Disentangling brain atrophy heterogeneity in Alzheimer's disease: A deep self-supervised approach with interpretable latent space.

Alzheimer's disease (AD) is heterogeneous, but existing methods for capturing this heterogeneity through dimensionality reduction and unsupervised clustering have limitations when it comes to extracting intricate atrophy patterns. In this study, we propose a deep learning based self-supervised framework that characterizes complex atrophy features using latent space representation. It integrates feature engineering, classification, and clustering to synergistically disentangle heterogeneity in Alzheimer's disease. Through this representation learning, we trained a clustered latent space with distinct atrophy patterns and clinical characteristics in AD, and replicated the findings in prodromal Alzheimer's disease. Moreover, we discovered that these clusters are not solely attributed to subtypes but also reflect disease progression in the latent space, representing the core dimensions of heterogeneity, namely progression and subtypes. Furthermore, longitudinal latent space analysis revealed two distinct disease progression pathways: medial temporal and parietotemporal pathways. The proposed approach enables effective latent representations that can be integrated with individual-level cognitive profiles, thereby facilitating a comprehensive understanding of AD heterogeneity.

Effects of 12-week Circuit Exercise Intervention on Blood Pressure, Vascular Function, and Inflammatory Cytokines in Obese Older Women with Sarcopenia.

Background: This study investigates the effects of a 12-week circuit exercise program on blood pressure, vascular function, and inflammatory cytokines in older obese women with sarcopenia. Methods: Twenty-eight older obese women with sarcopenia (mean age: 78.2 ± 3.7 years) were randomly divided into an exercise group (EG, n = 14) and a control group (CG, n = 14). The EG participated in a 12-week circuit exercise training regimen, conducted three times weekly, with each session lasting between 45 to 75 minutes (progressively increased over time). The CG was advised to maintain their regular daily routines throughout the intervention period. All dependent variables, including blood pressure, vascular function, and inflammation cytokines, were evaluated pre- and post-intervention. Results: Positive changes were observed in the EG in body composition (body fat mass; p < 0.001, body fat percentage; p < 0.01, free-fat mass; p < 0.01), blood pressure (heart rate; p < 0.05, rate pressure product; p < 0.01), vascular function (brachial-ankle pulse wave velocity; p < 0.05, flow-mediated dilation; p < 0.001), and inflammation cytokines (interleukin-6; p < 0.05). In the CG, there was an increase in body fat mass (p < 0.05) and body fat percentage (p < 0.05), while no changes were observed in other variables. Conclusions: The 12-week circuit exercise program significantly reduced blood pressure, improved vascular function, and decreased inflammatory cytokines in obese older women with sarcopenia. However, individual variations in response highlight the need for personalized exercise regimens.

A comparison of continuous, interval, and accumulated workouts with equalized exercise volume: excess post-exercise oxygen consumption in women.

BACKGROUND: Despite the well-known health benefits of exercise, women's participation in exercise is low worldwide. As women are at risk of developing various chronic diseases as they age, suggesting effective exercise methods that can maximize energy consumption is needed to prevent such conditions. Excess post-exercise oxygen consumption (EPOC) can maximize energy consumption. In this crossover, randomized controlled trial, we aimed to compare the EPOC for different exercise modalities including continuous exercise (CE), interval exercise (IE), and accumulated exercise (AE) that spent the homogenized energy expenditure during exercise in healthy women. METHODS: Forty-four participants (age, 36.09 ± 11.73 years) were recruited and randomly allocated to three groups. The intensity of each modality was set as follows: CE was performed for 30 min at 60% peak oxygen uptake (VO2peak). IE was performed once for 2 min at 80% VO2peak, followed by 3 min at 80% VO2peak, and 1 min at 40% VO2peak, for a total of six times over 26 min. AE was performed for 10 min with a 60% VO2peak and was measured thrice a day. RESULTS: During exercise, energy metabolism was higher for IE and CE than that for AE. However, this was reversed for AE during EPOC. Consequently, the greatest energy metabolism was shown for AE during total time (exercise and EPOC). CONCLUSIONS: By encouraging regular exercises, AE can help maintain and improve body composition by increasing compliance with exercise participation, given its short exercise times, and by efficiently increasing energy consumption through the accumulation of EPOC. TRIAL REGISTRATION: Clinical number (KCT0007298), 18/05/2022, Institutional Review Board of Konkuk University (7001355-202201-E-160).

Effects of Melatonin, GM-CSF, IGF-1, and LIF in Culture Media on Embryonic Development: Potential Benefits of Individualization.

The implantation of good-quality embryos to the receptive endometrium is essential for successful live birth through in vitro fertilization (IVF). The higher the quality of embryos, the higher the live birth rate per cycle, and so efforts have been made to obtain as many high-quality embryos as possible after fertilization. In addition to an effective controlled ovarian stimulation process to obtain high-quality embryos, the composition of the embryo culture medium in direct contact with embryos in vitro is also important. During embryonic development, under the control of female sex hormones, the fallopian tubes and endometrium create a microenvironment that supplies the nutrients and substances necessary for embryos at each stage. During this process, the development of the embryo is finely regulated by signaling molecules, such as growth factors and cytokines secreted from the epithelial cells of the fallopian tube and uterine endometrium. The development of embryo culture media has continued since the first successful human birth through IVF in 1978. However, there are still limitations to mimicking a microenvironment similar to the reproductive organs of women suitable for embryo development in vitro. Efforts have been made to overcome the harsh in vitro culture environment and obtain high-quality embryos by adding various supplements, such as antioxidants and growth factors, to the embryo culture medium. Recently, there has been an increase in the number of studies on the effect of supplementation in different clinical situations such as old age, recurrent implantation failure (RIF), and unexplained infertility; in addition, anticipation of the potential benefits from individuation is rising. This article reviews the effects of representative supplements in culture media on embryo development.

Age-Dependent Clinicopathological Characteristics of Patients with T1b Papillary Thyroid Carcinoma: Implications for the Possibility of Active Surveillance.

BACKGROUND: Active surveillance (AS) of low-risk T1a papillary thyroid carcinoma (PTC) is generally accepted as an alternative to immediate surgery. The cut-off in the size criterion for AS has recently been extended in select individuals, especially older patients. We evaluated the clinicopathological differences of T1b PTC according to age to investigate the possibility of AS in older patients. PATIENTS AND METHODS: From a cohort study of 1269 patients undergoing lobectomy for PTC, 1223 PTC patients with T1 stage disease (tumor ≤ 2 cm) were enrolled. The clinicopathological characteristics between T1a and T1b patients according to age were analyzed. RESULTS: Among the 1223 T1 cases, 918 (75.1%) were T1a (≤ 1 cm) and 305 (34.9%) T1b (> 1 and ≤ 2 cm). T1b PTC was associated with male sex, minimal extrathyroidal extension, lymphovascular invasion, occult central lymph node (LN) metastasis, and a higher number of metastatic LNs than T1a. However, in patients over 55 years of age, the clinicopathological features of the patients with T1a and T1b PTC were not significantly different except for minimal extrathyroidal extension, although many clinicopathological differences were observed in patients under 55 years of age. CONCLUSION: The clinicopathological features of patients with T1b PTC over 55 years of age are similar to those with T1a PTC and less aggressive than those with T1b PTC under 55 years of age. These findings suggest that AS may be possible in patients with T1b PTC over 55 years of age without high-risk features on preoperative examinations.

Effects of 12 Weeks of Resistance Training on Body Composition, Muscle Hypertrophy and Function, Blood Lipid Level, and Hemorheological Properties in Middle-Aged Obese Women.

Background: This study investigated the effects of 12-week resistance training on body composition, blood pressure, blood lipid levels, muscle cross-sectional area (CSA), isokinetic muscle function, and hemorheological properties in middle-aged obese women. Methods: Twenty-eight obese women with a mean age of 50.79 ± 5.80 years were randomly assigned to the control (CON, n = 13) or experimental (EXP, n = 15) group. The EXP group underwent a resistance training program composed of warm-up, main resistance exercise (deadlift, barbell squat, seated leg extension, and lying leg curl, bench press, preacher bench biceps curl, barbell rowing, and dumbbell shoulder press), and cool-down. The resistance exercise consisted of three sets of 8-10 repetitions (reps) performed with 70-80% of 1-rep maximum, and reps and sets were increased every 3 weeks. The training frequency was 80 min, 3 days per week for 12 weeks. The CON group maintained their daily lifestyle without training. All participants underwent measurements of body composition (weight, body mass index, lean body mass, fat mass, and % body fat), blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure), blood lipid levels (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), CSA of the muscles (quadriceps, hamstring, and total thigh muscle), isokinetic muscle function (peak torque [PT], relative PT, mean power, and total work [TW]), and hemorheological properties (erythrocyte deformability and aggregation) before and after 12 weeks of training. Results: The EXP group showed a significant improved muscle function, including PT (p < 0.001), relative PT (p < 0.001) in extension 60°/s, TW (p < 0.001) in extension 180°/s, and TW (p = 0.018) in flexion 180°/s. Regarding hemorheological properties, the EXP group showed significant improvement in erythrocyte aggregation (p < 0.001) and deformability (p < 0.001). Conclusions: The present study verified that our resistance training program resulted in greater muscle function, decreased fat mass, and improved hemorheological properties. Clinical Trial Registration: This study was registered with cris.nih.go.kr (No. KCT0007412).

Prediction of intradialytic hypotension using pre-dialysis features-a deep learning-based artificial intelligence model.

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD) that is associated with increased risks of cardiovascular morbidity and mortality. However, its accurate prediction remains a clinical challenge. The aim of this study was to develop a deep learning-based artificial intelligence (AI) model to predict IDH using pre-dialysis features. METHODS: Data from 2007 patients with 943 220 HD sessions at seven university hospitals were used. The performance of the deep learning model was compared with three machine learning models (logistic regression, random forest and XGBoost). RESULTS: IDH occurred in 5.39% of all studied HD sessions. A lower pre-dialysis blood pressure (BP), and a higher ultrafiltration (UF) target rate and interdialytic weight gain in IDH sessions compared with non-IDH sessions, and the occurrence of IDH in previous sessions was more frequent among IDH sessions compared with non-IDH sessions. Matthews correlation coefficient and macro-averaged F1 score were used to evaluate both positive and negative prediction performances. Both values were similar in logistic regression, random forest, XGBoost and deep learning models, developed with data from a single session. When combining data from the previous three sessions, the prediction performance of the deep learning model improved and became superior to that of other models. The common top-ranked features for IDH prediction were mean systolic BP (SBP) during the previous session, UF target rate, pre-dialysis SBP, and IDH experience during the previous session. CONCLUSIONS: Our AI model predicts IDH accurately, suggesting it as a reliable tool for HD treatment.

Viewpoint-Agnostic Taekwondo Action Recognition Using Synthesized Two-Dimensional Skeletal Datasets.

Issues of fairness and consistency in Taekwondo poomsae evaluation have often occurred due to the lack of an objective evaluation method. This study proposes a three-dimensional (3D) convolutional neural network-based action recognition model for an objective evaluation of Taekwondo poomsae. The model exhibits robust recognition performance regardless of variations in the viewpoints by reducing the discrepancy between the training and test images. It uses 3D skeletons of poomsae unit actions collected using a full-body motion-capture suit to generate synthesized two-dimensional (2D) skeletons from desired viewpoints. The 2D skeletons obtained from diverse viewpoints form the training dataset, on which the model is trained to ensure consistent recognition performance regardless of the viewpoint. The performance of the model was evaluated against various test datasets, including projected 2D skeletons and RGB images captured from diverse viewpoints. Comparison of the performance of the proposed model with those of previously reported action recognition models demonstrated the superiority of the proposed model, underscoring its effectiveness in recognizing and classifying Taekwondo poomsae actions.

Transcriptome Analysis Revealed Potential Genes of Skeletal Muscle Thermogenesis in Mashen Pigs and Large White Pigs under Cold Stress.

Pigs are susceptible to cold stress due to the absence of brown fat caused by the partial deletion of uncoupling protein 1 during their evolution. Some local pig breeds in China exhibit potential cold adaptability, but research has primarily focused on fat and intestinal tissues. Skeletal muscle plays a key role in adaptive thermogenesis in mammals, yet the molecular mechanism of cold adaptation in porcine skeletal muscle remains poorly understood. This study investigated the cold adaptability of two pig breeds, Mashen pigs (MS) and Large White pigs (LW), in a four-day cold (4 °C) or normal temperature (25 °C) environment. We recorded phenotypic changes and collected blood and longissimus dorsi muscle for transcriptome sequencing. Finally, the PRSS8 gene was randomly selected for functional exploration in porcine skeletal muscle satellite cells. A decrease in body temperature and body weight in both LW and MS pigs under cold stress, accompanied by increased shivering frequency and respiratory frequency, were observed. However, the MS pigs demonstrated stable physiological homeostasis, indicating a certain level of cold adaptability. The LW pigs primarily responded to cold stress by regulating their heat production and glycolipid energy metabolism. The MS pigs exhibited a distinct response to cold stress, involving the regulation of heat production, energy metabolism pathways, and robust mitochondrial activity, as well as a stronger immune response. Furthermore, the functional exploration of PRSS8 in porcine skeletal muscle satellite cells revealed that it affected cellular energy metabolism and thermogenesis by regulating ERK phosphorylation. These findings shed light on the diverse transcriptional responses of skeletal muscle in LW and MS pigs under cold stress, offering valuable insights into the molecular mechanisms underlying cold adaptation in pigs.

Identification of Gut Microbiota Affecting Fiber Digestibility in Pigs.

Dietary fiber plays an important role in porcine gut health and welfare. Fiber is degraded by microbial fermentation in the intestine, and most gut microbiota related to fiber digestibility in pigs are worth pursuing. The aim of this study was to identify gut microbiota associated with the apparent total tract digestibility (ATTD) of neutral detergent fiber (NDF) and of acid detergent fiber (ADF) in pigs. Large phenotypic variations in the ATTD of NDF and of ADF were separately found among 274 Suhuai pigs. Microbial community structures were significantly different between high and low fiber digestibility groups. Fourteen genera separately dominated the communities found in the high ATTD (H-AD) of NDF and ADF samples and were in very low abundance in the low ATTD (L-AD) of NDF and ADF samples. In conclusion, norank_f__Bacteroidales_S24-7_group (p < 0.05), Ruminococcaceae_UCG-005 (p < 0.05), unclassified_f__Lachnospiraceae (p < 0.05), Treponema_2 (p < 0.01), and Ruminococcaceae_NK4A214_group (p < 0.01) were the main genera of gut microbiota affecting the ATTD of NDF in pigs. Christensenellaceae_R-7_group (p < 0.01), Treponema_2 (p < 0.05), Ruminococcaceae_NK4A214_group (p < 0.05), Ruminococcaceae_UCG-002 (p < 0.05), and [Eubacterium]_coprostanoligenes_group (p < 0.05) were the main genera of gut microbiota affecting the ATTD of ADF in pigs. The most important functions of the above different potential biomarkers were: carbohydrate transport and metabolism, general function prediction only, amino acid transport and metabolism, cell wall/membrane/envelope biogenesis, translation, transcription, replication, energy production and conversion, signal transduction mechanisms, and inorganic ion transport and metabolism. The most important metabolic pathways of the above different potential biomarkers were: membrane transport, carbohydrate metabolism, amino acid metabolism, replication and repair, translation, cell motility, energy metabolism, poorly characterized, nucleotide metabolism, metabolism of cofactors and vitamins, and cellular processes and signaling.

Hypoxic Therapy as a New Therapeutic Modality for Cardiovascular Benefit: A Mini Review.

Cardiovascular diseases (CVDs) are recognized as one of the major causes of morbidity and mortality worldwide. Generally, most CVDs can be prevented by addressing behavioral risk factors, including smoking, unhealthy diet and obesity, lack of physical activity, and alcohol abuse. Therefore, it is important to have a healthy lifestyle by performing regular physical activity to improve cardiovascular health and diseases. However, a majority of adults worldwide do not meet the minimum recommendations for regular aerobic exercise, and overweight and obesity ratio continues to rise. In addition, obese individuals, with a high prevalence of CVDs, have a lower participation rate for exercise because of the strain on the musculoskeletal system. Hypoxic therapy, including exposure or exercise intervention under hypoxia, has been utilized as a new therapeutic modality for cardiovascular benefit and amelioration of CVDs. Hypoxic therapy shows various physiological and pathophysiological properties, including increased appetite suppression and dietary intake reduction, increased energy consumption, improved glycogen storage, enhanced fatty acid oxidation, improved myocardial angiogenesis or ventricular remodeling, augmentation of blood flow within the skeletal muscle vascular beds, and reduction of the burden on the musculoskeletal system making it applicable to patients with CVDs and obesity with attenuated cardiovascular function. In particular, hypoxic therapy is very effective in improving cardiovascular benefits and preventing CVDs by enhancing arterial function, vascular endothelial function, and hemorheological properties. These observations indicate that hypoxic therapy may be an important and essential strategy for improving cardiovascular health and reducing cardiovascular morbidity and mortality.

Impact of BRCA mutations and hormone receptor status on reproductive potential in breast cancer patients undergoing fertility preservation.

OBJECTIVE: To identify whether the BRCA mutations and hormone receptor status affect the ovarian reserve and ovarian stimulation outcomes in breast cancer patients undergoing fertility preservation. METHODS: A total of 117 women diagnosed with breast cancer who were referred to the fertility preservation clinics at Seoul National University Bundang Hospital and Seoul National University Hospital between September 2012 and July 2019 undergone ovarian stimulation for oocyte retrieval. Basal characteristics including age, BMI, basal AMH, basal FSH, and fertility preservation outcomes such as the number of retrieved oocytes and mature oocytes were compared retrospectively. RESULTS: BRCA1 mutation was noted in 25 women, and BRCA2 mutation was observed in 35 women. Positive estrogen receptor status was noted in 87 women, and positive progesterone receptor status was noted in 69 women. HER2 was positive in 55 women, and 19 women were diagnosed with triple-negative breast cancers. The number of total oocytes retrieved was lower in patients with BRCA mutation (8.3 ± 5.4 vs. 15.3 ± 8.7, p = .002). The number of mature oocytes retrieved was also lower in BRCA carriers (4.7 ± 4.2 vs. 8.7 ± 7.9, p = .025). Triple-negative breast cancer (TNBC) patients were younger than non-TNBC patients (30.3 ± 4.8 vs. 33.9 ± 5.0, p = .007). The rate of mature oocyte rate was higher in TNBC patients (68.6%±20.6 vs. 52.5%±29.7, p = .037). CONCLUSIONS: Our study demonstrated that BRCA carriers with breast cancer had comparable ovarian reserve to non-carriers but the response to ovarian stimulation was lower. We also observed that oocyte maturity was higher in TNBC patients, however age might be a confounding factor of this result.

Prediction model of persistent ovulatory dysfunction in Korean women with polycystic ovary syndrome.

AIM: There is no validated tool to predict persistent ovulatory dysfunction after medication with oral contraceptives in women with polycystic ovary syndrome (PCOS), which is the most severe subtype of PCOS. We aimed to build a model to predict persistent ovulatory dysfunction after medication of oral contraceptives in women with PCOS. METHODS: A total of 286 patients with PCOS were treated with and without oral contraceptives at a tertiary academic medical center. Data were obtained from the electronic medical record system between January 2016 and March 2019. A risk prediction model was developed using multivariable logistic regression. Model 1 was based on age and chief complaints and Model 2 further included predictors evaluated during a clinic visit. Model 3 additionally included laboratory findings. RESULTS: Of the study population, ovulatory dysfunction was persistent in 117 patients (40.9%). Compared with the simple model (Models 1 and 2), the full prediction model (Model 3) had better Akaike's information criterion (286, 244 vs. 225) and the area under the curve (AUC) increased from 0.74 and 0.79 to 0.84. The full model included 7 covariates measured during the evaluation of PCOS, and two covariates were significant predictors of persistent ovulatory dysfunction in PCOS: age (OR 0.91; 95% CI 0.84-0.97), and anti-Müllerian hormone (OR 1.17; 95% CI 1.09-1.26). This model demonstrated good discrimination (AUC, 0.84) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.74). CONCLUSIONS: This prediction model was shown to be a useful method for predicting persistent ovulatory dysfunction after oral contraceptive medication in patients with PCOS.

Transcriptome profiling of in vitro-matured oocytes from a korean native cow (hanwoo) after cysteamine supplementation.

This study elucidated the molecular markers that decrease oocyte quality during in vitro culture, restricting optimal developmental potential. Here, we evaluated the transcriptomic differences between cysteamine-treated and non-treated bovine cumulus oocyte complexes (COCs) after 22 h of co-culture in the maturation media using RNA sequencing. In total, 39,014 transcripts were sequenced between cysteamine-treated and non-treated mature COCs. We evaluated the relative expression of 21,472 genes, with 59 genes showing differential expression between the two COC groups. The cysteamine-treated group had 36 up-regulated gene transcripts and 23 down-regulated gene transcripts. Moreover, gene ontology (GO) enrichment analysis revealed that multiple biological processes were significantly enriched after cysteamine supplementation. Differentially expressed genes appeared to maintain normal oocyte physiology, regulation of apoptosis, differentiation, ossification or bone formation, cardiac and muscle physiology, hormonal secretion, and membrane construction for further embryonic development. In conclusion, cysteamine affects the mRNA level of COCs during oocyte maturation by upregulating potential molecular markers and downregulating genes that affect further embryonic development.

Dysregulation of the Acrosome Formation Network by 8-oxoguanine (8-oxoG) in Infertile Sperm: A Case Report with Advanced Techniques.

8-Hydroxyguanine (8-oxoG) is the most common oxidative DNA lesion and unrepaired 8-oxoG is associated with DNA fragmentation in sperm. However, the molecular effects of 8-oxoG on spermatogenesis are not entirely understood. Here, we identified one infertile bull (C14) due to asthenoteratozoospermia. We compared the global concentration of 8-oxoG by reverse-phase liquid chromatography/mass spectrometry (RP-LC/MS), the genomic distribution of 8-oxoG by next-generation sequencing (OG-seq), and the expression of sperm proteins by 2-dimensional polyacrylamide gel electrophoresis followed by peptide mass fingerprinting (2D-PAGE/PMF) in the sperm of C14 with those of a fertile bull (C13). We found that the average levels of 8-oxoG in C13 and C14 sperm were 0.027% and 0.044% of the total dG and it was significantly greater in infertile sperm DNA (p = 0.0028). Over 81% of the 8-oxoG loci were distributed around the transcription start site (TSS) and 165 genes harboring 8-oxoG were exclusive to infertile sperm. Functional enrichment and network analysis revealed that the Golgi apparatus was significantly enriched with the products from 8-oxoG genes of infertile sperm (q = 2.2 × 10-7). Proteomic analysis verified that acrosome-related proteins, including acrosin-binding protein (ACRBP), were downregulated in infertile sperm. These preliminary results suggest that 8-oxoG formation during spermatogenesis dysregulated the acrosome-related gene network, causing structural and functional defects of sperm and leading to infertility.

Molecular Mechanism and Prevention Strategy of Chemotherapy- and Radiotherapy-Induced Ovarian Damage.

Fertility preservation is an emerging discipline, which is of substantial clinical value in the care of young patients with cancer. Chemotherapy and radiation may induce ovarian damage in prepubertal girls and young women. Although many studies have explored the mechanisms implicated in ovarian toxicity during cancer treatment, its molecular pathophysiology is not fully understood. Chemotherapy may accelerate follicular apoptosis and follicle reservoir utilization and damage the ovarian stroma via multiple molecular reactions. Oxidative stress and the radiosensitivity of oocytes are the main causes of gonadal damage after radiation treatment. Fertility preservation options can be differentiated by patient age, desire for conception, treatment regimen, socioeconomic status, and treatment duration. This review will help highlight the importance of multidisciplinary oncofertility strategies for providing high-quality care to young female cancer patients.

Transcriptome Analyses Identify Potential Key microRNAs and Their Target Genes Contributing to Ovarian Reserve.

Female endocrinological symptoms, such as premature ovarian inefficiency (POI) are caused by diminished ovarian reserve and chemotherapy. The etiology of POI remains unknown, but this can lead to infertility. This has accelerated the search for master regulator genes or other molecules that contribute as enhancers or silencers. The impact of regulatory microRNAs (miRNAs) on POI has gained attention; however, their regulatory function in this condition is not well known. RNA sequencing was performed at four stages, 2-(2 W), 6-(6 W), 15-(15 W), and 20-(20 W) weeks, on ovarian tissue samples and 5058 differentially expressed genes (DEGs) were identified. Gene expression and enrichment were analyzed based on the gene ontology and KEGG databases, and their association with other proteins was assessed using the STRING database. Gene set enrichment analysis was performed to identify the key target genes. The DEGs were most highly enriched in 6 W and 15 W groups. Figla, GDF9, Nobox, and Pou51 were significantly in-creased at 2 W compared with levels at 6 W and 20 W, whereas the expression of Foxo1, Inha, and Taf4b was significantly de-creased at 20 W. Ccnd2 and Igf1 expression was maintained at similar levels in each stage. In total, 27 genes were upregulated and 26 genes interacted with miRNAs; moreover, stage-specific upregulated and downregulated interactions were demonstrated. Increased and decreased miRNAs were identified at each stage in the ovaries. The constitutively expressed genes, Ccnd2 and Igf1, were identified as the major targets of many miRNAs (p < 0.05), and Fshr and Foxo3 interacted with miRNAs, namely mmu-miR-670-3p and mmu-miR-153-3p. miR-26a-5p interacted with Piwil2, and its target genes were downregulated in the 20 W mouse ovary. In this study, we aimed to identify key miRNAs and their target genes encompassing the reproductive span of mouse ovaries using mRNA and miRNA sequencing. These results indicated that gene sets are regulated in the reproductive stage-specific manner via interaction with miRNAs. Furthermore, consistent expression of Ccnd2 and Igf1 is considered crucial for the ovarian reserve and is regulated by many interactive miRNAs.

Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice.

Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine disorder in reproductive-age women. Due to its various pathophysiological properties and clinical heterophenotypes, the mechanism of PCOS pathogenesis is still unclear. Several animal models have been used to study PCOS and allow the exploration of the specific mechanism underlying PCOS. We focused on streptozotocin (STZ) to develop a non-steroidal and non-diabetic PCOS model. We administered multiple STZ injections to female C57BL/6 mice (3-4 weeks old) at different concentrations: STZ-15 (15 mg/kg), STZ-30 (30 mg/kg), and STZ-60 (60 mg/kg) treatments. During the experimental period, we analyzed body weight, blood glucose levels, and estrous cycle pattern. Furthermore, five weeks after STZ administration, we examined hormone levels and the morphology of ovarian tissues. Mice in the STZ-15 group did not show differences in body weights, blood glucose level, insulin level, and insulin tolerance compared to wild-type and control groups whereas those in the STZ-60 group presented a typical diabetes phenotype. In the case of the STZ-30 group, only increased blood glucose level was observed. Total testosterone levels were significantly elevated in STZ-15 and STZ-30 groups. Luteinizing hormone (LH) and estradiol levels were not significantly changed in the STZ-treated groups. The number of ovarian antral follicles and atretic follicles significantly increased in the ovary of mice in the STZ-15 and STZ-30 groups. All STZ-treated groups manifested irregular estrus cycles. However, the patterns of estrous cycles were different between mice treated with different STZ concentrations. We found that PI3K-AKT and IRS-1 signaling in the ovary was enhanced by low doses of STZ treatment. Taken together, our finding indicates that multiple injections of STZ at low doses induce PCOS features in mice without induction of diabetes features.

Use of haemostatic gel in the management of cervical pregnancy: a case report.

PURPOSE: This case report aimed to describe haemostatic agents with systemic methotrexate (MTX) as an effective management for cervical pregnancy with bleeding. CASE PRESENTATION: A 34-year-old nulligravida patient was referred due to vaginal spotting and lower abdominal discomfort, and was diagnosed with a cervical pregnancy at 6 weeks of gestation. The patient was treated with a multi-dose MTX regimen, and the bleeding was successfully controlled with haemostatic agents, which were applied at the bleeding site of the cervix. After completion of MTX treatment, beta human chorionic gonadotropin (ß-hCG) decreased to undetectable range. Furthermore, patients could preserve her uterus and maintain fertility. CONCLUSION: Haemostatic agents can be regarded as an effective option for vaginal bleeding due to cervical pregnancy.

Dietary enzymatically-treated Artemisia annua L. supplementation could alleviate oxidative injury and improve reproductive performance of sows reared under high ambient temperature.

The medicinal plant Artemisia annua L. is well known for its antimalarial compound artemisinin and the antioxidant capacity of its active ingredients. However, low bioavailability of Artemisia annua L. limits its therapeutic potential, fermentation of Artemisia annua L. can improve its bioavailability. This study was aimed to investigate the effects of dietary supplementation of enzymatically-treated Artemisia annua L. (EA) on reproductive performance, antioxidant status, milk composition of heat-stressed sows and intestinal barrier integrity of their preweaning offspring. 135 multiparous sows of average parity 4.65 (Landrace × large white) at day 85 of pregnancy were randomly distributed into 3 treatments. Sows in the control group were housed at control rooms (temperature: 27.12 ± 0.18 °C, temperature-humidity index (THI): 70.90 ± 0.80) and fed the basal diet. Sows in the HS, HS + EA groups were fed the basal diet supplemented with 0 or 1.0 g/kg EA respectively, and reared at heat stress rooms (temperature: 30.11 ± 0.16 °C, THI: 72.70 ± 0.60). Heat stress increased the malondialdehyde (MDA) content, reduced the activities of total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) of sows and piglets, and seriously compromised the antioxidant capacity of the sows and the intestinal integrity of their offspring. However, dietary supplementation of 1.0 g/kg EA reduced the MDA content, increased the activities of T-SOD and T-AOC in serum, colostrum, and milk of heat-stressed sows, and increased colostrum yield and 14-d milk fat content. EA supplementation also increased piglet weaning weight and the activities of T-SOD and T-AOC in serum. In addition, the abundances of intestinal tight junction proteins claudin-1 and occludin were up-regulated in piglets in EA-supplemented group. In conclusion, dietary EA supplementation at 1.0 g/kg can alleviate the oxidative stress in heat-stressed sows, improve the antioxidant capacity in both sows and their offspring, and promote the intestinal barrier integrity in their offspring. EA may be a potent dietary supplement that ameliorates oxidative stress in livestock production by improving the antioxidant capacity.