Discussion comments on "Exponentiated Teissier distribution with increasing, decreasing and bathtub hazard functions".

In this note, we present some discussion comments on a note entitled 'A note on the unimodality and log-concavity of the exponentiated Teissier distribution' submitted in J. Appl. Stat. by some authors, about the paper by Sharma et al. (Exponentiated Teissier distribution with increasing, decreasing and bathtub hazard functions, J. Appl. Stat. 49 (2022), pp. 371-393).

Antibody conjugated targeted nanotherapy epigenetically inhibits calpain-mediated mitochondrial dysfunction to attenuate Parkinson's disease.

Many neurodegenerative and psychiatric malignancies like Parkinson' disease (PD) originate from an imbalance of 17ß-Estradiol (E2) in the human brain. However, the peripheral side effects of the usage of E2 for PD therapy and less understanding of the molecular mechanism hinder establishing its neurotherapeutic potential. In the present work, systemic side effects were overcome by targeted delivery using Dopamine receptor D3 (DRD3) conjugated E2-loaded chitosan nanoparticles (Ab-ECSnps) that showed a promising delivery to the brain. E2 is a specific calpain inhibitor that fosters neurodegeneration by disrupting mitochondrial function, while B-cell-specific Moloney murine leukemia virus integration region 1 (BMI1), an epigenetic regulator, is crucial in preserving mitochondrial homeostasis. We showed the administration of Ab-ECSnps inhibits calpain's translocation into mitochondria while promoting the translocation of BMI1 to mitochondria, thereby conferring neurotherapeutic benefits by enhancing cell viability, increasing mitochondrial DNA copy number, and preserving mitochondrial membrane potential. Further, we showed a novel molecular mechanism of BMI1 regulation by calpain that might contribute to maintaining mitochondrial homeostasis for attenuating PD. Concomitantly, Ab-ECSnps showed neurotherapeutic potential in the in vivo PD model. We showed for the first time that our brain-specific targeted delivery might regulate calpain-mediated BMI1 expression, thereby preserving mitochondrial homeostasis to alleviate PD.

Trends in atmospheric water vapour over the Thar Desert during Indian Summer Monsoon period of 2003-2020.

The Thar is the most densely populated desert in the world, which supports diverse ecosystems and human endeavours such as agriculture and socioeconomic activities. Water demand and supply in the Thar play an essential role in regulating the socioeconomic activities of the region. Inland water and precipitation aid the movement of water in the Thar Desert. Precipitation in the Thar is governed by the Indian Summer Monsoon (ISM), during which the winds distribute water vapour to regulate precipitation across the region. Therefore, we analyse the water vapour, its sources and its relation with precipitation using satellite measurements and reanalysis data in the Thar during ISM. Like other regions, a clear seasonal cycle of water vapour is observed in the Thar, with very high values (> 45 kg/m2) during ISM and low in winter (< 15 kg/m2). Evapotranspiration and moisture transport have significant effects on the amount of water vapour during ISM. There is a significant increase in water vapour in the troposphere, with high trends at the surface (0.032 g/kg/year) and small at the tropopause (0.00002 g/kg/year). A significant increase in column water vapour is also estimated in the Thar during ISM, with high trends in the eastern and southern areas, at about 0.15-0.35 kg/m2/year. The rise in water vapour in the Thar can be attributed to the increase in evapotranspiration (0.03-0.07 mm/day/year) and water vapour transport (> 0.5 kg/m/s/year) from the Arabian Sea and Indian Ocean. The rise in water vapour can lead to an increase in precipitation in the Thar, as it shows significant positive trends (0.05-0.1 mm/day/year) in the eastern areas during ISM. The increase in precipitation and water vapour in the arid Thar Desert can have significant implications for the regional environment and agriculture.

Developing and validating a tool for assessing the confidence in the competence of midwifery tutors in India on WHO core competency domains.

Negligible quantitative research evidence exists on standardisation and psychometric validation of questionnaires that measure midwifery educators' confidence in their competence. This study developed a self-assessment of confidence in competence questionnaire in India based on the WHO Midwifery Educator Core Competencies (2014) with an aim to develop and validate a self-assessment tool measuring midwifery tutors' confidence in competence in imparting quality midwifery education. The questionnaire was developed as part of a multi-centre study to identify confident midwifery tutors for further training as educators, supporting India's rollout of professional midwives. The questionnaire underwent rigorous psychometric testing among 2016 midwifery tutors in India. Following exploratory Principal Component Analyses (PCA), the nine core competencies outlined in the WHO document were analysed separately. The results indicate that the questionnaire is psychometrically valid, with an internal consistency range of 0.81-0.93 for the nine domains. This robust testing process ensures the reliability and validity of the questionnaire. The self-assessment questionnaire can potentially be a valuable tool in India and other high-, middle-, and low-income countries. From a programmatic perspective, it can help identify key gaps and prioritise training needs, particularly in low-resource settings, so that limited resources are best utilised to fill the most prominent gaps. Furthermore, it can provide a universal platform for comparing data from different settings, facilitating global collaboration and learning in midwifery education.

An in vitro model of adipose tissue-associated macrophages.

Obesity-related chronic low-grade inflammation plays a central role in the development of insulin resistance. Macrophages are key players in adipose tissue homeostasis, and their phenotypic shift from the anti-inflammatory or alternatively activated (M2) form to the pro-inflammatory, classically activated (M1) form is a hallmark of insulin resistance. However, adipose tissue macrophages (ATMs) have been identified as a distinct subpopulation of macrophages in several recent studies. These ATMs, described as metabolically activated macrophages (MMe), differ from M1 and are primarily found in the adipose tissue of obese individuals. In our study, we developed an in vitro model of MMe macrophages to establish a simple and reproducible system to understand their characteristics and role in the pathophysiology of insulin resistance. We examined their characteristics such as inflammatory patterns, surface markers, and metabolic features, and compared them with M1 and M2 macrophages. We found that a cell line-based in vitro model effectively mirrors the characteristics of ATMs, highlighting distinct inflammatory phenotypes, metabolism, surface markers, altered lysosomal activity, and ER stress akin to macrophages in vivo. This model captures the subtle distinctions between MMe and M1, and can be effectively used to study several features of macrophage-adipose interactions of therapeutic importance.

Navigating the complexities of a forgotten double J stent.

Double-J (DJ) stents are most commonly used urological tools these days. Serious complications may occur when stents are left in place for longer duration. We present a case of a woman in her 40s with a forgotten DJ stent for 4 years, leading to complications such as encrustations, bladder and renal stone formation. The patient underwent a comprehensive endourological approach, including endoscopic cystolithotomy and left-sided percutaneous nephrolithotomy. The case highlights the importance of timely stent removal to prevent complications such as encrustations and stone formation. Patient education and counselling are crucial to avoid poor compliance and the associated risks of forgotten stents. This case underscores the significance of a multidisciplinary approach and emphasises the need for proactive measures to prevent such complications, including the implementation of a stent placement registry.

Hyperandrogenemia elevates expression of apelin and apelin receptor protein in the mice pituitary.

Hyperandrogenemia is associated with polycystic ovarian syndrome (PCOS) and imbalances in the pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Apelin and its receptor, APJ (class A, rhodopsin-like G- protein-coupled receptor), belongs to adipokines, and its expression has been shown in the pituitary. It is also well known that, hyperandrogenism and PCOS have deregulation of different adipokines. Whether hyperandrogenism also deregulates the apelin system in the pituitary has yet to be investigated. Thus, we have investigated the expression and localization of apelin and its receptor, APJ, in the letrozole-induced hyperandrogenised pituitary of female mice. Our results showed that the apelin, APJ and androgen receptor (AR) expression were upregulated in the anterior pituitary. Furthermore, the immunostaining of LH exhibited increased abundance than FSH. The circulating LH was also found to be elevated compared to FSH levels. The increased LH synthesis and secretion coincides with elevated apelin system in the pituitary of hyperandrogenised mice. Recently, a direct role of apelin has also been reported in the female pituitary, where apelin inhibits LH secretion. Thus, apelin could be one of the factors for deregulated gonadotropin secretion in hyperandrogenised conditions. However, more research is needed to fully understand the complex interactions between apelin and androgen regarding gonadotropin secretion in hyperandrogenised conditions.

SpeedyPaddy: a revolutionized cost-effective protocol for large scale offseason advancement of rice germplasm.

BACKGROUND: Improving the rate of genetic gain of cereal crop will rely on the accelerated crop breeding pipelines to allow rapid delivery of improved crop varieties. The laborious, time-consuming traditional breeding cycle, and the seasonal variations are the key factor restricting the breeder to develop new varieties. To address these issues, a revolutionized cost-effective speed breeding protocol for large-scale rice germplasm advancement is presented in the present study. The protocol emphasises on optimizing potting material, balancing the double-edged sword of limited nutritional dose, mode and stage of application, plant density, temperature, humidity, light spectrum, intensity, photoperiod, and hormonal regulation to accelerate rice growth and development. RESULTS: The plant density of 700 plants/m2, cost-effective halogen tubes (B:G:R:FR-7.0:27.6:65.4:89.2) with an intensity of ∼ 750-800 µmol/m2/s and photoperiod of 13 h light and 11 h dark during seedling and vegetative stage and 8 h light and 16 h dark during reproductive stage had a significant effect (P < 0.05) on reducing the mean plant height, tillering, and inducing early flowering. Our results confirmed that one generation can be achieved within 68-75 days using the cost-effective SpeedyPaddy protocol resulting in 4-5 generations per year across different duration of rice varieties. The other applications include hybridization, trait-based phenotyping, and mapping of QTL/genes. The estimated cost to run one breeding cycle with plant capacity of 15,680 plants in SpeedyPaddy was $2941 including one-time miscellaneous cost which is much lower than the advanced controlled environment speed breeding facilities. CONCLUSION: The protocol offers a promising cost-effective solution with average saving of 2.0 to 2.6 months per breeding cycle with an integration of genomics-assisted selection, trait-based phenotyping, mapping of QTL/genes, marker development may accelerate the varietal development and release. This outstanding cost-effective break-through marks a significant leap in rice breeding addressing climate change and food security.

Effects of chronic CuNPs treatment followed by termination for two spermatogenic cycles in the testicular functions of mice.

The present study investigated the possible effects of copper nanoparticles (CuNPs) after discontinuing treatment on testicular activity in a mouse model. The male mice were given continuous CuNPs treatment for 70 days and left untreated for 70 days. The results show that even after the discontinuation of CuNPs treatment, the testicular impairment was persistent till 140 days at a higher dose (200 mg/kg group). The spermatogenesis, sperm parameters, proliferation and antioxidant status were suppressed in the higher dose groups. However, these effects were also observed at moderate levels in the other CuNPs treated groups, such as at 10 mg/kg and 100 mg/kg. The apoptosis was stimulated at a higher dose compared to the other groups. The testosterone, LH levels and AR expression were suppressed in all the CuNPs treated groups, along with slight elevation in the estrogen levels and up-regulated ERß expression. The fertility data also showed a decline in all CuNPs treated groups with the lowest litter size in the 200 mg/kg treated group. Despite testis, epididymis and accessory sex organs like prostate, seminal vesicle, and vas deferens, histoarchitecture also showed impairment. This is the first report on how CuNPs affect the male reproductive system in mice even after treatment was terminated. The current study also demonstrated possible negative effects on male reproductive function that might last for longer at higher dosages of chronic CuNPs exposure even after termination.

Ellagic acid mitigates heat-induced testicular detriment in a mouse model.

Heat stress has been shown to have a detrimental impact on testicular activity and spermatogenesis. Ellagic acid is a plant-derived organic compound that has a variety of biological functions. Thus, it is believed that ellagic acid may improve heat-stressed testicular dysfunction. There has been no research on the impact of ellagic acid on heat-stressed testicular dysfunction. The mice were divided into 4 groups. The first group was the normal control group (CN), and the second received heat stress (HS) by submerging the lower body for 15 min in a water bath with a thermostatically controlled temperature kept at 43°C (HS), and the third and fourth groups were subjected to heat-stress similar to group two and given two different dosages of ellagic acid (5 mg/kg (EH5) and 50 mg/kg (EH50) for 14 days. Ellagic acid at a dose of 50 mg/kg improved the level of circulating testosterone (increased 3ßHSD) and decreases the oxidative stress. The testicular and epididymal architecture along with sperm parameters also showed improvement. Ellagic acid treatment significantly increases the germ cell proliferation (GCNA, BrdU staining) and Bcl2 expression and decreases active caspase 3 expression. Heat stress downregulated the expression of AR, ER-α and ER-ß, and treatment with ellagic acid increased the expression of ER-α and ER-ß markers in the 50 mg/kg treatment group. Thus, our finding suggests that ellagic acid ameliorates heat-induced testicular impairment through modulating testosterone synthesis, germ cell proliferation, and oxidative stress. These effects could be manifested by regulating androgen and estrogen receptors. However, the two doses showed differential effects of some parameters, which require further investigation.

Integrating machine learning and geospatial data analysis for comprehensive flood hazard assessment.

Flooding is a major natural hazard worldwide, causing catastrophic damage to communities and infrastructure. Due to climate change exacerbating extreme weather events robust flood hazard modeling is crucial to support disaster resilience and adaptation. This study uses multi-sourced geospatial datasets to develop an advanced machine learning framework for flood hazard assessment in the Arambag region of West Bengal, India. The flood inventory was constructed through Sentinel-1 SAR analysis and global flood databases. Fifteen flood conditioning factors related to topography, land cover, soil, rainfall, proximity, and demographics were incorporated. Rigorous training and testing of diverse machine learning models, including RF, AdaBoost, rFerns, XGB, DeepBoost, GBM, SDA, BAM, monmlp, and MARS algorithms, were undertaken for categorical flood hazard mapping. Model optimization was achieved through statistical feature selection techniques. Accuracy metrics and advanced model interpretability methods like SHAP and Boruta were implemented to evaluate predictive performance. According to the area under the receiver operating characteristic curve (AUC), the prediction accuracy of the models performed was around > 80%. RF achieves an AUC of 0.847 at resampling factor 5, indicating strong discriminative performance. AdaBoost also consistently exhibits good discriminative ability, with AUC values of 0.839 at resampling factor 10. Boruta and SHAP analysis indicated precipitation and elevation as factors most significantly contributing to flood hazard assessment in the study area. Most of the machine learning models pointed out southern portions of the study area as highly susceptible areas. On average, from 17.2 to 18.6% of the study area is highly susceptible to flood hazards. In the feature selection analysis, various nature-inspired algorithms identified the selected input parameters for flood hazard assessment, i.e., elevation, precipitation, distance to rivers, TWI, geomorphology, lithology, TRI, slope, soil type, curvature, NDVI, distance to roads, and gMIS. As per the Boruta and SHAP analyses, it was found that elevation, precipitation, and distance to rivers play the most crucial roles in the decision-making process for flood hazard assessment. The results indicated that the majority of the building footprints (15.27%) are at high and very high risk, followed by those at very low risk (43.80%), low risk (24.30%), and moderate risk (16.63%). Similarly, the cropland area affected by flooding in this region is categorized into five risk classes: very high (16.85%), high (17.28%), moderate (16.07%), low (16.51%), and very low (33.29%). However, this interdisciplinary study contributes significantly towards hydraulic and hydrological modeling for flood hazard management.

Morin hydrate ameliorates Di-2-ethylhexyl phthalate (DEHP) induced hepatotoxicity in a mouse model via TNF-α and NF-κß signaling.

Di-(2-ethylhexyl) phthalic acid (DEHP) pollutes the environment, and posing a significant risk to human and animal health. Consequently, a successful preventative strategy against DEHP-induced liver toxicity needs to be investigated. Morin hydrate (MH), a flavanol compound, possesses toxic preventive attributes against various environmental pollutants. However, the effects of MH have not been investigated against DEHP-induced liver toxicity. Female Swiss albino mice were divided into four groups: control, DEHP (orally administered with 500 mg/kg, DEHP plus MH 10 mg/kg, and DEHP plus MH 100 mg/kg for 14 days. The results showed that the MH treatment ameliorated the DEHP-induced liver dysfunctions by decreasing the alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin, liver histoarchitecture, fibrosis, and markers of oxidative stress. Furthermore, DEHP increased apoptosis, increased active caspase 3 and decreased B cell lymphoma-2 (Bcl-2) expression. However, the MH treatment showed a differential effect on these proteins; a lower dose increased, and a higher dose decreased the expression. Thus, a lower dose of MH could be involved in the disposal of damaged hepatocytes. Expression of Estrogen receptors alpha (ERα) also showed a similar trend with active caspase 3. Furthermore, the expression of Tumor necrosis factor alpha (TNF-α) and Nuclear factor-κß (NF-κß) were up-regulated by DEHP treatment, and MH treatment down-regulated the expression of these two inflammatory markers. Since this down-regulation of TNF-α and NF-κß coincides with improved liver functions against DEHP-induced toxicity, it can be concluded that MH-mediated liver function involves the singling of TNF-α and NF-κß.

Hormonal dependent expression of apelin and apelin receptor in the ovary and uterus of mice.

Apelin and APJ have been shown to regulate female reproductive functions. However, its uterine expression during the oestrous cycle and its regulation by ovarian steroids, along with gonadotropin regulation in the ovary, has not been investigated. This study aimed to analyze the steroid-dependent uterine expression of apelin/APJ in the uterus along with the oestrous cycle. Furthermore, it also aimed to investigate gonadotropin-dependent ovarian expression of apelin and APJ. To investigate the uterine expression of apelin and APJ during estrous cycle in mice, uterus at different estrous stage were collected. To explore the ovarian steroids dependent expression of apelin system in the uterus, ovariectomized mice were treated with only estrogen at dose of 30 ng/g, only progesterone at dose of 150 µg/g and combined doses. To study the effect of gonadotropin on ovarian expression of apelin system, immature mice were injected with 2.5 IU of pregnant mare serum gonadotropin (PMSG) alone and both PMSG plus 2.5 IU of chorionic gonadotropin (hCG). Apelin and APJ protein expression are modulated by estrous phases in the uterus. The uterine apelin and APJ expression are up-regulated by estrogen and down-regulated by progesterone. The expression and localization of APJ showed increased abundance in the follicles of PMSG treated mice, however, the PMSG plus HCG treatment showed formation of corpus luteum with increased abundance of APJ and progesterone secretion. The expression of apelin and APJ are regulated by pituitary gonadotropin in the ovary and uterine apelin system by ovarian steroid hormone.

Effects of Different Types of Physical Activity on Respiratory Health Parameters in Elderly Males: A Cross-Sectional Study.

Background Population aging is a global phenomenon associated with declines in muscle mass, physical activity levels, and respiratory health among elderly individuals. Despite evidence suggesting the benefits of physical activity on respiratory function, there is limited research examining its effects on lung function in the Indian elderly population. Materials and methods This cross-sectional study aimed to investigate the impact of different intensities of physical activity on respiratory health parameters among apparently healthy elderly males aged 60-80 years. Participants were categorized into walking, swimming, and sedentary groups based on their level of physical activity. Anthropometric measurements, cardiovascular parameters, respiratory endurance tests, and spirometry were conducted to assess lung function. Statistical analysis included nonparametric tests to compare the groups. Results Age, height, weight, BMI, waist circumference, and hip circumference were similar across groups, but the waist-to-hip ratio was higher in the sedentary group. Systolic and diastolic blood pressure did not differ significantly, while the pulse rate was lower in the swimming group. The sedentary group exhibited lower respiratory endurance, with a significantly reduced 40 mmHg endurance test and maximum expiratory pressure compared to the walking and swimming groups. Spirometry results showed significant improvements in various parameters, including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow rate (PEFR), forced expiratory flow 25% (FEF-25), and maximum voluntary ventilation (MVV) in the walking and swimming groups compared to the sedentary group. Conclusion Regular physical activity, particularly walking and swimming, appears to positively influence respiratory health parameters among elderly males. Engaging in these activities may enhance respiratory muscle strength and lung function, potentially mitigating age-related declines in pulmonary function and promoting overall well-being.

Meta-QTL analysis and identification of candidate genes for multiple-traits associated with spot blotch resistance in bread wheat.

In bread wheat, a literature search gave 228 QTLs for six traits, including resistance against spot blotch and the following five other related traits: (i) stay green; (ii) flag leaf senescence; (iii) green leaf area duration; (iv) green leaf area of the main stem; and (v) black point resistance. These QTLs were used for metaQTL (MQTL) analysis. For this purpose, a consensus map with 72,788 markers was prepared; 69 of the above 228 QTLs, which were suitable for MQTL analysis, were projected on the consensus map. This exercise resulted in the identification of 16 meta-QTLs (MQTLs) located on 11 chromosomes, with the PVE ranging from 5.4% (MQTL7) to 21.8% (MQTL5), and the confidence intervals ranging from 1.5 to 20.7 cM (except five MQTLs with a range of 36.1-57.8 cM). The number of QTLs associated with individual MQTLs ranged from a maximum of 17 in MQTL3 to 8 each in MQTL5 and MQTL8 and 5 each in MQTL7 and MQTL14. The 16 MQTLs, included 12 multi-trait MQTLs; one of the MQTL also overlapped a genomic region carrying the major spot blotch resistance gene Sb1. Of the total 16 MQTLs, 12 MQTLs were also validated through marker-trait associations that were available from earlier genome-wide association studies. The genomic regions associated with MQTLs were also used for the identification of candidate genes (CGs) and led to the identification of 516 CGs encoding 508 proteins; 411 of these proteins are known to be associated with resistance against several biotic stresses. In silico expression analysis of CGs using transcriptome data allowed the identification of 71 differentially expressed CGs, which were examined for further possible studies. The findings of the present study should facilitate fine-mapping and cloning of genes, enabling Marker Assisted Selection.

Renal artery pseudoaneurysm post-COVID-19 infection: An unusual delayed complication.

This case report discusses a rare and severe complication of COVID-19 recovery - renal mucormycosis leading to right renal artery pseudoaneurysm. A 59-year-old patient, previously treated for COVID-19, presented with dry cough, flank pain, and hematuria. He was diagnosed with renal artery pseudoaneurysm with renal mucormycosis. Successful management included urgent angioembolization, systemic liposomal amphotericin B, and subsequent radical nephrectomy post-stabilization. The case underscores the importance of vigilant post-COVID-19 follow-up, particularly in patients treated with steroids, and highlights the need for a multidisciplinary approach for timely diagnosis and effective management of mucormycosis related complications.

Status of visfatin in female reproductive function under normal and pathological conditions: a mini review.

Adipokines are now well-known to regulate reproduction. Visfatin is an adipokine expressed in the hypothalamus, pituitary, ovary, uterus, and placenta of different species, and since it has been found to modulate the endocrine secretion of the hypothalamus, pituitary gland and ovary, it may be considered a novel regulator of female reproduction. Although the majority of the literature explored its role in ovarian regulation, visfatin has also been shown to regulate uterine remodeling, endometrial receptivity and embryo development, and its expression in the uterus is steroid dependent. Like other adipokines, visfatin expression and levels are deregulated in pathological conditions including polycystic ovary syndrome. Thus, the present mini-review focuses on the role of visfatin in female reproduction under both physiological and pathological conditions.

Apelin receptor modulation mitigates letrozole-induced polycystic ovarian pathogenesis in mice.

AIMS: Polycystic ovarian syndrome (PCOS) is one of the most common (about 5-20%) reproductive disorders in women of reproductive age; it is characterized by polycystic ovaries, hyperandrogenism, and oligo/ anovulation. The levels and expression of ovarian adipokines are deregulated in the PCOS. Apelin is an adipokine that acts through its receptor (APJ) and is known to express in the various tissues including the ovary. It has also been suggested that apelin and APJ could be targeted as therapeutic adjuncts for the management of PCOS. However, no study has been conducted on the management of PCOS by targeting the apelin system. Thus, we aimed to evaluate its impact on combating PCOS-associated ovarian pathogenesis. METHODS: The current work employed a letrozole-induced-hyperandrogenism PCOS-like mice model to investigate the effects of apelin13 and APJ, antagonist ML221. The PCOS model was induced by oral administration of letrozole (1 mg/kg) for 21 days. A total of four experimental groups were made, control, PCOS control, PCOS + aplein13, and PCOS + ML221. The treatment of apelin13 and ML221 was given from day 22 for two weeks. KEY FINDINGS: The letrozole-induced PCOS-like features such as hyperandrogenism, cystic follicle, decreased corpus luteum, elevated levels of LH/FSH ratio, and up-regulation of ovarian AR expression were ameliorated by apelin13 and ML221 treatment. However, the PCOS-augmented oxidative stress and apoptosis were suppressed by apelin 13 treatments only. ML221 treatment still showed elevated oxidative stress and stimulated apoptosis as reflected by decreased antioxidant enzymes and increased active caspase3 and Bax expression. The expression of ERs was elevated in all groups except control. Furthermore, the PCOS model showed elevated expression of APJ and apelin13 treatment down-regulated its own receptor. Overall, observing the ovarian histology, corpus luteum formation, and decreased androgen levels by both apelin13 and ML221 showed ameliorative effects on the cystic ovary. SIGNIFICANCE: Despite the similar morphological observation of ovarian histology, apelin13 and ML221 exhibited opposite effects on oxidative stress and apoptosis. Therefore, apelin13 (which down-regulates APJ) and ML221 (an APJ antagonist) may have suppressed APJ signalling, which would account for our findings on the mitigation of polycystic ovarian syndrome. In conclusion, both apelin13 and ML221 mediated mitigation have different mechanisms, which need further investigation.