Objectives To investigate to investigate the role of circ_0000075 levels and its regulatory mechanism in patients with acute myeloid leukemia (AML).Methods A total of 115 patients with AML and 60 patients with non-haematological tumors (control group) were included. Bone marrow fluid was collected, and the patients were followed-up for a 5-year postoperative prognosis. RT-qPCR was used to detect the expression of circ_0000075 and miR-218-5p, Kaplan-Meier curves recorded for prognostic survival, and multivariate Cox regression analysis to assess factors affecting patient mortality. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8), and Transwell assays were performed to study cell migration and invasion. A dual-luciferase reporter assay verified the interaction between the interaction between circ_0000075 and miR-218-5p.Results High levels of circ_0000075 were present in AML patients and correlated with their pathological features. AML patients with high circ_0000075 expression had lower survival rates, and circ_0000075 was predicted to be a risk factor for poor prognosis in AML patients. circ_0000075 levels were elevated in AML cells compared to normal cells, and silencing circ_0000075 attenuated cancer cell proliferation, migration, and invasion. miR-218-5p has abundant circ_0000075 binding sites, and its expression is markedly suppressed in cancer tissues. A dual-luciferase reporter assay demonstrated a targeting relationship between circ_0000075 and miR-218-5p. Response experiments suggested that the use of miRNA inhibitors promoted AML cell function.Conclusion circ_0000075 is a risk factor for poor prognosis in AML patients. Silenced circ_0000075 blocks the function of tumor cells mainly by promoting miR-218-5p expression.

ABSTRACT:Conventional medical sensors primarily function as passive transducers and often struggle to maintain accuracy and stability under complex physiological conditions. Their limited capacity for local data processing, adaptive compensation, and real-time interaction also constrains continuous monitoring and individualized clinical decision-making. The convergence of microelectronics, materials science, wireless communication, and artificial intelligence (AI) has therefore accelerated the development of intelligent medical sensors that integrate sensing, processing, communication, and decision-support functions. This review summarizes recent advances and remaining challenges in this field. We examine the technical architectures and core functions of next-generation sensors, including self-compensation, self-calibration, self-diagnosis, and bidirectional data interaction, and compare four major technological platforms: flexible wearable sensors, optical fiber sensors, electrochemical sensors, and functional nucleic acid and molecularly imprinted biosensors. We further discuss signal-transduction, anti-interference, and data-transmission mechanisms; advances in flexible materials, micro/nano-fabrication, multimodal integration, and AI-enabled signal processing; and applications in physiological monitoring, biomarker detection, chronic disease management, wearable therapy, interventional support, and extreme environments. Despite rapid progress, clinical translation remains limited by data security and privacy risks, insufficient standardization and regulatory alignment, long-term stability and biocompatibility concerns, and uneven validation maturity across technologies. Future development should prioritize clinically driven design, staged and technology-specific validation, multimodal and low-power integration, and coordinated regulatory and manufacturing strategies to support reliable, scalable, and patient-centered implementation.

Early identification of individuals at high risk of prediabetes may support timely prevention. Prediction models for large-scale health examination settings should balance predictive accuracy, interpretability, and feasibility. We aimed to develop and internally validate a Cox proportional hazards-based model for 3-, 4-, and 5-year risk of incident fasting plasma glucose (FPG)-defined prediabetes, and to compare a parsimonious model with an expanded metabolic model. This retrospective cohort study included 100,738 adults without diabetes or FPG-defined prediabetes at baseline from 32 healthcare centers across China. Incident prediabetes was defined by follow-up FPG of 5.6–6.9 mmol/L. Twenty-three routinely collected clinical and biochemical variables, including derived metabolic indices, were evaluated. Cox-LASSO regression was used for variable prioritization. Model discrimination was assessed using time-dependent AUCs, calibration was evaluated using bootstrap internal validation, and sensitivity analyses were performed in five missForest-imputed datasets, with pooled estimates combined using Rubin’s rules. During a median follow-up of 3.1 years, 12,389 participants developed FPG-defined prediabetes. In the parsimonious model, age, BMI, and FPG were independently associated with risk; adjusted hazard ratios per 1-SD increase were approximately 1.32, 1.27, and 2.06, respectively. Apparent AUCs were 0.762, 0.757, and 0.719 at 3, 4, and 5 years, with nearly identical optimism-corrected AUCs. Calibration was acceptable, with an optimism-corrected slope of 0.999 and 5-year O/E ratio of 1.048. The expanded model showed statistically higher AUCs, but absolute gains were modest. Subgroup analyses suggested attenuated 5-year discrimination among older adults. Age, BMI, and FPG provided stable, interpretable prediction of FPG-defined incident prediabetes. External validation is required before routine implementation.

Lysine lactylation (Kla) is a metabolite-sensing post-translational modification that bridges cellular metabolism to protein function. Here, we discover that heat stress triggers anaerobic glycolysis and lactate accumulation in brain microvascular endothelial cells. We find that plasma lactate inversely correlates with Glasgow Coma Scale scores in heat stroke patients and predicts poor outcomes. Mechanistically, AARS1 catalyzes the transfer of lactate to HSP90β at lysine 275 (K275). Critically, the lactylation of HSP90β disrupts its interaction with apoptotic protease-activating factor 1 (APAF-1). This modification compromises the protective function of HSP90β, liberating APAF-1 to activate the mitochondrial apoptosis pathway, resulting in blood-brain barrier (BBB) injury. Functional validation reveals that decreasing lactate production or inhibiting AARS1 confers protection. These findings establish HSP90β K275 lactylation as a metabolic switch that modulates protective mechanisms during heat stress-induced cerebrovascular injury. Collectively, our study provides insights into heat stress pathogenesis and identifies potential therapeutic targets for heat-related brain damage.

ASPSCR1::TFE3-rearranged renal cell carcinoma (RCC) represents the most common subtype of TFE3-rearranged RCC, yet clinicopathologic and prognostic data remain limited. We analyzed 30 cases confirmed by fluorescence in situ hybridization or RNA-based next-generation sequencing, representing the largest single-center series to date. The cohort demonstrated an overwhelming female predominance, with a median age of 23.6 years. Microscopically, tumors exhibited diverse histological patterns, including papillary, nested, or tubular architectures, with papillary structure being the most prevalent. Tumor cells characteristically showed abundant clear to eosinophilic cytoplasm with discrete cell borders. Psammoma bodies were frequently present. Rare morphologic patterns included TFEB-rearranged RCC-like and cystic changes that, to our knowledge, have not been reported previously. Immunohistochemically, all tested tumors showed nuclear TFE3 positivity, with variable PAX8 expression, weak or absent staining for epithelial markers (CK7 and EMA), and negativity for melanocytic markers (HMB45 and Melan-A). PD-L1 was positive in 4 of 18 cases. Over 5-173 months of follow-up, the 5-year disease-free survival (DFS) rate was 37.9

Natural background radiation is a pervasive element affecting biological organisms. However, the consequences of its absence are not well comprehended. This study investigates the effects of ultra-low background radiation on head and neck tumor cells using the China Jinping Underground Laboratory (CJPL), which effectively shields cosmic rays. Our results demonstrate that ultra-low background radiation significantly suppresses tumor cell proliferation and migration. Moreover, mitochondrial dysfunction is characterized by reduced membrane potential, impaired oxidative phosphorylation, and increased oxidative stress. Through RNA sequencing, the ATM gene is identified as a pivotal regulator in this process. Furthermore, the downregulation of ATM under ultra-low background radiation results in decreased expression of PGC-1α, NRF-1, and TFAM, all of which are associated with mitochondrial function. In contrast, the overexpression of ATM or TFAM partially ameliorates the inhibition of tumor cell behavior and mitochondrial function induced by ultra-low background radiation. Collectively, these findings demonstrate that ultra-low background radiation inhibits tumor cell behavior through mitochondrial dysfunction mediated by ATM downregulation, providing valuable insights into the potential therapeutic applications and molecular targets of ultra-low background radiation.

Heat acclimation (HA) is an evolutionarily conserved trait that enhances tolerance to novel stressors by inducing heat shock proteins (HSPs). However, the molecular mechanisms underlying this phenomenon remain elusive. In this study, we established a HA mouse model through intermittent heat stimulation. Subsequently, this model was evaluated using an array of physiological and histological assessments. In vitro, HA cell model with mouse brain microvascular endothelial cells (bEnd.3) was established and analyzed for cell viability and apoptosis markers. We investigated HA-mediated heat and hypoxia tolerance mechanisms using HIF-1α and HSP70 inhibitors and siRNA. Our results demonstrated that HA enhances the tolerance of bEnd.3 cells and mice to both heat and hypoxia, Mechanistically, HA upregulated the expression of HIF-1α and HSP70. However, inhibition of HIF-1α or HSP70 partially attenuated HA-induced tolerance to heat and hypoxia. Additionally, HA significantly decreased the ubiquitination levels of HIF-1α, whereas inhibition of HSP70 increased its ubiquitination. HA also substantially enhanced the interaction between HIF-1α and HSP70. In conclusion, our findings indicate that HA enhances tolerance to heat and hypoxia by stabilizing HIF-1α through increased interaction with HSP70. This discovery elucidates a novel mechanism of cellular protection conferred by HA and provides new strategies and potential targets for human adaptation to extreme environments.

Objective:To investigate the effects of low background radiation environments in deep underground settings on the biological behavior of NP69 human nasopharyngeal epithelial cells (NP69 cells) and the underlying molecular mechanisms. Methods:A parallel control experimental design was adopted and NP69 cells were synchronously cultured in settings of three underground depths at the China in situ Deep-Underground Facility & Life Observatory (DeUFO)-ground level (DeUFO-0 m), 1000 m underground (DeUFO-1000 m), and 1500 m underground (DeUFO-1500 m). Changes in cell proliferation and migration capabilities were assessed using the Cell Counting Kit-8 (CCK-8) assay and scratch assay, respectively. High-throughput RNA sequencing (RNA-Seq) was performed to identify differentially expressed genes (DEGs). Functional annotation and pathway enrichment analysis of the DEGs were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Results:CCK-8 assay revealed that, after 72 h of culture, the absorbance value of the DeUFO-0 m group was 1.35 times and 1.27 times those of the those of the DeUFO-1000 m and DeUFO-1500 m groups, respectively (both P < 0.0001). After 96 h of culture, the absorbance value of the DeUFO-0 m group was 1.52 times and 1.41 times those of the DeUFO-1000 m and DeUFO-1500 m groups, respectively (both P < 0.0001). Colony formation assays revealed that the number of cell colonies in the DeUFO-0 m group was 1.59 times and 1.27 times those in the DeUFO-1000 m group and DeUFO-1500 m group, respectively (both P < 0.001). The scratch assay revealed that the 36-hour wound healing rate of the DeUFO-0 m group was 2.22 times and 4.00 times those of the DeUFO-1000 m group and DeUFO-1500 m group, respectively (both P < 0.0001). Transwell assays revealed that the number of migrating cells in the DeUFO-0 m group was 2.08 times and 2.56 times those in the DeUFO-1000 m group and DeUFO-1500 m group, respectively (both P < 0.0001). Transcriptome sequencing analysis revealed consistent upregulation of CELF2, CELF4, CGB8, GRHL2, and DMRTA2 genes in the DeUFO-1000 m and DeUFO-1500 m groups. Pathway enrichment analysis indicated significant enrichment of extracellular matrix (ECM) remodeling-associated pathways and gene expression regulation pathways in the experimental groups (false discovery rate [FDR] < 0.05). Conclusion:The low background radiation environment in deep underground settings suppresses the proliferation and migration activities of NP69 cells by mediating ECM remodeling and post-transcriptional regulatory mechanisms through the regulation of target genes such as the CELF family. This study provides experimental evidence for establishing a dose-response relationship between environmental radiation and cellular effects.

Objectives: Recently, pre-/post-operative Local Estrogen Therapy (LET) has shown effectiveness in alleviating Pelvic Organ Prolapse (POP) symptoms in clinical therapy. However, there is a lack of scientific evidence to support these claims. Therefore, we aimed to explore the anti-senescence effects and mechanisms of 17[3-estradiol (E2) on POP-derived fibroblasts. Methods: The primary fibroblast cells were isolated and cultured from the surgical samples of postmenopausal women clinically diagnosed with pelvic organ prolapse (POP) at stages III-IV (quantified using the POP-Q system) and without any other treatment within 6 months. (n = 12, age 50-75). Colorimetric Cell Counting Kit (CCK-8) assay and Senescence-Associated-[3-Galactosidase (SA-[3-Gal) staining were used to test the cell proliferative capacity and the senescence rate. Western blotting (WB) was used to detect the expression of Collagen Type I (COL-I), Collagen Type III (COL-III), Cyclin-dependent kinase 4 inhibitor A (p16INK4a), Cyclin-dependent kinase inhibitor 1A (p21), Tumor Protein 53 (p53), Sirtuin 1 (SIRT-1) and Microtubule-associated protein 1A/1B-light chain 3-I/II (LC3I/II) protein. A transmission Electron Microscope (TEM) was used to observe the ultrastructure of fibroblasts. Results: The results showed that E2 significantly promoted the proliferation of fibroblasts derived from POP and reduced the staining rate of SA-[3-Gal. It markedly enhanced the extracellular matrix proteins COL-I and COL-III, accompanied by inhibition of the senescent maker p16INK4a. Additionally, our results improved the cells' autophagy and metabolic activity. Additionally, our results indicate the anti-senescence mechanism of E2 through the mediated SIRT-1/p53/p21 axis pathway. Conclusion: We provide preliminary evidence for the anti-aging effects and mechanisms of E2 on POP, hoping to provide a theoretical basis for estrogen against POP senescence and guide the clinical application and local administration of estrogen in POP treatment.

Mild photothermal therapy (PTT) in the near-infrared II region (NIR-II) window provides an effective and safe modality for nasopharyngeal carcinoma treatment, based on its superior tissue penetration and clinical suitability. However, its effectiveness is compromised by the overexpression of heat shock proteins (HSPs) with enhanced tumor resistance to heat. In this study, Au-polydopamine blackspheres (AuPBs) are synthesized and functionalized with the HSP70 inhibitors VER-155008 (AuPB-VER) via pi-pi stacking interactions, achieving enhanced photothermal conversion efficiency and controlled drug release. In vitro and organoid studies demonstrate the significant tumor-inhibitory effects of AuPB-VER treatment at a mild 40 degrees C PTT. Remarkably, AuPB-VER achieves complete tumor eradication at just 40 degrees C in vivo, indicating that AuPB-VER could effectively overcome heat resistance in deep tissues, enhancing the therapeutic efficacy of mild PTT and minimizing damage to surrounding tissues. These findings pave the way for a promising clinical approach to treating advanced or recurrent nasopharyngeal carcinoma.

Cardiovascular-kidney-metabolic (CKM) syndrome is a major public health concern associated with increased mortality. Inflammation plays a critical role in CKM progression and outcomes. This study investigates the relationship between inflammatory indices and mortality risk in CKM patients. A comprehensive analysis of data from 26,265 participants in the National Health and Nutrition Examination Survey (NHANES) database (2007–2016) with CKM syndrome stages 0–4 was conducted. The primary outcomes of the study were all-cause and cardiovascular mortality. The inflammatory indices encompassed the systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), aggregate index of systemic inflammation (AISI), and neutrophil-to-albumin ratio (NAR). Multivariable Cox models, adjusted for demographic and clinical confounders, were employed to examine nonlinearity, alongside restricted cubic splines and threshold analyses. The present study sought to compare the prognostic accuracy of the time-dependent ROC (Receiver Operating Characteristic) at 93 months. During a median follow-up of 93.4 months, 2,292 subjects experienced all-cause mortality and 701 experienced cardiovascular deaths. In the adjusted models, elevated SIRI (all-cause HR 1.11, 95

Heat acclimation (HA) is found to help decrease the incidence of heat-related illnesses such as heat syncope and exertional heat stroke. However, the response of vascular endothelial cells to HA remain to be elucidated. In this study, mouse brain microvascular endothelial cells (bEnd.3), human umbilical vein endothelial cells (HUVEC), and human aortic endothelial cells (HAEC) were selected. The cells were first subjected to HA at 40 ℃ for 2 h per day for 3 days, and then subjected to heat stress at 43 ℃ for 2 h or 4 h. After heat stress, HA-pretreated cells showed a significant increase in cell viability, cell integrity, a decrease in the proportion of S phase cells, cell apoptosis, and cytoskeletal shrinkage compared with the cells without HA pretreatment. Additionally, the expression of VEGF, ICAM-1, iNOS and EPO in HA-pretreated cells significantly increased. We also presented evidence that HA upregulated HSP70 and bcl-2, while downregulated p-p53 and bax. Notably, the suppression of HSP70 expression attenuated the protective role of heat acclimation. Furthermore, HA mitigated injuries in vital organs of mice exposed to heat stress. Conclusively, these findings indicated the HA can increase the vitality of vascular endothelial cells after heat stress, partially restore the function of vascular endothelial cells, and this protective effect may be related to the upregulation of HSP70 expression.

Capitalizing on breakthroughs in reproductive genetics, the utilization of in vitro embryo culture and stem cell technologies heralds a transformative era in addressing global challenges posed by rare genetic diseases. These cutting-edge practices illuminate the intricacies of early human development, elucidate the mechanisms behind rare diseases, and guide the development of potential therapies. Balancing this remarkable innovation with necessary ethical considerations, these technologies have the potential to revolutionize the trajectory of rare genetic disorders, transforming the landscape of diagnosis, treatment, and genetic counseling while offering renewed hope for affected individuals and families worldwide.

IntroductionExtreme heat events caused by occupational exposure and heat waves are becoming more common. However, the molecular changes underlying the response to heat exposure in humans remain to be elucidated.MethodsThis study used longitudinal multi-omics profiling to assess the impact of acute heat exposure (50°C for 30 min) in 24 subjects from a mine rescue team. Intravenous blood samples were collected before acute heat exposure (baseline) and at 5 min, 30 min, 1 h, and 24 h after acute heat exposure (recovery). In-depth multi-omics profiling was performed on each sample, including plasma proteomics (untargeted) and metabolomics (untargeted).ResultsAfter data curation and annotation, the final dataset contained 2,473 analytes, including 478 proteins and 1995 metabolites. Time-series analysis unveiled an orchestrated molecular choreography of changes involving the immune response, coagulation, acid–base balance, oxidative stress, cytoskeleton, and energy metabolism. Further analysis through protein–protein interactions and network analysis revealed potential regulators of acute heat exposure. Moreover, novel blood-based analytes that predicted change in cardiopulmonary function after acute heat exposure were identified.ConclusionThis study provided a comprehensive investigation of the dynamic molecular changes that underlie the complex physiological processes that occur in human males who undergo heat exposure. Our findings will help health impact assessment of extreme high temperature and inspire future mechanistic and clinical studies.

Penile schwannoma is an uncommonly seen peripheral nerve tumor, of which penile plexiform schwannomas (PS) is extremely rare that has only been reported in several adults. We present a case of penile PS with a similar lesion in inguinal region in a 9-year-old child, which appeared as painless masses and rapidly growing within one year. Penile ultrasonography suggested well-defined lesions with limited vascularity. Both masses presented with low-to-intermediated signal intensity and no definite enhancement in computed tomography. The lesions were completely resected with minimal intraoperative bleeding, and a diagnose of benign PS was confirmed based on H&E staining and positive S-100 expression in immunohistochemistry. There was no evidence of tumor recurrence or metastasis after 6 months of follow-up. Only 6 cases of penile schwannoma in children were recorded, of which 5 were malignant, and none was PS. The malignancy rate of penile schwannoma in children may be overestimated due to delayed diagnose of benign ones. A rapidly growing penile mass with a suspected metastatic lesion in inguinal region could be easily misdiagnosed as malignant. This case report and literature review is expected to assist clinicians in getting a comprehensive understanding of children penile schwannomas and choosing the best management strategy when faced with this rare condition.

Abstract Occupational exposure to extreme high temperatures and the increasing global temperatures necessitates a deeper understanding of the impact of heat exposure on human health. However, the molecular mechanisms underlying the response of monocytes and neutrophils to heat exposure in occupational population remain to be fully elucidated. This study used longitudinal transcriptome to assess the impact of acute heat exposure (50°C for 30 min) in 10 subjects from a mine rescue team before acute heat exposure (baseline) and at 5 min, 30 min, 1 h, and 24 h after acute heat exposure (recovery). The time‐series analysis revealed a coordinated molecular choreography of changes involving inflammation, coagulation, extracellular matrix, and energy metabolism. Importantly, the study characterized the inflammatory signature associated with heat exposure in monocytes and neutrophils, as evidenced by the rapid activation of the inflammation‐related transcriptome following heat exposure. Additionally, we pinpointed potential regulators, such as NR4A1, FOSL1, EGR3, and ATF3. In summary, the study suggested that the initial response to heat stress in monocytes and neutrophils from mine rescue team member was primarily characterized by a pro‐inflammatory stress response, which could potentially lead to the development of inflammation and ultimately result in a systemic inflammatory response in heatstroke.

With the development of clinical experience and technology, rare diseases (RDs) are gradually coming into the limelight. As they often lead to poor prognosis, it is urgent to promote the accuracy and rapidity of diagnosis and promote the development of therapeutic drugs. In recent years, with the rapid improvement of single-cell sequencing technology, the advantages of multi-omics combined application in diseases have been continuously explored. Single-cell metabolomics represents a powerful tool for advancing our understanding of rare diseases, particularly metabolic RDs, and transforming clinical practice. By unraveling the intricacies of cellular metabolism at a single-cell resolution, this innovative approach holds the potential to revolutionize diagnosis, treatment, and management strategies, ultimately improving outcomes for RDs patients. Continued research and technological advancements in single-cell metabolomics are essential for realizing its full potential in the field of RDs diagnosis and therapeutics. It is expected that single-cell metabolomics can be better applied to RDs research in the future, for the benefit of patients and society.

Background:Globally, ovarian cancer is the leading cause of female reproductive-related death, with a 5-year survival rate below 50%. Conventional therapies, such as cancer cell reduction and paclitaxel chemotherapy, have strong toxicity and are prone to drug resistance. Thus, the development of alternatives for the treatment of ovarian cancer is urgently needed. Methyl vanillate is a principal component of Hovenia dulcis Thunberg. It is known that several cancer cells are inhibited by methyl vanillate; however, whether methyl vanillate can inhibit the proliferation and migration of ovarian cancer cells still needs to be further studied.Methods:In this study, cell counting kit 8 (CCK8) was used to examine the effects of methyl vanillic acid on the proliferation of SKOV3 cell lines and human ovarian surface epithelial cell (HOSEpiC) lines. Wound healing and transwell assays were used to determine the effect of methyl vanillate on cell migration. The expression of epithelial-mesenchymal transition (EMT) marker proteins (E-cadherin and vimentin), transcription factors (Snail and ZEB2), and skeletal proteins (F-actin) were evaluated with Western blotting. F-actin was detected by immunofluorescence assay.Results:The proliferation and migration of SKOV3 cells were dose-dependently inhibited by methyl vanillate, but HOSEpiC cells were not inhibited by low concentrations of methyl vanillate. Western blotting analyses revealed a significant decrease in the expression of vimentin and a significant increase in the expression of E-cadherin in SKOV3 cells treated with methyl vanillate. This finding indicated that EMT inhibition was induced by the vanillate. Furthermore, methyl vanillate inhibited the expression of transcription factors (Snail and ZEB2) in SKOV3 cells as well as cytoskeletal F-actin assembly.Conclusions:Methyl vanillate plays an important role in inhibiting EMT and cell proliferation and the migration of ovarian cancer, likely via the inhibition of the ZEB2/Snail signaling pathway. Consequently, methyl vanillate may be a promising therapeutic drug for ovarian cancer.

Introduction In the pathology of pelvic organ prolapse (POP), little is known about the contributing role of pelvic microenvironment. Also, the age-related differences in pelvic microenvironment of POP patients is always ignored. In the present study, we investigated the age-related differences in pelvic microenvironment between Young POP patients and Old POP patients, and the novel cell types and critical regulators which contributes to the age-related differences. Methods Single-cell transcriptomic analyses were used to detect the changes in cell composition and gene expression from the pelvic microenvironment of control group (<60 years), Young POP group (<60 years) and Old POP group (>60 years). Then, immunohistochemistry and immunofluorescence were used to verify the novel cell types and critical regulators in the pelvic microenvironment. Furthermore, histopathological alteration and mechanical property alteration in POP with different ages were revealed by vaginal tissue histology and biomechanical testing. Results The up-regulated biological process in Old women with POP is mainly related to chronic inflammation, while the up-regulated biological process in Young women with POP is mainly related to extracellular matrix metabolism. Meantime, CSF3+ endothelial cells and FOLR2+ macrophages were found to play a central role in inducing pelvic chronic inflammation. Furthermore, the collagen fiber and mechanical property of POP patients decreased with aging. Conclusions Taken together, this work provides a valuable resource for deciphering the aging-related immune cell types and the critical regulators in pelvic microenvironment. With better understanding of normal and abnormal events in this pelvic microenvironment, we provided rationales of personalized medicine for POP patients with different ages.

Pelvic organ prolapse (POP) seriously affects elderly patients’ quality of life, and new repair materials are urgently needed. To solve this problem, we synthesized methacrylated gelatin (GelMA) hydrogels and incorporated photothermally active Prussian blue nanoparticles (PBNPs) to synthesize PBNP@GelMA. Then, MSCs were encapsulated in the PBNP@GelMA and exposed to a 1.0 W/cm2 of 808 nm laser for 10 min to perform heat shock pretreatment for the implantation of mesenchymal stem cells (MSCs). Next, we tested the repair efficacy of scaffold–cell complexes both in vitro and in vivo. Our results reveal that the heat shock treatment induced by PBNP@GelMA improved the viability of MSCs, and the underlying mechanism may be related to HSP70. Furthermore, 2 weeks after implantation in the SD rat model, the collagen content increased in the MSC implantation group and PBNP@GelMA implantation group. However, the muscle regeneration at the implanting position was mostly enhanced after the implantation of the heat-shock-pretreated MSCs, which illustrates that heat shock treatment can further promote the MSC-mediated muscle regeneration. Therefore, manipulating the cell environment and providing proper heat stimulus by using PBNP@GelMA with NIR is a novel strategy to enhance the regenerative potential of MSCs and to promote pelvic tissue repair.