Discovery of novel amide derivatives against VEGFR-2/tubulin with potent antitumor and antiangiogenic activity.

Dual-target agents have more advantages than drug combinations for cancer treatment. Here, we designed and synthesized a series of novel VEGFR-2/tubulin dual-target inhibitors through a molecular hybridization strategy, and the activities of all the synthesized compounds were tested against tubulin and VEGFR-2. Among which, compound 19 exhibited strong potency against tubulin and VEGFR-2, with IC50 values of 0.76 ± 0.11 µM and 15.33 ± 2.12 nM, respectively. Additionally, compound 19 not only had significant antiproliferative effects on a series of human cancer cell lines, especially MGC-803 cells (IC50 = 0.005 ± 0.001 µM) but also overcame drug resistance in Taxol-resistant MGC-803 cells, with an RI of 1.8. Further studies showed that compound 19 could induce tumor cell apoptosis by reducing the mitochondrial membrane potential, increasing the level of ROS, facilitating the induction of G2/M phase arrest, and inhibiting the migration and invasion of tumor cells in a dose-dependent manner. In addition, compound 19 also exhibits potent antiangiogenic effects by blocking the VEGFR-2/PI3K/AKT pathway and inhibiting the tubule formation, invasion, and migration of HUVECs. More importantly, compound 19 demonstrated favorable pharmacokinetic profiles, robust in vivo antitumor efficacy, and satisfactory safety profiles. Overall, compound 19 can be used as a lead compound for the development of tubulin/VEGFR-2 dual-target inhibitors.

Association between serum phosphate, magnesium, calcium and aortic valve sclerosis: a propensity score-matched case-control study.

OBJECTIVES: Aortic valve sclerosis has been proposed to signify greater cardiovascular risk; the correlation between serum trace elements and aortic valve sclerosis has been reported. Therefore, an in-depth exploration of the risk factors for aortic valve sclerosis and early intervention may reduce the risk of cardiovascular disease. METHODS: In this study, Patients with aortic valve sclerosis and non-aortic valve sclerosis who underwent echocardiographic diagnosis in the People's Hospital of Xinjiang Uygur Autonomous Region during the period from 2019 to 2021 were selected for this study. The correlation between aortic valve sclerosis and serum phosphorus, calcium, and magnesium levels was explored using the propensity score matching technique by pairing the two groups of patients 1:1. RESULTS: A total of 1,533 non-aortic valve sclerosis and 1,533 aortic valve sclerosis patients were included. Logistic regression analysis showed that serum magnesium [OR: 0.346; 95%CI: 0.227, 0.528] and serum calcium [OR: 7.022; 95%CI: 4.755, 10.369] were influential factors. Patients with low, intermediate, and high serum magnesium levels had a significantly lower risk of aortic valve sclerosis compared to patients with very low micronutrient levels (p < 0.05). Comparatively, patients with low or high serum calcium levels had an elevated risk of aortic valve sclerosis (p < 0.05). CONCLUSION: Serum magnesium may have a protective role against aortic valve sclerosis, while both low and high levels of serum calcium could be risk factor for the condition. These serum micronutrients may be indications of cardiovascular disease risk prediction or prevention, and more research is required.

Joint association of sedentary time and physical activity with abnormal heart rate recovery in young and middle-aged adults.

BACKGROUND: Abnormal heart rate recovery (HRR), representing cardiac autonomic dysfunction, is an important predictor of cardiovascular disease. Prolonged sedentary time (ST) is associated with a slower HRR. However, it is not clear how much moderate-to-vigorous physical activity (MVPA) is required to mitigate the adverse effects of sedentary behavior on HRR in young and middle-aged adults. This study aimed to examine the joint association of ST and MVPA with abnormal HRR in this population. METHODS: A cross-sectional analysis was conducted on 1253 participants (aged 20-50 years, 67.8% male) from an observational study assessing cardiopulmonary fitness in Fujian Province, China. HRR measured via cardiopulmonary exercise tests on a treadmill was calculated as the difference between heart rate at peak exercise and 2 min after exercise. When the HRR was ≤ 42 beats·minute-1 within this time, it was considered abnormal. ST and MVPA were assessed by the IPAQ-LF. Individuals were classified as having a low sedentary time (LST [< 6 h·day-1]) or high sedentary time (HST [≥ 6 h·day-1]) and according to their MVPA level (low MVPA [0-149 min·week-1], medium MVPA [150-299 min·week-1], high MVPA [≥ 300 min·week-1]). Finally, six ST-MVPA groups were derived. Associations between ST-MVPA groups with abnormal HRR incidence were examined using logistic regression models. RESULTS: 53.1% of the young and middle-aged adults had less than 300 min of MVPA per week. In model 2, adjusted for possible confounders (e.g. age, sex, current smoking status, current alcohol consumption, sleep status, body mass index), HST was associated with higher odds of an abnormal HRR compared to LST (odds ratio (OR) = 1.473, 95% confidence interval (CI) = 1.172-1.852). Compared with the reference group (HST and low MVPA), the HST and high MVPA groups have a lower chance of abnormal HRR (OR, 95% CI = 0.553, 0.385-0.795). Compared with individuals with HST and low MVPA, regardless of whether MVPA is low, medium, or high, the odds of abnormal HRR in individuals with LST is significantly reduced (OR, 95% CI = 0.515, 0.308-0.857 for LST and low MVPA; OR, 95% CI = 0.558, 0.345-0.902 for LST and medium MVPA; OR, 95% CI = 0.476, 0.326-0.668 for LST and high MVPA). CONCLUSION: Higher amounts of MVPA appears to mitigate the increased odds of an abnormal HRR associated with HST for healthy young and middle-aged adults.

Risk factors and prognostic analysis of right ventricular dysfunction after lung resection for NSCLC.

Objectives: Lung cancer is the leading cause of cancer death, and 80-85% of all lung cancer cases are non-small cell lung cancer (NSCLC). Surgical resection is the standard treatment for early-stage NSCLC. However, lung resection, a surgical procedure, can result in complications and increased mortality. Recent studies have shown a significant correlation between complications after lung resection and right ventricular dysfunction. Methods: Transthoracic echocardiography-derived right ventricular-pulmonary artery coupling (RV-PAC) was utilized to assess right ventricular function in these patients. Multivariate logistic regression analysis was also conducted to assess risk factors independently associated with RV-PA uncoupling. The 3- and 5-year cumulative survival rates were estimated with Kaplan-Meier curves, and differences between groups were analyzed using the Mantel-Cox log-rank test. Results: RV-PA uncoupling was defined as a TAPSE/PASP value < 0.67 mm/mm Hg according to spline analysis. The results of multivariable logistic regression analysis indicated that diabetes is an independent risk factor for right ventricular dysfunction after lung resection in patients with NSCLC. Kaplan-Meier analysis revealed a significant decrease in the survival rate of patients with RV-PA uncoupling at both the 3-year follow-up (73% vs 40%, p < 0.001) and 5-year follow-up (64% vs 37%, p < 0.001). Conclusions: After lung resection for NSCLC, the patient's right ventricular function predicts prognosis. Patients with right ventricular dysfunction, particularly those with diabetes mellitus, have a worse prognosis. It is crucial to actively prevent and correct risk factors to reduce the mortality rate in these patients.

A bioinspired doxorubicin-carried albumin Nanocage against aggressive Cancer via systemic targeting of tumor and lymph node metastasis.

Cancer metastasis and recurrence are obstacles to successful treatment of aggressive cancer. To address this challenge, chemotherapy is indispensable as an essential part of comprehensive cancer treatment, particularly for subsequent therapy after surgical resection. However, small-molecule drugs for chemotherapy always cause inadequate efficacy and severe side effects against cancer metastasis and recurrence caused by lymph node metastases. Here, we developed doxorubicin-carried albumin nanocages (Dox-AlbCages) with appropriate particle sizes and pH/enzyme-responsive drug release for tumor and lymph node dual-targeted therapy by exploiting the inborn transport properties of serum albumin. Inspired by the protein-templated biomineralization and remote loading of doxorubicin into liposomes, we demonstrated the controlled synthesis of Dox-AlbCages via the aggregation or crystallization of doxorubicin and ammonium sulfate within albumin nanocages using a biomineralization strategy. Dox-AlbCages allowed efficient encapsulation of Dox in the core protected by the albumin corona shell, exhibiting favorable properties for enhanced tumor and lymph node accumulation and preferable cellular uptake for tumor-specific chemotherapy. Intriguingly, Dox-AlbCages effectively inhibited tumor growth and metastasis in orthotopic 4T1 breast tumors and prevented postsurgical tumor recurrence and lung metastasis. At the same time, Dox-AlbCages had fewer side effects than free Dox. This nanoplatform provides a facile strategy for designing tumor- and lymph node-targeted nanomedicines for suppressing cancer metastasis and recurrence.

Determining the Size of Representative Volume Elements for a Two-Dimensional Random Aggregate Numerical Model of Asphalt Mortar without Damage.

The size of the representative volume element (RVE) for the two-dimensional (2D) random aggregate numerical model of asphalt mortar in a non-destructive state, which directly affects the time required to simulate the linear viscoelastic behavior from asphalt mastic to asphalt mortar. However, in the existing literature, limited research has been conducted on the size determination of the numerical model RVE for asphalt mortar. To provide a recommended size for the typical 2D random aggregate numerical model RVE of asphalt mortar in a nondestructive state, this paper first applies the virtual specimen manufacturing method of asphalt concrete 2D random aggregate to asphalt mortar. Then, it generates numerical model RVEs of asphalt mortar with different maximum particle sizes, after which geometric and numerical analyses are conducted on these models. Finally, based on the geometric and numerical analysis results, the recommended minimum sizes of RVE for the 2D asphalt mortar numerical model are provided.

Unveiling winter survival strategies: physiological and metabolic responses to cold stress of Monochamus saltuarius larvae during overwintering.

BACKGROUND: Monochamus saltuarius is a destructive trunk-borer of pine forest and an effective dispersal vector for pinewood nematode (PWN), a causative agent of pine wilt disease (PWD), which leads to major ecological disasters. Cold winter temperatures determine insect survival and distribution. However, little is known about the cold tolerance and potential physiological mechanisms of M. saltuarius. RESULTS: We demonstrated that dead Pinus koraiensis trunks do not provide larvae with insulation. The M. saltuarius larvae are freeze-tolerant species. Unlike most other freeze-tolerant insects, they can actively freeze extracellular fluid at higher subzero temperatures by increasing their supercooling points. The main energy sources for larvae overwintering are glycogen and the mid-late switch to lipid. The water balance showed a decrease in free and an increase in bound water of small magnitude. Cold stress promoted lipid peroxidation, thus activating the antioxidant system to prevent cold-induced oxidative damage. We found eight main pathways linked to cold stress and 39 important metabolites, ten of which are cryoprotectants, including maltose, UDP-glucose, d-fructose 6P, galactinol, dulcitol, inositol, sorbitol, l-methionine, sarcosine, and d-proline. The M. saltuarius larvae engage in a dual respiration process involving both anaerobic and aerobic pathways when their bodily fluids freeze. Cysteine and methionine metabolism, as well as alanine, aspartate, and glutamate metabolism, are the most important pathways linked to antioxidation and energy production. CONCLUSIONS: The implications of our findings may help strengthen and supplement the management strategies for monitoring, quarantine, and control of this pest, thereby contributing to controlling the further spread of PWD. © 2024 Society of Chemical Industry.

Cold tolerance and metabolism of red-haired pine bark beetle Hylurgus ligniperda (Coleoptera: Curculionidae) during the overwintering period.

Hylurgus ligniperda invaded Shandong, China, through imported forest timber, posing a threat to China's forest health. Exotic insects with broad environmental tolerance, including low temperatures, may have a better chance of surviving the winters and becoming invasive. Understanding the cold-tolerance strategies of H. ligniperda may help to design sustainable pest management approaches. In this study, we aim to investigate the cold-tolerance ability and relevant physiological indicators in overwintering H. ligniperda adults to determine any possible overwintering strategies. Supercooling points (SCPs) for adults H. ligniperda differed significantly across months and reached the lowest level in the mid- and post-overwintering period, the minimum SCPs -6.45 ±â€…0.18 °C. As the cold exposure temperature decreased, the survival rate of adults gradually decreased, and no adult survived more than 1 day at -15 °C, and the LLT50 for 1 day was -7.1 °C. Since H. ligniperda adults can survive internal ice formation, they are freeze-tolerant insects. Throughout the overwintering period, the SCPs and the water, protein, sorbitol, and glycerol content in adults decreased initially and then increased. We reported significant correlations between total protein, sorbitol, trehalose, and glycerol content in the beetles and SCPs. Glycogen, lipid, protein, trehalose, and sorbitol content in adult beetles may directly affect their cold-tolerance capacity and survival during winter. This study provides a physiological and biochemical basis for further study of metabolism and cold-tolerance strategies in H. ligniperda adults, which may help predict population dynamics and distribution potential of pests.

Glycerol Metabolism is Important for the Low-Temperature Adaptation of a Global Quarantine Pest Anoplophora glabripennis Larvae.

Anoplophora glabripennis is a critical global quarantine pest. Recently, its distribution has been extended to colder and higher-latitude regions. The adaptation to low temperatures is vital for the successful colonization of insects in new environments. However, the metabolic pathways of A. glabripennis larvae under cold stress remain undefined. This study analyzed the larval hemolymph under different low-temperature treatments using LC-MS/MS. The results showed that differential metabolites associated with sugar and lipid metabolism are pivotal in the larval chill coma process. Under low-temperature treatments, the glycerol content increased significantly compared with the control group. Cold stress significantly induced the expression of AglaGK2 and AglaGPDHs. After undergoing RNAi treatment for 48 h, larvae exposed to -20 °C for 1 h showed reduced recovery when injected with ds-AglaGK2 and ds-AglaGPDH1 compared to the control group, indicating that glycerol biosynthesis plays a role in the low-temperature adaptation of A. glabripennis larvae. Our results provide a theoretical basis for clarifying the molecular mechanism of A. glabripennis larvae in response to environmental stresses.

Transcriptome analysis reveals the pheromone synthesis mechanism and mating response in Monochamus saltuarius (Coleoptera, Cerambycidae).

The pinewood nematode Bursaphelenchus xylophilus (Steiner and Buhrer 1934) causes pine wilt disease, which severely affects the biodiversity and economy of Eurasian coniferous forests. Monochamus saltuarius (Coleoptera, Cerambycidae) was first identified as nematode vectors in Liaoning Province, China, in 2017. M. saltuarius has high mating efficiency and reproductive capabilities, pheromones are crucial in these processes. However, the mechanisms of pheromone synthesis in M. saltuarius are unclear. This study performed morphometric and transcriptomic analyses of the internal reproductive systems of males and females at different developmental stages and analyzed mate selection behavior. We found a significant difference in the morphology of internal reproductive systems between sexually immature and mature insects. A total of 58 and 64 pheromone biosynthesis genes were identified in females and males, respectively. The expression of the analyzed genes differed between males and females in the initial and subsequent synthesis processes. Interference experiment indicated that knocking down SDR1 gene in male M. saltuarius reduces the content of pheromones. Behavioral analyses found that males preferred virgin females. This study identified key pheromone genes and synthesis pathway that could serve as potential targets for disrupting mating in M. saltuarius through the development of novel biological agents using genetic engineering techniques.

Silencing the odorant co-receptor (Orco) in Anoplophora glabripennis disrupts responses to pheromones and host volatiles.

Insects rely primarily on a robust and precise olfactory recognition system to detect chemicals and environmental signals. Olfaction is mediated mainly by various odorant receptors (ORs) expressed on olfactory neurons. The odorant co-receptor (Orco) is a highly conserved and obligatory subunit of ORs, and its combination with conventional ORs to form ligand-gated ion channel heterodimeric complexes plays a crucial role in odor recognition. Anoplophora glabripennis Is a major quarantinable pest that affects broadleaved tree species worldwide. Odorant binding proteins (OBPs) and ORs have been identified in the A. glabripennis genome and the binding properties of some OBPs and their cognate ligands have been clarified. The role of the OR-mediated recognition pathway, however, remains largely uncharacterized. Here, we cloned and sequenced the full-length Orco gene sequence of A. glabripennis and performed structural characterization of the protein. We found that AglaOrco has high sequence homology with Orco from other orders of insects, and that it is highly conserved. Spatio-temporal differential expression analysis revealed that AglaOrco is highly expressed in adult antennae, and that expression at the sexually mature stage is significantly higher than at other developmental stages. There was no significant difference in expression between sexes. Silence AglaOrco using RNAi revealed that expression levels of AglaOrco mRNA fell significantly in both males and females at 72 h post-injection of 5 µg of dsOrco, with no obvious effect on expression of most other olfactory-related genes; however, some were up-or downregulated. For example, silenced Orco-expressing males and females showed a significant reduction in antennal potential responses to the odorants 3-carene, Ocimene, and 4-heptyloxy-1-butanol. Overall, the data suggest that AglaOrco plays an important role in mediating olfactory perception in A. glabripennis, and also identifies potential target genes for environmentally friendly pest control strategies.

Genome-wide identification and expression analysis of the heat shock protein gene superfamily in Hylurgus ligniperda.

Hylurgus ligniperda belongs to Hylurgus Latreille, Curculionidae, Coleoptera. It primarily damages the base and roots of the trunk of pine plants. Short-term treatment at 42 °C can damage Hylurgus ligniperda; therefore, temperature is a vital factor limiting its spread. Heat shock proteins (HSPs) can protect, remove, and repair proteins to help H. ligniperda withstand high temperatures. However, information on HSP genes in H. ligniperda remains limited. In the study, we considered H. ligniperda as the focus of research and identified 56 HligHSP genes at the genome-wide level. These genes were mapped to the cytoplasm or nucleus. An identical subfamily exhibited a closely similar distribution of conserved domains. Combined with the transcriptome data collected in previous studies, we screened six candidate genes, namely HligsHSP-3, HligsHSP-4, HligHSP60-16, HligHSP70-3, HligHSP70-4, and HligHSP90-1, which are specifically expressed during different high-temperature treatments. A quantitative polymerase chain reaction was performed to measure the expression of these six HligHSPs in seven temperature treatment conditions. These genes may be involved in the heat resistance mechanism in adults. Our findings provided a foundation for further studying the heat resistance mechanism in H. ligniperda.

Hepatoid adenocarcinoma of the lung: A case report.

BACKGROUND: Hepatoid adenocarcinoma of the lung (HAL) is a rare type of non-small cell lung cancer (NSCLC), histologically similar to hepatocellular carcinoma. HAL has high malignancy and poor prognosis, and a better treatment plan needs further study. CASE SUMMARY: In order to deeply understand the occurrence and development of HAL, here we report a case of HAL with extensive metastasis of alpha fetoprotein negative KRAS A146T mutation. The patient refused chemotherapy and received one course of treatment (immune checkpoint inhibitors), and died three months later due to progressive disease. CONCLUSION: HAL is a special type of NSCLC. The surgical treatment of HAL in the limited stage can achieve long-term survival, but most of them were in the advanced stage when they were found, and the prognosis was poor, which requires multidisciplinary comprehensive treatment.

Role of Exosomes in Cardiovascular Diseases.

Exosomes (EXOs) are a subgroup of extracellular vesicles (EVs) that contain numerous biologically active molecules. They exhibit an essential mode of cell communication, primarily between distinct cell populations, for the maintenance of tissue homeostasis and coordination of adaptive responses to various stresses. These intercellular communications are vital for the complex, multicellular cardiovascular system. In the last ten years, their potential role as effective tissue-to-tissue communicators has received increasing attention in cardiovascular physiology and pathology. There is growing evidence that repair of the heart and regeneration can be promoted by EXOs derived from cardiomyocytes or stem/progenitor cells. However, the underlying mechanisms remain unclear. EVs derived from different stem/progenitor cell populations have been used as cell-free therapies in different preclinical models involving cardiovascular diseases and have shown promising results. In this review, we have summarized the recent developments in EXOs research, the impact of EXOs derived from different cells on the cardiovascular system, their potential therapeutic roles as well as new diagnostic biomarkers, and the possible clinical translational outcomes.

Tai Chi-Induced Exosomal LRP1 is Associated With Memory Function and Hippocampus Plasticity in aMCI Patients.

OBJECTIVES: The study was designed to identify the potential peripheral processes of circulating exosome in response to Tai Chi (TC) exercise and the possibility of its loaded cargos in mediating the effects of TC training on cognitive function among older adults with amnestic mild cognitive impairment (aMCI). DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter randomized controlled trial. One hundred community-dwelling old adults with aMCI were randomly assigned (1:1) to experimental (n = 50) and control groups (n = 50). INTERVENTION: The experimental group participated in TC exercise 5 times/week, with each session lasting 60 minutes for 12 weeks. Both experimental and control groups received health education every 4 weeks. MEASUREMENTS: The primary outcome was global cognitive function. Neurocognitive assessments, MRI examination, and large-scale proteomics analysis of peripheric exosome were conducted at baseline and after 12-week training. Outcome assessors and statisticians were blinded to group allocation. RESULTS: A total of 96 participants (96%) completed all outcome measurements. TC training improved global cognitive function (adjusted mean difference [MD] = 1.9, 95%CI 0.93-2.87, p <0.001) and memory (adjusted MD = 6.42, 95%CI 2.09-10.74, p = 0.004), increased right hippocampus volume (adjusted MD = 88.52, 95%CI 13.63-163.4, p = 0.021), and enhanced rest state functional connectivity (rsFC) between hippocampus and cuneus, which mediated the group effect on global cognitive function (bootstrapping CIs: [0.0208, 1.2826], [0.0689, 1.2211]) and verbal delay recall (bootstrapping CI: [0.0002, 0.6277]). Simultaneously, 24 differentially expressed exosomal proteins were detected in tandem mass tag-labelling proteomic analysis. Of which, the candidate protein low-density lipoprotein receptor-related protein 1 (LRP1) was further confirmed by parallel reaction monitoring and ELISA. Moreover, the up-regulated LRP1 was both positively associated with verbal delay recall and rsFC (left hippocampus-right cuneus). CONCLUSION: TC promotes LRP1 release via exosome, which was associated with enhanced memory function and hippocampus plasticity in aMCI patients. Our findings provided an insight into potential therapeutic neurobiological targets focusing on peripheric exosome in respond to TC exercise.

The maternal drug exposure birth cohort (DEBC) in China.

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.

Blocking Sigmar1 exacerbates methamphetamine-induced hypertension.

AIM: Methamphetamine (METH) chronic exposure is an important risk factor for hypertension development. However, the mechanisms behind METH-induced hypertension remain unclear. Therefore, we aimed to reveal the potential mechanisms underlying METH-induced hypertension. METHODS AND RESULTS: We structured the mouse hypertension model by METH, and observed that METH-treated mice have presented vascular remodeling (large-and small-size arteries) with collagen deposit around the vessel and increasing blood pressure (BP) and Sigma1 receptor (Sigmar1) in vascular tissue. We hypothesized that Sigmar1 is crucial in METH-induced hypertension and vascular remodeling. Sigmar1 knockout (KO) mice and antagonist (BD1047) pretreated mice exposed to METH for six-week showed higher BP and more collagen deposited around vessels than wild-type (WT) mice exposed to METH for six-week, in contrast, mice pretreated with Sigmar1 agonist (PRE-084) had unchanged BP and perivascular collagen despite the six-week METH exposure. Furthermore, we found that METH exposure induced vascular smooth muscle cells (VSMCs) and mesenchymal stem cells to differentiate into the myofibroblast-like cell and secrete collagen into surrounding vessels. Mechanically, Sigmar1 can suppress the COL1A1 expression by blocking the classical fibrotic TGF-ß/Smad2/3 signaling pathway in METH-exposed VSMCs and mesenchymal stem cells. CONCLUSION: Our results suggest that Sigmar1 is involved in METH-induced hypertension and vascular fibrosis by blocking the activation of the TGF-ß/Smad2/3 signaling pathway. Accordingly, Sigmar1 may be a novel therapeutic target for METH-induced hypertension and vascular fibrosis.

Association between depression and infertility risk among American women aged 18-45 years: the mediating effect of the NHHR.

BACKGROUND/OBJECTIVE: Depression and infertility are major medical and social problems. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) serves as an innovative and reliable lipid marker for cardiovascular disease risk assessment. Previous research has indicated a potential correlation among lipid metabolism, depression, and infertility. Nonetheless, the exact involvement of lipid metabolism in modulating the pathological mechanisms associated with depression-induced infertility remains to be fully elucidated. The aim of this study was to explore the connection between depression and infertility and to assess whether the NHHR mediates this association. METHODS: A cross-sectional analysis was performed utilizing data from there cycles (2013-2018) of the National Health and Nutrition Examination Survey (NHANES) database. Female infertility was assessed according to the responses to the RHQ074 question in the reproductive health questionnaire module. Depression states were evaluated using the Patient Health Questionnaire-9 and classified into three grades based on the total scores: no depression (0-4 points), minimal-to-mild depression (5-9 points) and moderate-to-severe depression (10 or more points). The NHHR was calculated from laboratory cholesterol test results. Baseline population characteristics were compared, and subgroup analyses were carried out based on the stratification of age and body mass index (BMI). Weighted multivariable logistic regression and linear regression models, with adjustments for various covariables, were employed to examine the associations among depression, infertility and the NHHR. Finally, mediation analysis was utilized to explore the NHHR's potential mediating role in depression states and female infertility. RESULTS: Within this cross-sectional study, 2,668 women aged 18 to 45 years residing in the United States were recruited, 305 (11.43%) of whom experienced infertility. The study revealed a markedly higher prevalence of depression (P = 0.040) and elevated NHHR (P < 0.001) among infertile women compared to the control cohort. Furthermore, moderate-to-severe depression states independently correlated with increased infertility risk, irrespective of adjustments for various covariables. Subgroup analysis indicated a positive association between depression and infertility risk within certain age categories, although no such relationship was observed within subgroups stratified by BMI. The findings from the weighted logistic regression analysis demonstrated that the elevated NHHR is positively associated with heightened infertility risk. Additionally, the weighted linear regression analysis indicated that moderate-to-severe depression is positively linked to the NHHR levels as well. Finally, the association between depression states and female infertility was partially mediated by the NHHR, with the mediation proportion estimated at 6.57%. CONCLUSION: In the United States, depression is strongly correlated with an increased likelihood of infertility among women of childbearing age, with evidence suggesting that this relationship is mediated by the NHHR. Subsequent research efforts should further explore the underlying mechanisms connecting depression and infertility.