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Abstract Background By interacting with bone marrow mesenchymal stem cells (BMSCs) and regulating their function through exosomes, bone macrophages play crucial roles in various bone-related diseases. Research has highlighted a notable increase in the number of M1 macrophages in glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). Nevertheless, the intricate crosstalk between M1 macrophages and BMSCs in the glucocorticoid-stimulated environment has not been fully elucidated, and the underlying regulatory mechanisms involved in the occurrence of GA-ONFH remain unclear. Methods We employed in vivo mouse models and clinical samples from GA-ONFH patients to investigate the interactions between M1 macrophages and BMSCs. Immunofluorescence staining was used to assess the colocalization of M1 macrophages and BMSCs. Flow cytometry and transcriptomic analysis were performed to evaluate the impact of exosomes derived from normal (n-M1) and glucocorticoid-stimulated M1 macrophages (GC-M1) on BMSC differentiation. Additionally, miR-1a-3p expression was altered in vitro and in vivo to assess its role in regulating adipogenic differentiation. Results In vivo, the colocalization of M1 macrophages and BMSCs was observed, and an increase in M1 macrophage numbers and a decrease in bone repair capabilities were further confirmed in both GA-ONFH patients and mouse models. Both n-M1 and GC-M1 were identified as contributors to the inhibition of osteogenic differentiation in BMSCs to a certain extent via exosome secretion. More importantly, exosomes derived from GC-M1 macrophages exhibited a heightened capacity to regulate the adipogenic differentiation of BMSCs, which was mediated by miR-1a-3p. In vivo and in vitro, miR-1a-3p promoted the adipogenic differentiation of BMSCs by targeting Cebpz and played an important role in the onset and progression of GA-ONFH. Conclusion We demonstrated that exosomes derived from GC-M1 macrophages disrupt the balance between osteogenic and adipogenic differentiation in BMSCs, contributing to the pathogenesis of GA-ONFH. Inhibiting miR-1a-3p expression, both in vitro and in vivo, significantly mitigates the preferential adipogenic differentiation of BMSCs, thus slowing the progression of GA-ONFH. These findings provide new insights into the regulatory mechanisms underlying GA-ONFH and highlight potential therapeutic targets for intervention. Graphical Abstract

Abstract Our previous research revealed a close association between the acetylation of peroxisome proliferator-activated receptor γ (PPARγ) histone H3K27 and the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). We preliminarily explored the epigenetic mechanism of steroid-induced avascular necrosis of the femoral head (SANFH) development, but the specific histone deacetylase (HDAC) involved in this regulatory process remains unknown. In this study, we combined cell, animal, and clinical specimen experiments to screen for specific HDAC genes that could regulate BMSC adipogenic differentiation and to explore their roles. The results showed that dexamethasone (DEX) significantly exacerbated the imbalance between the adipogenic and osteogenic differentiation of BMSCs, and there were differences in HDAC expression in the adipogenic differentiation cell models, with histone deacetylase 10 (HDAC10) showing the most significant decrease in expression. Subsequent use of a chromatin immunoprecipitation assay kit and quantitative polymerase chain reaction (ChIP‒qPCR) revealed a decrease in HDAC10 expression at predicted potential sites within the PPARγ promoter, indicating a significant decrease in HDAC10 enrichment in the PPARγ promoter region of BMSCs, thereby promoting sustained PPARγ expression. Additionally, immunohistochemistry of samples collected from mice and humans with SANFH and normal femoral heads revealed an imbalance between adipogenic and osteogenic differentiation in the necrotic area of femoral heads, with a significant decrease in the relative expression of HDAC10 in the necrotic area of femoral heads with SANFH. In summary, we speculate that HDAC10 affects the progression of SANFH by regulating BMSC adipogenic differentiation, a process possibly related to PPARγ histone acetylation. These findings provide a promising direction for the treatment of SANFH. Graphical abstract

Endometriosis is an estrogen-dependent disorder of the reproductive tract, affecting approximately 10 ​% of women. The symptoms of this condition are vague and not correlated with the disease's stage. These associated symptoms significantly impact women's overall well-being. The etiology of endometriosis remains inadequately understood, with coelomic metaplasia, lymphatic and vascular dissemination being regarded as additional hypotheses in addition to the retrograde menstruation theory. Endometriosis is primarily treated with drug therapy and surgical intervention, but the recurrence rate of symptoms after five years remains approximately 50 ​%. Therefore, the advancement of more effective and safe therapies for the treatment of endometriosis is of paramount importance. In this review, we introduce the utilization of photodynamic therapy, hyperthermia, gene therapy, immunotherapy, stem cell therapy, nanotechnology, and micron technology in the management of endometriosis. The objective is to provide novel research perspectives for therapeutic approaches and facilitate future clinical translation to enhance patient outcomes.

Objective: PARPi offers less clinical benefit for HRP patients compared to HRD patients. PARPi has an immunomodulatory function. NRT therapy targets tumor neoantigens without off-target immune toxicity. We explored the synergy between Niraparib and NRT in enhancing antitumor activity in an HRP ovarian cancer mouse model. Methods: In the C57BL/6 mouse ID8 ovarian cancer model, the effect of Niraparib on reshaping TIME was evaluated by immune cell infiltration analysis of transcriptomic data. The antitumor effects of Niraparib, NRT, and their combined use were systematically evaluated. To corroborate alterations in TILs, TAMs, and chemokine profiles within the TIME, we employed immunofluorescence imaging and transcriptome sequencing analysis. Results: Niraparib increased the M1-TAMs and activated CD8+ T cells in tumor tissues of C57BL/6 mice with ID8 ovarian cancer. GSEA showed that gene set associated with immature DC and INFα, cytokines and chemokines were significantly enriched in immune feature, KEGG and GO gene sets, meanwhile CCL5, CXCL9 and CXCL10 play dominant roles together. In the animal trials, combined group had a tumor growth delay compared with Niraparib group (P < 0.01) and control group (P < 0.001), and longer survival compared with the single agent group (P

Managing bone defects remains a formidable clinical hurdle, primarily attributed to the inadequate orchestration of vascular reconstruction and osteogenic differentiation in both spatial and temporal dimensions. This challenge persists due to the constrained availability of autogenous grafts and the limited regenerative capacity of allogeneic or synthetic bone substitutes, thus necessitating continual exploration and innovation in the realm of functional and bioactive bone graft materials. While synthetic scaffolds have emerged as promising carriers for bone grafts, their efficacy is curtailed by deficiencies in vascularization and osteoinductive potential. Nitric oxide (NO) plays a key role in revascularization and bone tissue regeneration, yet studies related to the use of NO for the treatment of bone defects remain scarce. Herein, we present a pioneering approach leveraging a photothermal-responsive system to augment NO release. This system comprises macromolecular mPEG-P nanoparticles encapsulating indocyanine green (ICG) (NO-NPs@ICG) and a mPEG-PA-PP injectable thermosensitive hydrogel carrier. By harnessing the synergistic photothermal effects of near-infrared radiation and ICG, the system achieves sustained NO release, thereby activating the soluble guanylate cyclase (SGC)-cyclic guanosine monophosphate (cGMP) signaling pathway both in vitro and in vivo. This orchestrated cascade culminates in the facilitation of angiogenesis and osteogenesis, thus expediting the reparative processes in bone defects. In a nutshell, the NO release-responsive system elucidated in this study presents a pioneering avenue for refining the bone tissue microenvironment and fostering enhanced bone regeneration.

Abstract This study aims to explore the effects of different non-landslide sampling strategies on machine learning models in landslide susceptibility mapping. Non-landslide samples are inherently uncertain, and the selection of non-landslide samples may suffer from issues such as noisy or insufficient regional representations, which can affect the accuracy of the results. In this study, a positive-unlabeled (PU) bagging semi-supervised learning method was introduced for non-landslide sample selection. In addition, buffer control sampling (BCS) and K-means (KM) clustering were applied for comparative analysis. Based on landslide data from Qiaojia County, Yunnan Province, China, collected in 2014, three machine learning models, namely, random forest, support vector machine, and CatBoost, were used for landslide susceptibility mapping. The results show that the quality of samples selected using different non-landslide sampling strategies varies significantly. Overall, the quality of non-landslide samples selected using the PU bagging method is superior, and this method performs best when combined with CatBoost for predicting (AUC = 0.897) landslides in very high and high susceptibility zones (82.14%). Additionally, the KM results indicated overfitting, displaying high accuracy for validation but poor statistical outcomes for zoning. The BCS results were the worst.

BackgroundThe mammalian testicular interstitial cells are not well-defined. The present study characterized the interstitial cell types and their turnover dynamics in adult rats. Additionally, the heterogeneity of the mesenchymal population and the effects of Leydig cell elimination on interstitial homeostasis were further analyzed by scRNA-seq datasets and immunocytochemical techniques.MethodsInterstitial cells were defined at the transcriptomic level by scRNA-seq and then confirmed and quantified with protein markers. The dividing activity of the major cell types was determined by continuous EdU labeling of the animals for one week. Some of the rats were also treated with a dose of ethylenedimethylsulfonate (EDS) to examine how the loss of Leydig cells (LCs) could affect interstitial homeostasis for three weeks.ResultsSeven interstitial cell types were identified, including cell types (percentage of the whole interstitial population) as follows: Leydig (44.6%), macrophage and dendritic (19.1%), lymphoid (6.2%), vascular endothelial (7.9%), smooth muscle (10.7%), and mesenchymal (11.5%) cells. The EdU experiment indicated that most cell types were dividing at relatively low levels (

Abstract Geopolymer concrete has similar mechanical properties to ordinary Portland cement (OPC) concrete, and even better properties in high temperature, high corrosion environment. However, geopolymer still has the disadvantages of large shrinkage and high brittleness, which greatly limit its application. Fiber reinforcement is widely used in various geopolymer systems to overcome the brittleness issue, but still retains the high strength. Over the past 10 years, great progress has been made in the research of fiber reinforced geopolymers in the aspect of toughening efficiency and durability improvement. Many studies have been conducted on fiber reinforced geopolymers, but there are still few systematic summaries on the addition of inorganic fibers and organic fibers to geopolymers. What is more there are many novel studies such as the application of geopolymers to 3D printing and the new concept of fiber factor have not been reviewed. In this paper, inorganic fibers, natural fibers and synthetic fibers in geopolymers are briefly reviewed, and their specific effects on geopolymers' compressive, flexural, tensile strength, fracture toughness, shear strength and durability such as shrinkage, chemical resistance, freeze–thaw resistance are reviewed. The current understanding of bonding mechanism and fiber‐geopolymer interface are also discussed, and related knowledge gaps and future work challenges are correspondingly pointed out.

AbstractThe landslide morphology is quickly and accurately extracted from Unmanned Air Vehicle (UAV) images. It is of great significance for emergency rescue and quantitative evaluation of landslide disasters. However, due to the complexity of landslide morphology, choosing the reasonable extraction thresholds is a challenging issue. A threshold selection method of Topographic Profile along the Direction of Slope Movement (TP-DSM) was proposed. Firstly, a hierarchical extraction rule sets for landslide morphology was constructed by integrating multi-feature information such as spectral, texture, geometry, topography and space of UAV images. Second, TP-DSM was proposed to select the optimal elevation thresholds for classifying different landslide morphology. Finally, the thresholds were introduced into the rule sets to achieve effective extraction of landslide morphology. This study uses Digital Orthophoto Map (DOM) and Digital Elevation Model (DEM) generated by UAV images as data sources, and the landslide in Luquan County, Yunnan Province, China as the Study area, the results show that the overall accuracy (OA) of landslide morphology extraction was 89.58%, and the Kappa coefficient was 0.88, which is effective and more consistent with the reality. The proposed method can also be applied to other potential locations.

Background: Endometriosis is a common chronic gynecologic disorder with a significant negative impact on women’s health. Wilms tumor 1-associated protein (WTAP) is a vital component of the RNA methyltransferase complex for N6-methyladenosine modification and plays a critical role in various human diseases. However, whether single nucleotide polymorphisms (SNPs) of the WTAP gene predispose to endometriosis risk remains to be investigated.Methods: We genotyped three WTAP polymorphisms in 473 ovarian endometriosis patients and 459 control participants using the Agena Bioscience MassArray iPLEX platform. The logistic regression models were utilized to assess the associations between WTAP SNPs and the risk of ovarian endometriosis.Results: In the single-locus analyses, we found that the rs1853259 G variant genotypes significantly increased, while the rs7766006 T variant genotypes significantly decreased the association with ovarian endometriosis risk. Combined analysis indicated that individuals with two unfavorable genotypes showed significantly higher ovarian endometriosis risk (adjusted OR = 1.71 [1.23–2.37], p = 0.001) than those with zero risk genotypes. In the stratified analysis, the risk effect of the rs1853259 AG/GG and rs7766006 GG genotypes was evident in subgroups of age ≤30, gravidity≤1, parity≤1, rASRM stage I, and the rs7766006 GG genotype was associated with worse risk (adjusted OR = 1.64 [1.08–2.48], p = 0.021) in the patients with rASRM stage II + III + IV. The haplotype analysis indicated that individuals with GGG haplotypes had a higher risk of ovarian endometriosis than wild-type AGG haplotype carriers. Moreover, false positive report probability and Bayesian false discovery probability analysis validated the reliability of the significant results. The quantitative expression trait loci analysis revealed that rs1853259 and rs7766006 were correlated with the expression levels of WTAP.Conclusion: Our findings demonstrated that WTAP polymorphisms were associated with susceptibility to ovarian endometriosis among Chinese women.

Objective: To analyze and summarize the experience of single-port robotic-assisted laparoscopic ambulatory surgery (AS) for intraligamental myomectomy. Methods: We analyzed the basic conditions, preoperative myoma assessment, surgical operation, and perioperative management of two patients undergoing robotic-assisted laparoendoscopic single site (R-LESS) intraligamental myomectomy and reviewed in the literature to summarize the initial clinical experience of the robotic AS model. Results: Two cases of R-LESS intraligamental myomectomy were successfully discharged after 29.82 ​h and 25.95 ​h of hospitalization, respectively, with no complications. Conclusion: R-LESS intraligamental myomectomy to achieve AS is safe and feasible. Adequate preoperative myoma evaluation, staging and strict access criteria, combined with current advanced single-port robotic technology and meticulous intraoperative management, and a scientific perioperative Enhanced Recovery After Surgery (ERAS) management process are vital factors to enable AS for intraligamental myomectomy.

Abstract Background The imbalance of osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is closely related to steroid-induced avascular necrosis of the femoral head (SANFH). We aimed to investigate the epigenetic mechanism of intramedullary fat accumulation and continuous osteonecrosis after glucocorticoid (GC) withdrawal in SANFH. Methods An SANFH model was established in SD rats, which received an intermittent high GC dose for the first 4 weeks followed by an additional 4 weeks without GC. We explored the synergistic effects and mechanisms of C/EBPα and PPARγ on the differentiation of BMSCs by lentivirus-mediated gene knockdown and overexpression assays. A chromatin immunoprecipitation assay was performed to identify epigenetic modification sites on PPARγ in vivo and in vitro. Results In the SANFH model, intramedullary fat was significantly increased, and the transcription factors C/EBPα and PPARγ were upregulated simultaneously in the femoral head. In vitro, C/EBPα promoted adipogenic differentiation of BMSCs by targeting the PPARγ signalling pathway, while overexpression of C/EBPα significantly impaired osteogenic differentiation. Further studies demonstrated that histone H3K27 acetylation of PPARγ played an important role in the epigenetic mechanism underlying SANFH. C/EBPα upregulates the histone H3K27 acetylation level in the PPARγ promoter region by inhibiting HDAC1. Additionally, inhibiting the histone acetylation level of PPARγ effectively prevented adipogenic differentiation, thus slowing the progression of SANFH. Conclusions Our results demonstrate the molecular mechanism by which C/EBPα regulates PPARγ expression by acetylating histones and revealed the epigenetic phenomenon in SANFH for the first time. Graphical abstract

BackgroundTestosterone plays a critical role in maintaining reproductive functions and well-beings of the males. Adult testicular Leydig cells (LCs) produce testosterone and are generated from stem Leydig cells (SLCs) during puberty through adulthood. In addition, macrophages are critical in the SLC regulatory niche for normal testicular function. Age-related reduction in serum testosterone contributes to a number of metabolic and quality-of-life changes in males, as well as age-related changes in immunological functions. How aging and testicular macrophages may affect SLC function is still unclear.MethodsSLCs and macrophages were purified from adult and aged mice via FACS using CD51 as a marker protein. The sorted cells were first characterized and then co-cultured in vitro to examine how aging and macrophages may affect SLC proliferation and differentiation. To elucidate specific aging effects on both cell types, co-culture of sorted SLCs and macrophages were also carried out across two ages.ResultsCD51+ (weakly positive) and CD51++ (strongly positive) cells expressed typical SLC and macrophage markers, respectively. However, with aging, both cell types increased expression of multiple cytokine genes, such as IL-1b, IL-6 and IL-8. Moreover, old CD51+ SLCs reduced their proliferation and differentiation, with a more significant reduction in differentiation (2X) than proliferation (30%). Age matched CD51++ macrophages inhibited CD51+ SLC development, with a more significant reduction in old cells (60%) than young (40%). Crossed-age co-culture experiments indicated that the age of CD51+ SLCs plays a more significant role in determining age-related inhibitory effects. In LC lineage formation, CD51+ SLC had both reduced LC lineage markers and increased myoid cell lineage markers, suggesting an age-related lineage shift for SLCs.ConclusionThe results suggest that aging affected both SLC function and their regulatory niche cell, macrophages.

Measurement(s) RNA sequence of rat testicular cells Technology Type(s) scRNA-seq Factor Type(s) Time course in weeks Sample Characteristic - Organism Sprague Dawley Rattus

In order to reduce the degree of efflorescence in alkali-activated metakaolin geopolymers, a modified 5A zeolite with cation-exchange properties was used to reduce the content of free alkali metal cations in the geopolymer. This work aims to investigate the effect of different dosages of modified 5A zeolite on the microstructure and properties of geopolymer by using compressive strength testing, pore structure analysis (BET), and SEM-EDS. The cation content in the leachate was evaluated using inductively coupled plasma atomic emission spectrometry (ICP-OES). The efflorescence area of the geopolymer was calculated using Image Pro Plus (IPP) software to evaluate the effect of modified 5A zeolite on the degree of efflorescence of the geopolymer and to reveal the effect of modified 5A zeolite on the migration patterns of Na+ and Ca2+ in the geopolymer. The results showed that modified 5A zeolite with a 4 wt.% content could optimize the pore structure and enhance the mechanical properties of MK geopolymer through internal curing and micro-aggregate effects, which could also exchange cations with the pore solution to form (N, C)-A-S-H gels. The Na+ leaching was reduced by 19.4%, and the efflorescence area of the MK geopolymer was reduced by 57.3%.

Landslide traces are crucial geomorphological features of landslides. Through the recognition of landslide traces, a better grasp of the topographical features of landslides can be achieved, thereby aiding in the enhancement of capabilities for the prevention, response, and management of landslides. Aiming at the complex topographic features of landslide traces, only using a single DEM product could provide a complete and comprehensive recognition of landslide traces. A method of landslide tracing recognition based on the fusion of multi-feature information from the Unmanned Aerial Vehicle-based Light Detection and Ranging (UAV-based LiDAR) Digital Elevation Model (DEM) is proposed. First, a high-precision DEM is constructed by using the LiDAR point cloud data. Based on the DEM, four multi-feature images that can enhance the landslide geomorphology are generated: hillshading, slope, positive openness, and sky-view factor. Furtherore, the DEM multi-feature images were fused using the Visualization for Archaeological Topography (VAT) method to obtain the DEM Multi-Feature Fusion Image (DEM-DFFI). Finally, the landslide traces were extracted from the DEM-DFFI based on fractal theory. The method presented in this paper makes full use of DEM multi-feature images and fuses them, which can accurately and clearly show the topographic and geomorphological features of landslides. Based on this, it helps improve landslide trace recognition accuracy.

Bioorthogonal reactions are a class of chemical reactions that can be carried out in living organisms without interfering with other reactions, possessing high yield, high selectivity, and high efficiency. Since the first proposal of the conception by Professor Carolyn Bertozzi in 2003, bioorthogonal chemistry has attracted great attention and has been quickly developed. As an important chemical biology tool, bioorthogonal reactions have been applied broadly in biomedicine, including bio-labeling, nucleic acid functionalization, drug discovery, drug activation, synthesis of antibody–drug conjugates, and proteolysis-targeting chimeras. Given this, we summarized the basic knowledge, development history, research status, and prospects of bioorthogonal reactions and their biomedical applications. The main purpose of this paper is to furnish an overview of the intriguing bioorthogonal reactions in a variety of biomedical applications and to provide guidance for the design of novel reactions to enrich bioorthogonal chemistry toolkits.

The number of input factors affects the prediction accuracy of a model. Factor screening plays an important role as the starting point for data input. The aim of this study is to explore the influence of different factor screening methods on the prediction results. Taking the 2014 landslide inventory of Jingdong County as an example, a landslide database was constructed based on 136 landslide events and 11 selected factors, which were randomly divided into a training dataset and a test dataset according to a ratio of 7:3. Four factor screening methods, namely, the information gain ratio (IGR), GeoDetector, Pearson correlation coefficient and multicollinearity test (MT), were selected to screen the factors. A random forest (RF) model was then used in combination with each factor set for landslide susceptibility mapping (LSM). Finally, accuracy validation was performed using confusion matrices and ROC curves. The results show that factor screening is beneficial in improving the accuracy of the resulting model compared to the original model. Second, the IGR_RF model had the highest AUC value (0.9334), which was higher than that of the MT_RF model without factor screening (0.9194), and the IGR_RF model predicted the most landslides in the very high susceptibility zone (51.22%), indicating the good prediction performance of the IGR_RF model. Finally, the factor weighting analysis revealed that NDVI, elevation and aspect had the greatest influence on landslides in Jingdong County and that curvature had the least influence on landslides. This study can provide a reference for factor screening in LSM.

The electromagnetic radiation (EMR) data collected along a road have a largely empty region overall, while they have a linear distribution locally. Moreover, the traditional spatial interpolation method is not suitable for the electromagnetic radiation space field (EMR-SF) construction collected along the road. In this paper, a layered radial basis function (LRBF) method is proposed to generate the EMR-SF, which interpolates from outside to inside in a layered strategy. First, the regular grid points are constructed based on RBF within the range of sampling data and then are layered based on Ripley’s K function. Second, on the basis of layering, the EMR of grid points is generated layer by layer using the LRBF method. Finally, EMR-SF is constructed by using the sampling data and grid points. The LRBF method is applied to EMR data from an area of Yunnan Normal University in Kunming, China. The results show that the LRBF accuracy is higher than that of the ordinary kriging (OK) and inverse-distance-weighted (IDW) interpolation methods. The LRBF interpolation accuracy can be improved through the strategy of regular grid point construction and layering, and the EMR-SF constructed by LRBF is more realistic than OK and IDW.

The trade-offs and synergies reveal the profit and loss relationship between ecosystem services, which is of great significance to the sustainable development of natural resources. The ecosystem services in Jiangxi Province, such as net primary productivity (NPP), soil conservation (SC) and water yield (WY) during 2000–2020, were estimated in this study. The correlation coefficient was adopted to analyze the trade-offs and synergies between the three ecosystem services by static space correlation and dynamic space correlation from such perspectives as Watershed, county and grid. Moreover, the influence of the three ecosystem services and the relations between them were explored from four aspects: landform, NDVI, accumulated temperature and precipitation. The results showed that the ecological environment quality in Jiangxi Province was improved and that the distribution of ecosystem services had significant regional characteristics. In the static analysis, ecosystem services at all scales were remarkably synergistic, and synergies weakened rapidly and even turned into trade-offs as the scale decreased. In the dynamic analysis, ecosystem services at all scales were mainly synergistic; the proportion of significant samples was much lower than that in the static analysis, the degree of trade-offs/synergies decreased with the decrease in scale, and the decrease was smaller than that in the static analysis. The major constraints for SC were landform and NDVI. The main constraint for WY was precipitation, and that for NPP was NDVI. Affected by various factors, NPP and SC were stably synergistic, NPP and WY were in a stable trade-off relationship, and the relationship between SC and WY was unstable. The trade-offs and synergies changed with factors and zoning.

Abnormal synthesis of extracellular matrix (ECM), especially collagen type IV (Col IV), in human retinal capillary endothelial cells (HRCECs) and resultant basement membrane (BM) thickening is the most prominent and characteristic feature of early diabetic retinopathy (DR). Osteopontin (OPN) has been shown to play an important role in the pathogenesis of DR and specifically, found to be critically involved in diabetic nephropathy, as it can upregulate many factors, like collagen IV. However, the precise role of OPN in the pathogenesis of DR and the underlying mechanisms remain unclear. In this study, 51 differentially expressed microRNAs (miRNAs; 42 miRNAs upregulated and 9 miRNAs downregulated) were first identified in retina of streptozotocin (STZ)-induced diabetic mice with DR. Among these miRNAs, we identified miRNA (miR)-29a as a prominent miRNA that targeted and directly downregulated Col IV expression through database prediction and dual-luciferase reporter assay, which was further confirmed in HRCECs using miR-29a mimic, miR-29a inhibitor, and pre-miR-29a transfection. Furthermore, OPN upregulated Col IV expression via a miR-29a-repressed pathway in HRCECs. Taken together, these results provided a miR-29a-repressing mechanism through which OPN plays roles in abnormal synthesis of Col IV in HRCECs and resultant BM thickening, contributing to the pathogenesis of DR.

Stem Leydig cells (SLCs) play a critical role in the development and maintenance of the adult Leydig cell (ALC) population. SLCs also are present in the adult testis. Their identification, characteristics, and regulation in the adult testis remain uncertain. Using single-cell RNA-seq, we found that the mesenchymal stromal population may be involved in ALC regeneration. Upon ALC elimination, a fraction of stromal cells begins to proliferate while a different fraction begins to differentiate to ALCs. Transcriptomic analysis identified five stromal clusters that can be classified into two major groups representing proliferation and differentiation populations. The proliferating group represents stem cells expressing high levels of CD90, Nes, Lum, Fn and Gap43. The differentiating group represents a progenitor stage that is ready to form ALCs, and specifically expresses Vtn, Rasl11a, Id1 and Egr2. The observation that the actively dividing cells after ALC loss were not those that formed ALCs suggests that stem cell proliferation and differentiation are regulated separately, and that the maintenance of the stromal stem cell pool occurs at the population level. The study also identified specific markers for the major interstitial cell groups and potential paracrine factors involved in the regulation of SLCs. Our data suggest a new theory about SLC identity, proliferation, differentiation, and regulation.

The effects of attapulgite and montmorillonite calcinated at 750 °C for 2 h as supplementary cementing materials (SCMs) on the working properties, mechanical strength, phase composition, morphology, hydration and heat release of ordinary Portland cement (OPC) were studied. The results show that pozzolanic activity increased with time after calcination, and with the increase in content of calcined attapulgite and calcined montmorillonite, the fluidity of cement paste exhibited a downward trend. Meanwhile, the calcined attapulgite had a greater effect on the decrease in the fluidity of cement paste than calcined montmorillonite, and the maximum reduction was 63.3%. Within 28 days, the compressive strength of cement paste with calcined attapulgite and montmorillonite was higher than that of the blank group in the later stage, and the optimum dosages of calcined attapulgite and montmorillonite were 6% and 8%, respectively. In addition, the compressive strength of these samples reached 85 MPa 28 days later. The introduction of calcined attapulgite and montmorillonite increased the polymerization degree of silico-oxygen tetrahedra in C-S-H gels during cement hydration, thereby contributing to accelerating the early hydration process. In addition, the hydration peak of the samples mixed with calcined attapulgite and montmorillonite was advanced, and the peak value was lower than that of the control group.

Immunotherapy has played a significant role in the treatment of a variety of hematological and solid tumors, but its application in ovarian cancer (OC) remains unclear. This study aimed to identify immune subtypes of OC and delineate an immune landscape for selecting suitable patients for immunotherapy, thereby providing potent therapeutic targets for immunotherapy drug development. Three immune subtypes (IS1–IS3) with distinctive molecular, cellular, and clinical characteristics were identified from the TCGA and GSE32062 cohorts. Compared to IS1, IS3 has a better prognosis and exhibits an immunological “hot”. IS3, in contrast, exhibits an immunological “cold” and has a worse prognosis in OC patients. Moreover, gene mutations, immune modulators, CA125, CA199, and HE4 expression, along with sensitivity either to immunotherapy or chemotherapy, were significantly different among the three immune subtypes. The OC immune landscape was highly heterogeneous between individual patients. Poor prognosis was correlated with low expression of the hub genes CD2, CD3D, and CD3E, which could act not only as biomarkers for predicting prognosis, but also as potential immunotherapy targets. Our study elucidates the immunotyping and molecular characteristics of the immune microenvironment in OC, which could provide an effective immunotherapy stratification method for optimally selecting patients, and also has clinical significance for the development of new immunotherapy as well as rational combination strategies for the treatment of OC patients.

The development of new or modified cementitious materials is an important part of existing strategies to improve performance and minimize life-cycle costs and to eliminate the CO2's impact on durability. The high anion exchange capacity of layered double hydroxides (LDHs) materials makes their interlayer ion exchange by organic and inorganic anions versatile and easily achieved. LDH-like materials could be used in cementitious materials for their CO32− capturing capacity and to enhance carbonation resistance of cementitious materials.In this work, original LDHs were synthesized, LDHs calcined at 500, 550 and 600 °C, respectively, were prepared. Power X-ray diffraction (XRD), IR-spectroscopy and thermal analysis (TG–DSC) were employed to characterize the component and structural changes of these types of LDHs before and after CO2 capture. Carbonation resistance of cement paste incorporating LDHs was experimentally evaluated for assessment of CO2 capture capacity of LDHs. Ion exchange mechanism of LDHs was also analyzed from adsorption experiments.The results show that LDH-like materials could be used for their CO32− capturing capacity to enhance carbonation resistance of concrete as well as to eliminate CO2's impact on durability aspect especially the LDHs calcined at 600 °C. Calcined LDHs fulfill the structure regeneration after CO2 capture. LDHs have positive effect on improvement of carbonation resistance of cement paste especially at later curing stages. Keywords: Layered double hydroxides (LDHs), Carbonation, Anion exchange, Adsorption, Cementitious materials

Purpose. To report the outcome of sutured intrascleral posterior chamber intraocular lens (PC IOL) fixation with ciliary sulcus location guided by ultrasonic biological microscopy (UBM). Methods. Patients who underwent a sutured intrascleral PC IOL fixation were reviewed and divided into four groups. In group 1, the traditional sulcus fixation (2 mm from limbus) of IOL was performed. In groups 2, 3, and 4, UBM was performed before surgery to locate the position of the ciliary sulcus as the haptics insertion position. IOL power was selected by decreasing the calculated value of the IOL power by 1.0 D, 1.0 D, 0.5 D, and 0.0 D, respectively. Results. Sixty-one patients (63 eyes) were included in the four groups. After 4.1 ± 3.0 months’ follow-up, the postsurgery spherical equivalent (SE) was 0.73 ± 1.86, 0.71 ± 0.84, 1.14 ± 0.45, and 0.07 ± 0.89 diopters (D), respectively. Statistical significance was reached for the postsurgery SE with target refraction between group 1 (p=0.027, 0.05), and the postsurgery SE in group 4 was the nearest to target refraction. Conclusion. Intrascleral PC IOL fixation guided by UBM is helpful for locating the ciliary sulcus and satisfactory visual outcomes with a predictable IOL power calculation.

Background/Aims: The treatment options for diabetic retinopathy (DR) are limited. Mesenchymal stem cells (MSCs) are a promising treatment option for diabetes and its complications. In this pilot clinical trial, we evaluated the safety and efficacy of intravenous autologous bone marrow MSCs (ABMSC) for the treatment of DR. Methods: In total, 34 eyes with non-proliferative or proliferative DR (NPDR, n = 19; PDR, n = 15) from 17 patients were analyzed. Treatment involved one intravenous infusion of 3 × 106/kg ABSMCs. The patients’ vital signs were monitored, along with immune and allergic reactions. Treatment efficacy was evaluated via measurements of the following parameters at baseline, and at 1, 3, and 6 months after treatment: the levels of fasting blood glucose (FBG), Hemoglobin A1C (HbA1C), interleukin-6 (IL-6), and hypersensitive C-reactive protein (CRP); best corrected visual acuity (BCVA); and central macular and subfield thickness (via optical computed tomography). Results: ABMSC infusion led to a significant decrease in FBG and CRP levels (P < 0.05). There were no significant differences in HbA1C or IL-6 levels. Sub-group analysis revealed that only eyes in the NPDR group had the macular thickness reductions and a significant improvement in BCVA from baseline (P = 0.006 at 3 months and 0.027 at 6 months), while those in the PDR group did not. There were no acute reactions during the treatment or severe adverse events during the follow-up period. Conclusion: ABSMCs are a potentially safe and effective treatment option for DR, and the optimum therapeutic window appears to be during the NPDR stage.

Abstract Background Endometriosis is a common, benign, and estrogen-dependent disease characterized by pelvic pain and infertility. To date, the pathogenesis of endometriosis remains unclear. Recent studies have demonstrated that noncoding RNAs, including microRNAs and long noncoding RNAs, play important roles in the development of endometriosis. Methods Expression profiling of miRNAs in endometrial tissue was characterized using microarrays. The most differentially expressed miRNAs were confirmed using quantitative reverse transcriptase-polymerase chain reaction analysis in additional ectopic endometrial (n = 27) and normal endometrial (n = 12) tissues. For in-vitro functional studies, 5-ethynyl-2′-deoxyuridine incorporation assay, Transwell assay, and dual-luciferase reporter assay were used to measure the proliferation, migration, and luciferase activity of miR-200c and the predicted targets of miR-200c in primary endometrial stromal cells (HESCs) derived from human endometrial biopsies, respectively. For in-vivo therapeutic interventions, polymeric nanoparticles of polyethylenimine–polyethylene glycol–arginine–glycine–aspartic acid were used for delivery of miR-200c mimic and inhibitor to determine the therapeutic effect of miR-200c in a rat model of endometriosis. Results Exogenous overexpression of miR-200c inhibited the proliferation and migration of HESCs, which were mainly regulated by metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). In contrast, inhibition of miR-200c promoted the proliferation and migration of HESCs, while the simultaneous silencing of MALAT1 expression exerted the opposite effects. We demonstrated that expression of MALAT1 in ectopic endometrial specimens was negatively correlated with that of miR-200c and that MALAT1 knockdown increased the level of miR-200c in HESCs. Moreover, the transfection of endometrial stromal cells with the miR-200c mimic or MALAT1 siRNAs decreased the protein levels of mesenchymal markers ZEB1, ZEB2, and N-cadherin and increased the protein levels of the epithelial marker E-cadherin. Furthermore, using a rat endometriosis model, we showed that local delivery of the miR-200c mimic significantly inhibited the growth of ectopic endometriotic lesions. Conclusions The MALAT1/miR-200c sponge may be a potential therapeutic target for endometriosis.

Abstract Retinitis pigmentosa (RP) is one of hereditary retinal diseases characterized by the loss of photoreceptors. Cell transplantation has been clinically applied to treat RP patients. Human retinal progenitor cells (HRPCs) and human bone marrow-derived mesenchymal stem cells (HBMSCs) are the two commonly and practically used stem cells for transplantation. Since combined transplantation could be a promising way to integrate the advantages of both stem cell types, we transplanted HRPCs and HBMSCs into the subretinal space (SRS) of Royal College of Surgeons (RCS) rats. We report that HRPCs/HBMSCs combined transplantation maintains the electroretinogram results much better than HRPCs or HBMSCs single transplantations. The thickness of outer nuclear layer also presented a better outcome in the combined transplantation. Importantly, grafted cells in the combination migrated better, both longitudinally and latitudinally, than single transplantation. The photoreceptor differentiation of grafted cells in the retina of RCS rats receiving combined transplantation also showed a higher ratio than single transplantation. Finally, activation of microglia and the gliosis of Müller cells were more effectively suppressed in combined transplantation, indicating better immunomodulatory and anti-gliosis effects. Taken together, combining the transplantation of HRPCs and HBMSCs is a more effective strategy in stem cell-based therapy for retinal degenerative diseases.

The grinding process has become widely used to improve the fineness and performance of fly ash. However, most studies focus on the particle size distribution of ground fly ash, while the particle morphology is also an important factor to affect the performance of cement paste. This article aims at three different kinds of ground fly ash from the ball mill and vertical mill, and the particle morphology is observed by scanning electron microscopy (SEM) to calculate the spherical destruction (the ratio of spherical particles broken into irregular particles in the grinding process of fly ash), which provides a quantification of the morphology change in the grinding process. The fluidity of cement paste and the strength of cement mortar are tested to study the relation of spherical destruction and fluidity and strength. The results show that the spherical destruction of ground fly ash in a ball mill is more than 80% and that in a vertical mill with a separation system is only 11.9%. Spherical destruction shows a significant relation with the fluidity. To different addition of ground fly ash, the fluidity of cement paste decreases with the increase of spherical destruction. To the strength of cement paste, particle size distribution and spherical destruction are both the key factors. Therefore, spherical destruction is an important measurement index to evaluate the grinding effect of the fly ash mill.

Due to the low hydration activity and poor volume stability, extensive steel slag utilization is restricted. In this paper, the hydration process and microstructure of alkali-activated materials with steel slag as a cementitious material and fine aggregate were studied. The phase composition and micro-morphology of hydration products were measured using XRD, NMR and SEM. The response relationship between microstructure and mechanical properties during hydration was revealed. The results show that the main hydration products of the alkali-activated steel slag powder-granulated blast furnace slag powder cementitious system are Ca(OH)2 and calcium aluminosilicate hydrate (C-A-S-H) gel. With the progress of hydration, the amount of calcium silicate hydrate (C-S-H) gel and the average molecular chain length increase, Al[4]/Si decreases, while C/S increases first and then decreases, and the structure of cement paste becomes much more compact. The interface between steel slag sand and cement paste is denser than that of river sand, since the hydration occurs on the surface of steel slag sand, which leads to the formation of C-A-S-H gel and Ca(OH)2. As a result, the compressive strength of concrete prepared by steel slag sand is higher than that of river sand with the same mix proportion.

The effects of 10% metakaolin addition on compressive strength, water absorption, shrinkage and microstructure evolution of cement paste after elevated temperatures exposure from room temperature to 800 °C were evaluated. The experimental results show that compressive strength increases at 200 °C and 400 °C compared with that obtained at ambient temperature. Up to 800 °C, compressive strength decreases rapidly. The addition of 10% metakaolin leads to the enhancement of compressive strength regardless of exposure temperatures. After thermal exposure at 400 °C, compressive strength reaches the maximum value. Thermal exposure degrades pore structure. A polynomial equation was used to indicate the shrinkage of cement paste or metakaolin-blended cement paste with testing days. Mechanical properties, permeability resistance, and shrinkage in cement pastes are closely related to the microstructure development. 10% metakaolin addition presents better thermal resistance, lower shrinkage and denser microstructure compared with pure cement paste before and after thermal exposure.

Background: There is an increasing interest in generating retinal pigment epithelial (RPE) cells from stem cells for therapy against degenerative eye diseases. Human bone marrow stromal cells (hBMSCs) can be induced to express retinal neuron-specific markers when co-cultured with retinal neurons, however, whether hBMSCs can differentiate into RPE-like cells in a co-culture system has not been clarified. Methods: The induction of hBMSCs into RPE-like cells was performed by combining hBMSCs and pig RPE cells in a transwell system. The biomarkers of hBMSCs-derived RPE cells were determined by quantitative RT-PCR and immunofluorescence. The function of induced cells was assayed by ELISA for secretion of neurotrophic factors. Results: Intracellular pigment granules and many RPE markers existed in hBMSCs-derived RPE cells after co-culturing with pig RPE cells for 14 days. Typical RPE functions, such as phagocytosis of photoreceptor outer segments and secretion of the trophic factors, brain-derived neurotrophic factor (BDNF) and glia-derived neurotrophic factor (GDNF), were observed in these induced cells. Conclusion: hBMSCs can be induced toward functional RPE cells simply by transwell-based co-culture with RPE cells.

Oblique imagery obtained from an Unmanned Aerial Vehicle (UAV) has been widely applied to large-scale three-dimensional (3D) reconstruction; however, the problems of partially missing model details caused by such factors as occlusion, distortion, and airflow, are still not well resolved. In this paper, a loop-shooting-aided technology is used to solve the problem of details loss in the 3D model. The use of loop-shooting technology can effectively compensate for losses caused by occlusion, distortion, or airflow during UAV flight and enhance the 3D model details in large scene- modeling applications. Applying this technology involves two key steps. First, based on the 3D modeling construction process, the missing details of the modeling scene are found. Second, using loop-shooting image sets as the data source, incremental iterative fitting based on aerotriangulation theory is used to compensate for the missing details in the 3D model. The experimental data used in this paper were collected from Yunnan Normal University, Chenggong District, Kunming City, Yunnan Province, China. The experiments demonstrate that loop-shooting significantly improves the aerotriangulation accuracy and effectively compensates for defects during 3D large-scale model reconstruction. In standard-scale distance tests, the average relative accuracy of our modeling algorithm reached 99.87% and achieved good results. Therefore, this technique not only optimizes the model accuracy and ensures model integrity, but also simplifies the process of refining the 3D model. This study can be useful as a reference and as scientific guidance in large-scale stereo measurements, cultural heritage protection, and smart city construction.

Change in urban construction land use is an important factor when studying urban expansion. Many scholars have combined cellular automata (CA) with data mining algorithms to perform relevant simulation studies. However, the parameters for rule extraction are difficult to determine and the rules are simplex, and together, these factors tend to introduce excessive fitting problems and low modeling accuracy. In this paper, we propose a method to extract the transformation rules for a CA model based on the Classification and Regression Tree (CART). In this method, CART is used to extract the transformation rules for the CA. This method first adopts the CART decision tree using the bootstrap algorithm to mine the rules from the urban land use while considering the factors that impact the geographic spatial variables in the CART regression procedure. The weights of individual impact factors are calculated to generate a logistic regression function that reflects the change in urban construction land use. Finally, a CA model is constructed to simulate and predict urban construction land expansion. The urban area of Xinyang City in China is used as an example for this experimental research. After removing the spatial invariant region, the overall simulation accuracy is 81.38% and the kappa coefficient is 0.73. The results indicate that by using the CART decision tree to train the impact factor weights and extract the rules, it can effectively increase the simulation accuracy of the CA model. From convenience and accuracy perspectives for rule extraction, the structure of the CART decision tree is clear, and it is very suitable for obtaining the cellular rules. The CART-CA model has a relatively high simulation accuracy in modeling urban construction land use expansion, it provides reliable results, and is suitable for use as a scientific reference for urban construction land use expansion.

OBJECTIVE: To investigate the modulation of microRNAs (miRNAs) upon the neuronal differentiation of mesenchymal stem cells (MSCs) through targeting RE-1 Silencing Factor (REST), a mature neuronal gene suppressor in neuronal and un-neuronal cells. METHODS: Rat bone marrow derived-MSCs were induced into neuron-like cells (MSC-NCs) by DMSO and BHA in vitro. The expression of neuron specific enolase (NSE), microtubule-associated protein tau (Tau), REST and its target genes, including synaptosomal-associated protein 25 (SNAP25) and L1 cell adhesion molecular (L1CAM), were detected in MSCs and MSC-NCs. miRNA array analysis was conducted to screen for the upregulated miRNAs after neuronal differentiation. TargetScan was used to predict the relationship between these miRNAs and REST gene, and dual luciferase reporter assay was applied to validate it. Gain and loss of function experiments were used to study the role of miR-29a upon neuronal differentiation of MSCs. The knockdown of REST was conducted to show that miR-29a affected this process through targeting REST. RESULTS: MSCs were induced into neuron-like cells which presented neuronal cell shape and expressed NSE and Tau. The expression of REST declined and the expression of SNAP25 and L1CAM increased upon the neuronal differentiation of MSCs. Among 14 upregulated miRNAs, miR-29a was validated to target REST gene. During the neuronal differentiation of MSCs, miR-29a inhibition blocked the downregulation of REST, as well as the upregulation of SNAP25, L1CAM, NSE and Tau. REST knockdown rescued the effect of miR-29a inhibition on the expression of NSE and Tau. Meanwhile, miR-29a knockin significantly decreased the expression of REST and increased the expression of SNAP25 and L1CMA in MSCs, but did not significantly affect the expression of NSE and Tau. CONCLUSION: miR-29a regulates neurogenic markers through targeting REST in mesenchymal stem cells, which provides advances in neuronal differentiation research and stem cell therapy for neurodegenerative diseases.

In cardiomyocytes, Ca2+ entry through voltage-dependent Ca2+ channels (VDCCs) binds to and activates RyR2 channels, resulting in subsequent Ca2+ release from the sarcoplasmic reticulum (SR) and cardiac contraction. Previous research has documented the molecular coupling of small-conductance Ca2+-activated K+ channels (SK channels) to VDCCs in mouse cardiac muscle. Little is known regarding the role of RyRs-sensitive Ca2+ release in the SK channels in cardiac muscle. In this study, using whole-cell patch clamp techniques, we observed that a Ca2+-activated K+ current (IK,Ca) recorded from isolated adult C57B/L mouse atrial myocytes was significantly decreased by ryanodine, an inhibitor of ryanodine receptor type 2 (RyR2), or by the co-application of ryanodine and thapsigargin, an inhibitor of the sarcoplasmic reticulum calcium ATPase (SERCA) (p

The constitutive expression of the high-risk HPV E6 and E7 viral oncogenes is the major cause of cervical cancer. To comprehensively explore the composition of HPV16 early transcripts and their genomic annotation, cervical squamous epithelial tissues from 40 HPV16-infected patients were collected for analysis of papillomavirus oncogene transcripts (APOT). We observed different transcription patterns of HPV16 oncogenes in progression of cervical lesions to cervical cancer and identified one novel transcript. Multiple-integration events in the tissues of cervical carcinoma (CxCa) are significantly more often than those of low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). Moreover, most cellular genes within or near these integration sites are cancer-associated genes. Taken together, this study suggests that the multiple-integrations of HPV genome during persistent viral infection, which thereby alters the expression patterns of viral oncogenes and integration-related cellular genes, play a crucial role in progression of cervical lesions to cervix cancer.

SET (SE Translocation) protein carries out multiple functions including those for protein phosphatase 2A (PP2A) inhibition, histone modification, DNA repair, and gene regulation. SET overexpression has been detected in brain neurons of patients suffering Alzheimer’s disease, follicle theca cells of Polycystic Ovary Syndrome (PCOS) patients, and ovarian cancer cells, indicating that SET may play a pathological role for these disorders. SET transcript 2, produced by a specific promoter, represents a major transcript variant in different cell types. In this study, we characterized the transcriptional activation of human SET transcript 2 promoter in HeLa cells. Promoter deletion experiments and co-transfection assays indicated that ZFX, the Zinc finger and X-linked transcription factor, was able to transactivate the SET promoter. A proximal promoter region containing four ZFX-binding sites was found to be critical for the ZFX-mediated transactivation. Mutagenesis study indicated that the ZFX-binding site located the closest to the transcription start site accounted for most of the ZFX-mediated transactivity. Manipulation of ZFX levels by overexpression or siRNA knockdown confirmed the significance and specificity of the ZFX-mediated SET promoter activation. Chromatin immunoprecipitation results verified the binding of ZFX to its cognate sites in the SET promoter. These findings have led to identification of ZFX as an upstream factor regulating SET gene expression. More studies are required to define the in vivo significance of this mechanism, and specifically, its implication for several benign and malignant diseases related to SET dysregulation.

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Adult mammalian ovaries contain stem/progenitor cells necessary for folliculogenesis and ovulation-related tissue rupture repair. Theca cells are recruited and developed from progenitors during the folliculogenesis. Theca cell progenitors were not well defined. The aim of current study is to compare the potentials of four ovarian progenitors with defined markers (LY6A, EPCR, LGR5, and PDGFRA) to form steroidogenic theca cells in vitro. The location of the progenitors with defined makers was determined by immunohistochemistry and immunofluorescence staining of ovarian sections of adult mice. Different progenitor populations were purified by magnetic-activated cell sorting (MACS) and/or fluorescence-activated cell sorting (FACS) techniques from ovarian cell preparation and were tested for their abilities to generate steroidogenic theca cells in vitro. The cells were differentiated with a medium containing LH, ITS, and DHH agonist for 12 days. The results showed that EPCR+ and LGR5+ cells primarily distributed along the ovarian surface epithelium (OSE), while LY6A+ cells distributed in both the OSE and parenchyma. However, PDGFRA+ cells were exclusively located in interstitial compartment. When the progenitors were purified by these markers and differentiated in vitro, LY6A+ and PDGFRA+ cells formed steroidogenic cells expressing both CYP11A1 and CYP17A1 and primarily producing androgens, showing characteristics of theca-like cells, while LGR5+ cells generated steroidogenic cells devoid of CYP17A1 expression and androgen production, showing a characteristic of progesterone-producing cells (granulosaor lutea-like cells). In conclusion, progenitors from both OSE and parenchyma of adult mice are capable of generating steroidogenic cells with different steroidogenic capacities, showing a possible lineage preference. [ABSTRACT FROM AUTHOR]