Sex Expression Research Articles

Interference with sex expression, estimation of yield and bioactive compounds in bitter gourd under PGRs-induced conditions

BackgroundThe bitter gourd fruit yields are not at a desirable level due to maleness. Maleness is one of the biggest difficulties with bitter gourd, reducing fruit yields substantially. On the other hand, plant stages are the most important consideration for PGR application because of their sensitive responsiveness. Therefore, it is necessary to determine how bitter gourd plants respond to plant growth regulators, namely PGR0 (control: application of water as control treatment), PGR1 (GA3-Gibberellic acid, 100 mgL−1), PGR2 (NAA-Naphthalene acetic acid, 100 mgL−1), and PGR3 (MH- Maleic hydrazide, 100 mgL−1) at three application phases, S1: soaking of seeds; S2: four-leaf; and S3: flower bud in terms of vegetative development, male–female flower sex alteration, and fruit features including bioactive compounds.ResultsPhysiological, floral and yield characteristics of bitter gourd exposed significant changes by GA3 and MH at various stages. The number of leaves plant−1, the fresh mass of the plant, and the fresh mass of fruit and fruit dry matter content were enhanced remarkably for MH application at the seed soaking stage except for plant height and the number of branches plant−1. MH increased the number of female flowers plant−1, the number of fruits plant−1 and the yield at the 4-leaf stage of application. PGRs substantially influenced the quantity of sugar, chlorophyll, total carotenoids, protein, and water content at various phases of their application but not on ascorbic acid, TSS, or total phenol concentration.ConclusionsFor sex expression and yield attributes, 100 mgL−1 MH at the 4-leaf stage would be effective in bitter gourd. Exogenous NAA showed a considerable dual influence on plant development and antioxidant enzyme activity in bitter gourd fruits.

Life-history characteristics and historical factors are important to explain regional variation in reproductive traits and genetic diversity in perennial mosses.

Plants have evolved an unrivalled diversity of reproductive strategies, including variation in the degree of sexual vs. clonal reproduction. This variation has important effects on the dynamics and genetic structure of populations. We examined the association between large-scale variation in reproductive patterns and intraspecific genetic diversity in two moss species where sex is manifested in the dominant haploid generation and sex expression is irregular. We predicted that in regions with more frequent realized sexual reproduction, populations should display less skewed sex ratios, should more often express sex and should have higher genetic diversity than in regions with largely clonal reproduction. We assessed reproductive status and phenotypic sex in the dioicous long-lived Drepanocladus trifarius and D. turgescens, in 248 and 438 samples across two regions in Scandinavia with frequent or rare realized sexual reproduction, respectively. In subsets of the samples, we analysed genetic diversity using nuclear and plastid sequence information and identified sex with a sex-specific molecular marker in non-reproductive samples. Contrary to our predictions, sex ratios did not differ between regions; genetic diversity did not differ in D. trifarius and it was higher in the region with rare sexual reproduction in D. turgescens. Supporting our predictions, relatively more samples expressed sex in D. trifarius in the region with frequent sexual reproduction. Overall, samples were mostly female. The degree of sex expression and genetic diversity differed between sexes. Sex expression levels, regional sex ratios and genetic diversity were not directly associated with the regional frequency of realized sexual reproduction, and relationships and variation patterns differed between species. We conclude that a combination of species-specific life histories, such as longevity, overall degree of successful sexual reproduction and recruitment, and historical factors are important to explain this variation. Our data on haploid-dominated plants significantly complement plant reproductive biology.

Association Between California’s State Insurance Gender Nondiscrimination Act and Utilization of Gender-Affirming Surgery

Gender-affirming surgery is often beneficial for gender-diverse or -dysphoric patients. Access to gender-affirming surgery is often limited through restrictive legislation and insurance policies. To investigate the association between California's 2013 implementation of the Insurance Gender Nondiscrimination Act, which prohibits insurers and health plans from limiting benefits based on a patient's sex, gender, gender identity, or gender expression, and utilization of gender-affirming surgery among California residents. Population epidemiology study of transgender and gender-diverse patients undergoing gender-affirming surgery (facial, chest, and genital surgery) between 2005 and 2019. Utilization of gender-affirming surgery in California before and after implementation of the Insurance Gender Nondiscrimination Act in July 2013 was compared with utilization in Washington and Arizona, control states chosen because of geographic similarity and because they expanded Medicaid on the same date as California-January 1, 2014. The date of last follow-up was December 31, 2019. California's Insurance Gender Nondiscrimination Act, implemented on July 9, 2013. Receipt of gender-affirming surgery, defined as undergoing at least 1 facial, chest, or genital procedure. A total of 25 252 patients (California: n = 17 934 [71%]; control: n = 7328 [29%]) had a diagnosis of gender dysphoria. Median ages were 34.0 years in California (with or without gender-affirming surgery), 39 years (IQR, 28-49 years) among those undergoing gender-affirming surgery in control states, and 36 years (IQR, 22-56 years) among those not undergoing gender-affirming surgery in control states. Patients underwent at least 1 gender-affirming surgery within the study period in 2918 (11.6%) admissions-2715 (15.1%) in California vs 203 (2.8%) in control states. There was a statistically significant increase in gender-affirming surgery in the third quarter of July 2013 in California vs control states, coinciding with the timing of the Insurance Gender Nondiscrimination Act (P < .001). Implementation of the policy was associated with an absolute 12.1% (95% CI, 10.3%-13.9%; P < .001) increase in the probability of undergoing gender-affirming surgery in California vs control states observed in the subset of insured patients (13.4% [95% CI, 11.5%-15.4%]; P < .001) but not self-pay patients (-22.6% [95% CI, -32.8% to -12.5%]; P < .001). Implementation in California of its Insurance Gender Nondiscrimination Act was associated with a significant increase in utilization of gender-affirming surgery in California compared with the control states Washington and Arizona. These data might inform state legislative efforts to craft policies preventing discrimination in health coverage for state residents, including transgender and gender-diverse patients.

The proposed role of MSL-lncRNAs in causing sex lability of female poplars.

Labile sex expression is frequently observed in dioecious plants, but the underlying genetic mechanism remains largely unknown. Sex plasticity is also observed in many Populus species. Here we carried out a systematic study on a maleness-promoting gene, MSL, detected in the Populus deltoides genome. Our results showed that both strands of MSL contained multiple cis-activating elements, which generated long non-coding RNAs (lncRNAs) promoting maleness. Although female P. deltoides did not have the male-specific MSL gene, a large number of partial sequences with high sequence similarity to this gene were detected in the female poplar genome. Based on sequence alignment, the MSL sequence could be divided into three partial sequences, and heterologous expression of these partial sequences in Arabidopsis confirmed that they could promote maleness. Since activation of the MSL sequences can only result in female sex lability, we propose that MSL-lncRNAs might play a role in causing sex lability of female poplars.

Differences in genetic diversity and reproductive performance of a moss, a leafy liverwort, and a thalloid liverwort from forests of contrasting ages

Two competing predictions regarding highly dispersible clonal plants, such as bryophytes, expect levels of genetic diversity to either increase or decrease over time following a disturbance that opens habitat for colonization. Following up on previous research that found higher levels of genetic variation in bryophytes from relatively undisturbed forest sites, we examined unisexual, haploid species of a moss (Plagiomnium ciliare), a leafy liverwort (Porella platyphylloidea), and a thalloid liverwort (Conocephalum conicum sensu lato) from the Mountains, Piedmont, and Coastal Plain of the southeastern United States. In terms of time since last disturbance, sites were ranked Mountains > Piedmont > Coastal Plain. Measures of genetic variation, including percentage of loci polymorphic, mean number of alleles per locus, mean expected heterozygosity, and number of multilocus genotypes, all fit the prediction that genetic diversity should increase over time. We also examined several components of reproductive success expected to influence levels of genetic variation, including colony size, colony mixing, sex expression, phenotypic sex ratio, and sporophyte production (percentage of females producing sporophytes). Most, but not all, of our predictions for populations of varying time since last disturbance were fulfilled, although other ecological differences related to soil, climate, and vegetation are also likely to influence reproductive success.

Molecular mapping of genomic regions and identification of possible candidate genes associated with gynoecious sex expression in bitter gourd

Bitter gourd is an important vegetable crop grown throughout the tropics mainly because of its high nutritional value. Sex expression and identification of gynoecious trait in cucurbitaceous vegetable crops has facilitated the hybrid breeding programme in a great way to improve productivity. In bitter gourd, gynoecious sex expression is poorly reported and detailed molecular pathways involve yet to be studied. The present experiment was conducted to study the inheritance, identify the genomic regions associated with gynoecious sex expression and to reveal possible candidate genes through QTL-seq. Segregation for the gynoecious and monoecious sex forms in the F2 progenies indicated single recessive gene controlling gynoecious sex expression in the genotype, PVGy-201. Gynoecious parent, PVGy-201, Monoecious parent, Pusa Do Mausami (PDM), and two contrasting bulks were constituted for deep-sequencing. A total of 10.56, 23.11, 15.07, and 19.38 Gb of clean reads from PVGy-201, PDM, gynoecious bulk and monoecious bulks were generated. Based on the ΔSNP index, 1.31 Mb regions on the chromosome 1 was identified to be associated with gynoecious sex expression in bitter gourd. In the QTL region 293,467 PVGy-201 unique variants, including SNPs and indels, were identified. In the identified QTL region, a total of 1019 homozygous variants were identified between PVGy1 and PDM genomes and 71 among them were non-synonymous variants (SNPS and INDELs), out of which 11 variants (7 INDELs, 4 SNPs) were classified as high impact variants with frame shift/stop gain effect. In total twelve genes associated with male and female gametophyte development were identified in the QTL-region. Ethylene-responsive transcription factor 12, Auxin response factor 6, Copper-transporting ATPase RAN1, CBL-interacting serine/threonine-protein kinase 23, ABC transporter C family member 2, DEAD-box ATP-dependent RNA helicase 1 isoform X2, Polygalacturonase QRT3-like isoform X2, Protein CHROMATIN REMODELING 4 were identified with possible role in gynoecious sex expression. Promoter region variation in 8 among the 12 genes indicated their role in determining gynoecious sex expression in bitter gourd genotype, DBGy-1. The findings in the study provides insight about sex expression in bitter gourd and will facilitate fine mapping and more precise identification of candidate genes through their functional validation.

LGBTQ+ Bullying and Cyberbullying: Beyond Sexual Orientation and Gender Identity

ABSTRACT LGBTQ+ bullying has a serious impact on young people’s well-being. Many studies have analyzed this phenomenon in terms of the sexual orientation and/or gender identity of the victim, or taking just homophobic aggression into account. This view over-simplifies and limits our understanding of the phenomenon. The present study analyzes, exhaustively, in 2552 adolescents, the prevalence of both general and LGBTQ+ bullying and cyberbullying in accordance with age, assigned sex, gender identity, sexual orientation and gender expression. The results highlight the need to avoid general approaches and to consider the full spectrum of Affective-Sexual, Bodily, and Gender Diversity, given the differences that exist in the risk of victimization and cybervictimization among LGBTQ+ students. They also underscore the importance of taking these differences into consideration in order to design effective prevention and intervention strategies.

Influence of location-dependent sex difference on PD-L1, MMR/MSI, and EGFR in colorectal carcinogenesis.

The incidence and mortality rates of colorectal cancer (CRC) has been reported to be strongly associated to sex/gender difference. CRC shows sexual dimorphism, and sex hormones have been shown to affect the tumor immune microenvironment. This study aimed to investigate location-dependent sex differences in tumorigenic molecular characteristics in patients with colorectal tumors, including adenoma and CRC. A total of 231 participants, including 138 patients with CRC, 55 patients with colorectal adenoma, and 38 healthy controls, were recruited between 2015 and 2021 at Seoul National University Bundang Hospital. All patients underwent colonoscopy and acquired tumor lesion samples were further analyzed for programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) expression, deficient mismatch repair (dMMR), and microsatellite instability (MSI) status. This study was registered with ClinicalTrial.gov, number NCT05638542. The average of combined positive score (CPS) was higher in serrated lesions and polyps (lesions/polyps) compared to conventional adenomas (5.73 and 1.41, respectively, P < 0.001). No significant correlation was found between sex and PD-L1 expression within the groups, regardless of histopathological diagnosis. In multivariate analysis where each sex was further stratified by tumor location due to their interaction in CRC, PD-L1 expression was inversely correlated with males having proximal CRC with a CPS cutoff of 1 (Odds ratio (OR) 0.28, P = 0.034). Females with proximal CRC showed a significant association with dMMR/MSI-high (OR 14.93, P = 0.032) and high EGFR expression (OR 4.17, P = 0.017). Sex and tumor location influenced molecular features such as PD-L1, MMR/MSI status and EGFR expression in CRC, suggesting a possible underlying mechanism of sex-specific colorectal carcinogenesis.

Sex Determination and the Human Person

Abstract: For many species that reproduce sexually, how sex is expressed at different points across lifespan is highly contingent and dependent on various environmental factors. For example, in many species of fish, environmental cues can trigger a natural process of sex transition where a female transitions to male. For many species of turtle, incubation temperature influences the likelihood that turtle eggs will hatch males or females. What is the case for Homo sapiens? Is human sex expression influenced by contingent environmental factors like we see in fish and turtles, with whom we share common ancestry and DNA? Our paper explores the current biological science of sex determination and how it applies to philosophical and theological accounts of the human person. We argue that while human sex determination is not susceptible to environmental cues to the same degree we see in other species, there is sufficient variability among the pathways of human sex development to complicate simplistic biological categories of male and female.

Sporophyte frequency in British dioicous liverworts

ABSTRACT Introduction The extent and causes of variation in sporophyte production among British dioicous liverworts are assessed. Methods Reproductive attributes of dioicous species are taken from Paton’s The Liverwort Flora of the British Isles (1999). The extent to which sporophyte production is potentially restricted by low levels of sex expression, unbalanced phenotypic sex ratios, and probable spatial segregation of the sexes, is quantified. Patterns of variation in sexual reproduction are also characterised for species associated with different biogeographical zones in Europe. Results Of the 188 British liverwort species that are dioicous (62%), sporophytes are unknown in 65, rare in 58, occasional in 50 and frequent in 15. Some species are not or rarely sexually reproductive, but major causes of restricted sexual reproduction are sexual imbalance and probable isolation of the sexes. Among species with skewed sex ratios, female bias is substantially more common than male bias. Sporophyte frequency is relatively high among species widely distributed in temperate and boreal Europe, compared with taxa associated with other climatic zones, including the oceanic fringe. Conclusions Restricted sporophyte production implies that asexual reproduction and clonal longevity are critical for the persistence of many liverworts. Further insights will require field surveys of patterns of sex expression and sporophyte distribution, together with information on reproductive plasticity, genotypic sex ratios, and levels of genetic diversity and structure.

Substrain differences in Sry expression at the stage of sex determination in C57BL/6 mouse strains.

The expression of sex determining region of the Y chromosome (Sry) in the fetal gonads is important for male development. In a mouse model of disorders of sex development (C57BL/6 (B6)-XYPOS), the gonadal phenotype and the timing of Sry expression differ due to differences among B6 substrains as the genetic background. Since differences in Sry expression among B6 substrains have been speculated, the present study examined Sry expression in B6J, B6JJmsSlc, and B6NCrl mice. These substrains differed in the number of Sry-expressing cells in the gonads of embryonic mice at each developmental stage, with B6NCrl having more than the other strains. The substrains differed also in the number of Sry-expressing cells between the left and right gonads, with B6J and B6NCrl, but not B6JJmsSlc, showing left gonad-dominant Sry expression. Substrain differences existed also in the distribution of Sry-expressing cells in the medial and lateral directions of gonads. In addition, in the left gonad-dominant Sry-expressing substrains B6J and B6NCrl, the medial and central regions of the left gonad had more Sry-expressing cells than those of the right gonad. Substrains of B6 mice have not always been considered in sex differentiation studies. In the present study, however, we observed substrain differences in the number of Sry-expressing cells, left-right distribution, and medial/lateral distribution during the early stages of gonadal development in B6 mice. Therefore, future studies on sex differentiation in B6 mice should consider substrain differences.

Vegetative Growth Characteristics and Flower Sex Expression of Cucumis sativus Affected by Exogenous Application of Plant Growth Regulators

Vegetative Growth Characteristics and Flower Sex Expression of Cucumis sativus Affected by Exogenous Application of Plant Growth Regulators

Activation of cGAS-STING Pathway Is Associated with MSI-H Stage IV Colorectal Cancer

Colorectal cancer is the second most common cause of cancer-related mortality in adults. Understanding colorectal tumorigenesis at both the cellular and molecular levels is crucial for developing effective treatment options. Forty-one biopsy samples from patients with metastatic CRC (mCRC) were collected at Split University Hospital in Croatia. A total of 41 patients (21 with microsatellite unstable tumours and 20 with microsatellite stable tumours) were randomly included in the study. Immunolabelling of cGAS and STING in metastatic CRC was performed and further complemented by histological classification, tumour grade, and KRAS, NRAS, and BRAF mutational status of mCRC. In bivariate analysis, elevated expression of cGAS and STING was positively associated with MSI-H colon cancer (Fisher's exact test, both p = 0.0203). Combined expression analysis of cGAS and STING showed a significantly higher percentage of patients with mCRC MSI-H with a fully or partially activated cGAS-STING signalling pathway (chi-square test, p = 0.0050). After adjusting for age, sex, and STING expression, increased cGAS expression remained significantly associated with MSI-H colon cancer in a multiple logistic regression model (β = 1.588, SE = ±0.799, p = 0.047). The cGAS-STING signalling axis represents a compelling new target for optimization of immune checkpoint inhibitor therapeutic approaches in patients with MSI-H stage IV CRC.

Diversity and similarity of melon (Cucumis melo L.) groups and determination of distinguishing morphological characters

Abstract. Saputra HE, Syukur M, Suwarno WB, Sobir. 2022. Diversity and similarity of melon (Cucumis melo L.) groups and determination of distinguishing morphological characters. Biodiversitas 23: 6254-6261. Characterization is an important activity for the study of genotype diversity and similarity. The study was aiming at obtaining information about the diversity and similarity of melon groups and to determine morphological characters as differentiators between melon groups. The genotypes tested were IPB240, IPB283, IPBM21, IPBM23, IPBME5, IPBMETA9, UME20, UME38, UME39, UME90, UME91, UME98, UME99, UME100, UME101. Characterization was based on UPOV and IPGRI guidelines for qualitative and quantitative characters. Two qualitative characters showed no variation in all tested genotypes, namely sex expression (EK) and secondary skin color outside the groove (WKSDA). Qualitative characters that have high diversity were groove color (WA), maximum width between grooves (LMAA), groove color intensity (IWA), and flower stalk thickness (KTBN). The UME98 genotype had the most different color appearance from the other genotypes on the heatmap. The color and depth of fruit grooves are distinguishing characteristics of all genotypes. There were genotype differences in the inodorus and reticulatus types. Unlike the IPBMETA9 genotype, UME100, UME101, and UME38 formed the same clusters with the characteristics of the makuwa group. Melon group makuwa had different characteristics with the inodorus and reticulatus groups. The distinguishing characters for the makuwa type were groove depth, ratio length to diameter, the diameter of hermaphrodite flower stalks, fruit diameter, and fruit skin thickness. Melon groups in the inodorus and reticulatus groups had high similarities, making it difficult to find specific characters in all melon genotypes observed.

Response of cucumber (Cucumis sativus L. Cv. Bhaktapur local) to the application of plant growth regulators in plastic tunnel

The field experiment was conducted to know the yield performance of cucumber var. Bhaktapur Local with the application of plant growth regulators (PGRs) in the farmers’ field of Lamjung, Nepal during September to November, 2013. Five treatments (Four PGRs; NAA @10 ppm, GA3 @ 50ppm, GA3 @100ppm, MH@ 60ppm and distilled water as control) were replicated six times under walk-in plastic tunnel. The experiment was laid out in randomized complete block design. The first 30 flowers of each plant were used for the observation. PGRs were sprayed in 2-4 true leaf stage of seedling, 20 days after first spray and 10 days after second spray. The research revealed that NAA @ 10 ppm had higher effect in sex expression, fruit set and yield than rest of the treatments. GA3 @ 100 ppm had significantly higher number of male flowers and more vine growth than other treatments. Branch per plant was obtained as the highest with MH @60 ppm followed by NAA @10 ppm. The marketable fruit yield was significant with NAA @10 ppm followed by MH@ 60 ppm, GA3 @50 ppm, GA3 @100 ppm than control. It is concluded that thermo-sensitive variety of cucumber Bhaktapur Local can be grown with the use of plant growth regulators particularly, NAA@ 10 ppm, under walk-in plastic tunnels during the autumn-winter season in the mid hills of Nepal. The research further indicated that cucumber can be a profitable and a potential agriculture enterprise for the area.

Life-history traits and density dependence in metapopulations of a tropical moss: a monoicous species that is almost dioicous.

Life-history traits, such as reproductive allocation, sexual expression, sex ratio, and reproductive success, are central aspects of a species' ecology and evolution. For example, bias in male and female sex expression may play a large role in determining the viability of populations in the face of environmental pressures, such as population fragmentation, climate change and habitat occupancy. Thus, in this study, we investigated reproductive traits in 10 meta-populations of Fissidens flaccidus Mitt. From each meta-population, 30 patches were randomly selected, and 1 cm2 samples were collected form each patch. A total of 20,173 ramets were analyzed and classified into male, non-sporophytic female, sporophytic female, and non-sex expressing. In addition, population density in each patch was quantified. Our results showed that relative reproductive allocation in perigonia and sporophytes is greater than perichaetia. Trade-off between sexual relative reproductive allocation and asexual gemma production was observed, suggesting an important role of female ramets in asexual reproduction. The number of male ramets does not influence the reproductive success observed in each patch, and ramet density may induce male sex expression. Thus, we concluded that reproductive allocation in male function is efficient, since fewer male ramets can assure a considerable reproductive success. Furthermore, our results suggest that there may be a habitat preference between the sexes, since male ramets are found in patches with high density and mostly below female ramets, suggesting an avoidance of direct sunlight by male ramets.

Homophobic Bullying as Gender Policing: Population-Based Evidence

Although the policing of gendered embodiment is central to ethnographic accounts of sexual minority bullying, data limitations have prevented population-level analyses of how gender expression shapes bullying victimization. Using novel data on gender expression, I document the dynamics of gender policing in contemporary American high schools. Analyzing population-representative surveys from eight states and 10 school districts, I examine how students’ assigned sex, sexual identity, and gender expression intersectionally shape their risk for bullying. Consistent with patterns of cultural sexism that stigmatize male “femininity” more harshly than female “masculinity,” I find that gender expression powerfully stratifies bullying among boys but is seemingly unrelated to bullying for girls. Boys who report feeling seen as “very feminine” are 3.5 times more likely to be bullied than their “very masculine” peers. By contrast, girls’ bullying rates are roughly constant across the gender expression spectrum. Stratifying by sexuality, I find that highly conforming gender expression offers some protection against bullying for sexual minority boys but no protection for sexual minority girls. This study illustrates the value of gradational measures of gendered embodiment and makes newly visible the powerful sanctions pressuring boys into narrow, heteronormative enactments of masculinity.

Candidate gene based SSR and SNP markers for gynoecy in bitter gourd (Momordica charantia L.).

Even though the bitter gourd hybrids are shown to have significant heterosis for many of the economic traits, processes such as manual bagging and hand pollination make the hybrid seed production labour-intensive. Use of gynoecious line as female parent makes hybrid seed production more economical. This work was performed with the objective to identify the candidate gene based molecular markers for gynoecy in bitter gourd. Seven putative genes for flowering and sex expression, isolated from the monoecious (MC-136) and gynoecious (KAU-MCGy-101) bitter gourd accessions, were sequence characterized. MADS-box transcription factor genes AG6 and McAG2 had nucleotide polymorphisms at five sites each and were potential candidates for marker development. An In/Del polymorphism of 48bp ([TC]24) in AG6 gene was used to develop an SSR marker and a transition mutation of [A/G] in this gene was used to develop a set of SNP markers. These markers have developed distinct polymorphism between the monoecious and gynoecious genotypes and were found suited for the marker assisted selection. MADS box transcription factor genes AG6 and McAG2 are identified as candidates for sex expression in bitter gourd. Based on the InDels and transition in the intronic region of AG6, SSR marker BGAG6 and an SNP marker set segregating with the sex forms were developed. The markers have been validated using four other monoecious lines and are routinely used in our bitter gourd hybrid seed production programmes.

FOXC2 as a prognostic marker and a potential molecular target in patients with human solid tumors.

Forkhead Box Protein C2 (FOXC2) belongs to the Forkhead/Wing-helix family. The regulatory role of this transcription factor in physiological function and carcinogenic activity has been proven in subsequent investigations. However, there is still scarcity of evidence on the relationship between FOXC2 expression and prognosis in human solid tumors. We conducted this meta-analysis to evaluate the role of FOXC2 as a prognosis factor and a possible target marker in human solid tumors. PubMed, Web of Science, Embase, and the Cochrane library database were all searched methodically. Eligible publications on FOXC2 in human solid tumors were gathered and reviewed. The effect sizes were calculated using pooled hazard ratios (HRs) or odds ratios (ORs) with the corresponding 95% confidence interval (CI). Statistical analysis was conducted with Stata SE12.0. This meta-analysis comprised 3,267 patients from 20 studies covering a variety of solid tumors. Increased FOXC2 expression was related to shorter overall survival (OS) (HR = 2.05, 95% CI: 1.73-2.42). High expression of FOXC2 is associated with lymph node metastases (OR = 3.33, 95% CI: 2.65-4.19), TNM stage (OR = 3.09, 95% CI: 2.00-4.78), and age (OR = 1.26, 95% CI: 1.06-1.50), according to the pooled ORs. However, no significant association was observed between the high expression of FOXC2 and sex, tumor size or tumor differentiation. Increased expression of FOXC2 is associated with unfavored OS, lymph node metastases, TNM stage, and age. FOXC2 is a promising prognostic marker and a novel target marker in human solid tumors.

Chromosomal and gonadal sex drive sex differences in lipids and hepatic gene expression in response to hypercholesterolemia and statin treatment

BackgroundBiological sex impacts susceptibility and presentation of cardiovascular disease, which remains the leading cause of death for both sexes. To reduce cardiovascular disease risk, statin drugs are commonly prescribed to reduce circulating cholesterol levels through inhibition of cholesterol synthesis. The effectiveness of statin therapy differs between individuals with a sex bias in the frequency of adverse effects. Limited information is available regarding the mechanisms driving sex-specific responses to hypercholesterolemia or statin treatment.MethodsFour Core Genotypes mice (XX and XY mice with ovaries and XX and XY mice with testes) on a hypercholesteremic Apoe–/– background were fed a chow diet without or with simvastatin for 8 weeks. Plasma lipid levels were quantified and hepatic differential gene expression was evaluated with RNA-sequencing to identify the independent effects of gonadal and chromosomal sex.ResultsIn a hypercholesterolemic state, gonadal sex influenced the expression levels of more than 3000 genes, and chromosomal sex impacted expression of nearly 1400 genes, which were distributed across all autosomes as well as the sex chromosomes. Gonadal sex uniquely influenced the expression of ER stress response genes, whereas chromosomal and gonadal sex influenced fatty acid metabolism gene expression in hypercholesterolemic mice. Sex-specific effects on gene regulation in response to statin treatment included a compensatory upregulation of cholesterol biosynthetic gene expression in mice with XY chromosome complement, regardless of presence of ovaries or testes.ConclusionGonadal and chromosomal sex have independent effects on the hepatic transcriptome to influence different cellular pathways in a hypercholesterolemic environment. Furthermore, chromosomal sex in particular impacted the cellular response to statin treatment. An improved understanding of how gonadal and chromosomal sex influence cellular response to disease conditions and in response to drug treatment is critical to optimize disease management for all individuals.