Adiponectin affects estimated glomerular filtration rate: A two-sample bidirectional Mendelian randomization study.

BACKGROUND: The causal relationship between adiponectin (ADPN) and estimated glomerular filtration rate (eGFR) is unclear. This study adopts a two-sample bidirectional Mendelian randomization (MR) study to explore the causal relationship between ADPN and eGFR. METHODS: Using eight single nucleotide polymorphisms (SNP) of ADPN and 26 SNP of eGFR as instrumental variables, the study performs a two-sample bidirectional MR study using MR inverse-variance weighted (IVW), MR-Egger and weighted median approach to evaluate the causal relationship between ADPN and eGFR. Using the genetic risk score (GRS) of ADPN and eGFR as instrumental variables, the study performs a second MR analysis to assess the association between ADPN and eGFR. RESULTS: In ADPN to eGFR MR analysis, the IVW, weighted median and GRS analysis all showed that ADPN had a causal effect on eGFR after removing potential confounders of the ADPN-eGFR relation (IVW: ß = .016, P = .002; weighted median: ß = .012, P = .022; GRS: ß = .016, P = 1.48E-05). As both ADPN and eGFR were natural log-transformed in the corresponding GWAS, eGFR increased by 0.15% for any 10% increase in ADPN. In eGFR to ADPN MR analysis, eGFR had no causal effect on ADPN after removing potential confounders of the eGFR-ADPN relation (All P values > 0.05). The heterogeneity test and sensitivity analysis indicated some heterogeneity, but no directional pleiotropy. CONCLUSION: Adiponectin has a causal effect on eGFR, while eGFR has no causal effect on ADPN. ADPN may be a clinical target for improving eGFR and treating chronic kidney disease caused by decreased eGFR.

Single-Cell Transcriptomic Map of the Human and Mouse Bladders.

BACKGROUND: Having a comprehensive map of the cellular anatomy of the normal human bladder is vital to understanding the cellular origins of benign bladder disease and bladder cancer. METHODS: We used single-cell RNA sequencing (scRNA-seq) of 12,423 cells from healthy human bladder tissue samples taken from patients with bladder cancer and 12,884 cells from mouse bladders to classify bladder cell types and their underlying functions. RESULTS: We created a single-cell transcriptomic map of human and mouse bladders, including 16 clusters of human bladder cells and 15 clusters of mouse bladder cells. The homology and heterogeneity of human and mouse bladder cell types were compared and both conservative and heterogeneous aspects of human and mouse bladder evolution were identified. We also discovered two novel types of human bladder cells. One type is ADRA2A+ and HRH2+ interstitial cells which may be associated with nerve conduction and allergic reactions. The other type is TNNT1+ epithelial cells that may be involved with bladder emptying. We verify these TNNT1+ epithelial cells also occur in rat and mouse bladders. CONCLUSIONS: This transcriptomic map provides a resource for studying bladder cell types, specific cell markers, signaling receptors, and genes that will help us to learn more about the relationship between bladder cell types and diseases.

Imidazolium-Type Poly(ionic liquid) Endows the Composite Polymer Electrolyte Membrane with Excellent Interface Compatibility for All-Solid-State Lithium Metal Batteries.

Developing a poly(ethylene oxide) (PEO)-based polymer electrolyte with high ionic conductivity and robust mechanical property is beneficial for real applications of all-solid-state lithium metal batteries (ASSLMBs). Herein, an excellent organic/inorganic interface compatibility of all-solid-state composite polymer electrolytes (CPEs) is achieved using a novel imidazolium-type poly(ionic liquid) with strong electrostatic interactions, providing insights into the achievement of highly stable CPEs. The key properties such as micromorphologies, thermal behavior, crystallinity, tLi+, mechanical property, lithium anode surficial morphology, and electrochemical performance are systematically investigated. The combined experimental and density functional theory (DFT) simulation results exhibit that the strong electrostatic interaction and ion-dipole interaction cooperated to improve the compatibility of the CPE, with a high ionic conductivity of 1.46 × 10-4 S cm-1 at 40 °C and an incredible mechanical strain of 2000% for dendrite-free and highly stable all-solid-state LMBs. This work affords a promising strategy to accelerate the development of PEO-based polymer electrolytes for real applications in ASSLMBs.

A spatiotemporal steroidogenic regulatory network in human fetal adrenal glands and gonads.

Human fetal adrenal glands produce substantial amounts of dehydroepiandrosterone (DHEA), which is one of the most important precursors of sex hormones. However, the underlying biological mechanism remains largely unknown. Herein, we sequenced human fetal adrenal glands and gonads from 7 to 14 gestational weeks (GW) via 10× Genomics single-cell transcriptome techniques, reconstructed their location information by spatial transcriptomics. Relative to gonads, adrenal glands begin to synthesize steroids early. The coordination among steroidogenic cells and multiple non-steroidogenic cells promotes adrenal cortex construction and steroid synthesis. Notably, during the window of sexual differentiation (8-12 GW), key enzyme gene expression shifts to accelerate DHEA synthesis in males and cortisol synthesis in females. Our research highlights the robustness of the action of fetal adrenal glands on gonads to modify the process of sexual differentiation.

The role of age at menarche and age at menopause in Alzheimer's disease: evidence from a bidirectional mendelian randomization study.

The association between endogenous estrogen exposure and Alzheimer's disease (AD) remains inconclusive in previous observational studies, and few Mendelian randomization (MR) studies have focused on their causality thus far. We performed a bidirectional MR study to clarify the causality and causal direction of age at menarche and age at menopause, which are indicators of endogenous estrogen exposure, on AD risk. We obtained all genetic datasets for the MR analyses using publicly available summary statistics based on individuals of European ancestry from the IEU GWAS database. The MR analyses indicated no significant causal relationship between the genetically determined age at menarche (outlier-adjusted inverse variance weighted odds ratio [IVWOR] = 0.926; 95% confidence interval [CI], 0.803-1.066) or age at menopause (outlier-adjusted IVWOR = 0.981; 95% CI, 0.941-1.022) and AD risk. Similarly, AD did not show any causal association with age at menarche or age at menopause. The sensitivity analyses yielded similar results. In contrast, an inverse association was detected between age at menarche and body mass index (BMI, outlier-adjusted IVW ß = -0.043; 95% CI, -0.077 to -0.009). Our bidirectional MR study provides no evidence for a causal relationship between the genetically determined age at menarche or age at menopause and AD susceptibility, or vice versa. However, earlier menarche might be associated with higher adult BMI.

Female chronic posterior urethritis is underestimated in patients with lower urinary tract symptoms.

BACKGROUND: As one of the causes of urethral symptoms, female chronic posterior urethritis is a common and distressing disease; however, it is often neglected and misdiagnosed as overactive bladder (OAB) or interstitial cystitis/bladder pain syndrome (IC/BPS). Currently, little is known about the urothelium and lamina propria of the bladder neck and proximal urethra. Thus, identifying urethral lesions is necessary for the diagnosis and treatment of female chronic posterior urethritis. Transurethral electroresection is an effective and safe approach for treating female chronic posterior urethritis. This study sought to determine if urethral lesions are necessary for the diagnosis and treatment of female chronic posterior urethritis, and evaluate the efficacy and safety of the transurethral electroresection of mucosa and submucosa in treating female chronic posterior urethritis. METHODS: A single-center, retrospective, observational study was conducted at a teaching and referral hospital. A total of 147 female patients who had been diagnosed with chronic papillary urethritis underwent transurethral electroresection between 2015 and 2018. Each patient underwent a follow-up examination. A chart review was also performed. RESULTS: Patients had a mean age of 54 years (range, 23-82 years), and the average follow-up period was 54.8 months (range, 6-600 months). Urinary frequency and urgency (51.7%) were the most common clinical manifestations of chronic posterior urethritis. Forty-two-point two percent of patients had positive urine culture results, most commonly with Mycoplasma genitalium. The cystoscopic findings revealed that chronic posterior urethritis has tuft-like, pseudopodia-like, finger-like, and follicular-like polyps and villi, and a pebble-like appearance with mucosal hyperemia. The success rate of the transurethral electroresection was 88.6%, and patients showed no apparent or serious complications. CONCLUSIONS: This study showed that female chronic posterior urethritis is a cause that contributes to LUT symptoms. Its characteristic cystoscopic appearance and biopsy play a vital role in its diagnosis. The transurethral electroresection of urethral lesions is simple, effective, and minimally invasive without any apparent complications.

Assessment Causality in Associations Between Serum Uric Acid and Risk of Schizophrenia: A Two-Sample Bidirectional Mendelian Randomization Study.

PURPOSE: Although increasing lines of evidence showed associations between serum uric acid (UA) levels and schizophrenia, the causality and the direction of the associations remain uncertain. Thus, we aimed to assess whether the relationships between serum UA levels and schizophrenia are causal and to determine the direction of the association. PATIENTS AND METHODS: Two-sample bidirectional Mendelian randomization (MR) analyses and various sensitivity analyses were performed utilizing the summary data from genome-wide association studies within the Global Urate Genetics Consortium and the Psychiatric Genomics Consortium. Secondary MR analyses in both directions were conducted within summary data using genetic risk scores (GRSs) as instrumental variables. RESULTS: Three MR methods provided no causal relationship between serum UA and schizophrenia. Furthermore, GRS approach showed similar results in the three MR methods after adjustment for heterogeneity. By contrast, inverse variance weighted method, weighted median and GRS approach suggested a causal effect of schizophrenia risk on serum UA after adjustment for heterogeneity (per 10-symmetric percentage increase in schizophrenia risk, beta: -0.039, standard error (SE): 0.013, P = 0.003; beta: -0.036, SE: 0.018, P = 0.043; beta: -0.039, SE: 0.013, P = 0.002; respectively). Moreover, in both directions' analyses, the heterogeneity and sensitivity tests suggested no strong evidence of bias due to pleiotropy. CONCLUSION: Schizophrenia may causally affect serum UA levels, whereas the causal role of serum UA concentrations in schizophrenia was not supported by our MR analyses. These findings suggest that UA may be a useful potential biomarker for monitoring treatment or diagnosis of schizophrenia rather than a therapeutic target for schizophrenia.

Effects of Adiponectin on T2DM and Glucose Homeostasis: A Mendelian Randomization Study.

PURPOSE: The associations of adiponectin with type 2 diabetes mellitus (T2DM), glucose homeostasis (including ß-cell function index (HOMA-ß), insulin resistance (HOMA-IR), fasting insulin (FI) and fasting glucose (FG)) have reported in epidemiological studies. However, the previous observational studies are prone to biases, such as reverse causation and residual confounding factors. Herein, a Mendelian Randomization (MR) study was conducted to determine whether causal effects exist among them. MATERIALS AND AND METHODS: Two-sample MR analyses and multiple sensitivity analyses were performed using the summary data from the ADIPOGen consortium, MAGIC Consortium, and a meta-analysis of GWAS with a considerable sample of T2DM (62,892 cases and 596,424 controls of European ancestry). We got eight valid genetic variants to predict the causal effect among adiponectin and T2DM and glucose homeostasis after excluding the probable invalid or pleiotropic variants. RESULTS: Adiponectin was not associated with T2DM (odds ratio (OR) = 1.004; 95% confidence interval (CI): 0.740, 1.363) when using MR Egger after removing the invalid SNPs, and the results were consistent when using the other four methods. Similar results existed among adiponectin and HOMA-ß, HOMA-IR, FI, FG. CONCLUSION: Our MR study revealed that adiponectin had no causal effect on T2DM and glucose homeostasis and that the associations among them in observational studies may be due to confounding factors.

rs2274911 polymorphism in GPRC6A associated with serum E2 and PSA in a Southern Chinese male population.

BACKGROUND: rs2274911 (Pro91Ser, G > A) is a missense mutation located on the second exon of the GPRC6A gene. Increasing evidence revealed a significant association between the A allele of rs2274911 and male diseases, such as oligospermia, cryptorchidism, and prostate tumor. However, the function of rs2274911 in healthy males is unclear. SUBJECTS AND METHODS: A total of 1742 healthy men were selected from the Fangchenggang Area Male Health and Examination Survey (FAMHES). The association between rs2274911 and phenotype was evaluated. The cell characteristics of rs2274911 mutation (mu), wild-type GPRC6A (WT), and RFP control in human embryonic kidney (293T) and human prostate cancer (PC3) cells were analyzed. RNA sequencing was performed on PC3 cells. RESULTS: E2 and PSA serum levels increased with the accumulation of the A allele (E2: G vs. A, -0.029 [-0.050, -0.008], P < 0.01, P trend = 0.027; PSA: G vs. A, -0.040 [-0.079, 0.000], P < 0.05, P trend = 0.048). rs2274911 enhanced the proliferation and invasion ability of PC3 or 293T cells and activated the ERK pathway. The genes were identified as rs2274911 mu-affected genes through RNA sequential analysis of rs2274911 mu, GPRC6A WT, and RFP control of PC3 cells. Most of these genes were related to cancer development processes, cAMP, and the ERK cell signaling pathway. CONCLUSION: This project represents that rs2274911 is associated with E2 and PSA serum levels in Southern Chinese men. Rs2274991 mutation promotes 293T and PC3 cell proliferation in vitro. These results suggest that rs2274911 is a functional variant of GPRC6A.