking H1R could synergistically interact with LPS, further increasing the phosphorylation of p65, exacerbating the inflammatory response of neutrophils and endothelial cell damage. Conclusively, the disruption of histamine-H1R signaling exacerbates cardiac microthrombosis after periodontal disease via TLR4/NFκB-p65 pathway. Our findings not only reveal a link between periodontal inflammation and myocardial injury but also provided some thoughts for the use of H1R antagonist in clinical practice.

Rapamycin reverses ferroptosis by increasing autophagy in MPTP/MPP+-induced models of Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder, and ferroptosis plays a significant role in the pathological mechanism underlying Parkinson's disease. Rapamycin, an autophagy inducer, has been shown to have neuroprotective effects in Parkinson's disease. However, the link between rapamycin and ferroptosis in Parkinson's disease is not entirely clear. In this study, rapamycin was administered to a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model and a 1-methyl-4-phenylpyridinium-induced Parkinson's disease PC12 cell model. The results showed that rapamycin improved the behavioral symptoms of Parkinson's disease model mice, reduced the loss of dopamine neurons in the substantia nigra pars compacta, and reduced the expression of ferroptosis-related indicators (glutathione peroxidase 4, recombinant solute carrier family 7, member 11, glutathione, malondialdehyde, and reactive oxygen species). In the Parkinson's disease cell model, rapamycin improved cell viability and reduced ferroptosis. The neuroprotective effect of rapamycin was attenuated by a ferroptosis inducer (methyl (1S,3R)-2-(2-chloroacetyl)-1-(4-methoxycarbonylphenyl)-1,3,4,9-tetrahyyridoindole-3-carboxylate) and an autophagy inhibitor (3-methyladenine). Inhibiting ferroptosis by activating autophagy may be an important mechanism by which rapamycin exerts its neuroprotective effects. Therefore, the regulation of ferroptosis and autophagy may provide a therapeutic target for drug treatments in Parkinson's disease.

The downstream network of STAT6 in promoting vascular smooth muscle cell phenotypic switch and neointimal formation.

Intimal thickening caused by the excessive multiplication of vascular smooth muscle cells (VSMCs) is the pathological process central to cardiovascular diseases, including restenosis. In response to vascular injury, VSMCs would undergo phenotypic switching from a fully differentiated, low proliferative rate phenotype to a more pro-proliferative, promigratory, and incompletely-differentiated state. The lack of a full understanding of the molecular pathways coupling the vascular injury stimuli to VSMCs phenotype switching largely limits the development of medical therapies for treating intima hyperplasia-related diseases. The role of signal transducers and activators of transcription 6 (STAT6) in modulating the proliferation and differentiation of various cell types, especially macrophage, has been well investigated, but little is known about its pathophysiological role and target genes in restenosis after vascular injury. In the present work, Stat6-/- mice were observed to exhibit less severe intimal hyperplasia compared with Stat6+/+ mice after carotid injury. The expression of STAT6 was upregulated in VSMCs located in the injured vascular walls. STAT6 deletion leads to decreased proliferation and migration of VSMCs while STAT6 overexpression enhances the proliferation and migration of VSMCs companies with reduced expression of VSMCs marker genes and organized stress fibers. The effect of STAT6 in mouse VSMCs was conserved in human aortic SMCs. RNA-deep-sequencing and experiments verification revealed LncRNA C7orf69/LOC100996318-miR-370-3p/FOXO1-ER stress signaling as the downstream network mediating the pro-dedifferentiation effect of STAT6 in VSMCs. These findings broaden our understanding of vascular pathological molecules and throw a beam of light on the therapy of a variety of proliferative vascular diseases.

Peroxymonosulfate Activation by Facile Fabrication of α-MnO2 for Rhodamine B Degradation: Reaction Kinetics and Mechanism.

The persulfate-based advanced oxidation process has been an effective method for refractory organic pollutants' degradation in aqueous phase. Herein, α-MnO2 with nanowire morphology was facially fabricated via a one-step hydrothermal method and successfully activated peroxymonosulfate (PMS) for Rhodamine B (RhB) degradation. Influencing factors, including the hydrothermal parameter, PMS concentration, α-MnO2 dosage, RhB concentration, initial pH, and anions, were systematically investigated. The corresponding reaction kinetics were further fitted by the pseudo-first-order kinetic. The RhB degradation mechanism via α-MnO2 activating PMS was proposed according to a series of quenching experiments and the UV-vis scanning spectrum. Results showed that α-MnO2 could effectively activate PMS to degrade RhB and has good repeatability. The catalytic RhB degradation reaction was accelerated by increasing the catalyst dosage and the PMS concentration. The effective RhB degradation performance can be attributed to the high content of surface hydroxyl groups and the greater reducibility of α-MnO2, and the contribution of different ROS (reactive oxygen species) was 1O2 > O2·- > SO4·- > ·OH.

Mechanisms of ovarian aging in women: a review.

Ovarian aging is a natural and physiological aging process characterized by loss of quantity and quality of oocyte or follicular pool. As it is generally accepted that women are born with a finite follicle pool that will go through constant decline without renewing, which, together with decreased oocyte quality, makes a severe situation for women who is of advanced age but desperate for a healthy baby. The aim of our review was to investigate mechanisms leading to ovarian aging by discussing both extra- and intra- ovarian factors and to identify genetic characteristics of ovarian aging. The mechanisms were identified as both extra-ovarian alternation of hypothalamic-pituitary-ovarian axis and intra-ovarian alternation of ovary itself, including telomere, mitochondria, oxidative stress, DNA damage, protein homeostasis, aneuploidy, apoptosis and autophagy. Moreover, here we reviewed related Genome-wide association studies (GWAS studies) from 2009 to 2021 and next generation sequencing (NGS) studies of primary ovarian insufficiency (POI) in order to describe genetic characteristics of ovarian aging. It is reasonable to wish more reliable anti-aging interventions for ovarian aging as the exploration of mechanisms and genetics being progressing.

A new insight into the impact of systemic lupus erythematosus on oocyte and embryo development as well as female fertility.

Background: Systemic lupus erythematosus (SLE) is often associated with adverse reproductive outcomes. But it's currently unclear regarding the role of SLE in oocyte and embryonic development. Also, it's controversial whether SLE has an adverse effect on fertility. There is a lack of comprehensive understanding and assessment of fertility in patients with SLE. Objective: This study was aim to investigate oocyte and embryonic development as well as ovarian reserve, and clinical outcomes in SLE patients during in vitro fertilization (IVF) treatment. By combining data on embryonic and gamete development in SLE patients, we hope to provide new insights into a comprehensive assessment of fertility in SLE patients. Methods: In this study, we collected data from 34 SLE patients who were previously diagnosed and in remission for a total of 44 IVF cycles and matched 102 infertile women with a total of 148 IVF cycles by Propensity Score Matching (PSM) of 1:3 ratio. We then evaluated baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical outcomes between the two groups. Results: After PSM matching, baseline characteristics including age, infertility types, and duration, as well as infertility causes overall coincided between the two groups. Anti-müllerian hormone (AMH) was significantly lower in the SLE group vs comparison (1.9 vs. 3.3 ng/mL, P=0.001). The SLE group performed a significant reduction in available embryo rate (76.6% vs. 86.0%, P=0.001), good-quality blastocyst formation rate (35.1% vs. 47.0%, P=0.003), and blastocyst formation rate (51.0% vs. 67.7%, P=0.001) compared to the comparison. As for clinical outcomes, the implantation rate in the SLE group was notably lower (37.9% vs. 54.9%, P=0.022). The CLBR following every embryo-transfer procedure was distinctly lower (41.2% vs 64.7%, P=0.016) in the SLE group vs comparison. Also, the conservative and optimal CLBRs following every complete cycle procedure were significantly reduced in the SLE group vs the comparison (P=0.001, both). Conclusion: Patients with SLE present worse outcomes in oocyte and embryonic development, thus yielding compromised female fertility and clinical pregnancy. Individualized fertility assessment and early fertility guidance are necessary for these special groups.

Development and initial validation of the Partnership Scale-DanceSport Couples.

Introduction: DanceSport is described as a dance involving a male-female partner. It is important to comprehend the partnership between dance couples so that their competitive performance can be effectively supported. However, only a few studies have verified the influence of partnership between DanceSport couples on competitive performance and explored its psychological mechanism to provide means to deal with the partnership. The reason was that there was a lack of appropriate assessment tools. Aims: This multi-study outlines the development, content, and construct validity of a novel, mixed-method tool to assess DanceSport partnership. Methods: The development of the Partnership Scale-DanceSport Couples (PS-DSC) included four studies and data from four samples of Chinese elite dancers (N = 914 total). In stage 1, outlined in study 1, PS-DSC items were generated and then refined using the feedback provided by academics, sports coaches, and elite dancers. In stage 2, outlined in studies 2 and 3, exploratory factor analysis and confirmatory factor analysis were used to examine the structure of the PS-DSC items. In stage 3, outlined in study 4, composite reliability, discriminant validity, and convergent validity were assessed. The result of this process was a 13-item three-factor instrument. Based on these initial findings, the PS-DSC provided the first valid and reliable way of measuring partnerships between DanceSport couples. Conclusion: This study has taken the promising first step in developing a tool to comprehensively measure partnerships between DanceSport couples.

The effect of recryopreservation on embryo viability and outcomes of in vitro fertilization: a systematic review and meta-analysis.

OBJECTIVE: To investigate the impact of recryopreservation on embryo viability and the outcomes of in vitro fertilization (IVF) by comparison with single cryopreservation. There is a lack of consensus and reliable evidence regarding the impact of recryopreservation techniques on human embryos, particularly with respect to embryo viability and IVF outcomes. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. INTERVENTION(S): Various databases such as PubMed, Embase, Cochrane Library, and Scopus were searched until October 10, 2022. All comparative studies comparing embryonic and IVF outcomes between repeated and single cryopreservation of embryos were included. The random-effect and fixed-effect meta-analysis models were used to pool the odds ratio (OR) and corresponding 95% confidence intervals (CIs). A subgroup analysis was performed based on different methods of cryopreservation and different times of embryo cryopreservation or transfer. MAIN OUTCOME MEASURE(S): Outcomes referring to embryo surviva l, IVF outcomes (including clinical pregnancy rate, embryo implantation rate, miscarriage rate, and live birth rate), and neonatal outcomes (including low birth weight rate and preterm birth rate) were evaluated. RESULT(S): Fourteen studies were eligible for the present meta-analysis, involving 4,525 embryo transfer cycles in total (3,270 cycles with single cryopreservation [control group] and 1,255 with recryopreservation [experimental group]). Decreased embryo survival (OR, 0.51; 95% CI, 0.27-0.96) and clinical pregnancy rates (OR, 0.47; 95% CI, 0.23-0.96) were found in embryos that were recryopreserved by slow freezing. The live birth rate of revitrified embryos was also notably affected (OR, 0.60; 95% CI, 0.38-0.94). Overall, recryopreservation resulted in a decreased live birth rate (OR, 0.67; 95% CI, 0.50-0.90) and an increased miscarriage rate (OR, 1.52; 95% CI, 1.16-1.98) compared with single cryopreservation. No significant difference was found in neonatal outcomes. When embryos were cryopreserved and transferred at the blastocyst stage, both the embryo implantation rate (OR, 0.59; 95% CI, 0.39-0.89) and live birth rate (OR, 0.60; 95% CI, 0.37-0.96) were significantly different between the 2 groups. CONCLUSION(S): The present meta-analysis suggested that recryopreservation, compared with single cryopreservation, can lead to impaired embryo viability and a lower rate of IVF success, with no affected neonatal outcomes. Clinicians and embryologists should retain a cautious attitude toward recryopreservation strategies. REGISTRATION NUMBER: CRD42022359456.

Comprehensive analysis of metabolome and transcriptome reveals the mechanism of color formation in different leave of Loropetalum Chinense var. Rubrum.

BACKGROUND: Loropetalum chinense var. rubrum (L. chinense var. rubrum) is a precious, coloured-leaf native ornamental plant in the Hunan Province. We found an L. chinense var. rubrum tree with three different leaf colours: GL (green leaf), ML (mosaic leaf), and PL (purple leaf). The mechanism of leaf coloration in this plant is still unclear. Therefore, this study aimed to identify the metabolites and genes involved in determining the colour composition of L. chinense var. rubrum leaves, using phenotypic/anatomic observations, pigment content detection, and comparative metabolomics and transcriptomics. RESULTS: We observed that the mesophyll cells in PL were purple, while those in GL were green and those in ML were a mix of purple-green. The contents of chlorophyll a, b, carotenoids, and total chlorophyll in PL and ML were significantly lower than those in GL. While the anthocyanin content in PL and ML was significantly higher than that in GL. The metabolomics results showed the differences in the content of cyanidin 3-O-glucoside, delphinidin 3-O-glucoside, cyanidin 3,5-O-diglucoside, pelargonidin, and petunidin 3,5-diglucoside in ML, GL, and PL were significant. Considering that the change trend of anthocyanin content change was consistent with the leaf colour difference, we speculated that these compounds might influence the colour of L. chinense var. rubrum leaves. Using transcriptomics, we finally identified nine differentially expressed structural genes (one ANR (ANR1217); four CYP75As (CYP75A1815, CYP75A2846, CYP75A2909, and CYP75A1716); four UFGTs (UFGT1876, UFGT1649, UFGT1839, and UFGT3273) and nine transcription factors (two MYBs (MYB1057 and MYB1211), one MADS-box (MADS1235), two AP2-likes (AP2-like1779 and AP2-like2234), one bZIP (bZIP3720), two WD40s (WD2173 and WD1867) and one bHLH (bHLH1631) that might be related to flavonoid biosynthesis and then impacted the appearance of colour in L. chinense var. rubrum leaves. CONCLUSION: This study revealed potential molecular mechanisms associated with leaf coloration in L. chinense var. rubrum by analyzing differential metabolites and genes related to the anthocyanin biosynthesis pathway. It also provided a reference for research on leaf colour variation in other ornamental plants.

The Associations between Meeting 24-Hour Movement Guidelines (24-HMG) and Mental Health in Adolescents-Cross Sectional Evidence from China.

(1) Background: This study determined the prevalence of adolescents that meet 24-HMGs alone and in combination, and their association with the risk of developing adolescent anxiety and depression. (2) Methods: Participants were drawn from 9420 K8 grade adolescents (age 14.53 ± 0.69 years; 54.78% boys) from the China Education Tracking Survey (CEPS) 2014-2015 tracking data. Data on depression and anxiety were collected from the results of the questionnaire in the CEPS for the adolescent mental health test. Compliance with the 24-HMG was defined as: physical activity time (PA) ≥ 60 min/day was defined as meeting the PA. Screen time (ST) ≤ 120 min/day was defined as meeting the ST. Adolescents aged 13 years achieved 9-11 h of sleep per night and adolescents aged 14-17 years achieved 8-10 h of sleep per night, defined as meeting sleep. Logistic regression models were used to examine the association between meeting and not meeting the recommendations and the risk of depression and anxiety in adolescents. (3) Results: Of the sample studied, 0.71% of adolescents met all three recommendations, 13.54% met two recommendations and 57.05% met one recommendation. Meeting sleep, meeting PA+ sleep, meeting ST + sleep, and meeting PA + ST + sleep were associated with a significantly lower risk of anxiety and depression in adolescents. Logistic regression results showed that differences in the effects of gender on the odds ratio (ORs) for depression and anxiety in adolescents were not significant. (4) Conclusions: This study determined the risk of developing depression and anxiety in adolescents who met the recommendations for 24-HMG alone and in combination. Overall, meeting more of the recommendations in the 24-HMGs was associated with lower anxiety and depression risk outcomes in adolescents. For boys, reducing the risk of depression and anxiety can be prioritised by meeting PA + ST + sleep, meeting ST + sleep and meeting sleep in the 24-HMGs. For girls, reducing the risk of depression and anxiety may be preferred by meeting PA + ST + sleep or meeting PA+ sleep and meeting sleep in 24-HMGs. However, only a small proportion of adolescents met all recommendations, highlighting the need to promote and support adherence to these behaviours.

Partnership between Chinese Dance Sport Couples: A Consensual Qualitative Research Analysis.

The aim of our study was to explore the conceptions related to partnership between dance sport couples. We conducted in-depth interviews with 20 registered athletes of the Chinese Dance Sports Federation (CDSF) about partnership between dance couples, using the Consensual Qualitative Research (CQR) method. Results revealed that partnership tended to stem from seven domains: (1) mutual understanding, (2) instant intimacy, (3) long-term affection, (4) obligational ties, (5) instrumental ties, (6) tacit factors, and (7) mutual self-disclosure. Each domain included several categories of core ideas, most of which were general and typical across the respondents. The general and most typical core ideas were related to mutual understanding in all aspects (17T), pleasure (18T), sense of substitution (15T), intimacy (20G), harmony (20G), mutual help (20G), mutual tolerance (20G), mutual attraction (15T), responsibility (20G), training plan (12T), consistent goals (20G), skills improvement (20G), image matching (16T), mutual self-disclosure (18T), which suggested a general belief in the equity perspective regarding partnership between Chinese dance sport couples. Future studies need to examine diverse samples of athlete-athlete dyads to advance interpersonal theory in sports and add to emerging theories of performance behavior and expertise in sport.

Disruption of histamine/H1R-STAT3-SLC7A11 axis exacerbates doxorubicin-induced cardiac ferroptosis.

Doxorubicin (DOX) is widely used in the treatment of various cancers, increasing the great risk of adverse cardiovascular events, while the clinical intervention effect is not ideal. Histamine has been documented to participate in pathophysiological processes of cardiovascular diseases and inflammation-associated carcinogenesis. However, the potential roles of histamine in antitumor-related cardiotoxicity have not been fully elucidated. In this study, cardiomyocytes (hiPSC-CMs, HL-1 cells) and mice were treated with DOX to establish DOX-induced cardiotoxicity (DIC) models. Histidine decarboxylase knockout mice (HDC-/-) mice and histamine 1 receptor (H1R) antagonist were used to explore the effect of histamine/H1R signaling on DIC. Our results demonstrated that histamine deficiency or pharmaceutical inhibition of H1R accelerated myocardial ferroptosis, which is responsible for the aggravated DIC both in vivo and in vitro, while the supplementation of exogenous histamine reversed these changes. Our data revealed that the dysfunction of histamine/H1R signaling repressed the activation of transducer and activator of transcription 3 (STAT3), accompanying with decreased expression of solute carrier family7member11 (SLC7A11), a major modulator of ferroptosis. Conclusively, the disruption of histamine/H1R axis triggered ferroptosis and exacerbated DIC possibly by modulating STAT3-SLC7A11 pathway. Our findings point to a potential therapeutic target for DIC and provide more consideration on the usage of antihistamine drugs.

The effects of health insurance and physical exercise participation on life satisfaction of older people in China-Based on CHNS panel data from 2006 to 2015.

Background: In China, the problem of aging population has become more and more serious. The factors influencing life satisfaction of older people are becoming a significant issue. This study explores the effects of health insurance and physical exercise on life satisfaction of older people in China. Method: This study used an unbalanced panel dataset (n = 6,393, T = 4) of older adults aged 60-80 years from the 2006 to 2015 China Health and Nutrition Survey (CHNS). A panel ordered logistic regression model was developed to examine the effects of health insurance and physical exercise on older people' life satisfaction. Mediation tests were used to examine the mediating role of physical exercise in the effect of health insurance on life satisfaction of older people. Result: Life satisfaction of older people was positively associated with participation in health insurance (OR = 1.439) and physical exercise (OR = 1.033). Participation in government health insurance, urban employee health insurance (UEBMI), new rural cooperative health insurance (NRCMI), and other commercial health insurance all have positive effects on life satisfaction of older people. Physical exercise plays a masking role in the effect of health insurance on life satisfaction of older people. Conclusion: Participation in health insurance and physical exercise are important means to promote life satisfaction among older people. Physical exercise affects the impact of health insurance on older people's life satisfaction.

Minimizing Guidewire Unwilling Passage and Related Perforation During Transradial Procedures: Prevention Is Better Than Cure.

Background: Current guidewires for transradial coronary angiography had defects of passage difficulty or branch injury. This study sought to investigate the safety and efficiency of a novel method of active knuckle-angle 0.035-inch hydrophilic guidewire in transradial coronary angiography. Methods: Patients undergoing a transradial coronary procedure in our team from August 2015 to June 2020 were retrospectively investigated. We compared the demographic and interventional characteristics of 1,457 patients receiving advancement of unmodified guidewires (Traditional group) and 1,322 patients receiving advancement of the knuckle guidewire (Knuckle group). Afterwards we included 239 patients and randomized them according to a random number table to either the unmodified or the knuckle guidewire to further confirm the efficiency and safety of knuckle guidewire advancement. Results: In the retrospective analysis, unwilling passage of guidewire into branches occurred more in the Traditional group than in the Knuckle group (9.5 vs. 0.08%, p < 0.001). Two patients in the Traditional group experienced guidewire-associated perforation. One patient was treated with covered stent for internal mammarian artery perforation, while the other was managed with compression for brachial branch perforation. In the randomized controlled study, unwilling passage of guidewire also occurred more in the Traditional group (10.8 vs. 1%, p < 0.001). Median duration of guidewire advancement from the sheath to aortic root significantly decreased from 33 seconds in the Traditional group to 21 seconds in the Knuckle group. Conclusion: Active knuckle angle guidewire represented a novel method to prevent unwilling passage and associated perforation with efficiency improvement and a reduction in radiation exposure.

Abnormal histidine metabolism promotes macrophage lipid accumulation under Ox-LDL condition.

Distinct macrophage populations exert highly heterogeneity and perform various functions, among which, a crucial function of lipid metabolism is highlighted. However, the role of histidine metabolism disorder in macrophage lipid metabolism remains elusive. Addressed this question, we sorted and cultured the bone marrow-derived macrophages (BMDMs) of histidine decarboxylase (Hdc) knockout (Hdc-/-) mice with an in vitro oxidized low-density lipoprotein (ox-LDL) model, and detected the intracellular lipids by Oil Red O staining as well as lipid probe staining. Astemizole, a canonical and long-acting histamine H1 receptor (H1R) antagonist, was applied to elucidate the impact of antagonizing the H1R-dependent signaling pathway on macrophage lipid metabolism. Subsequently, the differential expressed genes were screened and analyzed in the bone marrow-derived CD11b+ immature myeloid cells of Hdc-/- and Hdc+/+ mice with a high fat diet by the microarray study. The expression levels of cholesterol metabolism-related genes were examined by qRT-PCR to explore underlying mechanisms. Lastly, we used a high-sensitivity histidine probe to detect the intracellular histidine in the BMDMs after oxidative stress. The results revealed that histidine metabolism disorder and histamine deficiency aggravated lipid accumulation in the ox-LDL-treated BMDMs. The expression level of H1R gene in the BMDMs was down-regulated after ox-LDL stimulation. The disruption of the H1R-dependent signaling pathway by astemizole further exacerbated ox-LDL-induced lipid deposition in the BMDMs partly by up-regulating scavenger receptor class A (SR-A) for lipid intake, down-regulating neutral cholesteryl ester hydrolase (nCEH) for cholesterol esterification and down-regulating ATP-binding cassette transporters A1 (ABCA1) and ABCG1 for reverse cholesterol transport. The intracellular histidine increased under ox-LDL condition, which was further increased by Hdc knockout. Collectively, these results partially reveal the relationship between histidine metabolism and lipid metabolism in the BMDMs and offer a novel strategy for lipid metabolism disorder-associated diseases.

Histamine Deficiency Promotes Myofibroblasts Transformation from HDC-Expressing CD11b+ Myeloid Cells in Injured Hearts Post Myocardial Infarction.

Myocardial infarction (MI) is a significant contributor to the development of heart failure. Histidine decarboxylase (HDC), the unique enzyme that converts L-histidine to histamine, is highly expressed in CD11b+ immature myeloid cells. However, the relationship between HDC-expressing macrophages and cardiac myofibroblasts remains to be explained. Here, we demonstrate that the GFP (green fluorescent protein)-labeled HDC+CD11b+ myeloid precursors and their descendants could differentiate into fibroblast-like cells in myocardial interstitium. Furthermore, we prove that CD11b+Ly6C+ monocytes/macrophages, but not CD11b+Ly6G+ granulocytes, are identified as the main cellular source for bone marrow-derived myofibroblast transformation, which could be regulated via histamine H1 and H2 receptor-dependent signaling pathways. Using HDC knockout mice, we find that histamine deficiency promotes myofibroblast transformation from Ly6C+ macrophages and cardiac fibrosis partly through upregulating the expression of Krüppel-like factor 5 (KLF5). Taken together, our data uncover a central role of HDC in regulating bone marrow-derived macrophage-to-myofibroblast transformation but also identify a histamine receptor (HR)-KLF5 related signaling pathway that mediates myocardial fibrosis post-MI. CD11b+Ly6C+ monocytes/macrophages are the main cellular source for bone marrow-derived myofibroblast transformation. Histamine inhibits myofibroblasts transformation via H1R and H2R-dependent signaling pathways, and ameliorates cardiac fibrosis partly through upregulating KLF5 expression.