Sex Determination in Homo sapiens as a Multi-Step Process: Potential for Development of Variants and Sex Differences in Disease Risk

Reproduction via cis-binary mechanisms appears to have evolved fairly early in the evolution of complex organisms, and a system committed to prior to evolution of humans. While the evolution of a chromosomal-specific approach has been a successful strategy for survival of a large variety of species including humans, the fidelity of sex determination leading to 100% cis-binary outcomes is not achieved in many species, with evidence for homosexual or bisexual behaviour evident in more than 1500 species. Thus, such outcomes indicates that sex determination is a multi-step process and not a single event, and as such, could lead to the appearance of variants during the process which developed much earlier than humans. Variants could arise either due to intrinsic variation in the steps of determination, or also be influenced by environmental factors of a biological or psychological nature. In contrast to homosexual variants which do not require interventions such as hormone therapy or surgery, expression of gender dysphoria, is more based in psychology, but also has biological underpinnings and can be influenced by such hormonal interventions and surgery. While the numbers of those with gender dysphoria is small (~0.6% - 1.0% of population), the attention given to this issue raises the possibility of biological and psychological environmental factors impacting the emergence of some of those expressing gender dysphoria. Furthermore, transitioning from male-to-female or female-to-male can have consequences regarding disease risks latter in life, including the appearance of autoimmune diseases. This review will attempt to review some of the evidence regarding sex determination, discuss why the system has potentially not been improved upon during evolution, how a potential role for sex chromosome function on neurodevelopment may be central to variation in humans, and how commitment to the current strategy is likely integrated into other sex-related events such as puberty, pregnancy, and menopause to ensure species survival. It will also discuss how variants in sex determination could contribute to sex differences in disease risk and how epigenetic modifications could play a role in such risk. .

Overexpression of Kdm6b induces testicular differentiation in a temperature-dependent sex determination system

In reptiles,such as the red-eared slider turtle(Trachemys scripta elegans),gonadal sex determination is highly dependent on the environmental temperature during embryonic stages.This complex process,which leads to differentiation into either testes or ovaries,is governed by the finely tuned expression of upstream genes,notably the testis-promoting gene Dmrt1 and the ovary-promoting gene Foxl2.Recent studies have identified epigenetic regulation as a crucial factor in testis development,with the H3K27me3 demethylase KDM6B being essential for Dmrt1 expression in T.s.elegans.However,whether KDM6B alone can induce testicular differentiation remains unclear.In this study,we found that overexpression of Kdm6b in T.s.elegans embryos induced the male development pathway,accompanied by a rapid increase in the gonadal expression of Dmrt1 at 31°C,a temperature typically resulting in female development.Notably,this sex reversal could be entirely rescued by Dmrt1 knockdown.These findings demonstrate that Kdm6b is sufficient for commitment to the male pathway,underscoring its role as a critical epigenetic regulator in the sex determination of the red-eared slider turtle.

Flower development and sexual dimorphism in Vernicia montana

The mu oil tree(Vernicia montana Lour.) is a dioecious species, but the genetic mechanisms underlying its phenotypic sexual dimorphism are unclear. In this study, we determined two pivotal phases of sex differentiation of mu oil tree via morphological and histological analyses of unisexual flowers:(Ⅰ) differentiation of male or female primordia to produce staminate flowers(SFs) or transient hermaphrodite flowers(HFs),and(Ⅱ) complete abortion of stamens in transient HFs to generate pistillate flowers(PFs). A total of 1621 sex-biased genes were identified by comparative transcriptome analysis which exhibited elevated rates of protein evolution than unbiased genes. The female-biased genes were enriched in the production of defense compounds while male-biased genes were focused on the production of viable pollens. Transcriptomebased analysis revealed that the differentially expressed genes(DEGs) between PFs and SFs in phase Ⅰ involved in abscisic acid(ABA), auxin(AUX), cytokinin(CK), ethylene(ET), and gibberellin(GA) biosynthesis and signaling showed higher expression levels in males than in females in general, whereas the DEGs involved in jasmonic acid(JA) and salicylic acid(SA) pathways displayed opposite expression patterns. Moreover,differentially expressed endogenous ABA, AUX, GAs, JA, and SA exhibited consistent biased expression patterns with the DEGs by UPLC-MSbased analysis. Exogenous application of an anti-ethylene plant growth regulator could promote the development of stamens in PFs and generated HFs. Comparative transcriptomic and hormonal analyses of PFs and SFs in phase Ⅱ indicated an increase in ET concentration when abortion of stamens in PFs occurred. This study suggested that phytohormones play key roles in sex dimorphism and ET may determine the development of stamens in PFs of mu oil tree, which provides an insight into plant sex differentiation mechanisms.

Changes in sexual activity in young women during pregnancy

Objective:To conduct changes in sexual activity during pregnancy and its related factors in pregnant women.Methods:The present descriptive cross-sectional study was conducted in 2017 on pregnant women who referred to the women's clinic of Afzalipour Hospital in the southeast of Iran.Participants were included in the study through convenient sampling.The data collection tool was a researcher-made questionnaire consisting of two parts of personal social information of the couple and questions to measure the level of sexual activity and the attitude of the subjects during pregnancy compared to before pregnancy.Results:201 Pregnant women were included.The average age of pregnant women was(27.3±6.1)years and their average gestational age was(24.7±11.8)years.More than 62%of women had decreased sexual activity.There was a significant relationship between the amount of changes in sexual activity and delivery time(P=0.013),abortion history(P=0.001)and premature birth history(P=0.002).Most pregnant women believed that sex during pregnancy caused damage to the fetus(67.7%).A decrease in the intensity of sexual desire was reported in 63%of pregnant women.More than 60%of the subjects did not consult with doctors and midwives with regards to sexual issues(63.5%).The most common reason for not consulting was not feeling the need(32%).Most women experienced back pain during(42.8%)and after(39.8%)intercourse.Conclusions:Changes in sex life during pregnancy are often caused by the lack of sexual knowledge and the increase in misconceptions among couples,which can affect the quality of relationships.The role of education is essential.Therefore,it is suggested that by including sexual counseling along with pregnancy care,wrong beliefs and information among women will be corrected.

Epidemiological Profile of Men Who Have Sex with Men: First Data about Male Sex Workers in Central African Republic (CAR)

Objectives: Sex work is not well documented among African men. The aim of this study was to describe the epidemiological profile of men who have sex with men (MSM) and eventually to determine the proportion of sex workers (SW) among them, as well as the proportion of MSM who have been victims of gender-based violence (GBV). Material and Methods: A cross-sectional study coordinated by the Direction de la Médecine du Travail was carried out at the headquarters of the association ALTERNATIVES in Bangui Bangui from July 1 to October 31, 2021. Consenting MSM present during the study period were systematically included. Sociodemographic variables, those relating to the future vision of the activity and to GBV were collected and analyzed using Epi-Info version 7 software. Results: Forty MSM with an average age of 23 years and mainly secondary education (75.0%) were included. The vast majority of MSM were unemployed (85.0%). 45.0% had been victims of GBV and wanted to stop working as an MSM (47.5%), and almost 2/3 (65.0%) would accept another income-generating activity in exchange for the MSM. Violence was sexual (32.5%), economic (22.5%), physical (20.0%), verbal (12.5%) and psychological (12.5%). Conclusion: The MSM were mainly young, poorly educated, unemployed, and almost half were victims of GBV. The desire to change MSM activity to another income-generating activity alongside that of MSM shows that many of them are SW, workers in the informal sector. This must be taken into account in prevention activities, even if the data needs to be confirmed on a much larger sample.

Sex and racial disparities in non-alcoholic fatty liver disease-related cardiovascular events: National inpatient sample analysis (2019)

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases cardiovascular disease(CVD)risk irrespective of other risk factors.However,large-scale cardiovascular sex and race differences are poorly understood.AIM To investigate the relationship between NAFLD and major cardiovascular and cerebrovascular events(MACCE)in subgroups using a nationally representative United States inpatient sample.METHODS We examined National Inpatient Sample(2019)to identify adult hospitalizations with NAFLD by age,sex,and race using ICD-10-CM codes.Clinical and demographic characteristics,comorbidities,and MACCE-related mortality,acute myocardial infarction(AMI),cardiac arrest,and stroke were compared in NAFLD cohorts by sex and race.Multivariable regression analyses were adjusted for sociodemographic characteristics,hospitalization features,and comorbidities.RESULTS We examined 409130 hospitalizations[median 55(IQR 43-66)years]with NFALD.NAFLD was more common in females(1.2%),Hispanics(2%),and Native Americans(1.9%)than whites.Females often reported non-elective admissions,Medicare enrolment,the median age of 55(IQR 42-67),and poor income.Females had higher obesity and uncomplicated diabetes but lower hypertension,hyperlipidemia,and complicated diabetes than males.Hispanics had a median age of 48(IQR 37-60),were Medicaid enrollees,and had non-elective admissions.Hispanics had greater diabetes and obesity rates than whites but lower hypertension and hyperlipidemia.MACCE,all-cause mortality,AMI,cardiac arrest,and stroke were all greater in elderly individuals(P<0.001).MACCE,AMI,and cardiac arrest were more common in men(P<0.001).Native Americans(aOR 1.64)and Asian Pacific Islanders(aOR 1.18)had higher all-cause death risks than whites.CONCLUSION Increasing age and male sex link NAFLD with adverse MACCE outcomes;Native Americans and Asian Pacific Islanders face higher mortality,highlighting a need for tailored interventions and care.

Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.

The Ca^(2+)/CaN/ACC and cAMP/PKA/HK signal pathways are required for PBAN-mediated sex pheromone biosynthesis in Conogethes punctiferalis

Conogethes punctiferalis is a crop and fruit pest that has caused serious economic losses to agricultural production.This pest relies heavily on its sex pheromone to ensure sexual encounters and subsequent mating success.However,the molecular mechanism underlying sex pheromone biosynthesis in this species remains elusive.The present study investigated the detailed mechanism underlying PBAN-regulated sex pheromone biosynthesis in C.punctiferalis by transcriptome sequencing of the C.punctiferalis pheromone glands(PGs)and subsequent functional identification of the target genes.The results showed that female mating started from the first scotophase,and peaked at the second to fifth scotophases in accordance with the release of sex pheromones.PBAN regulated sex pheromone biosynthesis by employing Ca^(2+)and cAMP as secondary messengers,as demonstrated by RNA interference(RNAi),pharmacological inhibitors,and behavioral assays.Further investigation revealed that calcineurin(CaN)and acetyl-CoA carboxylase(ACC)were activated by PBAN/Ca^(2+)signaling,and the RNAimediated knockdown of CaN and ACC transcripts significantly reduced sex pheromone production,ultimately leading to a significantly reduced ability of females to attract males.Importantly,hexokinase(HK)was found to regulate sex pheromone biosynthesis in response to the PBAN/cAMP/PKA signaling pathway,as demonstrated by RNAi,enzyme activity,and pharmacological inhibitor assays.Furthermore,Far2 and Desaturase1 were found to participate in PBAN-regulated sex pheromone biosynthesis.Altogether,our findings revealed that PBAN regulates sex pheromone biosynthesis through the PBANR/Ca^(2+)/CaN/ACC and PBANR/cAMP/PKA/HK pathways in C.punctiferalis,which enriches our comprehension of the details of sex pheromone biosynthesis in moths.

Silencing transformer and transformer-2 in Zeugodacus cucurbitae causes defective sex determination with inviability of most pseudomales

transformer is a switch gene for sex determination in many insects, which cooperates with transformer-2 that is expressed in both sexes to regulate female differentiation, particularly in dipterans. Zeugodacus cucurbitae(Coquillett) is a very destructive pest worldwide, however, its sex determination pathway remains largely uncharacterized. Here, we show that the female sex ratio is sharply reduced with knockdown of either transformer or transformer-2 by RNA interference in early embryos of Z. cucurbitae. Most of the males grown from the embryos with transient transformer and transformer-2 suppression mated with wild-type females and produced mixed sex progeny, with one exception that produced only female progeny, and all of the few remaining males failed to mate with wild-type females and produced no progeny. The exceptional male and those males with mating failure were XX pseudomales as determined by the detection of Y chromosome-linked Maleness-on-the-Y, indicating that most XX pseudomales are not viable. The phenotypes of transformer and transformer-2 suggest that they play a key role in regulating sex determination and are required for female sexual development of Z. cucurbitae. Our results will be beneficial to the understanding of sex determination in Z. cucurbitae and can facilitate the development of genetic sexing strains for its biological control.

Gut microbiota affects the estrus return of sows by regulating the metabolism of sex steroid hormones

Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown.Results In this study,we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows.Using metagenomic sequencing data from 85 fecal samples,we identified 37 bacterial species that were significantly associated with estrus return.Normally returning sows were characterized by increased abundances of L.reuteri and P.copri and decreased abundances of B.fragilis,S.suis,and B.pseudolongum.The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome.The results were confirmed in a validation cohort.Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis.An integrated analysis of differential bacterial species,metagenome,and fecal metabolome provided evidence that normal return-associated bacterial species L.reuteri and Prevotella spp.participated in the degradation of pregnenolone,progesterone,and testosterone,thereby promoting estrogen biosynthesis.Furthermore,the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return.Conclusions An integrated analysis of differentially abundant bacterial species,metagenome,and fecal metabolome revealed the involvement of L.reuteri and Prevotella spp.in sow estrus return.These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones,suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.

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.

Changes in the adult sex ratio of six duck species breeding populations over two decades

Despite all efforts,long-term changes in the adult sex ratios of breeding duck populations are still unclear;this uncertainty is especially true for male-bias populations,which are often under the scrutiny of researchers lacking convenient results for the active protection of endangered species.Species with male-bias populations are usually strongly affected by a decline in population size that leads to a higher extinction risk.In this study,we examined our long-term data of the abundance of breeding populations in six duck species(Mallard Anas platyrhynchos,Gadwall Mareca strepera,Red-crested Pochard Netta rufina,Common Pochard Aythya ferina,Tufted Duck Aythya fuligula,and Common Goldeneye Bucephala clangula)from fishponds in South Bohemia,Czechia,between 2004 and 2022.This evidence was used to assess long-term changes in the adult sex ratio in these breeding populations and investigate the possible effects of the NAO index(North Atlantic Oscillation index)on them,indicating climate conditions in winter.We determined a long-term decrease of the proportion of females in the breeding season in two of the six examined species:Common Pochard and Red-crested Pochard,which is driven by the long-term increase in the number of males in contrast to the decreasing or stable number of females likely caused by different migration behaviours between females and males.In the case of Common Pochard,in breeding populations,we estimated 60-65%of males in the early 2000s rising to 75-80%in the early 2020s.However,we establish no significant effects linked to climate conditions of the previous winter in these species as a crucial cause of the changes of the proportion of females in the breeding population.

Knock-in of exogenous sequences based on CRISPR/Cas9 targeting autosomal genes and sex chromosomes in the diamondback moth,Plutella xylostella

Genetic pest control strategies based on precise sex separation and only releasing sterile males can be accomplished by site-specific genome editing.In the current study,we showed that the mutation of single-allele Pxfl(2)d can significantly impair the normal mating behavior and testis development in male adults of the notorious cruciferous insect pest Plutella xylostella,in addition to its known functions in the ovarian development in female adults and egg hatching.Subsequent CRISPR/Cas9-based knock-in experiments revealed that site-specific integration of an exogenous green fluorescent protein(GFP)gene into autosomal Pxfl(2)d for labelling mutants could be achieved.However,this gene is not a suitable target for GFP insertion to establish a genetically stable knock-in strain because of the severe decline in reproductive capacity.We further screened for the W-chromosome-linked and Z-chromosome-linked regions to test the knock-in efficiency mediated by CRISPR/Cas9.The results verified that both types of chromosomes can be targeted for the site-specific insertion of exogenous sequences.We ultimately obtained a homozygous knock-in strain with the integration of both Cas9 and cyan fluorescent protein(CFP)expression cassettes on a Z-linked region in P.xylostella,which can also be used for early sex detection.By injecting the sgRNA targeting Pxfl(2)d alone into the eggs laid by female adults of the Z-Cas9-CFP strain,the gene editing efficiency reached 29.73%,confirming the success of expressing a functional Cas9 gene.Taken together,we demonstrated the feasibility of the knock-in of an exogenous gene to different genomic regions in P.xylostella,while the establishment of a heritable strain required the positioning of appropriate sites.This study provides an important working basis and technical support for further developing genetic strategies for insect pest control.

The interventional effect of Polygonatum cyrtonema Hua polysaccharide on atherosclerosis in mice of different sexes

In the present study,we investigated the intervention effects of a purified Polygonatum cyrtonema polysaccharide(PCP)on high-fat diet(HFD)-induced atherosclerosis in male and female LDLr-/-mice.Results showed that HFD caused severe dyslipidemia,atherosclerotic lesions,oxidative damages and inflammation in male and female mice,and these effects seemed to be more pronounced in males than in females.However,the above variations could be dose-dependently reversed by PCP treatment,and the intervention effects on males were greater than those on females.Nuclear factor kappa-B(NF-κB),mitogen-activated protein kinase(MAPKs)and protein kinase B(Akt)are 3 pivotal signaling pathways mediating the development of atherosclerosis.Consistently,PCP was also found to significantly decrease the phosphorylation of p65,p38,extracellular-regulated kinase 1/2(ERK1/2)and Akt,and increase the protein expression of inhibitor of NF-κB(IκB)in the aortas of male and female mice induced by HFD.Taken together,these findings indicated that PCP could be effective for the prevention of atherosclerosis,and the intervention effect of PCP on male mice was more obvious than that of female mice.

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.

Three-dimensional analysis of age and sex differences in femoral head asphericity in asymptomatic hips in the United States

BACKGROUND The sphericity of the femoral head is a metric used to evaluate hip pathologies and is associated with the development of osteoarthritis and femoral-acetabular impingement.AIM To analyze the three-dimensional asphericity of the femoral head of asymptomatic pediatric hips.We hypothesized that femoral head asphericity will vary significantly between male and female pediatric hips and increase with age in both sexes.METHODS Computed tomography scans were obtained on 158 children and adolescents from a single institution in the United States(8-18 years;50%male)without hip pain.Proximal femoral measurements including the femoral head diameter,femoral head volume,residual volume,asphericity index,and local diameter difference were used to evaluate femoral head sphericity.RESULTS In both sexes,the residual volume increased by age(P<0.05).Despite significantly smaller femoral head size in older ages(>13 years)in females,there were no sex-differences in residual volume and aspherity index.There were no age-related changes in mean diameter difference in both sexes(P=0.07)with no significant sex-differences across different age groups(P=0.06).In contrast,there were significant increases in local aspherity(maximum diameter difference)across whole surface of the femoral head and all quadrants except the inferior regions in males(P=0.03).There were no sex-differences in maximum diameter difference at any regions and age group(P>0.05).Increased alpha angle was only correlated to increased mean diameter difference across overall surface of the femoral head(P=0.024).CONCLUSION There is a substantial localized asphericity in asymptomatic hips which increases with age in.While 2D measured alpha angle can capture overall asphericity of the femoral head,it may not be sensitive enough to represent regional asphericity patterns.

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 differences in the association between the muscle quality index and the incidence of depression: A cross-sectional study

BACKGROUND Depression presents significant challenges to mental health care.Although phy-sical activity is highly beneficial to mental and physical health,relatively few stu-dies have conducted on the relationship between them.AIM To investigate the association between muscle quality index(MQI)and incidence of depression.METHODS The data used in this cross-sectional study were obtained from the 2011-2014 National Health and Nutritional Examination Survey,which included informa-tion on MQI,depression,and confounding factors.Multivariable logistic regre-ssion models were employed,while taking into account the complex multi-stage sampling design.A restricted cubic spline model was utilized to investigate the non-linear relationship between the MQI and depression.Additionally,subgroup analyses were performed to identify influential factors.RESULTS The prevalence of depression in this population was 8.44%.With the adjusted model,the MQI was associated with depression in females(odds ratio=0.68,95%confidence interval:0.49-0.95)but not in males(odds ratio=1.08,95%confidence interval:0.77-1.52).Restricted cubic spline adjustment of all covariates showed a significant negative non-linear relationship between depression and the MQI in females.The observed trend indicated an 80%decrease in the risk of depression for each unit increase in MQI,until a value of 2.2.Subsequently,when the MQI exceeded 2.2,the prevalence of depression increased by 20%for every unit increase in the MQI.Subgroup analyses further confirmed that the MQI was negatively associated with de-pression.CONCLUSION The MQI was inversely correlated with depression in females but not males,suggesting that females with a higher MQI might decrease the risk of depression.

Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism

BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

Associated Factors with Early Sexual Intercourse among In-School Adolescents in Brazzaville

Background: Early sexual intercourse (ESI) is a global public health problem. In Congo, associated factors with ESI have been under-studied. Objective: To analyse factors associated with early sexual intercourse among in-school adolescents in Brazzaville. Method: A cross-sectional analytic study with three-stage random sampling was carried out from March 2 to June 2, 2022 in Brazzaville secondary and high schools. Adolescents in the selected schools were interviewed about their sexual and social behaviour, and their family and school environment. Multivariate analysis using logistic regression was used to identify factors associated with ESI. The significance level of the p-value was set at 5% and the confidence interval at 95%. Results: Of a total of 1100 adolescents surveyed, 800 (72.7%) had ESI, 98% of them were female. The main reason for early initiation of sexual intercourse was curiosity (81.8%). Non-use of condoms and multiple sexual partnerships were noted respectively in 98.7% and 68.7% of adolescents who had experienced ESI. Female gender (p Conclusion: The prevalence of ESI is high, and the factors identified in this study may help to reduce it.