ROS-induced oxidative stress is a major contributor to sperm cryoinjury.

STUDY QUESTION: What is the mechanism behind cryoinjury in human sperm, particularly concerning the interplay between reactive oxygen species (ROS) and autophagy, and how does it subsequently affect sperm fate? SUMMARY ANSWER: The freeze-thaw operation induces oxidative stress by generating abundant ROS, which impairs sperm motility and activates autophagy, ultimately guiding the sperm toward programmed cell death such as apoptosis and necrosis, as well as triggering premature capacitation. WHAT IS KNOWN ALREADY: Both ROS-induced oxidative stress and autophagy are thought to exert an influence on the quality of frozen-thawed sperm. STUDY DESIGN, SIZE, DURATION: Overall, 84 semen specimens were collected from young healthy fertile males, with careful quality evaluation. The specimens were split into three groups to investigate the ROS-induced cryoinjury: normal control without any treatment, sperm treated with 0.5 mM hydrogen peroxide (H2O2) for 1 h, and sperm thawed following cryopreservation. Samples from 48 individuals underwent computer-assisted human sperm analysis (CASA) to evaluate sperm quality in response to the treatments. Semen samples from three donors were analyzed for changes in the sperm proteome after H2O2 treatment, and another set of samples from three donors were analyzed for changes following the freeze-thaw process. The other 30 samples were used for fluorescence-staining and western blotting. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm motility parameters, including progressive motility (PR %) and total motility (PR + NP %), were evaluated using the CASA system on a minimum of 200 spermatozoa. The proteomic profiles were determined with label-free mass spectrometry (MS/MS) and protein identification was performed via ion search against the NCBI human database. Subsequently, comprehensive bioinformatics was applied to detect significant proteomic changes and functional enrichment. Fluorescence-staining and western blot analyses were also conducted to confirm the proteomic changes on selected key proteins. The ROS level was measured using 2',7'-dichlorodihydrofluorescein diacetate labeling and the abundance of bioactive mitochondria was determined by evaluating the inner mitochondrial membrane potential (MMP) level. Molecular behaviors of sequestosome-1 (p62 or SQSTM1) and microtubule-associated proteins 1A/1B light chain 3 (LC3) were monitored to evaluate the state of apoptosis in human sperm. Fluorescent probes oxazole yellow (YO-PRO-1) and propidium iodide (PI) were utilized to monitor programmed cell death, namely apoptosis and necrosis. Additionally, gradient concentrations of antioxidant coenzyme Q10 (CoQ10) were introduced to suppress ROS impacts on sperm. MAIN RESULTS AND THE ROLE OF CHANCE: The CASA analysis revealed a significant decrease in sperm motility for both the H2O2-treatment and freeze-thaw groups. Fluorescence staining showed that high ROS levels were produced in the treated sperm and the MMPs were largely reduced. The introduction of CoQ10 at concentrations of 20 and 30 µM resulted in a significant rescue of progressive motility (P < 0.05). The result suggested that excessive ROS could be the major cause of sperm motility impairment, likely by damaging mitochondrial energy generation. Autophagy was significantly activated in sperm when they were under oxidative stress, as evidenced by the upregulation of p62 and the increased conversion of LC3 as well as the upregulation of several autophagy-related proteins, such as charged multivesicular body protein 2a, mitochondrial import receptor subunit TOM22 homolog, and WD repeat domain phosphoinositide-interacting protein 2. Additionally, fluorescent staining indicated the occurrence of apoptosis and necrosis in both H2O2-treated sperm and post-thaw sperm. The cell death process can be suppressed when CoQ10 is introduced, which consolidates the view that ROS could be the major contributor to sperm cryoinjury. The freeze-thaw process could also initiate sperm premature capacitation, demonstrated by the prominent increase in tyrosine phosphorylated proteins, verified with anti-phosphotyrosine antibody and immunofluorescence assays. The upregulation of capacitation-related proteins, such as hyaluronidase 3 and Folate receptor alpha, supported this finding. LARGE SCALE DATA: The data underlying this article are available in the article and its online supplementary material. LIMITATIONS, REASONS FOR CAUTION: The semen samples were obtained exclusively from young, healthy, and fertile males with progressive motility exceeding 60%, which might overemphasize the positive effects while possibly neglecting the negative impacts of cryoinjury. Additionally, the H2O2 treatment conditions in this study may not precisely mimic the oxidative stress experienced by sperm after thawing from cryopreservation, potentially resulting in the omission of certain molecular alterations. WIDER IMPLICATIONS OF THE FINDINGS: This study provides substantial proteomic data for a comprehensive and deeper understanding of the impact of cryopreservation on sperm quality. It will facilitate the design of optimal protocols for utilizing cryopreserved sperm to improve applications, such as ART, and help resolve various adverse situations caused by chemotherapy, radiotherapy, and surgery. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the Major Innovation Project of Research Institute of National Health Commission (#2022GJZD01-3) and the National Key R&D Program of China (#2018YFC1003600). All authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Dietary total antioxidant capacity and the risk of developing asthenozoospermia: a hospital-based case-control study in China.

STUDY QUESTION: Is dietary total antioxidant capacity (DTAC) associated with the odds of developing asthenozoospermia in Chinese men? SUMMARY ANSWER: There is no statistically significant association between DTAC indices and the odds of developing asthenozoospermia. WHAT IS KNOWN ALREADY: Both diet and oxidative stress may be related to sperm quality; however, few studies have investigated the association between DTAC and sperm quality. STUDY DESIGN, SIZE, DURATION: This case-control study was conducted from June 2020 to December 2020. Those diagnosed with asthenozoospermia were assigned to the case group, whereas those with normal sperm parameters were assigned to the control group. Data from a total of 553 cases and 586 controls were included in the final analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men who had been referred to the infertility clinic of Shengjing Hospital of China Medical University were enrolled. Dietary intake was assessed using a validated food frequency questionnaire. DTAC was based on ferric-reducing ability of plasma (FRAP), total oxygen radical absorbance capacity (T-ORAC), hydrophilic oxygen radical absorbance capacity (H-ORAC), lipophilic oxygen radical absorbance capacity (L-ORAC), total phenolics (TP), total radical-trapping antioxidant parameter (TRAP), and Trolox equivalent antioxidant capacity (TEAC). Asthenozoospermia was defined according to the criteria published in the fifth edition of the World Health Organization laboratory manual for the examination and processing of human semen. MAIN RESULTS AND THE ROLE OF CHANCE: No significant association was observed between the DTAC indices and the odds of asthenozoospermia after multivariable adjustment (T3 vs T1, odds ratio (OR) = 0.99, 95% CI: 0.73-1.33 for FRAP; OR = 1.05, 95% CI: 0.77-1.42 for T-ORAC; OR = 0.88, 95% CI: 0.65-1.18 for H-ORAC; OR = 0.98, 95% CI: 0.71-1.34 for L-ORAC; OR = 1.03, 95% CI: 0.76-1.39 for TP; OR = 1.18, 95% CI: 0.87-1.59 for TRAP; and OR = 1.15, 95% CI: 0.85-1.55 for TEAC). Both additive and multiplicative interaction analyses suggested that smoking might modify the association of T-ORAC with the odds of developing asthenozoospermia (relative excess risk due to interaction = 0.45, 95% CI: 0.07-0.83, attributable proportion due to interaction = 0.46, 95% CI: 0.07-0.84 for additive interaction; P = 0.033 for multiplicative interaction). LIMITATIONS, REASONS FOR CAUTION: Recall bias and protopathic bias were inevitable in this retrospective case-control study. The estimation accuracy of the DTAC indices may have also affected the findings. WIDER IMPLICATIONS OF THE FINDINGS: To the best of our knowledge, this is the first study to specifically investigate whether an association exists between DTAC and the odds of developing asthenozoospermia. Although no significant association was found, this study provides novel information pertaining to the fields of nutrition and human reproduction. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the JieBangGuaShuai Project of Liaoning Province (2021JH1/10400050), the Shengjing Hospital Clinical Research Project (M0071), and the Outstanding Scientific Fund of Shengjing Hospital (M1150). All authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Comorbid anxiety and depressive symptoms and the related factors among international medical students in China during COVID-19 pandemic: a cross-sectional study.

BACKGROUND: The two most prevalent mental health conditions are anxiety and depression and they often coexist (comorbidity) in an individual aggravating the person's psychological or medical conditions. College students suffered from anxiety and depressive symptoms during the COVID-19 pandemic, according to numerous studies. The lack of information on the comorbidity of anxiety and depression (CAD) among international medical students, however, makes it difficult to develop effective policies or strategies to support these students. OBJECTIVE: The present research seeks to investigate the incidence of CAD among international medical students in China and to identify the variables that may be useful in predicting CAD. METHOD: A cross-sectional study was conducted at China Medical University in Shenyang, China, for international medical students during November 2020. A total of 519 international students provided information on their demographics, stress related to the COVID-19 pandemic, generalized anxiety disorder assessment (GAD-7), patient health questionnaire-9 (PHQ-9), simplified coping style questionnaire (SCSQ), perceived stress scale (PSS-10), the multidimensional scale of perceived social support (MSPSS), revised life orientation test (LOT-R), and resilience scale-14 (RS-14). To investigate the potential predictors of CAD, a chi-square test, a nonparametric test, and multinomial logistic regression analyses were carried out as appropriate. RESULTS: The incidence of anxiety, depression, and CAD in the current study was 5.8%, 8.9%, and 22.7%, respectively. The predictors for students having symptoms of anxiety were observed to be the negative coping style (ß = 0.662, OR = 1.938, CI:1.07-3.694) and perceived stress (ß = 0.167, OR = 1.181, CI:1.076-1.297); the predictors for students having symptoms of depression were observed to be the COVID-19 pandemic-related stress (ß = 0.323,OR = 1.382,CI:1.211-1.577), negative coping style (ß = 0.693,OR = 2.000, CI:1.21-3.568), and perceived stress (ß = 0.135,OR = 1.145,CI:1.050-1.248); whereas the predictors for students with CAD were observed to be staying up late (Yes VS No) (ß = 1.028,OR = 2.794,CI:1.227-6.364), current place of residence (Other continents VS China) (ß = -1.413, OR = 0.243,CI:0.065-0.910), COVID-19 pandemic-related stress (ß = 0.371,OR = 1.450,CI:1.284-1.636), negative coping style (ß = 1.092,OR = 2.979,CI:1.706-5.203), and perceived stress (ß = 0.339,OR = 1.403,CI:1.289-1.527). CONCLUSION: Single anxiety and depressive symptoms were moderately prevalent among international medical students in China. However, CAD turned out to be the most prevalent mental health issue due to its relatively higher incidence. Negative coping style and perceived stress were the communal predictors of the three categories, whereas stress related to the COVID-19 pandemic was linked to both depression and CAD, and staying up late and in residential places were specific predictors for CAD. Study results suggest that COVID-19 pandemic-related stress was related to students' CAD and depressive symptoms, and specific intervention measures with stress reduction, proper coping strategy, and a good lifestyle might be useful in improving the international students' mental health status.

Stressors in university life and anxiety symptoms among international students: a sequential mediation model.

BACKGROUND: Anxiety is a common mental health problem among university students, and identification of its risk or associated factors and revelation of the underlying mechanism will be useful for making proper intervention strategies. The aim of our study is to test the sequential mediation of self-efficacy and perceived stress in the association between stressors in university life and anxiety symptoms. METHODS: A cross-sectional study design was adopted and a sample of 512 international students from a medical university of China completed the survey with measurements of stressors in university life, self-efficacy, perceived stress and anxiety symptoms. RESULTS: We found that 28.71% of the international students had anxiety symptoms, and stressors in university life were positively associated with anxiety symptoms (ß = 0.23, t = 5.83, p < 0.01). Moreover, sequential mediating role of self-efficacy and perceived stress in the association between the stressors and anxiety symptoms was revealed. CONCLUSIONS: Our study provided a new perspective on how to maintain the mental health, which suggested that self-efficacy improvement and stress reduction strategies should be incorporated in the training programs to support students.

Association of Covid-19 pandemic-related stress and depressive symptoms among international medical students.

BACKGROUND: The outbreak of Covid-19 had negative impacts on the mental stress and induced psychological distress among university students worldwide. This study proposed a moderated mediation model, and hypothesized that the Covid-19 pandemic-related stress was positively related to depressive symptoms among international medical students. METHODS: An online survey on stress and depressive symptoms of international students was conducted in a medical university. Questions on Covid-19 pandemic-related stress, Patient Health Quesionnaire-9, Simplified Coping Style Questionnaire and the Perceived Social Support Scale were used as measurements, and model analyses were conducted using Hayes' PROCESS macro for SPSS. RESULTS: It was found that 9.83%, 3.08% and 2.12% students had mild, moderate and severe depressive symptoms, respectively, and the positive association between Covid-19 pandemic-related stress and depressive symptoms was significant (ß = 0.27, t = 6.87, P < 0.01). Negative coping was also significantly correlated to depressive symptoms (ß = 0.26, t = 6.60, P < 0.01), and partially mediated the association between Covid-19 pandemic-related stress and depressive symptoms. Perceived social support had a negative association with depressive symptoms (ß=-0.26, t=-6.25, P < 0.01), played a negative moderating role in the relationship between negative coping and depressive symptoms, and moderated the indirect effect of Covid-19 pandemic-related stress on depressive symptoms via negative coping. CONCLUSIONS: Results of the study suggested that under the background of continuing pandemic, intervention or prevention of mental health problem is urgently needed for the international students, and depression may be alleviated through reducing negative coping and increasing perceived social support.

[Extracellular vesicles: Their physiological functions related to sperm maturation, sperm motility and fertilization].

Extracellular vesicles are cell-to-cell communication tools that play important roles in sperm maturation, motility, and fertilization. Epididymosomes provide proteins, lipids, and genetic materials to sperm as the latter go through the epididymis, not only promoting sperm maturation, but also influencing sperm and offspring phenotypes at the epigenetic level. After ejaculation, prostasomes fuse with sperm, leading to changes in the composition of the sperm plasma membrane and the contents of sperm, which maintains the stability of the sperm plasma membrane and increases sperm motility as well. Uterosomes can enhance sperm capacitation and acrosome reaction. Oviductosomes participate in sperm capacitation and motility, provide non-coding RNA to sperm, and influence the development of embryos. However, studies on extracellular vesicles and spermatozoa are mostly based on animal experiments, and their applicability to humans remains to be further explored.

Prevalence and predictors of anxiety and depressive symptoms among patients diagnosed with oral cancer in China: a cross-sectional study.

BACKGROUND: Anxiety and depression are common mental health problems among patients with cancer. While many psychological variables have been proven to influence anxiety and depressive symptoms, the variables are not mutually exclusive and their integrated effects on patients with oral cancer are yet unknown. The present study aims to explore the prevalence of anxiety and depressive symptoms among patients with oral cancer, to find out key potentially predictive factors associated with anxiety and depressive symptoms. METHOD: A cross-sectional study was carried out for Chinese patients with oral cancer between May 2016 and October 2017 in two Grade-A Tertiary Hospitals in Shenyang, China. Two hundred thirty patients with oral cancer were interviewed with questionnaires on demographic variables, Zung Self-Rating Anxiety Scale (SAS), Center for Epidemiologic Studies Depression Scale (CES-D), Herth Hope Index (HHI), Social Impact Scale, Multidimensional Scale of Perceived Social Support (MSPSS), Revised Life Orientation Test (LOT-R), Perceived Stress Scale-10 (PSS-10), and General Perceived Self-efficacy Scale(GSE). Chi-square test, nonparametric test, t-test and logistic regression analyses were conducted where appropriate to explore predictive factors of anxiety symptoms and depressive symptoms. RESULTS: The prevalence of anxiety symptoms and depressive symptoms in the sample population was 36.96% (85/230) and 65.21% (150/230), respectively. Social isolation dimension of stigma (ß = 0.436, OR = 1.547, CI:1.211 ~ 1.975), optimism (ß = - 0.276, OR = 0.759, CI:0.624 ~ 0.922), and perceived stress (ß = 0.217, OR = 1.243, CI:1.092 ~ 1.414) were predictors of anxiety symptoms. Marriage (ß = 1.648, OR = 5.198, CI:1.427 ~ 18.924), positive readiness and expectancy dimension of hope (ß = - 0.505, OR = 0.604, CI:0.395 ~ 0.923), social isolation dimension of stigma (ß = 0.314, OR = 1.368, CI:1.054 ~ 1.776) and perceived stress (ß = 0.273, OR = 1.314, CI:1.134 ~ 1.524) were predictors of depressive symptoms among oral cancer patients. CONCLUSION: The prevalence of anxiety symptoms and depressive symptoms was high among oral cancer patients in China. The communal predictors of anxiety and depressive symptoms in patients with oral cancer were levels of perceived stress and social isolation of stigma. In addition, optimism was a predictor of anxiety symptoms and hope was a predictor of depressive symptoms. TRIAL REGISTRATION: 2015-16, registered 20 Dec 2015.

[Biosafety in andrology laboratories during the outbreak of COVID-19].

The novel coronavirus disease 2019 (COVID-19) broke out in December 2019 and has been rapidly escalating throughout the world. Clinical findings show that the patients with either symptomatic or asymptomatic COVID-19 can be a potential source of infection. Although respiratory droplets and close contact are considered to be the main routes of transmission, there is the possibility of aerosol transmission in a relatively closed environment. The nucleic acid of the novel coronavirus can be detected in nasopharyngeal swabs, sputum and other lower respiratory tract secretions, blood, feces, urine and so on, but whether it exists in the semen has not been confirmed. It is reported that the novel coronavirus may affect the testis that highly expresses angiotensin-converting enzyme 2 (ACE2) and theoretically the semen is a possible carrier of the virus considering the fact that it is discharged from the same channel as the urine. Andrology laboratorians are exposed to most of the specimens above, including semen, and some open operations in the laboratory increase the risk of aerosol generation. Therefore, corresponding protective procedures are necessitated in andrology laboratories to reduce the risk of infection during the outbreak of COVID-19. Based on the knowledge and experience available as regards the pandemic and the characteristics of the work in the andrology laboratory, we summarize some biosafety points for andrology laboratorians to attend to during the outbreak of COVID-19.

Resilience and associated factors among Chinese patients diagnosed with oral cancer.

BACKGROUND: Resilience has been linked to psychological adaptation to many challenging life events. The present study aims to explore the level of resilience in oral cancer patients and the key factors associated with resilience, and to evaluate the relationship between resilience and anxiety. METHODS: A multiple center cross-sectional study was carried out for Chinese patients with oral cancer between May 2016 and October 2017 in the Stomatology Hospital of China Medical University and Department of Stomatology, Shengjing Hospital of China Medical University. Two hundred and thirty oral cancer patients replied to the questionnaires on resilience, hope, perceived social support, optimism, perceived stress and anxiety which were measured with Resilience Scale-14 (RS-14), Herth Hope Index (HHI), Multidimensional Scale of Perceived Social Support (MSPSS), Revised Life Orientation Test (LOT-R), Perceived Stress Scale-10 (PSS-10) and Zung Self-Rating Anxiety Scale (SAS), respectively. Univariate one-way ANOVA/t-test, Pearson's r and hierarchical linear regression analysis were conducted to explore the influence factors of resilience and the relationship between resilience and anxiety. RESULTS: The level of resilience was 67.93 ± 12.65. Resilience was positively correlated with hope, optimism and perceived social support, and negatively correlated with perceived stress. Hierarchical linear regression analysis showed that hope (ß = 0.386, P < 0.01), optimism (ß = 0.190, P < 0.01) and education (ß = 0.175, P < 0.01) were positively associated with resilience. The three variables in combination could explain 48.9% of the total variance in resilience. Higher level of resilience was associated less anxiety symptoms (X2 = 39.216, p = 0.000); and there was linear trend between resilience level and anxiety level among patients with oral cancer (X2 = 35.624, p = 0.000). CONCLUSION: Patients with oral cancer in China had moderate level of resilience. Hope, optimism and education were positively and significantly associated with resilience, indicating that higher level of hope, optimism and education may improve resilience in oral cancer patients, which in turn may help alleviate anxiety symptoms in patients.

[Semen expulsion under the ureterocystoscope].

OBJECTIVE: To determine the exact location of the opening of the ejaculatory duct in men and provide some basic anatomical evidence for seminal vesiculoscopy and the treatment of ejaculatory duct obstruction. METHODS: We performed ureterocystoscopy for 21 male patients aged 26 - 47 years with hematuria (n = 12), hematospermia (n = 2), glandular cystitis (n = 6), and anejaculation after radical resection of rectal carcinoma (n = 1), and meanwhile, with the consent of the patients, massaged the prostate and ejaculatory duct and observed the outlet of the expelled fluid. Under the microscope, we described the fluid samples with sperm as the expulsion from the ejaculatory duct. RESULTS: Ureterocystoscopy showed that the exact anatomical sites of the expulsion of prostatic fluid and semen in the patients were the side and lower side of the prostatic utricle opening above the verumontanum and the ventral side of the verumontanum. Quantities of sperm were found in the expulsion fluid of 13 of the patients, and no expulsion, including semen, was seen from the prostatic utricle opening. CONCLUSION: Anatomically, the ejaculatory duct openings of males are located at the two sides of the verumontanum adjacent to the opening of the prostatic utricle, rather than in the prostatic utricle above the verumontanum.

Engineering of methionine sulfoxide reductase A with simultaneously improved stability and activity for kinetic resolution of chiral sulfoxides.

Methionine sulfoxide reductase A (MsrA) has emerged as promising biocatalysts in the enantioselective kinetic resolution of racemic (rac) sulfoxides. In this study, we engineered robust MsrA variants through directed evolution, demonstrating substantial improvements of thermostability. Mechanism analysis reveals that the enhanced thermostability results from the strengthening of intracellular interactions and increase in molecular compactness. Moreover, these variants demonstrated concurrent improvements in catalytic activities, and notably, these enhancements in stability and activity collectively contributed to a significant improvement in enzyme substrate tolerance. We achieved kinetic resolution on a series of rac-sulfoxides with high enantioselectivity under initial substrate concentrations reaching up to 93.0 g/L, representing a great improvement in the aspect of the substrate concentration for biocatalytic preparation of chiral sulfoxide. Hence, the simultaneously improved thermostability, activity and substrate tolerance of MsrA represent an excellent biocatalyst for the green synthesis of optically pure sulfoxides.

Predicting mitophagy-related genes and unveiling liver endothelial cell heterogeneity in hepatic ischemia-reperfusion injury.

Background: Hepatic Ischemia-Reperfusion Injury (HIRI) is a major complication in liver transplants and surgeries, significantly affecting postoperative outcomes. The role of mitophagy, essential for removing dysfunctional mitochondria and maintaining cellular balance, remains unclear in HIRI. Methods: To unravel the role of mitophagy-related genes (MRGs) in HIRI, we assembled a comprehensive dataset comprising 44 HIRI samples alongside 44 normal control samples from the Gene Expression Omnibus (GEO) database for this analysis. Using Random Forests and Support Vector Machines - Recursive Feature Elimination (SVM-RFE), we pinpointed eight pivotal genes and developed a logistic regression model based on these findings. Further, we employed consensus cluster analysis for classifying HIRI patients according to their MRG expression profiles and conducted weighted gene co-expression network analysis (WGCNA) to identify clusters of genes that exhibit high correlation within different modules. Additionally, we conducted single-cell RNA sequencing data analysis to explore insights into the behavior of MRGs within the HIRI. Results: We identified eight key genes (FUNDC1, VDAC1, MFN2, PINK1, CSNK2A2, ULK1, UBC, MAP1LC3B) with distinct expressions between HIRI and controls, confirmed by PCR validation. Our diagnostic model, based on these genes, accurately predicted HIRI outcomes. Analysis revealed a strong positive correlation of these genes with monocytic lineage and a negative correlation with B and T cells. HIRI patients were divided into three subclusters based on MRG profiles, with WGCNA uncovering highly correlated gene modules. Single-cell analysis identified two types of endothelial cells with different MRG scores, indicating their varied roles in HIRI. Conclusions: Our study highlights the critical role of MRGs in HIRI and the heterogeneity of endothelial cells. We identified the macrophage migration inhibitory factor (MIF) and cGAS-STING (GAS) pathways as regulators of mitophagy's impact on HIRI. These findings advance our understanding of mitophagy in HIRI and set the stage for future research and therapeutic developments.

Associations between dietary macronutrient quality and asthenozoospermia risk: a hospital-based case-control study.

Background & aims: Macronutrients are the main part of the human diet and can affect multiple health outcomes. Nevertheless, associations between dietary macronutrient quality and asthenozoospermia risk have not been reported to date. Thus, this study aimed to be the first to explore the associations between macronutrient quality and asthenozoospermia risk using the novel multidimensional macronutrient quality index (MQI). Methods: A case-control study was conducted at infertility clinics of Shengjing Hospital of China Medical University during June and December 2020, including 552 asthenozoospermia cases and 585 normozoospermia controls. Data on diet were collected using a validated food frequency questionnaire. MQI was estimated according to the carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Binary logistic regression models were performed to calculate the odds ratio (OR) with a 95% confidence interval (CI). Subgroup and interaction analyses were performed based on age, body mass index, physical activity, smoking, drinking, and education level. Dose-response relationships were evaluated by restricted cubic splines. Sensitivity analyses were performed in two ways. First, participants with a dietary change were excluded to lower potential reverse causation. Then, we used the healthy plate protein source quality index instead of PQI to redefine MQI. Results: No statistically significant association was observed between dietary MQI and asthenozoospermia risk (OR = 1.24, 95% CI: 0.88-1.73). The sub-indices of MQI, CQI, FQI, and PQI, failed to be identified as having a statistically significant association with asthenozoospermia risk (OR = 1.35, 95% CI: 0.92-1.97 for CQI; OR = 1.13, 95% CI: 0.84-1.53 for FQI; OR = 1.28, 95% CI: 0.92-1.78 for PQI). However, CQI showed a positive association with the risk of asthenozoospermia among non-drinkers (Ptrend < 0.05) and highly educated participants (OR = 1.82, 95% CI: 1.13-2.94; Ptrend < 0.05). Additionally, there was a multiplicative interaction between CQI and education level for asthenozoospermia risk (P < 0.05). Conclusions: Our findings demonstrated no association of MQI and its sub-indices with asthenozoospermia risk except for CQI. Although our findings are mostly non-significant, they contribute novel knowledge to this research field and lay the foundation for future studies.

[Impact of male infertility on men's self-esteem and satisfaction with sexual relationship].

OBJECTIVE: To investigate the impact of infertility on men's self-esteem, self-confidence, sexual satisfaction and overall relationship with their spouses. METHODS: Using Self-Esteem and Relationship questionnaire (SEAR), we conducted an investigation among 253 infertile men and 52 fertile male controls. We divided the infertile men into four subgroups according to their perceived causes of infertility: male (M) factors, female (F) factors, both M and F factors, and unknown factors, and compared the SEAR scores among different groups. RESULTS: In the infertile men, the total SEAR score was significantly higher in those with < 3 years than in those with > or = 3 years of infertility duration (75.50 +/- 17.05 vs 68.66 +/- 17.19, P < 0.05) and so was it in those with above-high-school than in those with high-school or lower education background (81.42 +/- 13.99 vs 67.61 +/- 17. 8, P < 0.01), but showed no significant difference between the > or = 30- and < 30-year-olds (71.77 +/- 17.42 vs 72.74 +/- 18.38, P > 0.05). The total SEAR scores in the M factor, M & F factor, unknown factor and F factor groups were 65.69 +/- 18.68, 68.52 +/- 17.68, 74.85 +/- 15.19 and 83.21 +/- 12.61, respectively, with significant differences between the first two and the latter two groups (P < 0.05), as well as between the unknown factor and F factor groups (P < 0.05). In the fertile male controls, the total SEAR score and subdomain scores on sexual relationship, self-confidence, self-esteem and overall relationship were 90.04 +/- 9.85, 88.40 +/- 10.74, 92.23 +/- 9.41, 91.95 +/- 10.67 and 90.38 +/- 14.14, respectively, all remarkably higher than in the M factor, M&F factor and unknown factor groups of the infertile men after adjustment of their infertility duration and education levels (P < 0.05). CONCLUSION: Infertility reduces men's self-esteem, self-confidence, sexual satisfaction and relationship with their spouses, and the degree of its impact is correlated with the patients' infertility duration and education level.

[Oral tadalafil on alternate days for erectile dysfunction that fails to respond to on-demand sildenafil: a report of 15 cases].

OBJECTIVE: To sum up the experience in administering oral tadalafil on alternate days for the treatment of erectile dysfunction (ED) that fails to respond to on-demand medication. METHODS: We retrospectively analyzed the clinical data of 15 cases of ED treated with oral tadalafil on alternate days from September 2010 to March 2012. All the patients had failed to respond to on-demand medication of sildenafil previously. RESULTS: After 4 weeks of tadalafil treatment, 11 (73.3%) of the cases were remarkably improved, with significant difference in IIEF-5 scores before and after treatment (P < 0.05). Transient adverse reactions were observed in the other 4 cases, including mild headache in 2, slight backache in 1, and facial flush in 1. CONCLUSION: Oral tadalafil on alternate days is safe and effective in the treatment of ED that fails to respond to on-demand medication of sildenafil.

[Impact of perceived male infertility factors on penile erectile function].

OBJECTIVE: To evaluate the impact of the factors of perceived male infertility on men's penile erectile function. METHODS: Using the 5-item version of the International Index of Erectile Function (IIEF-5), we investigated the penile erectile function among 245 infertile men (infertility group) and another 52 males having physical checkup for planned conception (checkup group), the former further divided into four subgroups according to the factors of infertility: male factor, female factor, bilateral factor, and unknown factor. We compared the total and item scores of IIEF-5 among different groups. RESULTS: Mild or mild-moderate ED was found in 50.61% of the infertile men, with a total IIEF-5 score of 21.24 +/- 2.58. The total and item scores of IIEF-5 were markedly higher in the male factor than in the female factor subgroup (P < 0.01), but with no significant difference between the male factor subgroup and the bilateral and unknown factor subgroups (P > 0.05), except the score on confidence. The scores were significantly lower in the bilateral and unknown factor subgroups than in the female factor subgroup (P < 0.05), with no remarkable difference between the former two. In the infertility group, the total and item scores of IIEF-5 were markedly higher in those with education above high school than in those with high school or lower education (P < 0.01), but not correlated with age and infertility duration. After adjustment for education background, the total IIEF-5 score and the scores on confidence and satisfaction were significantly lower in the infertility than in the checkup group (P < 0.05), and 15.38% of the men in the latter group had mild ED, dramatically lower than in the former (P < 0.01). CONCLUSION: Perceived infertility may cause ED in males, and a higher incidence rate is associated with lower education background of the men.

Network pharmacology and molecular docking elucidate potential mechanisms of Eucommia ulmoides in hepatic ischemia-reperfusion injury.

Eucommia ulmoides (EU) and its diverse extracts have demonstrated antioxidative, anti-inflammatory, and cytoprotective properties against hepatic ischemia-reperfusion injury (HIRI). However, the primary constituents of EU and their putative mechanisms remain elusive. This study aims to explore the potential mechanisms of EU in the prevention and treatment of HIRI by employing network pharmacology and molecular docking methodologies. The main components and corresponding protein targets of EU were searched in the literature and TCMSP, and the compound target network was constructed by Cytoscape 3.9.1. Liver ischemia-reperfusion injury targets were searched in OMIM and GeneCards databases. The intersection points of compound targets and disease targets were obtained, and the overlapping targets were imported into the STRING database to construct the PPI network. We further analyzed the targets for GO and KEGG enrichment. Finally, molecular docking studies were performed on the core targets and active compounds. The component-target network unveiled a total of 26 efficacious bioactive compounds corresponding to 207 target proteins. Notably, the top-ranking compounds based on degree centrality were quercetin, ß-sitosterol, and gallic acid. Within the PPI network, the highest degree centrality encompassed RELA, AKT1, TP53. GO and KEGG enrichment analysis elucidated that EU in HIRI primarily engaged in positive regulation of gene expression, positive transcriptional regulation via RNA polymerase II promoter, negative modulation of apoptotic processes, positive regulation of transcription from DNA templates, and drug responsiveness, among other biological processes. Key pathways included cancer pathways, RAGE signaling pathway, lipid metabolism, atherosclerosis, TNF signaling pathway, PI3K-Akt signaling pathway, and apoptotic pathways. Molecular docking analysis revealed robust affinities between quercetin, ß-sitosterol, gallic acid, and RELA, AKT1, TP53, respectively. This study reveals EU exhibits substantial potential in mitigating and treating HIRI through multifaceted targeting and involvement in intricate signaling pathways.

Progress and prospects of polysaccharide-based nanocarriers for oral delivery of proteins/peptides.

The oral route has long been recognized as the most preferred route for drug delivery as it offers high patient compliance and requires minimal expertise. Unlike small molecule drugs, the harsh environment of the gastrointestinal tract and low permeability across the intestinal epithelium make oral delivery extremely ineffective for macromolecules. Accordingly, delivery systems that are rationally constructed with suitable materials to overcome barriers to oral delivery are exceptionally promising. Among the most ideal materials are polysaccharides. Depending on the interaction between polysaccharides and proteins, the thermodynamic loading and release of proteins in the aqueous phase can be realized. Specific polysaccharides (dextran, chitosan, alginate, cellulose, etc.) endow systems with functional properties, including muco-adhesiveness, pH-responsiveness, and prevention of enzymatic degradation. Furthermore, multiple groups in polysaccharides can be modified, which gives them a variety of properties and enables them to suit specific needs. This review provides an overview of different types of polysaccharide-based nanocarriers based on different kinds of interaction forces and the influencing factors in the construction of polysaccharide-based nanocarriers. Strategies of polysaccharide-based nanocarriers to improve the bioavailability of orally administered proteins/peptides were described. Additionally, current restrictions and future trends of polysaccharide-based nanocarriers for oral delivery of proteins/peptides were also covered.

Dietary fat and fatty acid consumptions and the odds of asthenozoospermia: a case-control study in China.

STUDY QUESTION: Are dietary fat and fatty acid (FA) intakes related to the odds of asthenozoospermia? SUMMARY ANSWER: Plant-based fat consumption was associated with decreased asthenozoospermia odds, while the consumption of animal-based monounsaturated fatty acid (MUFA) was positively related to asthenozoospermia odds. WHAT IS KNOWN ALREADY: Dietary fat and FA are significant ingredients of a daily diet, which have been demonstrated to be correlated to the reproductive health of men. However, to date, evidence on fat and FA associations with the odds of asthenozoospermia is unclear. STUDY DESIGN SIZE DURATION: The hospital-based case-control study was performed in an infertility clinic from June 2020 to December 2020. Briefly, 549 asthenozoospermia cases and 581 controls with normozoospermia were available for final analyses. PARTICIPANTS/MATERIALS SETTING METHODS: We collected dietary data through a verified food frequency questionnaire of 110 food items. Asthenozoospermia cases were ascertained according to the World Health Organization guidelines. To investigate the correlations of dietary fat and FA consumptions with the odds of asthenozoospermia, we calculated the odds ratios (ORs) and corresponding 95% CIs through unconditional logistic regression models. MAIN RESULTS AND THE ROLE OF CHANCE: Relative to the lowest tertile of consumption, the highest tertile of plant-based fat intake was inversely correlated to the odds of asthenozoospermia (OR = 0.68, 95% CI = 0.50-0.91), with a significant dose-response relation (OR = 0.85, 95% CI = 0.75-0.97, per standard deviation increment). Inversely, animal-based MUFA intake (OR = 1.49, 95% CI = 1.04-2.14) was significantly correlated to increased odds of asthenozoospermia, and an evident dose-response relation was also detected (OR = 1.24, 95% CI = 1.05-1.45, per standard deviation increment). Subgroup analyses showed similar patterns of associations to those of the primary results. Moreover, we observed significant interactions on both multiplicative and additive scales between animal-based MUFA and cigarette smoking. LIMITATIONS REASONS FOR CAUTION: Selection bias and recall bias were unavoidable in any of the observational studies. As we failed to obtain the information of trans-fatty acid (TFA) consumption, the relation of TFA intake and asthenozoospermia odds was unclear. WIDER IMPLICATIONS OF THE FINDINGS: This study indicated that different sources of fat and FAs might exert different effects on the etiology of asthenozoospermia, and cigarette smoking could exacerbate the adverse effect of high animal-based MUFA intake on asthenozoospermia. Our findings provide novel evidence pertaining to the fields of prevention of asthenozoospermia through decreasing animal-derived fat and FA consumptions and smoking cessation. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the JieBangGuaShuai Project of Liaoning Province, Natural Science Foundation of Liaoning Province, Clinical Research Cultivation Project of Shengjing Hospital, and Outstanding Scientific Fund of Shengjing Hospital. All authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Phytochemical consumption and the risk of teratozoospermia: findings from a hospital-based case-control study in China.

STUDY QUESTION: Are dietary phytochemicals associated with the risk of teratozoospermia? SUMMARY ANSWER: Dietary intake of carotene, including total carotene, α-carotene, ß-carotene as well as retinol equivalent, and lutein + zeaxanthin, were inversely correlated with the risk of teratozoospermia. WHAT IS KNOWN ALREADY: Phytochemicals are natural plant derived bioactive compounds, which have been reported to be potentially associated with male reproductive health. To date, no study has investigated the association between phytochemical intake and the risk of teratozoospermia. STUDY DESIGN SIZE DURATION: This hospital-based case-control study, which included 146 newly diagnosed teratozoospermia cases and 581 controls with normozoospermia from infertile couples, was conducted in a hospital-based infertility clinic in China, from June 2020 to December 2020. PARTICIPANTS/MATERIALS SETTING METHODS: Dietary information was collected using a validated semi-quantitative 110-item food frequency questionnaire. Unconditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between phytochemical (i.e. phytosterol, carotene, flavonoid, isoflavone, anthocyanidin, lutein + zeaxanthin, and resveratrol) intake and the risk of teratozoospermia. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a decreased risk of teratozoospermia for the highest compared with the lowest tertile consumption of total carotene (OR = 0.40, 95% CI = 0.21-0.77), α-carotene (OR = 0.53, 95% CI = 0.30-0.93), ß-carotene (OR = 0.47, 95% CI = 0.25-0.88), retinol equivalent (OR = 0.47, 95% CI = 0.24-0.90), and lutein + zeaxanthin (OR = 0.35, 95% CI = 0.19-0.66), with all of the associations showing evident linear trends (all P trend <0.05). In addition, significant dose-response associations were observed between campestanol and α-carotene consumption and the risk of teratozoospermia. Moreover, there was a significant multiplicative interaction between BMI and lutein + zeaxanthin intake (P interaction <0.05). LIMITATIONS REASONS FOR CAUTION: The cases and controls were not a random sample of the entire target population, which could lead to admission rate bias. Nevertheless, the controls were enrolled from the same infertility clinic, which could reduce the bias caused by selection and increase the comparability. Furthermore, our study only included a Chinese population, therefore caution is required regarding generalization of our findings to other populations. WIDER IMPLICATIONS OF THE FINDINGS: Dietary phytochemicals, namely carotene, lutein, and zeaxanthin, might exert a positive effect on teratozoospermia. These phytochemicals are common in the daily diet and dietary supplements, and thus may provide a preventive intervention for teratozoospermia. STUDY FUNDING/COMPETING INTERESTS: This study was funded by Natural Science Foundation of Liaoning Province (No. 2022-MS-219 to X.B.W.), Outstanding Scientific Fund of Shengjing Hospital (No. M1150 to Q.J.W.), Clinical Research Cultivation Project of Shengjing Hospital (No. M0071 to B.C.P.), and JieBangGuaShuai Project of Liaoning Province (No. 2021JH1/1040050 to Y.H.Z.). All authors declared that there was no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.