Design and Algorithm Integration of High-Precision Adaptive Underwater Detection System Based on MEMS Vector Hydrophone.

Real-time DOA (direction of arrival) estimation of surface or underwater targets is of great significance to the research of marine environment and national security protection. When conducting real-time DOA estimation of underwater targets, it can be difficult to extract the prior characteristics of noise due to the complexity and variability of the marine environment. Therefore, the accuracy of target orientation in the absence of a known noise is significantly reduced, thereby presenting an additional challenge for the DOA estimation of the marine targets in real-time. Aiming at the problem of real-time DOA estimation of acoustic targets in complex environments, this paper applies the MEMS vector hydrophone with a small size and high sensitivity to sense the conditions of the ocean environment and change the structural parameters in the adaptive adjustments system itself to obtain the desired target signal, proposes a signal processing method when the prior characteristics of noise are unknown. Theoretical analysis and experimental verification show that the method can achieve accurate real-time DOA estimation of the target, achieve an error within 3.1° under the SNR (signal-to-noise ratio) of the X channel of -17 dB, and maintain a stable value when the SNR continues to decrease. The results show that this method has a very broad application prospect in the field of ocean monitoring.

[Value of the human chorionic gonadotropin stimulation test in the diagnosis of disorder of sexual development in children]. / äººç»’æ¯›è†œä¿ƒæ€§è ºæ¿€ç´ æ¿€å‘è¯•éªŒåœ¨æ€§å‘è‚²å¼‚å¸¸å„¿ç«¥ä¸­çš„è¯Šæ–­ä½œç”¨è¯„ä¼°.

OBJECTIVES: To investigate the value of the human chorionic gonadotropin (hCG) stimulation test in the diagnosis of disorder of sexual development (DSD) in children. METHODS: A retrospective analysis was conducted on 132 children with DSD. According to the karyotype, they were divided into three groups: 46,XX group (n=10), 46,XY group (n=87), and sex chromosome abnormality group (n=35). The above groups were compared in terms of sex hormone levels before and after hCG stimulation test, and the morphological manifestation of the impact of testicular tissue on the results of the hCG stimulation test was analyzed. RESULTS: There was no significant difference in the multiple increase of testosterone after stimulation among the three groups (P>0.05). In the 46,XY group, the children with 5α-reductase type 2 deficiency had a testosterone-to-dihydrotestosterone ratio higher than that of the 46,XY DSD children with other causes. Morphological analysis showed that DSD children with testicular tissue demonstrated a significantly higher multiple increase in testosterone after stimulation compared to children without testicular tissue (P<0.05). CONCLUSIONS: The hCG stimulation test has an important value in assessing the presence and function of testicular interstitial cells in children with different types of DSD, and it is recommended to perform the hCG stimulation test for DSD children with unclear gonadal type.

PABPC1L induces IDO1 to promote tryptophan metabolism and immune suppression in renal cell carcinoma.

The tumor microenvironment (TME) in renal cell carcinomas (RCC) is marked by substantial immunosuppression and immune resistance despite having extensive T-cell infiltration. Elucidation of the mechanisms underlying immune evasion could help identify therapeutic strategies to boost the efficacy of immune checkpoint blockade (ICB) in RCC. This study uncovered a mechanism wherein the polyadenylate-binding protein PABPC1L modulates indoleamine 2,3-dioxygenase 1 (IDO1), a prospective target for immunotherapy. PABPC1L was markedly upregulated in RCC, and high PABPC1L expression correlated with unfavorable prognosis and resistance to ICB. PABPC1L bolstered tryptophan metabolism by upregulating IDO1, inducing T-cell dysfunction and Treg infiltration. PABPC1L enhanced the stability of JAK2 mRNA, leading to increased JAK2-STAT1 signaling that induced IDO1 expression. Additionally, PABPC1L-induced activation of the JAK2-STAT1 axis created a positive feedback loop to promote PABPC1L transcription. Conversely, loss of PABPC1L diminished IDO1 expression, mitigated cytotoxic T-cell suppression, and enhanced responsiveness to anti-PD-1 therapy in patient-derived xenograft models. These findings reveal the crucial role of PABPC1L in facilitating immune evasion in RCC and indicate that inhibiting PABPC1L could be a potential immunotherapeutic approach in combination with ICB to improve patient outcomes.

WDR4 gene polymorphisms and Wilms tumor susceptibility in Chinese children: A five-center case-control study.

Wilms tumor is the most common embryonal renal malignancy in children. WDR4 is an indispensable noncatalytic subunit of the RNA N7-methylguanosine (m7G) methyltransferase complex and plays an essential role in tumorigenesis. However, the relationship between polymorphisms in the WDR4 gene and susceptibility to Wilms tumor remains to be fully investigated. We performed a large case-control study involving 414 patients and 1199 cancer-free controls to investigate whether single nucleotide polymorphisms (SNPs) in the WDR4 gene are associated with Wilms tumor susceptibility. WDR4 gene polymorphisms (rs2156315 C > T, rs2156316 C > G, rs6586250 C > T, rs15736 G > A, and rs2248490 C > G) were genotyped using the TaqMan assay. In addition, unconditioned logistic regression analysis was performed, odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between WDR4 gene SNPs and Wilms tumor susceptibility as well as the strength of the associations. We found that only the rs6586250 C>T polymorphism was significantly associated with an increased risk of Wilms tumor (adjusted OR=2.99, 95% CI = 1.28-6.97, P = 0.011 for the rs6586250 TT genotype; adjusted OR=3.08, 95% CI = 1.33-7.17, P = 0.009 for the rs6586250 CC/CT genotype). Furthermore, the stratification analysis revealed that patients with the rs6586250 TT genotype and carriers with 1-5 risk genotypes exhibited statistically significant associations with increased Wilms tumor risk in specific subgroups. However, the rs2156315 CT/TT genotype was identified as having a protective effect against Wilms tumor in the age >18 months subgroup compared with the rs2156315 CC genotype. In brief, our study demonstrated that the rs6586250 C > T polymorphism of the WDR4 gene was significantly associated with Wilms tumor. This finding may contribute to the understanding of the genetic mechanism of Wilms tumor.

A Flexible Pressure Sensor Based on Silicon Nanomembrane.

With advances in new materials and technologies, there has been increasing research focused on flexible sensors. However, in most flexible pressure sensors made using new materials, it is challenging to achieve high detection sensitivity across a wide pressure range. Although traditional silicon-based sensors have good performance, they are not formable and, because of their rigidity and brittleness, they are not suitable for fitting with soft human skin, which limits their application in wearable devices to collect various signals. Silicon nanomembranes are ultra-thin, flexible materials with excellent piezoresistive properties, and they can be applied in various fields, such as in soft robots and flexible devices. In this study, we developed a flexible pressure sensor based on the use of silicon nanomembranes (with a thickness of only 340 nm) as piezoresistive units, which were transferred onto a flexible polydimethylsiloxane (PDMS) substrate. The flexible pressure sensor operated normally in the range of 0-200 kPa, and the sensitivity of the sensor reached 0.0185 kPa-1 in the low-pressure range of 0-5 kPa. In the high-pressure range of 5-200 kPa, the sensitivity of the sensor was maintained at 0.0023 kPa-1. The proposed sensor exhibited a fast response and excellent long-term stability and could recognize human movements, such as the bending of fingers and wrist joints, while maintaining a stable output. Thus, the developed flexible pressure sensor has promising applications in body monitoring and wearable devices.

Clinical characteristics, socioeconomic factors and COVID-19 were associated with delayed surgery in children with hypospadias: a retrospective study of 4439 cases in a single center.

BACKGROUND: Hypospadias is one of the most common congenital diseases of the genitourinary system in children. The European Association of Urology (EAU) Guidelines recommend that children undergoing hypospadias surgery should be between 6 and 18 months. In China, where many children have hypospadias, it remains unknown whether clinical characteristics, socioeconomic factors and COVID-19 were associated with delayed surgery in children with hypospadias. METHODS: We retrospectively analyzed children with hypospadias who underwent primary surgery at the Department of Pediatric Urology in Guangzhou Women and Children's Medical Center between January 2010 and October 2021. Patients who had two-stage surgery or a second round of surgery due to complications were excluded to eliminate data duplication. The clinical characteristics and demographic information were collected. We defined delayed surgery as primary surgery performed after 18 months following the EAU Guidelines. RESULTS: A total of 4439 children diagnosed with hypospadias were included in the study. The median age (29.1 ± 16.7 months) of surgery for hypospadias in our study was much higher than the recommended age reported in the EAU guidelines, and 76.6% of the children underwent surgery after the age of 18 months. Children without comorbidities including cryptorchidism (odds ratio [OR] = 1.562; 95% confidence interval [CI] 1.199-2.034; p = 0.001), prostatic cyst (OR = 2.613; 95% CI 1.579-4.324; p < 0.001), penile hypoplasia (OR = 1.778; 95% CI 1.225-2.580; p = 0.002), inguinal hernia (OR = 2.070; 95% CI 1.394-3.075; p < 0.001), and penoscrotal transposition (OR = 4.125; 95% CI 1.250-13.619; p = 0.020) were more likely to receive delayed surgery. Living in a low economic area (OR = 1.731; 95% CI 1.068-2.806; p = 0.026) or not close to a main medical center (OR = 1.580; 95% CI 1.370-1.824; p < 0.001) was highly associated with delayed surgery. The proportion of children undergoing delayed surgery and the median age of surgery during the COVID-19 pandemic were significantly higher than those before the COVID-19 pandemic (p = 0.004 and < 0.001, respectively). CONCLUSIONS: Most children with hypospadias received delayed surgery (surgical age > 18 months). Comorbidities, living in a low economic area, too far from a main medical center and the COVID-19 pandemic were highly associated with delayed surgery. It is vital to improve the public awareness of hypospadias and strengthen the re-education of primary community doctors to reduce delayed surgery.

Quality of Internet Videos Related to Pediatric Urology in Mainland China: A Cross-Sectional Study.

Background: Pediatric urological diseases pose serious threats to children's physical and mental health. The COVID-19 pandemic has resulted in poor pediatric outcomes for cryptorchidism, hypospadias, and testicular torsion. Presently, many people tend to seek health information via social media platforms. This study aims to quantitatively assess the quality of videos as an information source for pediatric urology in mainland China. Methods: In this cross-sectional study, a search was performed on social media platforms (Tiktok, Bilibili, and Weibo) with the search terms "cryptorchidism", "hypospadias", and "testicular torsion". The first 30 results with any search term listed by relevance were selected in each platform. Video features (duration, number of likes, comments, and shares) and video sources were collected. Each video included in the study was assessed using DISCERN, Journal of the American Medical Association (JAMA) Benchmark Criteria, and Hexagonal Radar Schema. A correlation analysis was performed considering video features, video source, DISCERN scores and JAMA scores. Results: A total of 152 videos were included and analyzed. The majority of videos were from physicians (65.8%). According to the DISCERN classification, most videos were rated as "very poor" (48.0%) and "poor" (36.8%). The mean DISCERN and JAMA scores were 36.56 and 2.68, respectively. The duration of videos uploaded by physicians was the shortest (P < 0.001). The video source had no relevance to numbers of "likes", "comments", "shares", DISCERN scores, and JAMA scores (all P-values > 0.05). Other than video duration (P < 0.001), there was no statistically significant difference between groups for any of the recorded or calculated video data (all P values > 0.05). Hexagonal Radar Charts showed the severe imbalance and deficiency of video information. In general, Tiktok videos with the shortest duration received the most numbers of "likes", "comments", and "shares", whereas the overall quality of videos on Weibo was relatively high. Conclusions: Despite most of the videos on social media platforms being uploaded by medical authors, the overall quality was poor. The misleading, inaccurate and incomplete information may pose a health risk to the viewers, especially during the COVID-19 pandemic. Much effort needs to be undertaken to improve the quality of health-related videos regarding pediatric urology.

High-Efficiency Water Recovery from Urine by Vacuum Membrane Distillation for Space Applications: Water Quality Improvement and Operation Stability.

Water recovery by membrane distillation (MD) is an attractive alternative to existing urine treatment systems because it could improve the water recovery rate and reliability in space missions. However, there are few studies of urine MD, particularly on the removal of the remaining contaminants from distillate water and the assessment of its long-term performance. In this study, the influences of various operation parameters on distillate water quality and operation stability were investigated in batch mode. The low pH of feedstock reduced the conductivity and total ammonium nitrogen (TAN) in distillate water because the low pH promoted the ionization of ammonia to ammonium ions. However, the low pH also facilitated the formation of free chlorine hydride, which resulted in the minor deterioration of the conductivity in the distillate due to the increasing volatility of chlorine hydride in the feedstock. Thirty batches of vacuum membrane distillation (VMD) experiments demonstrated that the permeate flux and the distillate water quality slightly decreased due to the small range of membrane wetting but still maintained an over 94.2% and 95.8% removal efficiency of the total organic carbon (TOC) and TAN, and the conductivity was <125 µs cm−1 in the distillate water after 30 test batches. VMD is a feasible option for urine treatment in space missions.

Quality Assessment of YouTube Videos as an Information Source for Testicular Torsion.

Background: Testicular torsion is an acute scrotal disease requiring urgent management, and the COVID-19 pandemic has been demonstrated to lead to poor outcomes for this disease. Presently, many people tend to seek health information via YouTube. This study aims to quantitatively assess the quality of English YouTube video content as an information source of testicular torsion. Methods: In this cross-sectional study, a search was performed with the search term "testicular torsion" on YouTube, and the first 100 videos listed by relevance were selected for our analysis. Duplicate, non-English, videos without audio and surgical videos were excluded. Video features (duration, number of days online, views, likes, comments), source of the video, and author's country were collected. Each video included in the study was assessed using DISCERN and Journal of the American Medical Association (JAMA) Benchmark Criteria. A correlation analysis was performed considering video features, video source, DISCERN scores and JAMA scores. Results: A total of 66 videos were included and analyzed. The most common video content was general information, including etiology, symptoms, and treatment. The majority of videos were from education and training websites (30%), physicians (23%), and independent users (21%). The mean DISCERN and JAMA scores were 36.56 and 2.68, respectively. According to DISCERN, the quality of video uploaded by physicians was relatively high (P < 0.001), and the quality of video uploaded by independent users was relatively low (P < 0.001). The JAMA score had no relevance to the video source (P = 0.813). The correlation between the video features, DISCERN and JAMA scores was controversial by different assessment methods. Conclusions: Despite most of the videos on YouTube being uploaded by medical or education-related authors, the overall quality was poor. The misleading, inaccurate and incomplete information may pose a health risk to the viewers, especially during the COVID-19 pandemic. Much effort needs to be undertaken to improve the quality of health-related videos regarding testicular torsion.

The inhibition of CFTR in the descended testis of SD rats with unilateral cryptorchidism induced by di-(2-ethylhexyl) phthalate (DEHP).

Di-(2-ethylhexyl) phthalate (DEHP) is a kind of environmental endocrine disruptors (EEDs), which has been confirmed to cause serious consequences, such as cryptorchidism. Patients with unilateral cryptorchidism still had oligospermia or infertility even if they received orchidopexy before puberty. Testicular dysgenesis syndrome (TDS) attributes this kind of problems to the abnormal testicular development during the embryonic period, and considers that the environmental exposure factors during pregnancy play a major role. Therefore, for unilateral cryptorchidism, even if one testicle has dropped to scrotum, it may be exposed to these substances and cause damage. Cystic fibrosis transmembrane conduction regulator (CFTR) is very important for the maturation of male reproductive system. Previously, cryptorchidism was thought to cause abnormal expression of heat sensitive protein CFTR in testis, but the expression of CFTR in healthy side (descended side) testis was not clear. In this study, we established SD rats with unilateral cryptorchidism by exposure to DEHP (500 mg/kg/day) during pregnancy, and detected the expression of CFTR and downstream signal NF-κB/COX-2/PGE2 in bilateral testis. Finally, we found that the expression of CFTR and downstream signal NF-κB/COX-2/PGE2 in the undescended testis was significantly abnormal, but the expression of them in the descended testis was also abnormal to some extent. Therefore, we speculate that in addition to high temperature will affect the expression of CFTR, there may be other factors that cause abnormal expression of CFTR induced by DEHP, and lead to abnormal male reproductive function eventually, but the specific mechanism needs to be further studied.

Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study.

BACKGROUND: The 2019 coronavirus disease pandemic (COVID-19) poses an enormous threat to public health worldwide, and the ensuing management of social isolation has greatly decreased opportunities for physical activity (PA) and increased opportunities for leisure sedentary behaviors (LSB). Given that both PA and LSB have been established as major influencing factors for obesity, diabetes and cardiometabolic syndrome, whether PA/LSB in turn affects the susceptibility to COVID-19 by disrupting metabolic homeostasis remains to be explored. In this study, we aimed to systematically evaluate the causal relationship between PA/LSB and COVID-19 susceptibility, hospitalization and severity using a Mendelian randomization study. METHODS: Data were obtained from a large-scale PA dataset (N = 377,000), LSB dataset (N = 422,218) and COVID-19 Host Genetics Initiative (N = 2,586,691). The causal effects were estimated with inverse variance weighted, MR-Egger, weighted median and MR-PRESSO. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot. Risk factor analyses were further conducted to investigate the potential mediators. RESULTS: Genetically predicted accelerometer-assessed PA decreased the risk for COVID-19 hospitalization (OR = 0.93, 95% CI 0.88-0.97; P = 0.002), while leisure television watching significantly increased the risk of COVID-19 hospitalization (OR = 1.55, 95% CI 1.29-1.88; P = 4.68 × 10-6) and disease severity (OR = 1.85, 95% CI 1.33-2.56; P = 0.0002) after Bonferroni correction. No causal effects of self-reported moderate to vigorous physical activity (MVPA), accelerometer fraction of accelerations > 425 milligravities, computer use or driving on COVID-19 progression were observed. Risk factor analyses indicated that the above causal associations might be mediated by several metabolic risk factors, including smoking, high body mass index, elevated serum triglyceride levels, insulin resistance and the occurrence of type 2 diabetes. CONCLUSION: Our findings supported a causal effect of accelerometer-assessed PA on the reduced risk of COVID-19 hospitalization as well as television watching on the increased risk of COVID-19 hospitalization and severity, which was potentially mediated by smoking, obesity and type 2 diabetes-related phenotypes. Particular attention should be given to reducing leisure sedentary behaviors and encouraging proper exercise during isolation and quarantine for COVID-19.

HAAO rs3816183 Polymorphisms [T] Increase Anterior/Middle Hypospadias Risk in Southern Han Chinese Population.

Hypospadias is one of the most common congenital external genital malformations, which is characterized by abnormal urethral meatus. However, the etiology remains to be incompletely understood. HAAO is a gene that encodes a protein, which catalyzes the synthesis of quinolinic acid, and has been identified as a risk gene for hypospadias. Thus, this study was conducted to elaborate the association between HAAO gene polymorphism rs3816183 T>C and hypospadias in the largest hypospadias cohort from Asia, including 577 patients and 654 healthy controls in China. The strength of interrelation was evaluated using 95% confidence intervals (CIs) and odds ratios (ORs). Based on the stratified analysis of hypospadias subtypes, it was found that the HAAO risk allele rs386183[T] enhances the susceptibility for hypospadias among patients with anterior/middle hypospadias subtypes (adjusted OR = 1.31, 95% CI = 1.05-1.64, p = 0.017). Enhanced risk of hypospadias in the entirety could not be demonstrated (OR = 1.20, 95% CI = 1.00-1.47, p = 0.054). In summary, our study found that the rs3816183[T] polymorphism is associated with increased risk of anterior/middle hypospadias among Southern Han Chinese children. The mechanisms by which the variations in the HAAO gene require further research.

Aggregation caused quenching to aggregation induced emission transformation: a precise tuning based on BN-doped polycyclic aromatic hydrocarbons toward subcellular organelle specific imaging.

Polycyclic aromatic hydrocarbons (PAHs) with boron-nitrogen (BN) moieties have attracted tremendous interest due to their intriguing electronic and optoelectronic properties. However, most of the BN-fused π-systems reported to date are difficult to modify and exhibit traditional aggregation-caused quenching (ACQ) characteristics. This phenomenon greatly limits their scope of application. Thus, continuing efforts to seek novel, structurally distinct and functionally diverse structures are highly desirable. Herein, we proposed a one-stone-two-birds strategy including simultaneous exploration of reactivity and tuning of the optical and electronic properties for BN-containing π-skeletons through flexible regioselective functionalization engineering. In this way, three novel functionalized BN luminogens (DPA-BN-BFT, MeO-DPA-BN-BFT and DMA-DPA-BN-BFT) with similar structures were obtained. Intriguingly, DPA-BN-BFT, MeO-DPA-BN-BFT and DMA-DPA-BN-BFT exhibit completely different emission behaviors. Fluorogens DPA-BN-BFT and MeO-DPA-BN-BFT exhibit a typical ACQ effect; in sharp contrast, DMA-DPA-BN-BFT possesses a prominent aggregation induced emission (AIE) effect. To the best of our knowledge, this is the first report to integrate ACQ and AIE properties into one BN aromatic backbone with subtle modified structures. Comprehensive analysis of the crystal structure and theoretical calculations reveal that relatively large twisting angles, multiple intermolecular interactions and tight crystal packing modes endow DMA-DPA-BN-BFT with strong AIE behavior. More importantly, cell imaging demonstrated that luminescent materials DPA-BN-BFT and DMA-DPA-BN-BFT can highly selectively and sensitively detect lipid droplets (LDs) in living MCF-7 cells. Overall, this work provides a new viewpoint of the rational design and synthesis of advanced BN-polycyclic aromatics with AIE features and triggers the discovery of new functions and properties of azaborine chemistry.

Seismic Random Noise Denoising Using Mini-Batch Multivariate Variational Mode Decomposition.

Seismic noise attenuation plays an important role in seismic interpretation. The empirical mode decomposition, synchrosqueezing wavelet transform, variational mode decomposition, etc., are often applied trace by trace. Multivariate empirical mode decomposition, multivariate synchrosqueezing wavelet transform, and multivariate variational mode decomposition were proposed for lateral continuity consideration. Due to large input data, mini-batch multivariate variational mode decomposition is proposed in this paper. The proposed method takes advantages both of variational mode decomposition and multivariate variational mode decomposition. This proposed method firstly segments the input data into a series of smaller ones with no overlapping and then applies multivariate variational mode decomposition to these smaller ones. High frequency-domain noise is filtered through sifting. Finally, the denoised smaller ones are concatenated to form components (or intrinsic mode functions) of the input signal. Synthetic and field data experiments validate the proposed method with different batch sizes and achieve higher signal-to-noise ratio than the variational mode decomposition method.

Causal relationship between 14 site-specific cancers and venous thromboembolism.

Background: It has been observed that cancer and venous thromboembolism (VTE) are associated, but anticancer therapy may violate the causality. Therefore, this study aimed to elucidate the causal relationship of various cancers to VTE using Mendelian randomization (MR). Methods: Three MR methods were used to estimate causal effects: Inverse variance weighted (IVW), MR-Egger and weighted median. Sensitivity analyses included Cochran's Q-test, MR-Egger intercept test and MR-PRESSO. Gene ontology enrichment analysis was performed to elucidate the underlying mechanisms of VTE development in cancer patients. Results: The primary IVW approach showed that non-Hodgkin's lymphoma (NHL) might increase the risk of VTE (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.00-1.44, p = 0.045), while melanoma possibly reduced the risk of VTE (OR: 0.89, 95% CI: 0.82-0.97, p = 0.006), although there was no significance after adjustment for multiple testing. No association was observed between VTE risk and other site-specific cancers. Gene ontology enrichment analysis revealed that vitamin D played an important role in the development of VTE in cancer patients. Conclusions: Our findings suggested that genetically predicted NHL was associated with higher VTE risk, whereas melanoma had lower VTE risk compared with other site-specific cancers. Moreover, this study suggested that anticancer therapy and increased extensive examination might play a more important role in VTE development than the nature of cancer.

Association between LIN28B gene polymorphisms and Wilms' tumor susceptibility.

Aim: To survey the association between LIN28B gene polymorphisms and the increased risk of Wilms' tumor (WT). Methods: Five LIN28B polymorphisms (rs314276 C>A, rs221634 A>T, rs221635 T>C, the rs4145418 A>C and rs9404590 T>G) were genotyped in 355 WT patients and 1070 healthy controls to assess the association. Result: The rs314276 CA/AA genotype was a protective factor against WT (corrected odds ratio [OR]: 0.71; p = 0.006). Individuals older than 18 months (corrected OR: 0.60; p = 0.001), males (corrected OR: 0.65; p = 0.011) and in clinical stage I + II patients (corrected OR: 0.60; p = 0.0008) with this genotype were less susceptible to WT. Conclusion: The rs314276 CA/AA genotype may protect against WT.

Prenatal exposure to environmentally relevant levels of PBDE-99 leads to testicular dysgenesis with steroidogenesis disorders.

Polybrominated diphenyl ethers (PBDEs) are a widely used class of brominated flame retardants. Exposure to PBDEs could induce testicular damage in mammals, but the effects and potential mechanism of action of prenatal exposure to environmentally relevant PBDEs on testicular development remain unclear. For the in vivo study, pregnant ICR mice were exposed to environmentally relevant levels of 2,2',4,4',5-pentabromodiphenyl ether (PBDE-99), a major component of commercial PBDE mixtures. We found that the anogenital index and testicular organ coefficient were significantly decreased, the incidence of cryptorchidism was increased, and testicular histology was disturbed in male offspring. Transcriptomic profiling showed that steroidogenesis disorders were significant in all PBDE-99 exposure groups. The testosterone levels, expressions of testosterone regulators, and the number of CYP11A1-positive and 11ß-HSD1-positive Leydig cells were significantly decreased after PBDE-99 exposure. For the in vitro study, TM3 Leydig cells were exposed to PBDE-99 at gradient concentrations. Transcriptomic profiling and validation experiments showed that PBDE-99 upregulated reactive oxygen species, activated the ERK1/2 pathway, inhibited the ubiquitination degradation pathway, and finally induced Leydig cell apoptosis. Cumulatively, these findings revealed that prenatal exposure to environmentally relevant levels of PBDE-99 leads to steroidogenesis disorders by inducing the apoptosis of Leydig cells, causing testicular dysgenesis.

METTL14 gene polymorphisms decrease Wilms tumor susceptibility in Chinese children.

BACKGROUND: Wilms tumor is a highly heritable malignancy. Aberrant METTL14, a critical component of N6-methyladenosine (m6A) methyltransferase, is involved in carcinogenesis. The association between genetic variants in the METTL14 gene and Wilms tumor susceptibility remains to be fully elucidated. We aimed to assess whether variants within this gene are implicated in Wilms tumor susceptibility. METHODS: A total of 403 patients and 1198 controls were analyzed. METTL14 genotypes were assessed by TaqMan genotyping assay. RESULT: Among the five SNPs analyzed, rs1064034 T > A and rs298982 G > A exhibited a significant association with decreased susceptibility to Wilms tumor. Moreover, the joint analysis revealed that the combination of five protective genotypes exerted significantly more protective effects against Wilms tumor than 0-4 protective genotypes with an OR of 0.69. The stratified analysis further identified the protective effect of rs1064034 T > A, rs298982 G > A, and combined five protective genotypes in specific subgroups. The above significant associations were further validated by haplotype analysis and false-positive report probability analysis. Preliminary mechanism exploration indicated that rs1064034 T > A and rs298982 G > A are correlated with the expression and splicing event of their surrounding genes. CONCLUSIONS: Collectively, our results suggest that METTL14 gene SNPs may be genetic modifiers for the development of Wilms tumor.