Crosstalk between fibroblasts and immunocytes in fibrosis: From molecular mechanisms to clinical trials.

BACKGROUND: The impact of fibroblasts on the immune system provides insight into the function of fibroblasts. In various tissue microenvironments, multiple fibroblast subtypes interact with immunocytes by secreting growth factors, cytokines, and chemokines, leading to wound healing, fibrosis, and escape of cancer immune surveillance. However, the specific mechanisms involved in the fibroblast-immunocyte interaction network have not yet been fully elucidated. MAIN BODY AND CONCLUSION: Therefore, we systematically reviewed the molecular mechanisms of fibroblast-immunocyte interactions in fibrosis, from the history of cellular evolution and cell subtype divisions to the regulatory networks between fibroblasts and immunocytes. We also discuss how these communications function in different tissue and organ statuses, as well as potential therapies targeting the reciprocal fibroblast-immunocyte interplay in fibrosis. A comprehensive understanding of these functional cells under pathophysiological conditions and the mechanisms by which they communicate may lead to the development of effective and specific therapies targeting fibrosis.

A negative biological Indian Ocean dipole event in 2022.

The biological dipole mode index (BDMI) showed a negative biological Indian Ocean dipole (BIOD) event occurred in the Equatorial Indian Ocean with the corresponding BIOD index BDMI(Ratio) at - 0.31 in October 2022. The chlorophyll-a (Chl-a) ratio (or Chl-a anomaly) between Chl-a in October 2022 and October Chl-a climatology from the Visible Infrared Imaging Radiometer Suite (VIIRS) showed negative dipolar features with the depressed and enhanced Chl-a in the east and west IOD zones, respectively. During this negative BIOD event, Chl-a ratio dropped to ~ 0.4-0.5 in the offshore region of the west Sumatra Coast in the east IOD zone, while it increased to ~ 1.5-1.6 in the northern west IOD zone. Temporal variations of the longitudinal averaged Chl-a ratio and the 20 °C isothermal (ISO20) depth anomaly generally coincided and collocated with each other. The positive and negative BIOD events in 2019 and 2022, respectively, were attributed to the nutrient dynamics driven by the physical dynamics in these two phases of IOD events. In the negative BIOD event in 2022, the depressed Chl-a in the east IOD zone was attributed to low sea surface nutrient levels due to dampened upwelling and deepened thermocline, while anomalously high Chl-a in the west IOD zone were driven by higher sea surface nutrient concentrations caused by the surface water divergence and shoaling thermocline.

Transperineal anastomotic posterior urethroplasty with bulbocavernosus flap and fibrin sealant in the complicated posterior urethral stricture reconstruction: a retrospective cohort study.

BACKGROUND: Management of complicated posterior urethral stricture is challenging. Modified transperineal anastomotic urethroplasty (TAU) with bulbocavernosus flap interposition and human fibrin sealant provides another treatment option. The authors aimed to evaluate whether this technique could improve the success rate in the complicated posterior urethral stricture reconstruction in this study. MATERIALS AND METHODS: Between 2016 and 2019, 48 patients underwent either conventional or modified TAU. The criteria for success included both the absence of clinical symptoms and no need for further surgical intervention during follow-up. RESULTS: Twelve patients underwent the modified TAU (group A) using bulbocavernosus flap interposition and human fibrin sealant. Thirty-six patients underwent the traditional end-to-end anastomotic urethroplasty (group B). Follow-up was 24.3-57.2 months. The patients in group A had a higher surgery success rate compared to the patients in group B (91.7 vs. 63.9%, P =0.067), with a quasi-significant result. Besides, no postoperative complications were observed in group A, while two individuals in group B had urinary incontinence, but the difference was not significant (0 vs. 5.6%, P =0.404). CONCLUSION: Based on the preliminary results, modified TAU with bulbocavernosus flap interposition and human fibrin sealant is a safe and feasible technique for complicated posterior urethral stricture reconstruction.

Is antibiotic prophylaxis generally safe and effective in surgical and nonsurgical scenarios? Evidence from an umbrella review of randomized controlled trials.

BACKGROUND: The authors aimed to comprehensively evaluate the efficacy and safety of antibiotic prophylaxis through surgical and nonsurgical scenarios and assess the strength of evidence. MATERIALS AND METHODS: The authors performed an umbrella review of meta-analyses of randomized controlled trials (RCTs). An evidence map was created to summarize the absolute benefits of antibiotic prophylaxis in each scenario and certainty of evidence. RESULTS: Seventy-five meta-analyses proved eligible with 725 RCTs and 78 clinical scenarios in surgical and medical prophylaxis. Of 119 health outcomes, 67 (56.3%) showed statistically significant benefits, 34 of which were supported by convincing or highly suggestive evidence from RCTs. For surgeries, antibiotic prophylaxis may minimize infection occurrences in most surgeries except Mohs surgery, simple hand surgery, herniorrhaphy surgery, hepatectomy, thyroid surgery, rhinoplasty, stented distal hypospadias repair, midurethral sling placement, endoscopic sinus surgery, and transurethral resection of bladder tumors with only low to very low certainty evidence. For nonsurgery invasive procedures, only low to very low certainty evidence showed benefits of antibiotic prophylaxis for cystoscopy, postoperative urinary catheterization, and urodynamic study. For medical prophylaxis, antibiotic prophylaxis showed greater benefits in nonemergency scenarios, in which patients were mainly with weakened immune systems, or at risk of recurrent chronic infections. Antibiotics prophylaxis may increase antibiotic resistance or other adverse events in most scenarios and reached significance in cystoscopy, afebrile neutropenia following chemotherapy and hematopoietic stem cell transplantation. CONCLUSIONS: Antibiotic prophylaxis in surgical and nonsurgical scenarios is generally effective and seems independent of surgical cleanliness and urgency of diseases. Its safety is not well determined due to lack of available data. Nevertheless, the low quality of current evidence limits the external validity of these findings, necessitating clinicians to judiciously assess indications, balancing low infection rates with antibiotic-related side effects.

Where does floating Sargassum in the East China Sea come from?

Floating macroalgae of Sargassum horneri (S. horneri) in the East China Sea (ECS) has increased in recent years, with ocean warming being one of the driving factors. Yet their possible origins, based on a literature review, are unclear. Here, using multi-sensor high-resolution remote sensing data and numerical experiments for the period of 2015-2023, we show two possible origins of the ECS floating S. horneri, one being local near the Zhejiang coast with initiation in January-February and the other being remote (> 800 km from the first) in the Bohai Sea with initiation in June-November. While their drifting pathways are revealed in the sequential remote sensing imagery, numerical experiments suggest that S. horneri from the remote origin (Bohai Sea) can hardly meander through the strong Yangtze River frontal zone, which may serve as a "wall" to prevent trespassing of surface floating seaweed to the south of the frontal zone, where S. horneri has a local origin. PLAIN LANGUAGE SUMMARY: Sargassum horneri (S. horneri) is a brown macroalgae (seaweed) abundant in surface waters of the East China Sea (ECS), which can serve as a moving habitat, but can also cause major beaching events and environmental problems. Knowledge of its origins is important to help implement mitigation strategies and understand possible ecological impacts along its drifting pathways. Using high-resolution remote sensing images and numerical experiments, we track floating S. horneri in space and time between 2015 and 2023. Two possible origins are identified, one being far away from the ECS and the other being local, both of which are known to have benthic S. horneri. The study also reveals how S. horneri are transported from their source regions resulting in large-scale distributions previously observed in medium-resolution satellite imagery.

Do Obesity-Related Traits Affect Prostate Cancer Risk through Serum Testosterone? A Mendelian Randomization Study.

OBJECTIVE: This study aimed to investigate whether testosterone mediates or confounds the effect of obesity-related traits on prostate cancer (PCa) using Mendelian randomization (MR) analysis. MATERIALS AND METHODS: Data of obesity-related traits (body mass index [BMI], waist-to-hip ratio [WHR], and waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) were obtained from up to 806,834 people of European ancestry; data of testosterone (bioavailable testosterone [BT], total testosterone [TT], and sex hormone-binding globulin [SHBG]) were extracted from up to 194,453 participants in the UK Biobank; and the summary-level data of PCa (79,194 cases and 61,112 controls) were obtained from the PRACTICAL consortium. RESULT: The results supported the causal relationship between higher BMI and a reduced risk of PCa (OR = 0.91, 95% confidence interval [CI]: 0.86-0.96). Furthermore, increased BT levels were associated with an elevated risk of PCa (OR = 1.15, 95% CI: 1.06-1.24). Importantly, our analysis revealed a unidirectional causal effect-higher BMI was linked to lower BT levels (beta = -0.27, 95% CI: -0.3--0.24), but not the other way around. This suggests that BT may mediate the effect of BMI on PCa rather than confound it. Our multivariable MR results further demonstrated that considering BT as a mediator led to the weakening of BMI's effect on PCa risk (OR = 0.97, 95% CI: 0.90-1.05), while the impact of BT on PCa remained unchanged when accounting for BMI. Moreover, we identified a significant indirect effect of BMI on PCa risk (OR = 0.96, 95% CI: 0.94-0.98). CONCLUSION: Our study provided genetic evidence that serum BT can mediate the effect of BMI on the risk of PCa, indicating the possible mechanism by which obesity reduces PCa risk.

Association Between Sleep Duration and Urinary Incontinence in Female Adults: A Cross-sectional Study in National Health and Nutrition Examination Survey 2007-2018.

OBJECTIVE: To elaborate on the effect of sleep duration on urinary incontinence (UI), we investigated the association between sleep duration with the risk of UI from the National Health and Nutrition Examination Survey (NHANES) dataset. METHODS: A cross-sectional survey of female participants aged 20years old and above were enrolled from the year 2007-2018. We performed weighted multivariable logistic regression models to assess the association between sleep duration and UI. RESULTS: A total of 6838 female participants were included. Compared with sleep duration less than 6 hours, other sleep duration was found to be not significantly correlated with total UI, stress urinary incontinence, and mixed urinary incontinence in all three models Compared to sleep duration less than 6 hours, multivariate regression demonstrated that moderate sleep (6-8 hours) indicated a lower urgent urinary incontinence (UUI, odds ratio=0.764, 95% confidence interval=0.620-0.944, P = .013). Inadequate sleep (<6 hours) indicated a higher UUI (odds ratio=1.308, 95% confidence interval=1.060-1.614, P = .013) compared to moderate sleep duration (6-8 hours). The association might be modified by the family income-to-poverty ratio. CONCLUSION: Inadequate sleep (<6 hours) was associated with a higher incidence of UUI. A moderate sleep duration (6-8 hours) was related to a lower rate of UUI. Further studies are warranted for clinical prevention and treatment guidance.

Association between marijuana use and kidney stone: a cross-sectional study of NHANES 2009 to 2018.

Objective: The purpose of this investigation is to determine whether regular marijuana use is related to history of kidney stones in the US population. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. Kidney stone and marijuana use data were collected from self-report questionnaires. Multivariate logistic regression and multiple sensitivity analyses were applied to examine the relationship between marijuana usage and kidney stones. Results: There are approximately 26.04% of the US population have admitted to using marijuana in their lifetime. Compared with none regular users, those with a higher frequency of marijuana use were more males, more non-Hispanic races, lower than high school education, overweight, no recreational activity, without diabetes mellitus, and more coronary heart disease. After adjusting for potential confounders, multivariate regression analysis demonstrated that marijuana use was inversely correlated to kidney stones in males (Odds ratio [OR] = 0.72, 95% Confidence interval [CI] = 0.54-0.97). One to seven times/week regular consumption of marijuana was associated with kidney stones in males (OR = 0.62, 95% CI = 0.43-0.89). Sensitivity analyses validated the robustness of our outcomes. Conclusion: Our findings revealed that regular marijuana male users were inversely associated with kidney stones. Marijuana use one to six times/week was inversely related to the risk of kidney stones in males. Further studies are required to explore the dose and type associations of marijuana with kidney stones.

Reductases Produce Nitric Oxide in an Alternative Pathway to Form the Diazeniumdiolate Group of l-Alanosine.

l-Alanosine is a diazeniumdiolate (N-nitrosohydroxylamine) antibiotic that inhibits MTAP-deficient tumor cells by blocking de novo adenine biosynthesis. Previous work revealed the early steps in the biosynthesis of l-alanosine. In the present study, we used genome mining to discover two new l-alanosine-producing strains that lack the aspartate-nitrosuccinate pathway genes found in the original l-alanosine producer. Instead, nitrate is reduced with a unique set of nitrate-nitrite reductases. These enzymes are typically used as part of the nitrogen cycle for denitrification or assimilation, and our report here shows how enzymes from the nitrogen cycle can be repurposed for the biosynthesis of specialized metabolites. The widespread distribution of nitric-oxide-producing reductases also indicates a potential for the discovery of new nitric-oxide-derived natural products.

Floating Debris in the Northern Gulf of Mexico after Hurricane Katrina.

Hurricane Katrina (category 5 with maximum wind of 280 km/h when the eye is in the central Gulf of Mexico) made landfall near New Orleans on August 29, 2005, causing millions of cubic meters of disaster debris, severe flooding, and US$125 billion in damage. Yet, despite numerous reports on its environmental and economic impacts, little is known about how much debris has entered the marine environment. Here, using satellite images (MODIS, MERIS, and Landsat), airborne photographs, and imaging spectroscopy, we show the distribution, possible types, and amount of Katrina-induced debris in the northern Gulf of Mexico. Satellite images collected between August 30 and September 19 show elongated image features around the Mississippi River Delta in a region bounded by 92.5°W-87.5°W and 27.8°N-30.25°N. Image spectroscopy and color appearance of these image features indicate that they are likely dominated by driftwood (including construction lumber) and dead plants (e.g., uprooted marsh) and possibly mixed with plastics and other materials. The image sequence shows that if aggregated together to completely cover the water surface, the maximal debris area reached 21.7 km2 on August 31 to the east of the delta, which drifted to the west following the ocean currents. When measured by area in satellite images, this perhaps represents a historical record of all previously reported floating debris due to natural disasters such as hurricanes, floodings, and tsunamis.

Identification of the Azaserine Biosynthetic Gene Cluster Implicates Hydrazine as an Intermediate to the Diazo Moiety.

Azaserine (1) is a natural product and nonproteinogenic amino acid containing a diazo group. Here we report the biosynthetic gene cluster for 1 from Glycomyces harbinensis. We then use isotopic feeding, gene deletion, and biochemical experiments to support a pathway whereby hydrazinoacetic acid (2) and a peptidyl carrier protein-loaded serine (3) are intermediates on route to the final natural product 1.

Establishment of hairy root system of transgenic IRT1 brassica campestris L. and preliminary study of its effect on cadmium enrichment.

Cadmium (Cd) is the main heavy metal pollutant in soil. The combination of genetic engineering technology and Rizobium rhizogenes mediated technology can effectively improve the enrichment efficiency of heavy metals in super accumulators and reduce soil heavy metal pollution. In this study, the transgenic hairy root system containing the IRT1 gene of Cd hyperaccumulator-Brassica campestris L. was successfully constructed by the R. rhizogenes mediated method (IRT1 gene come from Arabidopsis thaliana). The hairy roots of each subculture can grow stably within 6 weeks, and IRT1 gene will not be lost within 50 subcultures., which is detected using PCR method. The results of Cd enrichment experiments showed that after treatment with 100 µmol/L Cd for 14 days, the growth state of transgenic IRT1 hairy roots only showed slight browning. Also, the accumulation value of Cd reached 331.61 µg/g and the enrichment efficiency of transgenic IRT1 hairy roots was 13.8% higher than that of wild-type hairy roots. Western blotting results showed that the expression of IRT1 protein in transgenic hairy roots was significantly higher than that of wild-type hairy roots under Cd stress. The above results indicated that the overexpression of IRT1 gene can help B. campestris L. hairy roots to effectively cope with Cd stress and improve its ability to enrich Cd.

In this study, the transgenic hairy root system containing the IRT1 gene of Cd hyperaccumulator-Brassica campestris L. was successfully constructed by the Rizobium rhizogenes mediated method. At the same time, the growth state and cadmium enrichment efficiency of transgenic hairy roots under different concentrations of Cd stress were studied. Overexpression of IRT1 gene can effectively improve the tolerance of hairy root to Cd. The enrichment efficiency of transgenic IRT1 hairy roots was 13.8% higher than that of wild-type hairy roots. The transgenic IRT1 hairy root system established in this study can be used as a reliable experimental model for the study of Cd adsorption mechanism, and can be further regenerated to obtain transgenic IRT1 B. campestris L. plants for the study of heavy metal Cd pollution remediation.

A bibliometric analysis of top-cited journal articles in interstitial cystitis and bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: To identify and compare the top-cited articles from all indexed journals and urology-nephrology and obstetrics-gynecology journals in the Institute for Scientific Information Web of Science's Citation Index Expanded on interstitial cystitis and bladder pain syndrome (IC/BPS). METHODS: Cross-sectional bibliometric analysis of top-cited articles in Web of ScienceTM (WoS) from 1900-2022. The articles were retrieved by the MeSH terms from NCBI. The characteristics of top 100 cited articles from all indexed journals and specialized journals were evaluated. RESULTS: A total of 5547 articles were collected from 1115 journals, in which 3225 articles were from 141 urological and gynecological specialized journals. The USA and the UK were the top two origins for articles on interstitial cystitis. The articles from non-specialized journals were more frequently cited than those from specialized journals (median [IQR], 221.5 [189.8-313.5] vs 131.0 [126.0-142.8], P < 0.0001). The citation number per year showed similar results (median [IQR], 239.9 [194.5-311.8] vs 132.0 [126.7-140.5], P < 0.0001). There were many more open-access articles in non-specialized than specialized journals (P = 0.0018). CONCLUSIONS: The current study initially queried the articles published on WoS on IC/BPS by the number of citations to identify the differences between two journal categories. The characteristics and trends of research were analyzed by citations to provide insights into the current research status and future direction.

Depression increases the risk of kidney stone: Results from the National Health and Nutrition Examination Survey 2007-2018 and Mendelian randomization analysis.

BACKGROUND: To investigate whether depression increases the kidney stone risk. METHODS: First, we performed an observational study in the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Depression severity was evaluated using the Patient Health Questionnaire-9 (PHQ-9) and classified into no, mild, moderate, and severe depression groups. Multivariable-adjusted logistic regression was used to assess the correlation between depression severity and kidney stone risk. Second, Mendelian randomization (MR) was applied to decrease the bias and avoid the reverse causality in the observational study. Genetic instruments were obtained from a large genome-wide association study (GWAS) meta-analysis of depression involved 246,363 cases and 561,190 controls. We obtained summary data for kidney stone from another large GWAS, which integrates data from 6536 stone formers and 388,508 controls. Inverse variance weighted (IVW) was the primary analytical method. RESULTS: In the observational study, a total of 24,892 individuals were enrolled. Individuals with moderate (OR 1.38, 95 % CI 1.05-1.83, P = 0.022) and severe (OR 1.56, 95 % CI 1.02-2.40, P = 0.040) depression had a higher risk of kidney stone (P for trend = 0.006) compared with the control. For the MR, results also showed that genetically predicted depression was causally associated with a higher risk of kidney stone disease (OR 1.26, 95 % CI 1.04-1.53, P = 0.017) in IVW. CONCLUSIONS: Depression might be associated with kidney stone risk. This finding is needed to be verified in further prospective cohort studies with a large sample size and enough follow-up time.

Exosomal Circsafb2 Reshaping Tumor Environment to Promote Renal Cell Carcinoma Progression by Mediating M2 Macrophage Polarization.

Background: Macrophages are the most abundant infiltrating immune-related stromal cells present in and around tumors, showing different phenotypes and functions. M2 macrophages mainly exert immunosuppressive functions and promote tumor growth. Exosomes are emerging as important mediators of cross-talk between tumor cells and the microenvironment. CircRNAs are novel members of non-coding RNAs that regulate cancer proliferation and progression. However, the mechanism by which exosomal circRNA regulates macrophage polarization in renal cell carcinoma (RCC) is still largely unknown. Methods: RCC-derived exosomes were characterized using transmission electron microscopy and nanoparticle tracking analysis (NTA). CCK-8, wound healing, and Transwell assays were performed to assess whether exosomes would affect the proliferation, migration, and invasion of RCC. Furthermore, we performed a bioinformatics analysis to identify circRNAs in RCC serum-derived exosomes from the GEO database. The fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circSAFB2. Bioinformatics analyses (StarBase 2.0) were used to pool the miRNA targets of circSAFB2. Luciferase assays were performed to verify the direct interactions. Western blotting was used to detect markers of macrophage M2 polarization. Lastly, mouse xenograft and bioluminescence imaging were used to examine the clinical relevance of exosomal circSAFB2 in vivo. Results: We report the circRNA derived from SAFB2 and evaluate its biological function in promoting the immune escape of RCC. We found that circSAFB2 was highly expressed in RCC tissues and RCC-derived exosomes. Furthermore, we demonstrated that exosomal circSAFB2 mediates the polarization of M2 macrophages through the miR-620/JAK1/STAT3 axis to promote RCC metastasis. Conclusions: Our data first demonstrated that circSAFB2 leads to immune escape from RCC by mediating M2 macrophage polarization via the miR-620/JAK1/STAT3 axis. These findings indicate a novel molecular mechanism of exosomal circSAFB2 in the progression of RCC and implicate circSAFB2 as a target for exosome-mediated tumor immune evasion.

Type 2 diabetes mellitus increases risk of erectile dysfunction independent of obesity and dyslipidemia: A Mendelian randomization study.

BACKGROUND: The causal effects of individual risk factors of metabolic syndrome on erectile dysfunction (ED) are still unclear. OBJECTIVES: To evaluate the causal effect of risk factors of metabolic syndrome on ED through Mendelian randomization (MR). MATERIALS AND METHODS: Data for risk factors were obtained from multiple databases with 173,082-757,601 individuals, and that for ED were collected from a genome-wide association study including 223,805 Europeans. We performed univariate MR analysis using inverse-variance weighted, MR-Egger, weighted-median, weighted mode methods and multivariable MR analysis to evaluate the total and direct causal effects. RESULTS: The univariable MR supported that type 2 diabetes mellitus (odds ratios [OR] = 1.14, 95% confidence intervals [CI]: 1.08-1.21, p < 0.001) and body mass index (BMI) (OR = 1.27, 95% CI: 1.12-1.44, p < 0.001) were associated with ED. After excluding the SNPs associated with BMI and other risk factors, the results of multivariable MR for T2D (OR = 1.15, 95% CI: 1.05-1.25, p = 0.001) remained consistent. However, the results of multivariable MR provided limited evidence for the causality between BMI and ED (OR = 1.06, 95% CI: 0.88-1.29, p = 0.532). For systolic blood pressure and lipid components (low-density lipoprotein, high-density lipoprotein and triglycerides), both univariable and multivariable MR failed to offer sufficient evidence to confirm their causal effect on ED. CONCLUSION: T2D showed a direct causal effect on ED independent of obesity and dyslipidemia.

Tropical instability wave modulation of chlorophyll-a in the Equatorial Pacific.

The global daily gap-free chlorophyll-a (Chl-a) data derived using the data interpolating empirical orthogonal functions (DINEOF) technique from observations of the Visible Infrared Imaging Radiometer Suite (VIIRS) in 2020 and the in situ measurements at the Tropical Ocean Atmosphere (TAO) moorings are used to characterize and quantify the biological variability modulated by the tropical instability wave (TIW). Our study aims to understand how ocean physical processes are linked to biological variability. In this study, we use the TAO in situ measurements and the coincident VIIRS Chl-a data to identify the mechanism that drives ocean biological variability corresponding to the TIW. Satellite observations show that the TIW-driven Chl-a variability stretched from 90°W to 160°E in the region. The enhanced Chl-a pattern propagated westward and moderately matched the cooler sea surface temperature (SST) patterns in the Equatorial Pacific Ocean. In fact, the Chl-a variation driven by the TIW is about ± 30% of mean Chl-a values. Furthermore, the time series of Chl-a at 140°W along the equator was found to be in phase with sea surface salinity (SSS) at 140°W along the equator at the TAO mooring since late May 2020. The cross-correlation coefficients with the maximum magnitude between Chl-a and SST, Chl-a and SSS, and Chl-a and dynamic height were -0.46, + 0.74, and -0.58, respectively, with the corresponding time lags of about 7 days, 1 day, and 8 days, respectively. The different spatial patterns of the cooler SST and enhanced Chl-a are attributed to the phase difference in Chl-a and SST. Indeed, a Chl-a peak normally coincided with a SSS peak and vice versa. This could be attributed to the consistency in the change in nutrient concentration with respect to the change of SSS. The vertical distributions of the temperature and salinity at 140°W along the equator reveal that the TIW leads to changes in both salinity and nutrient concentrations in the sea surface, and consequently drives the Chl-a variability from late May until the end of the year 2020.

Causal Associations Between Educational Attainment and 14 Urological and Reproductive Health Outcomes: A Mendelian Randomization Study.

Background: The impact of educational attainment (EA) on multiple urological and reproductive health outcomes has been explored in observational studies. Here we used Mendelian randomization (MR) to investigate whether EA has causal effects on 14 urological and reproductive health outcomes. Methods: We obtained summary statistics for EA and 14 urological and reproductive health outcomes from genome-wide association studies (GWAS). MR analyses were applied to explore the potential causal association between EA and them. Inverse variance weighted was the primary analytical method. Results: Genetically predicted one standard deviation (SD) increase in EA was causally associated with a higher risk of prostate cancer [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05-1.25, P = 0.003] and a reduced risk of kidney stone (OR 0.73, 95% CI 0.62-0.87, P < 0.001) and cystitis (OR 0.76, 95% CI 0.67-0.86, P < 0.001) after Bonferroni correction. EA was also suggestively correlated with a lower risk of prostatitis (OR 0.76, 95% CI 0.59-0.98, P = 0.037) and incontinence (OR 0.64, 95% CI 0.47-0.87, P = 0.004). For the bioavailable testosterone levels and infertility, sex-specific associations were observed, with genetically determined increased EA being related to higher levels of testosterone in men (ß 0.07, 95% CI 0.04-0.10, P < 0.001), lower levels of testosterone in women (ß -0.13, 95% CI-0.16 to-0.11, P < 0.001), and a lower risk of infertility in women (OR 0.74, 95% CI 0.64-0.86, P < 0.001) but was not related to male infertility (OR 0.79, 95% CI 0.52-1.20, P = 0.269) after Bonferroni correction. For bladder cancer, kidney cancer, testicular cancer, benign prostatic hyperplasia, and erectile dysfunction, no causal effects were observed. Conclusions: EA plays a vital role in urological diseases, especially in non-oncological outcomes and reproductive health. These findings should be verified in further studies when GWAS data are sufficient.

Exosomal miR-4488 and miR-1273g-5p inhibit the epithelial-mesenchymal transition of transforming growth factor ß2-mediated retinal pigment epithelial cells by targeting ATP-binding cassette A4.

Exosomal microRNAs (miRNAs) have been shown to be involved in the regulation of many disease progression, including proliferative vitreoretinopathy (PVR). However, the roles of exosomal miR-4488 and miR-1273 g-5p in PVR progression have not been demonstrated. Transforming growth factor ß2 (TGF-ß2)-induced ARPE-19 cells were used to stimulate the epithelial-mesenchymal transition (EMT) of cells. Exosomes derived from TGF-ß2-induced ARPE-19 cells were identified by transmission electron microscopy and nanoparticle tracking analysis. The expression levels of miR-4488, miR-1273 g-5p and ATP-binding cassette A4 (ABCA4) were measured by quantitative real-time PCR. The promotion levels of exosomes markers, EMT markers, apoptosis markers and ABCA4 were determined by western blot analysis. The migration, invasion and apoptosis of cells were determined by transwell assay, wound healing assay and flow cytometry. Our data showed that miR-4488 and miR-1273 g-5p were lowly expressed in TGF-ß2-induced ARPE-19 cells. Overexpressed exosomal miR-4488 and miR-1273 g-5p could inhibit the EMT, migration, invasion, and promote apoptosis in TGF-ß2-induced ARPE-19 cells. In addition, ABCA4 was a target of miR-4488 and miR-1273 g-5p. Overexpressed ABCA4 also could reverse the negatively regulation of exosomal miR-4488 and miR-1273 g-5p on the EMT, migration, and invasion of TGF-ß2-induced ARPE-19 cells. In conclusion, our data showed that exosomal miR-4488 and miR-1273 g-5p could inhibit TGF-ß2-stimulated EMT in ARPE-19 cells through targeting ABCA4.

Coffee Consumption and Prostate Cancer Risk: Results from National Health and Nutrition Examination Survey 1999-2010 and Mendelian Randomization Analyses.

The aim of this study was to examine the association between coffee and prostate cancer. Firstly, we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 1999-2010. Coffee intake was derived from 24 h dietary recalls. Weighted multivariable-adjusted logistic regression was applied to evaluate the association. Then, we performed Mendelian randomization (MR) to explore the possible causal effect of coffee on prostate cancer risk. Primary and secondary genetic instruments were obtained from genome-wide association studies among 375,833 and 91,462 individuals separately. Prostate cancer summary statistics were extracted from Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome (PRACTICAL) (79,194 cases and 61,112 controls) and FinnGen project (4754 cases and 63,465 controls). Inverse variance weighted (IVW) was the primary analytical method. Through selection, we enrolled 8336 individuals (weighted number = 58,796,070) for our observational study in NHANES. Results suggested that there was no association between coffee and prostate cancer. MR analyses with primary genetic instruments also did not support a causal association between coffee intake and prostate cancer risk, whether using summary data from PRACTICAL (IVW: OR 1.001, 95% CI 0.997-1.005) or FinnGen (IVW: OR 1.005, 95% CI 0.998-1.012). Similar results were observed when using secondary genetic instruments. Therefore, our study did not support a causal association between coffee intake and prostate cancer risk. Further studies with a larger sample size are needed to examine if an association exists by different coffee bean types, roasting procedures, and brewing methods.