Effect of Perinatal Bisphenol A Exposure on Serum Lipids and Lipid Enzymes in Offspring Rats of Different Sex

Rats were exposed to1 or 10 μg/mL bisphenol A （BPA） in water during pregnancy and lactation. Offspring rats were given normal water and a standard diet from weaning to postnatal day （PND） 50. Perinatal exposure to BPA resulted in significantly increased body weight, visceral adipose tissue, abnormal serum lipids, and lower adiponectin （ADP） levels in both female and male offspring rats. Liver adipose triglyceride lipase （Atgl） mRNA levels and ADP protein in visceral adipose tissue were significantly decreased in BPA-exposed offspring rats. In both female or male offspring rats, obesity and dyslipidemia induced by perinatal exposure to BPA were associated with down regulation of Atgl mRNA in liver and ADP protein in visceral adipose tissue.

Hard life for sons in the nest?Sex-dependent offspring mortality in Great Tits in urban and forest areas

Sex-biased mortality can occur in birds during development,for example due to sexual differences in energy requirement and/or environmental sensitivity,or the effects of sex hormones or sex differences in the expression of mutations linked to sex chromosomes.The extent of sex-bias in mortality may also be related to environmental conditions that influence offspring development and survival.Urban areas often provide poorer conditions for nestling development resulting in higher offspring mortality compared to natural areas,which may accelerate sex differences in offspring mortality in cities.To test this hypothesis,we examined the sex ratio of dead offspring in Great Tits(Parus major),using 427 samples of unhatched eggs and dead nestlings collected in two urban and two forest sites between 2013 and 2019.The ratio of males in the whole sample of dead offspring(56.9%)was significantly higher than expected by an 1:1 ratio,and the strongest sex biases were detected in urban areas(57.6%males)and in young nestlings(<14 days old,59.0%males).However,the sex ratios of dead offspring did not differ significantly among study sites and between offspring developmental stages.29.3%of unhatched eggs contained a visible embryo,and the proportion of embryo-containing unhatched eggs did not differ significantly between urban and forest study sites.These results suggest male-biased offspring mortality in Great Tits,and highlight the need of large datasets to detect subtle differences between habitats and developmental stages.

Study on sex differences and potential clinical value of threedimensional computerized tomography pelvimetry in rectal cancer patients

BACKGROUND Laparoscopic rectal cancer radical surgery is a complex procedure affected by various factors.However,the existing literature lacks standardized parameters for the pelvic region and soft tissues,which hampers the establishment of consistent conclusions.AIM To comprehensively assess 16 pelvic and 7 soft tissue parameters through computerized tomography(CT)-based three-dimensional(3D)reconstruction,providing a strong theoretical basis to address challenges in laparoscopic rectal cancer radical surgery.METHODS We analyzed data from 218 patients who underwent radical laparoscopic surgery for rectal cancer,and utilized CT data for 3D pelvic reconstruction.Specific anatomical points were carefully marked and measured using advanced 3D modeling software.To analyze the pelvic and soft tissue parameters,we emp-loyed statistical methods including paired sample t-tests,Wilcoxon rank-sum tests,and correlation analysis.RESULTS The investigation highlighted significant sex disparities in 14 pelvic bone parameters and 3 soft tissue parameters.Males demonstrated larger measurements in pelvic depth and overall curvature,smaller measurements in pelvic width,a larger mesorectal fat area,and a larger anterior-posterior abdominal diameter.By contrast,females exhibited wider pelvises,shallower depth,smaller overall curvature,and an increased amount of subcutaneous fat tissue.However,there were no significant sex differences observed in certain parameters such as sacral curvature height,superior pubococcygeal diameter,rectal area,visceral fat area,waist circumference,and transverse abdominal diameter.CONCLUSION The reconstruction of 3D CT data enabled accurate pelvic measurements,revealing significant sex differences in both pelvic and soft tissue parameters.This study design offer potential in predicting surgical difficulties and creating personalized surgical plans for male rectal cancer patients with a potentially“difficult pelvis”,ultimately improving surgical outcomes.Further research and utilization of these parameters could lead to enhanced surgical methods and patient care in laparoscopic rectal cancer radical surgery.

Keep in mind sex differences when prescribing psychotropic drugs

Women represent the majority of patients with psychiatric diagnoses and also the largest users of psychotropic drugs.There are inevitable differences in efficacy,side effects and long-term treatment response between men and women.Psychopharmacological research needs to develop adequately powered animal and human trials aimed to consider pharmacokinetics and pharmacodynamics of central nervous system drugs in both male and female subjects.Healthcare professionals have the responsibility to prescribe sex-specific psychopharmacotherapies with a priority to differentiate between men and women in order to minimize adverse drugs reactions,to maximize therapeutic effectiveness and to provide personalized management of care.

Sex dimorphism and metabolic profiles in management of metabolic-associated fatty liver disease

Metabolic-associated fatty liver disease(MAFLD)refers to the build-up of fat in the liver associated with metabolic dysfunction and has been estimated to affect a quarter of the population worldwide.Although metabolism is highly influenced by the effects of sex hormones,studies of sex differences in the incidence and progression of MAFLD are scarce.Metabolomics represents a powerful approach to studying these differences and identifying potential biomarkers and putative mechanisms.First,metabolomics makes it possible to obtain the molecular phenotype of the individual at a given time.Second,metabolomics may be a helpful tool for classifying patients according to the severity of the disease and obtaining diagnostic biomarkers.Some studies demonstrate associations between circulating metabolites and early and established MAFLD,but little is known about how metabolites relate to and encompass sex differences in disease progression and risk management.In this review,we will discuss the epidemiological metabolomic studies for sex differences in the development and progression of MAFLD,the role of metabolic profiles in understanding mechanisms and identifying sex-dependent biomarkers,and how this evidence may help in the future management of the disease.

Kidney disease in patients with chronic liver disease:Does sex matter?

Kidney disease in patients with liver disease is serious and increases mortality.Up to 50%of patients hospitalized experience an episode of acute kidney injury.In general,men with liver disease are thought to be at increased risk of kidney disease.However,this association should be considered with caution because most studies use creatinine-based inclusion criteria,which is negatively biased against women.In this review,we synthesize data on sex differences in kidney disease in patients with chronic liver disease in the clinical setting and discuss potential physiologic underpinnings.

Sex differences in the scored Patient-Generated Subjective Global Assessment in 19,528 cancer patients

Background:The scored Patient-Generated Subjective Global Assessment(PG-SGA)has been widely used to assess the nutritional status of cancer patients.The purpose of this study is to compare the differences in PG-SGA scores and the 7 domain scores of the PG-SGA in male and female cancer patients.Methods:This study was conducted at 72 hospitals from July 2013 to December 2018,a part of the Investigation on Nutritional Status and its Clinical Outcomes of Common Cancers.The PG-SGA was recorded to evaluate the nutritional status of patients.A total of 19,528 patients with 13 common malignancies were included in this study.Student t test and the χ^(2) test were applied to analyze the sex diferences in the 7 domain scores.The Cancer Genome Atlas(TCGA)database was used to analyze the expression levels of symptom-related genes.Results:There were significant sex dfferences in the PG-SGA(P=0.032),notably in patients with gastric cancer(male vs female:9.09±4.86 vs 9.58±5.07,P=0.005)and esophageal cancer(9.64±4.90 vs 10.46±4.96,P=0.011)and the average total PG-SGA of female patients was slightly higher than that of male patients(7.64±4.98 vs 7.77±5.14).The differences were mainly related to the weight,eating,symptom,as well as activity and physical function scores in the stratified analysis.Possible causes of the sex differences were the rates of nausea,vomiting,dry mouth,and other symptoms,in both gastric and esophageal cancer patients.Analysis of the TCGA database suggested that most of the related genes were sex neutral,except for genes related to dysphagia in gastric cancer(VEGFC was higher in female patients,VEGFA and VEGFB higher in male patients).Conclusions:There are sex differences in the PG-SGA scores in patients with various tumor types(female patients generally had higher scores than male patients),with differences mainly in the weight,eating,symptom,as well as activity and physical function scores.The sex differences in PG-SGA scores might be due to the differences in the clinical manifestations of the disease,and further studies should be carried out to investigate other factors influencing the PG-SGA scores in cancer patients.This study provides basic data supporting the individualized nutritional treatment of cancer patients in clinical practice.

Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker!

Alanine aminotransferase(ALT)serum levels increase because of hepatocellular damage.Metabolic dysfunction-associated fatty liver disease(MAFLD),which identifies steatotic liver disease(SLD)associated with≥2 metabolic abnormalities,has prominent sexual differences.The Metabolic Syndrome defines a cluster comprising abdominal obesity,altered glucose metabolism,dyslipidemia,and hypertension.Male sex,body mass index,glucose,lipids,ferritin,hypertension,and age independently predict ALT levels among blood donors.Over the last few decades,the reference range of ALT levels has been animatedly debated owing to attempts to update sex-specific reference ranges.With this backset,Chen et al have recently published a study which has two main findings.First,>80%of indi-viduals with MAFLD had normal ALT levels.Second,there was a linear increa-sing trend in the association between cumulative excess high-normal ALT levels and the rate of incident MAFLD.This study has biologically credible findings.However,it inaccurately considered sex differences in the MAFLD arena.Therefore,future studies on SLD owing to metabolic dysfunction should adopt locally determined and prospectively validated reference ranges of ALT and carefully consider sex differences in liver enzymes and MAFLD pathobiology.

Influence of biological sex and exercise on murine cardiac metabolism

Although the structural and functional effects of exercise on the heart are well established,the metabolic changes that occur in the heart during and after exercise remain unclear.In this study,we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill exercise.After the exercise bout,we also recorded blood lactate,glucose,and ketone body levels and measured cardiac mitochondrial respiration.In both male and female mice,moderate-and high-intensity exercise acutely increased blood lactate levels.In both sexes,low-and moderate-intensity exercise augmented circulating 3-hydroxybutryrate levels immediately after the exercise bout;however,only in female mice did high-intensity exercise increase 3-hydroxybutyrate levels,with significant increases occurring 1 h after the exercise session.Untargeted metabolomics analyses of sedentary female and male hearts suggest considerable sex-dependent differences in basal cardiac metabolite levels,with female hearts characterized by higher levels of pantothenate,pyridoxamine,homoarginine,tryptophan,and several glycerophospholipid and sphingomyelin species and lower levels of numerous metabolites,including acetyl coenzyme A,glucuronate,gulonate,hydroxyproline,prolyl-hydroxyproline,carnosine,anserine,and carnitinylated and glycinated species,as compared with male hearts.Immediately after a bout of treadmill exercise,both male and female hearts had higher levels of corticosterone;however,female mice showed more extensive exercise-induced changes in the cardiac metabolome,characterized by significant,time-dependent changes in amino acids(e.g.,serine,alanine,tyrosine,tryptophan,branched-chain amino acids)and the ketone body 3-hydroxybutyrate.Results from experiments using isolated cardiac mitochondria suggest that high-intensity treadmill exercise does not acutely affect respiration or mitochondrial coupling;however,female cardiac mitochondria demonstrate generally higher adenosine diphosphate sensitivity compared with male cardiac mitochondria.Collectively,these findings in mice reveal key sex-dependent differences in cardiac metabolism and suggest that the metabolic network in the female heart is more responsive to physiological stress caused by exercise.

Sex-based differences in histology,staging,and prognosis among 2983 gastric cancer surgery patients

BACKGROUND Few studies have been conducted on sex differences in the incidence, pathophysiology, and prognosis of gastric cancer(GC).AIM To analyze the differences in GC characteristics according to sex in patients who underwent surgical treatment for GC.METHODS A total of 2983 patients diagnosed with gastric adenocarcinoma who received surgical treatment at the Seoul National University Bundang Hospital between 2003 and 2017 were included.Baseline clinicopathological characteristics, histologic type of GC, overall and GC-specific survival rates, and associated risk factors were analyzed.RESULTS Among the 2983 patients, 2005(67.2%) and 978(32.8%) were males and females, respectively.The average age of the female group(59.36 years) was significantly younger than that of the male group(61.66 years;P < 0.001).Cancer of the gastric body(P < 0.001) and diffuse-type histology(P < 0.001) were more common in females than in males.This trend was more prominent in females younger than 60 years of age, with a significantly higher proportion of diffuse-type cancer than in the male group.Regardless of sex, diffuse-type GC was more common in younger patients, and the proportion of intestinal-type GC increased with age.The overall survival rate was significantly higher in females(P < 0.001).However, this difference disappeared for GC-specific survival(P = 0.168), except for the poor GC-specific survival rate in advanced-stage cancer(stage Ⅲ or above) in females(P = 0.045).The risk factors for GC-related mortality were older age, upper location of GC, and diffuse-or mixed-type histology.In terms of comorbidities, more males died from diseases other than GC, including other malignancies such as lung cancer, hepatocellular carcinoma, and pancreatic cancer, and respiratory diseases such as interstitial lung disease and chronic obstructive pulmonary disease, while there were relatively more cardiovascular or cerebrovascular deaths in females.CONCLUSION Sex-based differences in GC were observed in clinicopathological features, including age at diagnosis, tumor location, histologic type, survival rate, and comorbidities.

Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats

AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia(HEEP) leaves on gastric ulcer healing.METHODS In this rat study involving males, intact(cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity.RESULTS Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males(52.44%), intact females(85.22%), and ovariectomized females(65.47%), confirming that HEEP accelerates the healing of acetic acidinduced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor(intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2(intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed.CONCLUSION In gastric ulcers, HEEP-induced healing(modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration.

Association between physiological responses after exercise at low altitude and acute mountain sickness upon ascent is sex-dependent

Background:Acute mountain sickness(AMS)is the mildest form of acute altitude illnesses,and consists of nonspecific symptoms when unacclimatized persons ascend to elevation of≥2500 m.Risk factors of AMS include:the altitude,individual susceptibility,ascending rate and degree of pre-acclimatization.In the current study,we examined whether physiological response at low altitude could predict the development of AMS.Methods:A total of 111 healthy adult healthy volunteers participated in this trial;and 99(67 men and 32 women)completed the entire study protocol.Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude(500 m).Heart rate,blood pressure(BP)and pulse oxygen saturation(SpO2)were recorded prior to and during the last minute of exercise.The ascent from 500 m to 4100 m was completed in 2 days.AMS was defined as≥3 points in a 4-item Lake Louise Score,with at least one point from headache wat 6–8 h after the ascent.Results:Among the 99 assessable subjects,47(23 men and 24 women)developed AMS at 4100 m.In comparison to the subjects without AMS,those who developed AMS had lower proportion of men(48.9%vs.84.6%,P<0.001),height(168.4±5.9 cm vs.171.3±6.1 cm,P=0.019),weight(62.0±10.0 kg vs.66.7±8.6 kg,P=0.014)and proportion of smokers(23.4%vs.51.9%,P=0.004).Multivariate regression analysis revealed the following independent risks for AMS:female sex(odds ratio(OR)=6.32,P<0.001),SpO2 change upon exercise at low altitude(OR=0.63,P=0.002)and systolic BP change after the ascent(OR=0.96,P=0.029).Women had larger reduction in SpO2 after the ascent,higher AMS percentage and absolute AMS score.Larger reduction of SpO2 after exercise was associated with both AMS incidence(P=0.001)and AMS score(P<0.001)in men but not in women.Conclusions:Larger SpO2 reduction after exercise at low altitude was an independent risk for AMS upon ascent.Such an association was more robust in men than in women.Trial registration:Chinese Clinical Trial Registration,ChiCTR1900025728.Registered 6 September 2019.

Sex-based differences in the prevalence of acute mountain sickness: a meta-analysis

Background:When lowlanders rapidly ascend to altitudes>2500 m,they may develop acute mountain sickness(AMS).The individual susceptibility,ascending velocity,time spent at altitude,activity levels and altitude reached are considered risk factors for AMS.However,it is not clear whether sex is a risk factor.The results have been inconclusive.We conducted a meta-analysis to test whether there were sex-based differences in the prevalence of AMS using Lake Louise Scoring System.Methods:Systematic searches were performed in August 2019 in EMBASE,PubMed,and Web of Science for prospective studies with AMS data for men and women.The titles and abstracts were independently checked in the primary screening step,and the selected full-text articles were independently assessed in the secondary screening step by the two authors(YPH and JLW)based on pre-defined inclusion criteria.The meta-analysis was performed using by the STATA 14.1 software program.A random-effects model was employed.Results:Eighteen eligible prospective studies were included.A total of 7669 participants(2639[34.4%]women)were tested.The results showed that there was a statistically significant higher prevalence rate of AMS in women than in men(RR=1.24,95%CI 1.09–1.41),regardless of age or race.However,the heterogeneity was significant in the analysis(Tau2=0.0403,Chi2=50.15,df=17;I2=66.1%,P=0.000),it was main caused by different numbers of subjects among the studies(coefficient=–2.17,P=0.049).Besides,the results showed that there was no evidence of significant publication bias in the combined studies on the basis of Egger’s test(bias coefficient=1.48,P=0.052)and Begg’s test(P=0.130).Conclusions:According to this study,the statistically significant finding emerging from this study was that women have a higher prevalence of AMS.However,the authors could not exclude studies where patients were on acetazolamide.Our analysis provided a direction for future studies of the relationship of sex and the risk of AMS,such as the pathological mechanism and prevention research.

Nonalcoholic fatty liver disease shows significant sex dimorphism

Nonalcoholic fatty liver disease(NAFLD),which has been renamed metabolic dysfunction-associated fatty liver disease,is a growing global medical problem.The incidence of NAFLD and its associated end-stage liver disease is increasing each year,and many research advancements have been achieved to date.This review focuses on the current knowledge of the sex differences in NAFLD and does not elaborate on areas without differences.Studies have revealed significant sex differences in the prevalence,influencing factors,pathophysiology,complications and therapies of NAFLD.Men have a higher incidence than women.Compared with women,men exhibit increased visceral fat deposition,are more susceptible to leptin resistance,lack estrogen receptors,and tend to synthesize fatty acids into fat storage.Male patients will experience more severe hepatic fibrosis and a higher incidence of liver cancer.However,once NAFLD occurs,women show a faster progression of liver fibrosis,higher levels of liver cell damage and inflammation and are less likely to undergo liver transplantation than men.In general,men have more risk factors and more severe pathophysiological reactions than women,whereas the development of NAFLD is faster in women,and the treatments for women are more limited than those for men.Thus,whether sex differences should be considered in the individualized prevention and treatment of NAFLD in the future is worth considering.

Mediation Effects of Placental Inflammatory Transcriptional Biomarkers on the Sex-Dependent Associations between Maternal Phthalate Exposure and Infant Allergic Rhinitis: A Population-Based Cohort Study

Objective Prenatal phthalate exposure has been associated with placental inflammatory factors and infant allergic rhinitis(AR).However,the results are inconclusive.We designed a population-based cohort study to examine the effects of placental inflammatory biomarkers on the sex-dependent associations between maternal phthalate exposure and infant AR.Methods A total of 2,348 pregnant women from Ma’anshan,Anhui Province,China,who were screened before antenatal visits and met the inclusion criteria,were included in the present study.We assessed AR in their offspring aged 36 months with a questionnaire.Quantitative PCR was performed to measure placental inflammatory factor m RNAs.The independent samples t-test and multivariable logistic regression were used to determine the associations between infant AR and maternal phthalates.Results Childhood AR may be related to education and family monthly income(P = 0.01).The phthalate metabolites,mono(2-ethylhexyl) phthalate(MEHP),mono(2-ethyl-5-hydroxyl) phthalate(MEHHP),in pregnant women were associated with a significantly increased risk for infant AR in males[P < 0.05;odds ratio(OR):1.285;95% confidence interval(CI):1.037-1.591,and OR:1.232,95% CI:1.008-1.507,respectively],but not females.Additionally,irritably-increased expression levels of HO-1 and IL-4 were associated with AR in male infants(OR:1.175;95% CI:1.038-1.329 and OR:1.181;95% CI:1.056-1.322,respectively).The association between maternal urinary MEHHP and placental HO-1 was marginally significant according to mediation analysis.Conclusion The associations of maternal MEHHP and MEOHP levels with fetal AR in males were significant.Placental HO-1 was a fractional mediator in the associations between MEHHP and AR.Thus,the placenta should be further investigated as a potential mediator of maternal exposure-induced disease risk in children.

Sex differences and effects of oestrogen in rat gastric mucosal defence

AIM To evaluate sex differences and the effects of oestrogen administration in rat gastric mucosal defence.METHODS Sex differences in gastric mucus thickness and accumulation rate, absolute gastric mucosal blood flow using microspheres, the integrity of the gastric mucosal epithelium in response to a chemical irritant and the effects of oestrogen administration on relative gastric mucosal blood flow in an acute setting was assessed in an in vivo rat experimental model. Subsequently, sex differences in the distribution of oestrogen receptors and calcitonin gene related peptide in the gastric mucosa of animals exposed to oestrogen in the above experiments was evaluated using immunohistochemistry.RESULTS The absolute blood flow in the GI-tract was generally higher in males, but only significantly different in the corpus part of the stomach (1.12 ± 0.12 m L/min·g in males and 0.51 ± 0.03 m L/min·g in females) (P = 0.002). After removal of the loosely adherent mucus layer the thickness of the firmly adherent mucus layer in males and females was 79 ± 1 μm and 80 ± 3 μm respectively. After 60 min the mucus thickness increased to 113 ± 3 μm in males and 121 ± 3 μm in females with no statistically significant difference seen between the sexes. Following oestrogen administration(0.1 followed by 1 μg/kg·min), mean blood flow in the gastric mucosa decreased by 31% [68 ± 13 perfusion units (PFU)] in males which was significantly different compared to baseline(P = 0.02). In females however, mean blood flow remained largely unchanged with a 4% (5 ± 33 PFU) reduction. The permeability of the gastric mucosa increased to a higher level in females than in males (P = 0.01) after taurocholate challenge. However, the calculated mean clearance increase did not significantly differ between the sexes [0.1 ± 0.04 to 1.1 ± 0.1 m L/min·100 g in males and 0.4 ± 0.3 to 2.1 ± 0.3 m L/min·100 g in females(P = 0.065)]. There were no significant differences between 17β-Estradiol treated males (mean ratio of positive staining ± SEM)(0.06 ± 0.07) and females(0.11 ± 0.11) in the staining of ERα (P = 0.24). Also, there were no significant differences between 17β-Estradiol treated males (0.18 ± 0.21) and females (0.06 ± 0.12) in the staining of ERβ (P = 0.11). Finally, there were no significant differences between 17β-Estradiol treated males (0.04 ± 0.05) and females (0.11 ± 0.10) in the staining of CGRP(P = 0.14).CONCLUSION Gastric mucosal blood flow is higher in male than in female rats and is reduced in male rats by oestrogen administration.

Olympic sports and transsexuals

Sex segregation in competitive sports is regarded as fair. Before puberty boys and girls do not differ in height, muscle and bone mass. Testosterone （T） exposure during puberty leads to an ultimate average greater height in men of 12-15 cm, longer and larger bones and muscle mass and strength and higher hemoglobin levels. Postpubertal androgen ablation reverses, at least in part, previous anabolic effects of T on muscle, bone mineral density and hemoglobin but the long bones remain longer and wider. T administration dose dependently increases muscle mass and maximal voluntary strength. Therefore, exogenous androgens, being performance enhancing drugs, are banned for all athletes. An issue is the participation in competitive sports of people with errors of sexual differentiation and particularly transsexuals who have been sex-reassigned. In view of the effects of T, a clear demarcation is whether sex reassignment has taken place before or after hormonal puberty. Pubertal effects of T are in part reversible but there is no reliable evidence as to its completeness. The International Olympic Committee （IOC） has taken an inevitably arbitrary decision with regard to participation of sex-reassigned transsexuals in elite sports： sex reassign- ment must have taken place at least two years earlier, hormone treatment must be appropriate for the reassigned sex and the reassigned sex must be legally recognized. The IOC policy is not binding for other organizations.

Sex differences in SARS-CoV-2 infections,anti-viral immunity and vaccine responses

The COVID-19 pandemic has revealed sex-based differences in anti-viral responses,with a higher rate of SARS-CoV-2 infections as well as a higher rate of morbidity and mortality in men than in women.Males and females also show disparate immune responses to COVID-19 infection,which may be important contributors to lower rates of infection,disease severity and deaths in women than in men.Here,the authors review sex differences in SARS-CoV-2 infections,anti-viral immunity and vaccine responses,putting forth the importance of sex,the underappreciated variables in vaccine response and disease infectivity.

Associations of gut microbiota with dyslipidemia based on sex differences in subjects from Northwestern China

BACKGROUND The gut microbiota(GM)has been proven to play a role in the regulation of host lipid metabolism,which provides a new theory about the pathogenesis of dyslipidemia.However,the associations of GM with dyslipidemia based on sex differences remain unclear and warrant elucidation.AIM To investigate the associations of GM features with serum lipid profiles based on sex differences in a Chinese population.METHODS This study ultimately recruited 142 participants(73 females and 69 males)at Honghui Hospital,Xi’an Jiaotong University.The anthropometric and blood metabolic parameters of all participants were measured.According to their serum lipid levels,female and male participants were classified into a high triglyceride(H_TG)group,a high total cholesterol(H_CHO)group,a low high-density lipoprotein cholesterol(L_HDL-C)group,and a control(CON)group with normal serum lipid levels.Fresh fecal samples were collected for 16S rRNA gene sequencing.UPARSE software,QIIME software,the RDP classifier and the FAPROTAX database were used for sequencing analyses.RESULTS The GM composition at the phylum level included Firmicutes and Bacteroidetes as the core GM.Different GM features were identified between females and males,and the associations between GM and serum lipid profiles were different in females and males.The GM features in different dyslipidemia subgroups changed in both female patients and male patients.Proteobacteria,Lactobacillaceae,Lactobacillus and Lactobacillus_salivarius were enriched in H_CHO females compared with CON females,while Coriobacteriia were enriched in L_HDL-C females.In the comparison among the three dyslipidemia subgroups in females,Lactobacillus_salivarius were enriched in H_CHO females,and Prevotellaceae were enriched in L_HDL-C females.Compared with CON or H_TG males,Prevotellaceae,unidentified_Ruminococcaceae,Roseburia and Roseburia_inulinivorans were decreased in L_HDL-C males(P value<0.05),and linear discriminant analysis effect size analysis indicated an enrichment of the above GM taxa in H_TG males compared with other male subgroups.Additionally,Roseburia_inulinivorans abundance was positively correlated with serum TG and total cholesterol levels,and Roseburia were positively correlated with serum TG level.Furthermore,Proteobacteria(0.724,95%CI:0.567-0.849),Lactobacillaceae(0.703,95%CI:0.544-0.832),Lactobacillus(0.705,95%CI:0.547-0.834)and Lactobacillus_salivarius(0.706,95%CI:0.548-0.835)could distinguish H_CHO females from CON females,while Coriobacteriia(0.710,95%CI:0.547-0.841),Coriobacteriales(0.710,95%CI:0.547-0.841),Prevotellaceae(0.697,95%CI:0.534-0.830),Roseburia(0.697,95%CI:0.534-0.830)and Roseburia_inulinivorans(0.684,95%CI:0.520-0.820)could discriminate H_TG males from CON males.Based on the predictions of GM metabolic capabilities with the FAPROTAX database,a total of 51 functional assignments were obtained in females,while 38 were obtained in males.This functional prediction suggested that cellulolysis increased in L_HDL-C females compared with CON females,but decreased in L_HDL-C males compared with CON males.CONCLUSION This study indicates associations of GM with serum lipid profiles,supporting the notion that GM dysbiosis may participate in the pathogenesis of dyslipidemia,and sex differences should be considered.

Sex Difference in the Repolarization Currents of Rabbit Ventricular Cells

The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, I_to, I_K,tail, I_K1 and I_Ca,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD_90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), P<0.05. In female rabbit myocytes, I_K,tail, I_to, I_K1 and I_Ca,L were 0.71±0.05 pA/pF (n=17), 8.28±1.03 pA/pF (n=18), 24.5±3.6 pA/pF (n=12) and 9.0±2.3 pA/pF (n=15) respectively. In male rabbit myocytes, they were 0.84±0.07 pA/pF (n=18), 8.60±1.20 pA/pF (n=18), 25.9±4.5 pA/pF (n=14) and 9.3±2.6 pA/pF (n=16) respectively. I_K,tail in female rabbits was significantly lower than that of male rabbits (P<0.05), but there was no difference in I_to, I_K1 and I_Ca,L between male rabbits and female rabbits (P>0.05). The lower I_K,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.