The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers.

PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging evidences have indicated that apart from the reproductive function, PIWI/piRNAs with abnormal expression, also involve greatly in varieties of human cancers. Moreover, human PIWI proteins are usually expressed only in germ cells and hardly in somatic cells, so the abnormal expression of PIWI proteins in different types of cancer offer a promising opportunity for precision medicine. In this review, we discussed current researches about the biogenesis of piRNA, its epigenetic regulatory mechanisms in human cancers, such as N6-methyladenosine (m6A) methylation, histone modifications, DNA methylation and RNA interference, providing novel insights into the markers for clinical diagnosis, treatment and prognosis in human cancers.

Mechanical Loading Promotes the Migration of Endogenous Stem Cells and Chondrogenic Differentiation in a Mouse Model of Osteoarthritis.

Osteoarthritis (OA) is a major health problem, characterized by progressive cartilage degeneration. Previous works have shown that mechanical loading can alleviate OA symptoms by suppressing catabolic activities. This study evaluated whether mechanical loading can enhance anabolic activities by facilitating the recruitment of stem cells for chondrogenesis. We evaluated cartilage degradation in a mouse model of OA through histology with H&E and safranin O staining. We also evaluated the migration and chondrogenic ability of stem cells using in vitro assays, including immunohistochemistry, immunofluorescence, and Western blot analysis. The result showed that the OA mice that received mechanical loading exhibited resilience to cartilage damage. Compared to the OA group, mechanical loading promoted the expression of Piezo1 and the migration of stem cells was promoted via the SDF-1/CXCR4 axis. Also, the chondrogenic differentiation was enhanced by the upregulation of SOX9, a transcription factor important for chondrogenesis. Collectively, the results revealed that mechanical loading facilitated cartilage repair by promoting the migration and chondrogenic differentiation of endogenous stem cells. This study provided new insights into the loading-driven engagement of endogenous stem cells and the enhancement of anabolic responses for the treatment of OA.

Intervertebral disc degeneration and inflammatory microenvironment: expression, pathology, and therapeutic strategies.

BACKGROUND: Intervertebral disc degeneration (IDD) is a leading cause of low back pain (LBP), posing a significant socioeconomic burden. Recent studies highlight the crucial role of inflammatory microenvironment in IDD progression. METHOD: A keyword-based search was performed using the PubMed database for published articles. RESULTS AND CONCLUSIONS: Dysregulated expression of inflammatory cytokines disrupts intervertebral disc (IVD) homeostasis, causing atrophy, fibrosis, and phenotypic changes in nucleus pulposus cells. Modulating the inflammatory microenvironment and restoring cytokine balance hold promise for IVD repair and regeneration. This comprehensive review systematically examines the expression regulation, pathological effects, therapeutic strategies, and future challenges associated with the inflammatory microenvironment and relevant cytokines in IDD. Key inflammatory cytokines, including interleukins (IL), tumor necrosis factor-alpha (TNF-α), and chemokines, exhibit significant pathological effects in IDD. Furthermore, major therapeutic modalities such as chemical antagonists, biologics, plant extracts, and gene transcription therapies are introduced to control and ameliorate the inflammatory microenvironment. These approaches provide valuable insights for identifying potential targets in future anti-inflammatory treatments for IDD.

The Clinical Efficacy of Suture-Button Fixation and Trans-Syndesmotic Screw Fixation in the Treatment of Ankle Fracture Combined With Distal Tibiofibular Syndesmosis Injury: A Retrospective Study.

Twenty percent of ankle fractures present with concomitant syndesmosis injury which results in poor clinical outcomes. Surgical stabilization of the syndesmosis can be achieved with either trans-syndesmotic screws or a suture button device. The aim of this study is to investigate the clinical efficacy of suture button fixation and trans-syndesmotic screw fixation in the treatment of ankle fracture combined with distal tibiofibular syndesmosis injury. A retrospective analysis was conducted by enrolling 76 patients with ankle fractures combined with distal tibiofibular syndesmosis injury who were admitted in our trauma center from January 2018 to January 2019, including 34 cases of suture button group and 42 cases of the syndesmotic screw group with a mean follow-up period of 16 ± 7 (range 12-21) months. The demographic data included gender, age, injury mechanism, AO classification and the operation duration were recorded, the radiographic and clinical outcomes were determined by tibiofibular clear space, tibiofibular overlap distance, complications, and the Olerud-Molander Ankle Score at the last follow-up. All the indexes were compared between the 2 groups to discover the related statistical differences. With the numbers available, no significant difference could be detected in the surgical duration, tibiofibular clear space, tibiofibular overlap distance, total complication rate, and middle-term Olerud-Molander Ankle scores between the 2 groups. However, the suture button fixation group showed higher early stage Olerud-Molander Ankle scores (p = .027) and shorter full weightbearing time (p = .018) than that of syndesmotic screw fixation group. Considering the outcomes, we conclude that the suture button fixation not only shows equivalent efficacy to the traditional syndesmotic screw, but also has advantages of allowing early weightbearing, low requirements for routine removal.

Is There an Association Between Schizophrenia and Sexual Dysfunction in Both Sexes? A Systematic Review and Meta-Analysis.

BACKGROUND: Mounting clinical studies have reported patients with schizophrenia are at high risk of developing sexual dysfunction (SD), but a directly calculated prevalence of SD is currently lacking. AIM: To further quantify the association between schizophrenia and SD. METHODS: MEDLINE (PubMed), Embase (OVID), the Cochrane Library databases, and the PsycINFO were systematically searched for eligible studies reporting the sexual functioning in patients with schizophrenia. This meta-analysis has been registered on PROSPERO (ID: CRD42019121720, http://www.crd.york.ac.uk/PROSPERO). OUTCOMES: The relationship between schizophrenia and SD was detected by calculating the relative risk (RR) with a 95% confidence interval (CI). The GRADE-profiler was employed to rank the quality of the evidence. RESULTS: 10 observational studies (3 case-control studies and 7 cross-sectional studies) were finally included, enrolling a total of 3,570 participants (mean age 28.6-46.2 years), of whom 1,161 had schizophrenia and the remainders were the healthy control subjects. Synthetic results indicated that schizophrenia was significantly associated with an increased risk of SD regardless of gender (3 studies reporting both sexes: RR = 2.24, 95%CI: 1.66-3.03, P < .001, heterogeneity: I2 = 0.0%, P = .431; 7 studies reporting men: RR = 2.63, 95%CI: 1.68-4.13, P < .001, heterogeneity: I2 = 82.7%, P < .001; 5 studies reporting women: RR = 2.07, 95%CI: 1.46-2.94, P < .001; heterogeneity: I2 = 79.7%, P = .001). In accordance with the GRADE-profiler, the quality of the evidence of primary outcomes was LOW, MODERATE, and LOW in studies including both sexes, men, and women, respectively. CLINICAL IMPLICATIONS: Our findings confirmed the potential link between schizophrenia and SD. Clinicians should routinely assess the sexual functioning for those patients with schizophrenia and further recommend the preferred antipsychotics for them. STRENGTHS & LIMITATIONS: This is the first meta-analysis investigating the association between schizophrenia and the risks of SD in both sexes. Nonetheless, substantial heterogeneities were identified across the selected studies. CONCLUSION: Robust data from this meta-analysis showed increased rates of SD in patients with schizophrenia compared with the general populations. Therefore, more specific psychological and pharmaceutical interventions are needed to help patients with schizophrenia gain a better sexual life. Zhao S, Wang X, Qiang X, et al. Is There an Association Between Schizophrenia and Sexual Dysfunction in Both Sexes? A Systematic Review and Meta-Analysis. J Sex Med 2020;17:1476-1488.

Elucidating Mechanisms of Long-Term Gasoline Vehicle Exhaust Exposure-Induced Erectile Dysfunction in a Rat Model.

INTRODUCTION: Exposure to air pollution poses a risk for morbidity in multiple diseases. However, the role of ambient air pollutant emissions in public sexual health is just beginning to be understood and remains controversial. AIM: We have determined to elucidate the specific role of gasoline vehicle exhaust (VE), a crucial source and toxicant of air pollution, in the penile erectile function via a rat model. METHODS: 40 male Sprague Dawley rats, 12 weeks of age, were used in this experiment. Except for the control group (10 rats), rats were equally exposed to VE for total 2 hours, 4 hours, and 6 hours daily for 3 months consecutively. During each VE exposure periods, particulate matter (PM) mass concentrations of PM1, PM2.5, and PM10 were 1.43 ± 0.036, 1.45 ± 0.033, and 1.47 ± 0.037 mg/m3, respectively. MAIN OUTCOME MEASURE: Erectile function, pulmonary function, serum inflammatory factors, and histologic examinations of the lung and penile tissues were evaluated. RESULTS: Our study indicates that in vivo, 4-hour, and 6-hour daily exposure to VE causes significant reduction of erectile function, as judged by intracavernous pressure measurement. Meanwhile, we have observed that the 4-hour and 6-hour VE exposure rats exhibited remarkable increased levels of serum inflammatory factors, decreased total lung capacity and chord compliance, thickened alveoli septum, destroyed alveoli, pulmonary fibrosis, as well as down-regulation of the messenger RNA and protein expression of endothelial and neuronal nitric oxide synthase in the penile tissue when compared with normal control rats. CLINICAL IMPLICATIONS: We speculated that the underlying mechanisms of VE inducing erectile dysfunction could be attributed to systemic inflammation, pulmonary dysfunction, and the reduction of nitric oxide synthase activity in the corpus cavernosum. STRENGTH & LIMITATIONS: For the first time, our study revealed the deleterious effect of VE on penile erection in vivo. However, the VE exposure model might not entirely mimic the natural condition of ambient air pollution. CONCLUSION: Our results raise concerns about the potential role played by long-term exposure to gasoline VE in the development of erectile dysfunction. Zhao S, Wang J, Xie Q, et al. Elucidating Mechanisms of Long-Term Gasoline Vehicle Exhaust Exposure-Induced Erectile Dysfunction in a Rat Model. J Sex Med 2019;16:155-167.

Bone marrow mesenchymal stem cells reduce ureteral stricture formation in a rat model via the paracrine effect of extracellular vesicles.

With no effective therapy to prevent or treat ureteral stricture (US), a multifactorial fibrotic disease after iatrogenic injury of the ureter, the need for new therapies is urgent. Mesenchymal stem cells (MSCs) have been widely studied for treating tissue defects and excessive fibrosis, and recent studies established that one of the main therapeutic vectors of MSCs is comprised in their secretome and represented by extracellular vesicles (EVs). Thus, we have determined to explore the specific role of MSCs-derived EVs (MSC-EVs) treatment in a pre-clinical model of US. The results firstly showed that either a bolus dose of MSCs or a bolus dose of MSC-EVs (administration via renal-arterial) significantly ameliorated ureteral fibrosis and recuperated ureter morphological development in a US rat model. We confirmed our observations through MSCs or MSC-EVs treatment alleviated hydronephrosis, less renal dysfunction and blunted transforming growth factor-ß1 induced fibration. Due to MSC-EVs are the equivalent dose of MSCs, and similar curative effects of transplantation of MSCs and MSC-EVs were observed, we speculated the curative effect of MSCs in treating US might on account of the release of EVs through paracrine mechanisms. Our study demonstrated an innovative strategy to counteract ureteral stricture formation in a rat model of US.

PSCA promotes prostate cancer proliferation and cell-cycle progression by up-regulating c-Myc.

BACKGROUND: The Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored protein. Increasing evidence has indicated PSCA plays an important role in tumorigenesis. However, its function and the underlying molecular mechanisms in prostate cancer (PCa) are still not fully elucidated. In this study, we aimed to explore the effect of PSCA on cell cycle of PCa cells and its mechanism research. METHODS: Immunohistochemistry, quantitative reverse transcription-PCR (qRT-PCR) and Western blotting were used to quantify PSCA expression pattern in PCa tissues and cell lines. The association of PSCA expression with the biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients were analyzed using Kaplan-Meier method. The roles of PSCA in PCa were confirmed based on both in vitro and in vivo systems. RESULTS: Immunohistochemistry results showed that PSCA was upregulated in PCa tissue. PSCA overexpression were significantly associated with high Gleason score (GS) (P = 0.028), positive BCR (P = 0.002), and poor OS (P = 0.032) and high c-Myc expression (P = 0.019). PSCA promoted PCa cell cycle progression and tumor growth via increased c-Myc expression. Additional, PI3K/AKT signaling pathways was involved in PSCA-mediated c-Myc expression and cell proliferation. CONCLUSIONS: PSCA is a novel cell cycle regulator with a key role in mediating c-Myc-induced proliferation. PSCA may be a potential diagnostic marker and therapeutic target for patients with PCa.

Transcriptome profiling analysis of differentially expressed mRNAs and lncRNAs in HepG2 cells treated with peptide 9R-P201.

OBJECTIVE: To characterize the transcriptome profile of hepatocellular carcinoma (HCC) HepG2 cells treated with peptide 9R-P201 for further functional verification and HCC drug development. RESULTS: 1557 mRNAs (1125 upregulated and 432 downregulated) and 881 lncRNAs (640 upregulated and 241 downregulated) with significant differential expression were identified using RNA-seq. The qRT-PCR results showed that the differential expression of several mRNAs and lncRNAs coincided with the RNA-seq results. Differentially expressed mRNAs and lncRNAs presented a significant difference in genomic characteristics but no preference under 9R-P201 treatment compared with control. The GO and KEGG functional enrichment analyses showed that differentially expressed mRNAs and lncRNAs remarkably enriched in cancer-related biological processes and signaling pathways. Finally, we screened out 33 TFs, 273 lncRNAs and 94 target genes with high degree interaction which were remarkably associated with the tumorigenesis and progression of cancers using betweenness centrality analysis. CONCLUSION: These findings offer novel insights into the mechanism of 9R-P201 in HepG2 cells and provide new opportunities for the future 9R-P201-based drug development and the treatment of hepatocellular carcinoma.

[A Study on Predicting Model of Organic Matter Contend Incorporating Soil Moisture Variation].

Soil organic matter (SOM) is one of the most important measuring indexes of soil fertility. How to predict SOM spatial distribution precisely has great significance to soil carbon storage estimation and precision agriculture development. Traditional measurement of SOM, although with higher accuracy, consumes a lot of labor resources and costs long-term monitoring period, therefore, it is hard to achieve dynamic monitor of SOM. Spectroscopy technique has been used in SOM and other soil physicochemical parameters quick measurement. However spatial inversion model accuracy of SOM based on remote sensing images is relatively lower than laboratory model accuracy due to the influence of soil moisture, roughness and so on. In recent years, most studies have not eliminated the effect of moisture. Since moisture has great influence on SOM spectra reflectance, this study introduced the temporal information combined with the spectral information in order to solve this problem. Soil moisture has differences in multi period remote sensing images, and the spectra reflectance is also different. Based on the combination of reflectance from of two periods remote sensing images, the spectral index was constructed to predict SOM in this study. MODIS images of study area acquired in this study area (Blacksoil zone) because of the advantage of high temporal resolution. Spectra reflectance of MODIS images were used to analyze the effect of moisture on soil spectral reflectance, and then the spectral prediction models of SOM were built based on the comprehensive impacts of SOM and soil moisture. The results shows that: (1) the accuracy of SOM prediction model based on single image was lower without consideration of moisture effect, The Root mean square error (RMSE) of SOM prediction model were 0.591, 0.522, 0.545, 0.553, and the determination coefficient (R(2)) were 0.505, 0.614, 0.562, 0.568, 0.645 respectively based on the day of year (DOY) 117, 119, 130, 140, 143 single image. (2) Model with multi temporal images (DOY119 and 143) which considered the effect of moisture and SOM showed better predictive ability. RMSE was 0.442 while R2 was 0.723. Therefore the accuracy and stability of the model were significantly improved, and it can be used to predict the spatial distribution of SOM in regional scale. This study provides important information for regional soil fertility evaluation, soil carbon storage estimation, and precision agriculture development.

RNA interference targeting PSCA suppresses primary tumor growth and metastasis formation of human prostate cancer xenografts in SCID mice.

BACKGROUND AND OBJECTIVES: Prostate stem cell antigen (PSCA) is a cell surface, glycosylphosphatidylinositol (GPI)-anchored glycoprotein. Its overexpression has been detected in both local and metastatic prostate cancer (PCa), making it a potential therapeutic target. We previously reported that silencing PSCA by small interfering RNA targeting human PSCA (siRNA-PSCA) inhibited biological activity of PSCA-positive PCa cells leading to reduced proliferation, motility and invasion in vitro. In this study, we extended this in vitro findings to in vivo settings in order to investigate the effects of this specific siRNA on the tumor growth and metastasis development of PCa in vivo. MATERIALS AND METHODS: The siRNA-PSCA and ectopically overexpressed-PSCA vector were constructed and transfected into human PCa PC-3M and LNCaP cells, respectively, and were subcutaneously inoculated into the male SCID mice. Tumor growth was measured with a caliper, and formation of metastasis in mice bearing xenograft tumors was studied by magnetic resonance imaging (MRI) and autopsy analysis. Western blot and immunohistochemistry were used to assess the expression levels of PSCA protein in tumor tissues from xenograft and distant metastases. RESULTS: Consistent with our previous in vitro findings, the subcutaneous xenografts of PC-3M-siPSCA exhibited the almost completely inhibited expression of PSCA protein in their tumors tissues (P < 0.001 and P < 0.001, respectively), and consequently had a significant reduction in tumor growth volumes (P < 0.05 for all), and metastasis onset and sites (P < 0.001 for all) compared to those of PC-3M and PC-3M-siScrm. Conversely, LNCaP-PSCA showed significantly enhanced primary tumor growth and metastasis formation of xenografts compared to LNCaP-vehicle and LNCaP cells (P < 0.001 for all). Moreover, the up-regulated expression of PSCA protein was detected in the distant metastases of xenograft tumors from all groups. CONCLUSIONS: Taken together, these observations suggest that PSCA has a promoting role in the growth and metastasis of PCa and siRNA-PSCA may be a potential therapeutic strategy for PSCA-positive PCa.

Knockdown of PSCA induces EMT and decreases metastatic potentials of the human prostate cancer DU145 cells.

BACKGROUND: Prostate stem cell antigen (PSCA) expression has been shown to correlate with prostatic carcinogenesis and prostate cancer (PCa) progression. The underlying mechanisms for these processes are currently unknown. Epithelial to mesenchymal transition (EMT) has been associated with the invasiveness and the distant metastasis of PCa. In this study, we investigated the effects of knocking down the PSCA on the cell migration, the invasiveness, and the EMT of the PCa cell line DU145 in vitro and in vivo. METHODS: Four target sequences of the small hairpin RNA for PSCA were designed, and the best effect knockdown sequence shRNA#1 was screened to construct the stable transfected DU145 cell line (DU145 shRNA#1), the scramble sequence was also designed to construct the stable transfected DU145 cell line(DU145 scramble). Cell migration and invasion were studied using Transwell assay. Quantitative RT-PCR, Western blot (WB) were used to quantify PSCA, E-cadherin, ß-catenin, Vimentin, Fibronectin expression in DU145, DU145 scramble, DU145 shRNA#1 in vitro and in vivo. RT-PCR, immunofluorescent staining were used to quantify PSCA, E-cadherin, and Vimentin expression in vitro. EMT-related genes Snail, Slug, and Twist, were quantified by quantitative RT-PCR in vitro. RESULTS: The constructed stable knockdown of the PSCA in the DU145 cell had a silencing effect up to 90.5 %. DU145 shRNA#1 became scattered from the tightly packed colonies. It was associated with decreased cell migration and invasion. There was also an increased Vimentin and Fibronectin expression, an inhibited E-cadherin and ß-catenin expression at both the mRNA and the protein levels when compared to the DU145 and the DU145 scramble in vitro and vivo. Furthermore, with the exception of the Snail, the expression of EMT-related Slug and Twist genes were upregulated. CONCLUSIONS: Our data indicated that knockdown of PSCA induced EMT and reduced metastatic potentials of the DU145 cells, suggesting that PSCA played an important role in prostatic carcinogenesis and progression.

Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.

INTRODUCTION: 5α-Reductase inhibitors (5ARIs) are widely used for the treatment of benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA). AIM: To review all the available data on the effect of 5ARIs on sexual function and assess whether 5ARIs increase the risk of sexual dysfunction. METHODS: A systematic search of the literature was conducted using the Medline, Embase, and Cochrane databases. The search was limited to articles published in English and up to October 2015. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Data were analyzed using Stata 12.0. A fixed- or a random-effects model was used to calculate the overall combined risk estimates. Publication bias was assessed using Begg and Egger tests. MAIN OUTCOME MEASURES: Sexual dysfunction, erectile dysfunction, and decreased libido. RESULTS: After screening 493 articles, 17 randomized controlled trials with 17,494 patients were included. Nine studies evaluated the efficacy of 5ARIs in men with BPH. The other eight reported using 5ARIs in the treatment of men with AGA. The mean age of participants was 60.10 years across all studies. We included 10 trials (6,779 patients) on the efficacy and safety of finasteride, 4 trials (6,222 patients) on the safety and tolerability of dutasteride, and 3 trials (4,493 patients) using finasteride and dutasteride for AGA. The pooled relative risks for sexual dysfunction were 2.56 (95% CI = 1.48-4.42) in men with BPH and 1.21 (95% CI = 0.85-1.72) in men with AGA; those for erectile dysfunction were 1.55 (95% CI = 1.14-2.12) in men with BPH and 0.66 (95% CI = 0.20-2.25) in men with AGA; and those for decreased libido were 1.69 (95% CI = 1.03-2.79) in men with BPH and 1.16 (95% CI = 0.50-2.72) in men with AGA. Estimates of the total effects were generally consistent with the sensitivity analysis. No evidence of publication bias was observed. CONCLUSION: Evidence from the randomized controlled trials suggested that 5ARIs were associated with increased adverse effects on sexual function in men with BPH compared with placebo. However, the association was not statistically significant in men with AGA. Well-designed randomized controlled trials are indicated to study further the mechanism and effects of 5ARIs on sexual function.

[Study on the Prediction of Cotton Yield within Field Scale with Time Series Hyperspectral Imagery].

Pixel-based processing method mainly extracts spectral information from hyperspectral remote sensing images, but site specific management zone (SSMZ) delineation and crop yield estimation with images need to take spatiotemporal heterogeneity into account. As the spatial resolution of remote sensing data increases, the so-called "salt-and-pepper" problem of pixel-based classification becomes more serious. The spatiotemporal heterogeneity of soil properties and crop biophysical parameters are mainly delineated with grid sampling and geostatistics interpolation, but the widely used method has some problems: time consuming and high cost. Satellite imageries are introduced to delineate SSMZ, but there are also problems needed to be resolved: (1) single date imagery is used to map SSMZ which is difficult to determine the optimal date for SSMZ delineation; (2) only few SSMZs were mapped, which limited application of site specific fertilizing and management; (3) pixel-based method for SSMZ delineation didn't concern the spatial relationship between pixels and site specific management does not implement at pixel level, but at SSMZ level. To improve the accuracy of crop yield estimation, a time-series of hyperspectral airborne images with high spatial resolution (1 m) of a cotton field, which is located in San Joaquin Valley, California US, were acquired and classified by using object-oriented segmentation, then yield predicting models were built, and the accuracy and stability of yield models were validated with determining coefficients R2 and the root mean square error (RMSE). Results are as follows: (1) object-oriented SSMZ delineating method combines spectral, spatial and temporal information, reduces noises in images and yield data, improves the accuracy of yield prediction; (2) for same SSMZ number, first derivative predicting model is more accurate; (3) for same spectral input, models with fewer SSMZs show higher accuracy, which is due to spatial errors of airborne images and yield data. The results will improve monitoring methods for crop growth and yield while accelerate the application of UAV remote sensing in precision agriculture.

Sexual Dysfunction in Patients with Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

INTRODUCTION: Sexual dysfunction is an under-recognized problem in men and women with obstructive sleep apnea (OSA). Epidemiologic findings were inconclusive regarding the risk for sexual dysfunction associated with OSA. AIM: The aim of this study was to examine the association between OSA and sexual dysfunction. METHODS: The PubMed, Cochrane Library, and Embase databases were searched for observational studies on the OSA and the risk of sexual dysfunction. The methodologic quality of the case-control and cohort studies was assessed with Newcastle-Ottawa Scale (NOS). The cross-sectional study quality methodology checklist was used for cross-sectional study. Data were pooled for the random-effects model. Sensitivity analyses were conducted to assess potential bias. MAIN OUTCOME MEASURE: The association between OSA and sexual dysfunction was summarized using relative risk (RR) with a 95% confidence interval (CI). RESULTS: This meta-analysis included 1,275 participants from nine studies. Five studies reported the incidence of erectile dysfunction (ED); the remaining four studies reported the incidence of female sexual dysfunction (FSD). Pooled results demonstrated that OSA was associated with increased risk of ED (pooled RR = 1.82, 95% CI: 1.12-2.97) as well as FSD (pooled RR = 2.00, 95% CI: 1.29-3.08). Estimates of the total effects were generally consistent in the sensitivity analysis. No evidence of publication bias was observed. CONCLUSIONS: Evidence from the observational studies suggested that OSA individuals might have an increased incidence of sexual dysfunction despite significant heterogeneity. More researches are warranted to clarify the relationship between OSA and the increased risk of sexual dysfunction.

Intervertebral disc degenerative changes after intradiscal injection of TNF-α in a porcine model.

PURPOSE: To investigate whether exogenous tumor necrosis factor-α (TNF-α) will initiate a degenerative process in intervertebral disc in vivo. METHODS: Exogenous TNF-α in dosages of 50 and 100 ng in 50 µL Dulbecco's Modified Essential Medium (DMEM) was injected into porcine lumbar discs; a third disc was injected only with 50 µL DMEM as a control. Magnetic resonance imaging (MRI) yielding T1- and T2-weighted images, T2-mapping, and post-contrast T1 images was performed and histology was studied as well. RESULTS: After 3 months, a significant decrease in T2 value calculated from T2-mapping MRI was observed in the annulus and nucleus of both groups injected with TNF-α along with a slight decrease in disc height and nucleus volumes in comparison to the control discs. No obvious visual differences among the groups were observed in the normal T1- and T2-weighted MRI images. Post-contrast T1 MRI showed increased annulus enhancement in both TNF-α-injected groups compared to the control discs, while no enhancement difference was observed in the nucleus. Histological analysis showed degenerative changes with annulus fissure, cell cluster, nucleus matrix loss, vascularization and interleukin-1ß expression in the outer annulus of both TNF-α-injected discs, while no degenerative changes were observed in the control discs. CONCLUSIONS: Intradiscal injection of exogenous TNF-α caused early stage disc degeneration in a porcine model. It may thus support the hypothesis of exogenic TNF-α being an important early pathogenetic factor in disc degeneration.

Interference in the endplate nutritional pathway causes intervertebral disc degeneration in an immature porcine model.

PURPOSE: Previous studies have shown that blocking the endplate nutritional pathway with bone cement did not result in obvious intervertebral disc degeneration (IDD) in mature animal models. However, there are very few comparable studies in immature animal models. As vertebroplasty currently is beginning to be applied in young, even biologically immature patients, it is important to investigate the effect of cement blocking at the endplate in an immature animal model. METHODS: Two lumbar intervertebral discs in eight immature pigs were either blocked by cement in both endplate pathways or stabbed with a scalpel in the annulus fibrosus (AF) as a positive control, and with a third disc remaining intact as a normal control. Magnetic resonance imaging (MRI) and histology study were performed. RESULTS: After three months, the cement-blocked discs exhibited severe IDD, with the percentage of disc-height index (DHI), nucleus pulposus (NP) area, and NP T2 value significantly lower than the normal control. These IDD changes were histologically confirmed. Post-contrast MRI showed diseased nutritional diffusion patterns in the cement-blocked discs. Moreover, the degenerative changes of the cement-blocked discs exceeded those of the injured AF positive controls. CONCLUSIONS: The endplate nutritional pathway was interfered with and diseased after three months of bone cement intervention in an immature porcine model. Severe interference in the endplate nutritional pathway in an immature porcine model caused IDD. These findings also draw attention to the fact that interference in endplate nutritional pathways in immature or young patients may affect the vitality of adjacent discs.

Assessing the responses of ecosystem patterns, structures and functions to drought under climate change in the Yellow River Basin, China.

Understanding how ecosystems respond and adapt to drought has become an urgent issue as drought stress intensifies under climate change, yet this topic is not fully understood. Currently, conclusions on the response of ecosystems in different regions to drought disturbance are inconsistent. Based on long MODIS data and observed data, this study systematically explored the relationships between ecosystem patterns, structures and functions and drought, taking a typical climate change-sensitive area and an ecologically fragile area-the Yellow River Basin-as a case study. Drought assessment results revealed that the Yellow River Basin has experienced meteorological and hydrological drought during most of the last two decades, predominantly characterized by medium and slight droughts. The ecosystem patterns and structures changed dramatically as the grassland decreased and the landscape fragmentation index (F) increased with increasing wetness. The annual gross primary productivity (GPP) increased, the water use efficiency (WUE) declined and ecosystem service value (ESV) exhibited a W-shaped increase at the watershed scale, but there were significant regional differences. There were positive correlations between F, GPP, ESV and drought indices, while there was a negative correlation between WUE and drought indices at the watershed scale. Under drought stress, the ecosystem structure in the basin was disrupted, the GPP and ESV decreased, but the WUE increased. Notably, approximately 106 %, 20 %, and 1 % of the maximum reductions in F, GPP, and ESV, respectively, were caused by drought, while the maximum 4 % of WUE increased. Responses of some functions in the wetland and grassland to drought vary from those in other ecosystems. The mechanisms underlying ecosystem responses to drought were further investigated. This study enhances the understanding of these responses and will help stakeholders formulate drought mitigation policies and protect ecosystem health.

Novel insights into RB1 in prostate cancer lineage plasticity and drug resistance.

Prostate cancer is the second most common malignancy among men in the world, posing a serious threat to men's health and lives. RB1 is the first human tumor suppressor gene to be described, and it is closely associated with the development, progression, and suppression of a variety of tumors. It was found that the loss of RB1 is an early event in prostate cancer development and is closely related to prostate cancer development, progression and treatment resistance. This paper reviews the current status of research on the relationship between RB1 and prostate cancer from three aspects: RB1 and prostate cell lineage plasticity; biological behavior; and therapeutic resistance. Providing a novel perspective for developing new therapeutic strategies for RB1-loss prostate cancer.

The Sanbi Decoction alleviates intervertebral disc degeneration in rats through intestinal flora and serum metabolic homeostasis modulation.

BACKGROUND: Intervertebral disc degeneration (IVDD) is an essential cause of low back pain (LBP), the incidence of which has risen in recent years and is progressively younger, but treatment options are limited, placing a serious economic burden on society. Sanbi decoction (SBD) is an important classical formula for the treatment of IVDD, which can significantly improve patients' symptoms and is a promising alternative therapy. PURPOSE: The aim of this study is to investigate the safety and efficacy of SBD in the treatment of IVDD and to explore the underlying mechanisms by using an integrated analytical approach of microbiomics and serum metabolomics, as well as by using molecular biology. METHODS: A rat IVDD puncture model was established and treated by gavage with different concentrations of SBD, and clean faeces, serum, liver, kidney, and intervertebral disc (IVD) were collected after 4 weeks. We assessed the safety by liver and kidney weighing, functional tests and tissue staining, the expression of tumor necrosis factor-alpha (TNF-ɑ), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) inflammatory factors in serum was detected by ELISA kits, and X-ray test, magnetic resonance imaging (MRI) examination, immunohistochemistry (IHC), western blotting (WB), hematoxylin-eosin (HE) staining and safranin O-fast green (SO/FG) staining were used to assess the efficacy. Finally, we performed 16S rRNA sequencing analysis on the faeces of different groups and untargeted metabolomics on serum and analyzed the association between them. RESULTS: SBD can effectively reduce the inflammatory response, regulate the metabolic balance of extracellular matrix (ECM), improve symptoms, and restore IVD function. In addition, SBD can significantly improve the diversity of intestinal flora and maintain the balance. At the phylum level, SBD greatly increased the relative abundance of Patescibacteria and Actinobacteriota and decreased the relative abundance of Bacteroidota. At the genus level, SBD significantly increased the relative abundance of Clostridia_UCG-014, Enterorhabdus, and Adlercreutzia, and decreased the relative abundance of Ruminococcaceae_UCG-005 (p < 0.05). Untargeted metabolomics indicated that SBD significantly improved serum metabolites and altered serum expression of 4alpha-phorbol 12,13-didecanoate (4alphaPDD), euscaphic acid (EA), alpha-muricholic acid (α-MCA), 5-hydroxyindoleacetic acid (5-HIAA), and kynurenine (Kyn) (p < 0.05), and the metabolic pathways were mainly lipid metabolism and amino acid metabolism. CONCLUSIONS: This study demonstrated that SBD can extensively regulate intestinal flora and serum metabolic homeostasis to reduce inflammatory response, inhibit the degradation of ECM, restore IVD height and water content to achieve apparent therapeutic effect for IVDD.