Search

Abstract Background Spermatogonial stem cells (SSCs) are essential for the maintenance and initiation of male spermatogenesis. Despite the advances in understanding SSC biology in mouse models, the mechanisms underlying human SSC development remain elusive. Results Here, we analyzed the signaling pathways involved in SSC regulation by testicular somatic cells using single-cell sequencing data (GEO datasets: GSE149512 and GSE112013) and identified that Leydig cells communicate with SSCs through pleiotrophin (PTN) and its receptor syndecan-2 (SDC2). Immunofluorescence, STRING prediction, and protein immunoprecipitation assays confirmed the interaction between PTN and SDC2 in spermatogonia, but their co-localization was observed only in approximately 50% of the cells. The knockdown of SDC2 in human SSC lines impaired cell proliferation, DNA synthesis, and the expression of PLZF, a key marker for SSC self-renewal. Transcriptome analysis revealed that SDC2 knockdown downregulated the expression of GFRA1, a crucial factor for SSC proliferation and self-renewal, and inhibited the HIF-1 signaling pathway. Exogenous PTN rescued the proliferation and GFRA1 expression in SDC2 knockdown SSC lines. In addition, we found downregulation of PTN and SDC2 as well as altered localization in non-obstructive azoospermia (NOA) patients, suggesting that downregulation of PTN and SDC2 may be associated with impaired spermatogenesis. Conclusions Our results uncover a novel mechanism of human SSC regulation by the testicular microenvironment and suggest a potential therapeutic target for male infertility.

Background: Spermatogonial stem cells (SSCs) are essential for male fertility, maintaining sperm production throughout life. While mouse SSCs have been studied extensively, the mechanisms regulating human SSCs are less understood. Objectives: To investigate the role of EEF1B2 in regulating human SSC proliferation and apoptosis. Material and methods: Single cell RNA sequencing (scRNA-seq) analysis was utilized to investigate the differentially expressed genes of SSC. The distribution of EEF1B2 in the human testis was examined using immunofluorescence and immunohistochemistry techniques. Cell proliferation, DNA replication, and self-renewal were analyzed using CCK8, EdU, Western blot, and flow cytometry. RNA sequencing was employed to analyze the downstream target molecules and signaling pathways of EEF1B2. Results: In this study, we analyzed single-cell sequencing data from human testicular samples and identified EEF1B2 as a protein highly expressed in SSCs, with expression decreasing during development. Immunohistochemistry and immunofluorescence confirmed this pattern and showed co-localization with the proliferation marker KI67. Knockdown of EEF1B2 in human SSC lines impaired proliferation and viability, reducing self-renewal proteins like PLZF and CCNE1. RNA sequencing revealed decreased TAF4B following EEF1B2 knockdown, which could be rescued by replenishing TAF4B. Testicular SSCs from non-obstructive azoospermia (NOA) patients also showed reduced EEF1B2. Discussion and conclusion: Our findings reveal a novel regulatory mechanism involving EEF1B2 and TAF4B in human SSCs, suggesting EEF1B2 deficiency may contribute to male infertility.

The model-based polarimetric interferometric synthetic aperture radar forest height inversion is inherently affected by nonideal system parameters, including channel imbalance, crosstalk, and noise. To investigate the impact of nonideal system parameters on the estimated forest height, this article introduces an analytical forest height inversion error model based on the two-layer randomly oriented volume over ground model. First, the error transfer function is derived to present the forest height error caused by the disturbance of the volume coherence. Then, the coupled effects of the nonideal system parameters on the volume coherence are established and demonstrated to reduce the amplitude of the volume coherence. The effects of channel imbalance and crosstalk are explicitly derived and found to be coupled together to amplify the noise. Finally, the error model is established by combining the error transfer function and the disturbance of the volume coherence caused by the nonideal system parameters. The proposed error model is verified by simulation analyses on real airborne repeat-pass BioSAR 2008 datasets. The results demonstrate that the proposed model can accurately capture the relationship between the height estimation errors and the system parameters.

(1) Background: Nonobstructive azoospermia (NOA) etiologies affect the sperm retrieval rate (SRR) by microdissection testicular sperm extraction (micro-TESE) and the clinical outcomes following intracytoplasmic sperm injection (ICSI); (2) Methods: We investigated seven NOA etiologies. The SRR and clinical outcomes of 627 patients were analyzed between November 2017 and July 2022 in the Reproductive and Genetic Hospital of China International Trust and Investment Corporation-Xiangya (CITIC-Xiangya); (3) Results: The overall SRR was 39.4% (247/627). The SRR according to NOA etiologies were: Y chromosome azoospermia factor c microdeletions (26/46, 56.5%), Klinefelter syndrome (KS), 36/85, 42.4%), idiopathic (110/398, 27.6%), cryptorchidism (20/29, 69.0%), chromosome anomalies (7/13, 53.9%), orchitis (45/50, 90.0%), and cancer (3/6, 50.0%). The SRR were different for spermatogonia arrest (26/96, 27.1%), maturation arrest (76/177, 42.9%), and SCOS (30/80, 37.5%) according to histological examinations. The clinical pregnancy rate was similar among the NOA etiologies. The high-quality embryo rate differed between successful (54.7%) and unsuccessful (40.9%) pregnancies. Moreover, the successfully pregnant women (28.99 years) were younger than the unsuccessfully pregnant ones (30.92 years); (4) Conclusions: The SRR from patients with NOA was associated with the etiology and histological categories, while the clinical outcome was associated with the high-quality embryo rate and the female partner’s age.

This paper presents a method for extracting the digital elevation model (DEM) of forested areas from polarimetric interferometric synthetic aperture radar (PolInSAR) data. The method models the ground phase as a Von Mises distribution, with a mean of the topographic phase computed from an external DEM. By combining the prior distribution of the ground phase with the complex Wishart distribution of the observation covariance matrix, we derive the maximum a posterior (MAP) inversion method based on the RVoG model and analyze its Cramer–Rao Lower Bound (CRLB). Furthermore, considering the characteristics of the objective function, this paper introduces a Four-Step Optimization (FSO) method based on gradient optimization, which solves the inefficiency problem caused by exhaustive search in solving ground phase using the MAP method. The method is validated using spaceborne L-band repeat-pass SAOCOM data from a test forest area. The test results for FSO indicate that it is approximately 5.6 times faster than traditional methods without compromising accuracy. Simultaneously, the experimental results demonstrate that the method effectively solves the problem of elevation jumps in DEM inversion when modeling the ground phase with the Gaussian distribution. ICESAT-2 data are used to evaluate the accuracy of the inverted DEM, revealing that our method improves the root mean square error (RMSE) by about 23.6% compared to the traditional methods.

Background: Few studies have focused on the associations between air pollutants and multiple organ system diseases in the entire hospitalized population. The present study aims to explore the short-term effects of six routinely monitored air pollutants on the broad causes of hospital admissions and estimate the resulting hospital admission burdens. Methods: Daily hospital admission records from 2017 to 2019 were obtained from the Wuhan Information center of Health and Family Planning. Generalized additive models (GAMs) were employed to evaluate the effects of air pollutants on the percent increase in the cause-specific daily number of hospital admissions. Increased hospital admission numbers, days, and expenses were also estimated. Results: A total of 2636,026 hospital admissions were identified. We found that both PM2.5 and PM10 increased the risk of hospital admissions for most disease categories. Short-term exposure to PM2.5 was positively associated with hospitalizations of several rarely studied disease categories, such as diseases of the eye and adnexa (2.83%, 95%CI: 0.96–4.73%, P

Spermatogonial stem cells are committed to initiating and maintaining male spermatogenesis, which is the foundation of male fertility. Understanding the mechanisms underlying SSC fate decisions is critical for controlling spermatogenesis and male fertility. However, the key molecules and mechanisms responsible for regulating human SSC development are not clearly understood. Here, we analyzed normal human testis single-cell sequencing data from the GEO dataset (GSE149512 and GSE112013). Melanoma antigen gene B2 (MAGEB2) was found to be predominantly expressed in human SSCs and further validated by immunohistology. Overexpression of MAGEB2 in SSC lines severely weakened cell proliferation and promoted apoptosis. Further, using protein interaction prediction, molecular docking, and immunoprecipitation, we found that MAGEB2 interacted with early growth response protein 1 (EGR1) in SSC lines. Reexpression of EGR1 in MAGEB2 overexpression cells partially rescued decreased cell proliferation. Furthermore, MAGEB2 was shown to be downregulated in specific NOA patients, implying that abnormal expression of MAGEB2 may impair spermatogenesis and male fertility. Our results offer new insights into the functional and regulatory mechanisms in MAGEB2-mediated human SSC line proliferation and apoptosis.

Study questionIs vacuolization in embryos on Days 3 and 4 associated with parent-related factors, stimulation protocols, embryo development, embryo ploidy, pregnancy and neonatal outcomes?Study design, size, durationThis is a retrospective cohort study that comprised 5,703 embryos from 611 patients who underwent preimplantation genetic testing and time-lapse monitoring of their embryos from August 2017 to September 2021.Main resultsEmbryo vacuolization on Days 3 and 4 is associated with the LH level on the day of the hCG trigger and the number of retrieved oocytes. Compared to vacuole-negative embryos, the rates of blastocyst formation and good-blastocyst formation was significantly lower in vacuole-positive embryos. We observed no significant difference in the rates of euploidy, implantation, ongoing pregnancy, and live birth between vacuole-positive and vacuole-negative embryos. In vacuole-positive embryos, the embryos of which the vacuole-positive blastomeres were involved in embryo compaction exhibited significantly higher mosaicism rate compared with those of which the vacuole-positive blastomeres were not involved in embryo compaction.ConclusionVacuolization in embryos on Days 3 and 4 is associated with reduced blastocyst formation rate and high-quality blastocyst rate. Blastocysts had a low mosaicism rate if the vacuole-containing cells were rejected in compaction process, which supports the hypothesis that exclusion of abnormal blastomeres from compaction is a self-correction mechanism.

Matrine (MAR), a quinolone alkaloid, was employed to augment the stability of zein nanoparticles. The incorporation of MAR into the hydrophobic shell of zein nanoparticles was primarily achieved through hydrogen bonding. Curcumin (CUR), a hydrophobic active substance, was encapsulated in the hydrophobic core of zein/matrine nanoparticles (ZMNPs). The preparation of ZMNPs and curcumin-loaded zein/matrine nanoparticles (CZMNPs) was accomplished using an antisolvent precipitation method. The encapsulation efficiency of curcumin in ZMNPs (zein/MAR = 8:1, 20 mg zein and 2.5 mg matrine) was significantly greater (52.64%) than that of nanoparticles produced from a single zein (2.50%). CZMNPs demonstrated a notable encapsulation efficiency and loading capacity (88.30% and 7.84%, respectively) upon the addition of 2 mg of curcumin, and were capable of sustained and gradual release of curcumin in simulated intestinal fluid. Furthermore, the stability of ZMNPs was observed to be favorable across a range of environmental conditions, including pH levels of 2–4 and 6–9, salt concentrations of ≤150 mM, temperatures of ≤90 °C, and storage at room temperature for a duration of 30 days. Additionally, the inherent anti-cancer properties of MAR make CZMNPs a more efficacious inhibitor of tumor cell proliferation in vitro . Moreover, the uptake of CZMNPs by A549 cells was significantly enhanced, potentially through the process of endocytosis. Therefore, the incorporation of matrine in zein-based nanoparticles confers anticancer properties to the resulting ZMNPs. These nanoparticles can serve as encapsulating agents for bioactive compounds in pharmaceutical formulations and as a novel delivery strategy for long-term cancer care. Specifically, matrine is anticipated to function as a potential stabilizer for other nanosystems.

Radargrammetry is a widely used methodology to generate the large-scale Digital Surface Model (DSM). Stereo matching is the most challenging step in radargrammetry due to the significant geometric differences and the inherent speckle noise. The speckle noise results in significant grayscale differences of the same feature points, which makes the traditional Horn–Schunck (HS) flow or multi-window zero-mean normalized cross-correlation (ZNCC) methods degrade. Therefore, this paper proposes an algorithm named Epipolar HS-NCC Flow (EHNF) for dense stereo matching, which is an improved HS flow method with normalized cross-correction constraint based on epipolar stereo images. First, the epipolar geometry is applied to resample the image to realize the coarse stereo matching. Subsequently, the EHNF method forms a global energy function to achieve fine stereo matching. The EHNF method constructs a local normalized cross-correlation constraint term to compensate for the grayscale invariance constraint, especially for the SAR stereo images. Additionally, two assessment methods are proposed to calculate the optimal cross-correlation parameter and smoothness parameter according to the refined matched point pairs. Two GaoFen-3 (GF-3) image pairs from ascending and descending orbits and the open Light Detection and Ranging (LiDAR) data are utilized to fully evaluate the proposed method. The results demonstrate that the EHNF algorithm improves the DSM elevation accuracy by 9.6% and 27.0% compared with the HS flow and multi-window ZNCC methods, respectively.

Cyclophosphamide (CYP)-induced cardiotoxicity is a common side effect of cancer treatment. Although it has received significant attention, the related mechanisms of CYP-induced cardiotoxicity remain largely unknown. In this study, we used cell and animal models to investigate the effect of CYP on cardiomyocytes. Our data demonstrated that CYP-induced a prolonged cardiac QT interval and electromechanical coupling time courses accompanied by JPH2 downregulation. Moreover, N6-methyladenosine (m6A) methylation sequencing and RNA sequencing suggested that CYP induced cardiotoxicity by dysregulating calcium signaling. Importantly, our results demonstrated that CYP induced an increase in the m6A level of JPH2 mRNA by upregulating methyltransferases METTL3, leading to the reduction of JPH2 expression levels, as well as increased field potential duration and action potential duration in cardiomyocytes. Our results revealed a novel mechanism for m6A methylation-dependent regulation of JPH2, which provides new strategies for the treatment and prevention of CYP-induced cardiotoxicity.

Spermatogonial stem cells (SSCs) are the initial cells for the spermatogenesis. Although much progress has been made on uncovering a number of modulators for the SSC fate decisions in rodents, the genes mediating human SSCs remain largely unclear. Here we report, for the first time, that TCF3, a member of the basic helix-loop-helix family of transcriptional modulator proteins, can stimulate proliferation and suppress the apoptosis of human SSCs through targeting podocalyxin-like protein (PODXL). TCF3 was expressed primarily in GFRA1-positive spermatogonia, and EGF (epidermal growth factor) elevated TCF3 expression level. Notably, TCF3 enhanced the growth and DNA synthesis of human SSCs, whereas it repressed the apoptosis of human SSCs. RNA sequencing and chromatin immunoprecipitation (ChIP) assays revealed that TCF3 protein regulated the transcription of several genes, including WNT2B, TGFB3, CCN4, MEGF6, and PODXL, while PODXL silencing compromised the stem cell activity of SSCs. Moreover, the level of TCF3 protein was remarkably lower in patients with spermatogenesis failure when compared to individuals with obstructive azoospermia with normal spermatogenesis. Collectively, these results implicate that TCF3 modulates human SSC proliferation and apoptosis through PODXL. This study is of great significance since it would provide a novel molecular mechanism underlying the fate determinations of human SSCs and it could offer new targets for gene therapy of male infertility.

In this paper, we introduce a refined three-stage inversion algorithm (TSIA) for forest height estimation using polarimetric interferometric synthetic aperture radar (PolInSAR). Specifically, the iterative extraction of the boundary of the coherence region (IEBCR) and iterative look-up table (ILUT) are proposed to improve the efficiency of traditional TSIA. A class of refined TSIA utilizes the boundary of the coherence region (BCR) to alleviate the underestimation phenomenon in forest height estimation. Given many eigendecompositions in the extraction of BCR (EBCR), we analyze the relationship of eigenvectors between the adjacent points on the BCR and propose the IEBCR utilizing the power methods. In the final inversion stage of TSIA, the look-up table (LUT) uses the exhaustive search method to minimize the loss function in the 2-D grid with defined step sizes and thus costs high computational complexity. To alleviate the deficiency, we define the random volume over ground (RVoG) function based on the RVoG model and prove its monotonicity and convergence from the analytical and numerical points of view. After analyzing the relationship between the RVoG function and the loss function, we propose the ILUT for the inversion stage. The simulation and experiments based on the BioSAR 2008 campaign data illustrate that the IEBCR and ILUT greatly improve the computational efficiency almost without compromising on accuracy.

Objectives: To assess associations between short-time air pollution exposure and outpatient visits for pneumonia by the distributed lag nonlinear model (DLNM). Methods: Daily outpatient visits for pneumonia and air pollutant data were collected from Wuhan Basic Medical Insurance Database in China and 10 national air quality monitoring stations in Wuhan from 2014 to 2017, respectively. Taking the first percentile of the concentration as the reference, DLNM was used to estimate the impact of moderate (50th) and high levels (99th) of pollutants on pneumonia. Results: A total of 133,882 outpatient visits were identified during the period of the study. Moderate-level (P50) fine particulate matter (PM2.5) or sulfur dioxide (SO2) and high-level nitrogen dioxide (NO2) (P99) can increase the risk of pneumonia. The maximum RR was 1.198 (95% CI: 1.094–1.311) at lag0-11, 1.304 (95% CI: 1.166–1.458) at lag0-13, and 1.286 (95% CI: 1.060–1.561) at lag0-14, respectively. Females and children had greater risks. Conclusions: Short-time PM2.5, SO2, and NO2 exposure were associated with outpatient visits for pneumonia in Wuhan, China.

Stress-strain relationship of geomaterials is important to numerical analysis in geotechnical engineering. It is difficult to be represented by conventional constitutive model accurately. Artificial neural network (ANN) has been proposed as a more effective approach to represent this complex and nonlinear relationship, but ANN itself still has some limitations that restrict the applicability of the method. In this paper, an alternative method, support vector machine (SVM), is proposed to simulate this type of complex constitutive relationship. The SVM model can overcome the limitations of ANN model while still processing the advantages over the traditional model. The application examples show that it is an effective and accurate modeling approach for stress-strain relationship representation for geomaterials. [ABSTRACT FROM AUTHOR]