Understanding oocyte and ovarian aging has become critically important, as trends in family planning evolve, with many women choosing to have children later in life. The ovary, a crucial organ in female reproduction, is particularly susceptible to age-related changes and is one of the organs that exhibit functional deterioration most distinctly with age. The aging of female reproductive systems also affects longevity and various health outcomes. A better understanding of both oocyte and ovarian aging will lay the cornerstone to elucidate the phenomenon of longevity in women. Here, clinical data from 400 women of various ages undergoing intracytoplasmic sperm injection (ICSI) have been analyzed, including Anti-Müllerian Hormone (AMH) and Follicle-Stimulating Hormone (FSH) levels, the number of recovered oocytes, blastocyst rates, pregnancy rates, and live birth rates. Our analyses revealed significant differences in the aforementioned rates between patients of young and advanced age. For the biomarker analysis, we further utilised a novel predictive performance of age-associated gene expression signatures for oocyte aging, demonstrating its potential to provide molecular-level insights into oocyte quality over time. By analyzing RNA sequencing data generated from human oocytes of different ages, a genome-wide landscape of age-associated gene expression has been described. Additionally, metabolome profiling has been performed on young and reproductively aged mice, serving as a model for human ovaries. Changes in metabolites of the murine ovaries during aging have been recorded. In conjunction with traditional biomarkers, multiomics data represent a transformative approach in reproductive health, and they may offer personalised risk assessments and interventions to mitigate age-related fertility decline in women. Our metabolome profiling provides a valuable resource for elucidating the metabolomic basis of ovarian aging. Our findings offer novel insights into systemic shifts associated with oocyte and ovarian aging. This integrated approach may unlock new avenues for fertility preservation, ovarian rejuvenation, and assisted reproduction.
Publications by Year: 2026
2026
Hepatocellular carcinoma (HCC) is an aggressive cancer with limited therapeutic targets and a poor prognosis. Aberrant energy metabolism plays a pivotal role in HCC progression by fulfilling the energy demands of rapidly proliferating tumor cells. In this study, tripartite motif-containing protein 47 (TRIM47) was found to be significantly upregulated in patient-derived HCC tissues, with clinical data revealing that higher TRIM47 expression correlates with poorer patient outcomes. Mechanistic investigations demonstrated that TRIM47 remodels energy metabolism by glycolytic reprogramming through its interaction with the K51 site of fructose-1,6-bisphosphatase (FBP1) through K48-linked ubiquitination, thereby promoting HCC proliferation and tumor metastasis. Rescue experiments and bortezomib intervention experiments further confirmed that FBP1 is essential for mediating the oncogenic effects of TRIM47 in HCC progression. To explore its therapeutic potential, TRIM47 siRNA was developed and loaded into poly (lactic acid)-DC-Chol nanoparticles (siTRIM47@PD NPs), which significantly reduced tumor growth and metastasis in an orthotopic HCC animal model, highlighting the potential of TRIM47 as a therapeutic target. Together, these findings underscore the pivotal role of TRIM47 in HCC progression through FBP1-mediated regulation of energy metabolism, and highlight siRNA-based TRIM47 targeting as a promising approach to improve HCC treatment outcomes.
Functional precision oncology complements genomic approaches by directly testing treatment options on patient-derived models. However, existing platformssuch as patient-derived xenografts (PDXs) and patient-derived organoids (PDOs), face major barriers in clinical use due to technical challenges, including limited standardization, high costs, long assay times, scalability constraints, and incomplete recapitulation of the patient tumor microenvironment (TME). Here, we present a scalable, low-cost Organ Chip (OC) platform fabricated entirely from thermoplastics via injection molding. Leveraging a patented channel geometry and surface treatment, the device achieves barrier-free hydrogel confinement through capillary pinning without porous membranes, micropillars, or other barrier structures. This automation-compatible platform supports tissue-specific extracellular matrices and co-culture through versatile perfusion modes, with robust imaging compatibility. We demonstrate its feasibility for drug sensitivity testing using multiple cell lines and patient-derived primary cells, with imaging-based phenotypic profiling for accurate quantification of drug responses, closely aligning with clinical outcomes. Additionally, we integrated a deep learning-based image translation model that predicts fluorescence staining from bright-field images. This approach enables longitudinal, label-free phenotypic analysis with higher sensitivity than conventional endpoint staining. Together, this integrated cancer OC system overcomes key technical challenges and offers a promising framework for functional precision oncology through high-throughput, patient-relevant drug testing.
OBJECTIVES: To assess all-cause healthcare resource utilization (HCRU) and costs among patients with α- or β-non-transfusion-dependent thalassemia (NTDT) vs. matched controls in the United States.
METHODS: Adults with ≥1 inpatient setting or ≥2 outpatient settings claims for α- or β‑thalassemia between January 1, 2013 and June 30, 2021 were identified from the Merative MarketScan Commercial/Medicare database. Patients with <8 transfusions or ≥6 weeks between any two adjacent transfusions in a 1-year period post-index date (date of first observed α- or β-thalassemia diagnosis code) were considered to have NTDT. Patients were required to have mean hemoglobin (Hgb) levels <10 g/dL during follow-up as an additional measure to ensure exclusion of patients with thalassemia trait. Each patient was matched with five controls based on age, sex, length of follow-up, availability of lab data, and payer type. All-cause HCRU and costs were assessed over ≥12 months post-index. Data were also analyzed for the non-transfusion-dependent α- and β-thalassemia subgroups.
RESULTS: A total of 149 patients with NTDT and Hgb levels <10 g/dL were matched with 745 controls. The mean follow-up period was approximately 3 years. All-cause inpatient admissions (48.3% vs. 16.5%; p < 0.001) and emergency room visits (61.1% vs. 39.1%; p < 0.001) during follow-up were higher with NTDT vs. controls, and total costs (total medical + outpatient pharmacy) were $29,107 per patient per year (PPPY) in patients with NTDT vs. $9,042 PPPY in controls (p < 0.001). Similar trends were seen in the subgroups of patients with non-transfusion-dependent α- and β-thalassemia vs. matched controls.
CONCLUSIONS: Patients with NTDT in the United States, including those with α- and β-thalassemia, have significantly higher all-cause HCRU and costs vs. matched controls. There is a need for effective treatment options to reduce the healthcare burden of NTDT and improve patient outcomes.
BACKGROUND: Rotator cuff repair (RCR) is increasingly performed due to advancements in surgical techniques and an aging population. While generally successful, complications like re-tear, stiffness, infection, and thromboembolic events remain concerns. The rising use of testosterone replacement therapy (TRT) in middle-aged and older men raises questions about its impact on surgical outcomes, as its effect on RCR complications remains unclear.
METHODS: A retrospective cohort study was conducted using the PearlDiver Database. Patients who underwent arthroscopic RCR between January 2010 and April 2023 were identified using Current Procedural Terminology code 29827. Those with at least two years of continuous follow-up were included, while patients under 21 or with unknown procedural laterality were excluded. Patients were categorized into 2 cohorts: those who received TRT within three months preoperatively and a control group who did not. Propensity score matching (1:1, caliper = 0.001) was performed to control for age, gender, Charlson Comorbidity Index, obesity, tobacco use, and hypogonadism. The primary outcomes included 2-year postoperative complications and reoperations. Secondary outcomes included 90-day major medical complications such as surgical site infection, pneumonia, pulmonary embolism, deep vein thrombosis, urinary tract infection, wound dehiscence, sepsis, acute kidney injury, and readmissions. Statistical analyses were performed using chi-square tests, and odds ratios with 95% confidence intervals were calculated.
RESULTS: A total of 8,241 TRT users and 673,982 control patients were identified before matching. After propensity score matching, 5,109 patients remained in each cohort with no significant baseline differences. No significant differences were observed in 90-day postoperative complications, including surgical site infection (0.5% vs. 0.4%, P = .64), pneumonia (0.6% vs. 0.5%, P = .79), sepsis (0.4% vs. 0.3%, P = .51), acute kidney injury (0.7% vs. 0.5%, P = .18), or readmissions (1.2% vs. 1.0%, P = .29). Similarly, no significant differences were found in pulmonary embolism or deep vein thrombosis. Over the 2-year follow-up, TRT use was associated with a higher incidence of total shoulder arthroplasty (0.7% vs. 0.4%, P = .037) but a lower incidence of lysis of adhesions (0.5% vs. 0.9%, P = .032). No significant differences were observed in revision RCR rates (2.6% vs. 2.3%, P = .41).
CONCLUSION: Preoperative TRT use was not linked to increased short-term complications after arthroscopic RCR. Over two years, TRT was associated with higher rates of total shoulder arthroplasty but lower rates of lysis of adhesions, with no difference in revision RCR.
The incidence of cancer in humans has been rising in association with extended life spans. Incidence rates of early onset cancers in humans <55 years of age have also been increasing for unclear reasons. One potential contributory factor is an antagonistic pleiotropy in which certain genes that appeared in mammals to increase fitness for reproduction contribute to cancer susceptibility later in life. A related concept is an evolutionary mismatch in which humans have adapted to certain environmental and dietary factors that change over time and thereby increase cancer incidence. The MUCIN 1 (MUC1) gene emerged in mammals and represents an example of antagonistic pleiotropy and evolutionary mismatch that is posited here as a contributing factor to the increasing incidence of cancer in humans. This Review focuses on the roles of MUC1 and the oncogenic M1C protein in reproductive fitness and barrier tissue protection that in settings of chronic inflammation promote pan-cancer progression and treatment resistance. Also highlighted are therapeutic approaches targeting MUC1 and M1C that are under clinical and pre-clinical development.
OBJECTIVE: The negative effects of discrimination on mental health are well-established. Few longitudinal studies have investigated protective factors that could mitigate these effects for Mexican-origin youth in the U.S. This three-wave longitudinal study examines individual-, family-, peer-, and neighborhood-level protective factors attenuating the effect of discrimination-related stress on youth depressive and anxiety symptoms.
METHOD: We surveyed 344 Mexican-origin youth (aged 12-15) from two Midwestern counties longitudinally over three annual waves. Youth completed self-report measures of depression, anxiety, and discrimination as well as six potential protective factors: perceived social position, parent-child relationship, peer relationships, perceived social support, school connectedness, and neighborhood collective efficacy. Multilevel models with time-varying variables were used to analyze the effect of the potential protective factors on the association between discrimination and depressive and anxiety symptoms.
RESULTS: Perceived social position, parent-child relationship, peer relationships, and perceived social support significantly attenuated the impact of racial discrimination on depressive symptoms at the between-youth level, but not at the within-youth level. No significant protective factors emerged for racial discrimination and anxiety symptoms at either the between-youth or within-youth level. No cross-moderation effects were observed.
CONCLUSION: Results highlight the importance of self-perceived social position and support in combating the effects of discrimination on Mexican-origin youth's depressive symptoms. Most protective factors centered on interpersonal relationships with caregivers and peers. Findings indicate the need for a greater understanding of school connectedness and neighborhood collective efficacy as non-significant protective factors, perhaps because these continue to be discriminatory rather than supportive contexts.
A finely tuned immune regulation within the epididymis and testis is essential for male reproductive health. This balance is especially critical in the epididymis, where sperm mature and ascending infections frequently disrupt homeostasis, resulting in regionally different immune responses and potential long-term fertility impairments. We previously demonstrated that the epididymis harbors a region-specific immunological scaffold, with CX3CR1+ macrophages as the most prominent epithelium-associated immune cell population. Here, we established a transgenic mouse model to selectively deplete these intraepithelial CX3CR1+ macrophages within the epididymis, resulting in focal epithelial damage and impaired sperm maturation processes essential for proper sperm functionality. Additionally, a mild reduction of the testicular macrophage pool resulted in transient disruptions in spermatogenesis and steroidogenesis. Although the macrophage niche was repopulated after depletion, the newly recruited cells displayed altered phenotypes consistent with persistent sperm alterations. Following infection with uropathogenic Escherichia coli (UPEC), macrophage-depleted mice exhibited exacerbated immune responses - particularly in normally protected proximal epididymal regions - with earlier onset and more severe tissue damage. Transcriptomic analysis revealed a failure to restrain inflammatory responses, especially in genes involved in immune regulation and antibacterial defense, accompanied by elevated immune cell infiltration in infected macrophage-depleted mice. Overall, our findings confirm a crucial role for CX3CR1+ macrophages in preserving epithelial integrity and modulating immune responses, supporting a stable tissue environment necessary for efficient organ function of both epididymis and testis.
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