Examining the causal association between psoriasis and bladder cancer: A two-sample Mendelian randomization analysis.

BACKGROUND: Previous epidemiological observational studies have potentially associated psoriasis with bladder cancer, but the results are inconsistent, and the causality remains unknown. The present study aimed to examine whether there are causal associations between psoriasis and bladder cancer using bidirectional two-sample Mendelian randomization (MR) analysis. MATERIALS AND METHODS: A two-sample MR analysis was conducted using publicly available genome-wide association study (GWAS) data for individuals diagnosed with psoriasis and bladder cancer. The inverse variance weighted (IVW) method was the primary method. The complementary methods used included the weighted median, MR-Egger, weighted mode, and simple mode methods. Heterogeneity and pleiotropy of the MR results were detected. Moreover, leave-one-out sensitivity analysis was also employed to evaluate the robustness and validity of the findings. RESULTS: No significant causal association was detected between psoriasis incidence and the risk of bladder cancer using the IVW method (OR = 0.999, 95% CI 0.977-1.022; P = 0.956). Similarly, the IVW model revealed no evidence of a causal relationship between bladder cancer and the risk of psoriasis (OR = 0.979, 95%CI = 0.873-1.098; P = 0.716). The results of the complementary methods were consistent with those of the IVW method. There was no notable horizontal pleiotropy or heterogeneity (P > 0.05) in our MR analysis. The results of sensitivity analysis confirmed that the MR estimates were not driven by single-nucleotide polymorphisms (SNPs). CONCLUSION: This study does not support a causal relationship between psoriasis and bladder cancer.

From remotely-sensed solar-induced chlorophyll fluorescence to ecosystem structure, function, and service: Part II-Harnessing data.

Although our observing capabilities of solar-induced chlorophyll fluorescence (SIF) have been growing rapidly, the quality and consistency of SIF datasets are still in an active stage of research and development. As a result, there are considerable inconsistencies among diverse SIF datasets at all scales and the widespread applications of them have led to contradictory findings. The present review is the second of the two companion reviews, and data oriented. It aims to (1) synthesize the variety, scale, and uncertainty of existing SIF datasets, (2) synthesize the diverse applications in the sector of ecology, agriculture, hydrology, climate, and socioeconomics, and (3) clarify how such data inconsistency superimposed with the theoretical complexities laid out in (Sun et al., 2023) may impact process interpretation of various applications and contribute to inconsistent findings. We emphasize that accurate interpretation of the functional relationships between SIF and other ecological indicators is contingent upon complete understanding of SIF data quality and uncertainty. Biases and uncertainties in SIF observations can significantly confound interpretation of their relationships and how such relationships respond to environmental variations. Built upon our syntheses, we summarize existing gaps and uncertainties in current SIF observations. Further, we offer our perspectives on innovations needed to help improve informing ecosystem structure, function, and service under climate change, including enhancing in-situ SIF observing capability especially in "data desert" regions, improving cross-instrument data standardization and network coordination, and advancing applications by fully harnessing theory and data.

From remotely sensed solar-induced chlorophyll fluorescence to ecosystem structure, function, and service: Part I-Harnessing theory.

Solar-induced chlorophyll fluorescence (SIF) is a remotely sensed optical signal emitted during the light reactions of photosynthesis. The past two decades have witnessed an explosion in availability of SIF data at increasingly higher spatial and temporal resolutions, sparking applications in diverse research sectors (e.g., ecology, agriculture, hydrology, climate, and socioeconomics). These applications must deal with complexities caused by tremendous variations in scale and the impacts of interacting and superimposing plant physiology and three-dimensional vegetation structure on the emission and scattering of SIF. At present, these complexities have not been overcome. To advance future research, the two companion reviews aim to (1) develop an analytical framework for inferring terrestrial vegetation structures and function that are tied to SIF emission, (2) synthesize progress and identify challenges in SIF research via the lens of multi-sector applications, and (3) map out actionable solutions to tackle these challenges and offer our vision for research priorities over the next 5-10 years based on the proposed analytical framework. This paper is the first of the two companion reviews, and theory oriented. It introduces a theoretically rigorous yet practically applicable analytical framework. Guided by this framework, we offer theoretical perspectives on three overarching questions: (1) The forward (mechanism) question-How are the dynamics of SIF affected by terrestrial ecosystem structure and function? (2) The inference question: What aspects of terrestrial ecosystem structure, function, and service can be reliably inferred from remotely sensed SIF and how? (3) The innovation question: What innovations are needed to realize the full potential of SIF remote sensing for real-world applications under climate change? The analytical framework elucidates that process complexity must be appreciated in inferring ecosystem structure and function from the observed SIF; this framework can serve as a diagnosis and inference tool for versatile applications across diverse spatial and temporal scales.

Spindle pole body component 24 homolog potentiates tumor progression via regulation of SRY-box transcription factor 2 in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of human kidney cancer with a high probability of metastasis. To understand the molecular processing essential for ccRCC tumorigenicity, we conducted an integrative in silico analysis of The Cancer Genome Atlas (TCGA) ccRCC dataset and clustered randomly interspersed short palindromic repeats (CRISPR) screening dataset of ccRCC cell lines from Depmap. We identified spindle pole body component 24 homolog (SPC24) as an essential gene for ccRCC cell lines with prognostic significance in the TCGA database. Targeting SPC24 by CRISPR/Cas9-mediated gene knockout attenuated ccRCC proliferation, metastasis, and in vivo tumor growth. Furthermore, we found that SPC24 regulates metastasis genes expression in a SRY-box transcription factor 2 (SOX2)-dependent manner. The anti-proliferative effects of SPC24 knockout were strengthened with SOX2 knockdown. Collectively, our findings suggest SPC24 has a pivotal function in promoting ccRCC progression, providing a new insight for the treatment of ccRCC.

The physiological basis for estimating photosynthesis from Chla fluorescence.

Solar-induced Chl fluorescence (SIF) offers the potential to curb large uncertainties in the estimation of photosynthesis across biomes and climates, and at different spatiotemporal scales. However, it remains unclear how SIF should be used to mechanistically estimate photosynthesis. In this study, we built a quantitative framework for the estimation of photosynthesis, based on a mechanistic light reaction model with the Chla fluorescence of Photosystem II (SIFPSII ) as an input (MLR-SIF). Utilizing 29 C3 and C4 plant species that are representative of major plant biomes across the globe, we confirmed the validity of this framework at the leaf level. The MLR-SIF model is capable of accurately reproducing photosynthesis for all C3 and C4 species under diverse light, temperature, and CO2 conditions. We further tested the robustness of the MLR-SIF model using Monte Carlo simulations, and found that photosynthesis estimates were much less sensitive to parameter uncertainties relative to the conventional Farquhar, von Caemmerer, Berry (FvCB) model because of the additional independent information contained in SIFPSII . Once inferred from direct observables of SIF, SIFPSII provides 'parameter savings' to the MLR-SIF model, compared to the mechanistically equivalent FvCB model, and thus avoids the uncertainties arising as a result of imperfect model parameterization. Our findings set the stage for future efforts to employ SIF mechanistically to improve photosynthesis estimates across a variety of scales, functional groups, and environmental conditions.

Inference of photosynthetic capacity parameters from chlorophyll a fluorescence is affected by redox state of PSII reaction centers.

Solar-induced chlorophyll fluorescence (SIF) has been used to infer photosynthetic capacity parameters (e.g., the maximum carboxylation rate Vcmax , and the maximum electron transport rate Jmax ). However, the precise mechanism and practical utility of such approach under dynamic environments remain unclear. We used the balance between the light and carbon reactions to derive theoretical equations relating chlorophyll a fluorescence (ChlF) emission and photosynthetic capacity parameters, and formulated testable hypotheses regarding the dynamic relationships between the true total ChlF emitted from PSII (SIFPSII ) and Vcmax and Jmax . We employed concurrent measurements of gas exchanges and ChlF parameters for 15 species from six biomes to test the formulated hypotheses across species, temperatures, and limitation state of carboxylation. Our results revealed that SIFPSII alone is incapable of informing the variations in Vcmax and Jmax across species, even when SIFPSII is determined under the same environmental conditions. In contrast, the product of SIFPSII and the fraction of open PSII reactions qL , which indicates the redox state of PSII, is a strong predictor of both Vcmax and Jmax , although their precise relationships vary somewhat with environmental conditions. Our findings suggest the redox state of PSII strongly influences the relationship between SIFPSII and Vcmax and Jmax .

Adjustable single-incision mini-slings (Ajust®) versus other slings in surgical management of female stress urinary incontinence: a meta-analysis of effectiveness and complications.

BACKGROUND: Adjustable single-incision mini-sling (SIMS) is a new category of SIMS for stress urinary incontinence (SUI). The aim of this study was to compare the efficacy and safety of adjustable single-incision mini-sling with other slings. METHODS: Literature search in databases such as Pubmed, and Conchrane Library was performed up to December, 2015. The outcomes including cure rate, operation time, postoperative pain score and complications were reanalyzed. The pooled relative risk (RR) and mean difference (MD) with their 95% confidence interval (95% CI) were calculated by RevMan v5.0. RESULTS: Eight studies with 1093 SUI female patients were included. There was no significant difference between adjustable SIMS and other slings (transobturator slings and MiniArc) in patients subjective cure rate and objective cure rate. In addition, adjustable SIMS was associated with a significantly shorter operative time and lower postoperative pain score when comparing adjustable SIMS with transobturator tape (MD = - 1.35; 95%CI: -2.24 to - 0.46, P = 0.003). For the complications, there was also no significant difference between adjustable SIMS and transobturator slings. CONCLUSIONS: Adjustable SIMS had equally efficacy for SUI compared with transobturator slings and MiniArc. However, the significantly shorter operative time and lower postoperative pain score than transobturator tape supported the clinical application of adjustable SIMS.

Thymol inhibits bladder cancer cell proliferation via inducing cell cycle arrest and apoptosis.

Thymol is a phenolic compound with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-tumor effects. However, the effect of thymol on bladder cancer cell growth is still elusive. The purpose of this study is to investigate the efficacy of thymol in bladder cancer cells and its underlying mechanism. Thymol inhibited bladder cancer cell proliferation in a dose and time-dependent manner. We also observed cell cycle arrest at the G2/M phase after the treatment of thymol. Moreover, thymol could induce apoptosis in bladder cancer cells via the intrinsic pathway along with caspase-3/9 activation, release of cytochrome c and down-regulation of anti-apoptotic Bcl-2 family proteins. The activation of JNK and p38 was also critical for thymol-induced apoptosis since it was abrogated by the treatment of JNK inhibitor (SP600125), and p38 inhibitor (SB203580) but not ERK inhibitor (SCH772984). Furthermore, the generation of ROS (reactive oxygen species) was detected after the treatment of thymol. ROS scavenger NAC (N-acetyl cysteine) could block the thymol-triggered apoptosis and activation of MAPKs. These findings offer a novel therapeutic approach for bladder cancer.

PSAD Test in the Diagnosis of Prostate Cancer: a Meta-Analysis.

BACKGROUND: The aim of this study is to evaluate the diagnostic value of prostate-specific antigen density (PSAD) test in detecting prostate cancer. METHODS: We searched public databases including PubMed, Medline, Springer, Elsevier Science Direct, Cochrane Library, and Google scholar before June 2015. In this meta-analysis, specificity, positive LR, negative LR, and dOR of PSAD test in patients with prostate cancer were analyzed from published studies. We applied Meta-DiSc 1.4 and Stata 11.0 software to the meta-analysis. RESULTS: A total of 11 separate studies consisting of 1821 participants were considered in the meta-analysis. The results of this meta-analysis indicated that sensitivity, specificity, positive Likelihood Ratio (LR), negative LR, and Diagnostic Odds Ratio (dOR) of PSAD test for prostate cancer were 0.73 (95% CI = 0.69 to 0.78), 0.64 (95% CI = 0.61 to 0.66), 2.13 (95% CI = 1.64 to 2.76), 0.45 (95% CI = 0.35 to 0.57), and 5.87 (95% CI = 4.42 to 7.81), respectively. It also showed that the AUC and Q* index were 0.77 and 0.71, respectively. The results of the Egger's linear regression test showed that no publication bias existed (p > 0.05). CONCLUSIONS: In general, our results show that specificity, positive LR, negative LR, dOR, the area under the curve (AUC), and Q * index of PSAD test may be appropriate for detecting prostate cancer.

Hypoxia-induced autophagy promotes human prostate stromal cells survival and ER-stress.

Benign prostatic hyperplasia (BPH) is emerging as one of the most common diseases seriously threatening the health of elderly men. Accumulating evidences indicate that hypoxia could induce BPH. However, the underlying mechanism of BPH induced by hypoxia is not clear. In the study, hypoxia-induced autophagy could promote cell survival and endoplasmic reticula stress (ER stress) in WPMY-1 cells. Cell viability induced by hypoxia could been decreased by autophagy inhibitors (3-methyladenine, bafilomycin A1) or siRNA interference in two autophagy genes (Beclin1, ATG5) in WPMY-1 cells. Furthermore, ER stress was present in hypoxia-treated WPMY-1 cells, while autophagy and cell survival could been inhibited by C/EBP-homologous protein siRNA (CHOP), which is an important protein of ER stress pathway. Taken together, our data support a novel model that autophagy as a cytoprotective response promotes cell survival via ER stress under hypoxia in human prostate stromal cells.

Excess adenosine A2B receptor signaling contributes to priapism through HIF-1α mediated reduction of PDE5 gene expression.

Priapism is featured with prolonged and painful penile erection and is prevalent among males with sickle cell disease (SCD). The disorder is a dangerous urological and hematological emergency since it is associated with ischemic tissue damage and erectile disability. Here we report that phosphodiesterase-5 (PDE5) gene expression and PDE activity is significantly reduced in penile tissues of two independent priapic models: SCD mice and adenosine deaminase (ADA)-deficient mice. Moreover, using ADA enzyme therapy to reduce adenosine or a specific antagonist to block A(2B) adenosine receptor (ADORA2B) signaling, we successfully attenuated priapism in both ADA(-/-) and SCD mice by restoring penile PDE5 gene expression to normal levels. This finding led us to further discover that excess adenosine signaling via ADORA2B activation directly reduces PDE5 gene expression in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. Overall, we reveal that excess adenosine-mediated ADORA2B signaling underlies reduced penile PDE activity by decreasing PDE5 gene expression in a HIF-1α-dependent manner and provide new insight for the pathogenesis of priapism and novel therapies for the disease.

A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats.

Diabetes is an important risk factor for erectile dysfunction (ED). Recent studies have indicated that A2B adenosine receptor (ADORA2B) signaling is essential for penile erection. Thus, we hypothesize that diabetic ED may be attributed to impaired A2B adenosine signaling. To test this hypothesis, we generated diabetic rats by injecting streptozocin as animal model. After 12 weeks, immunohistochemistry staining was used to localize the expression of ADORA2B. Western Blot and quantitative PCR were employed to determine ADORA2B expression level. Intracavernosal pressure (ICP) measurement was used to evaluate erectile function. Diabetic rats received a single intravenous injection of BAY 60-6583, an ADORA2B agonist, or vehicle solution, at 60 min before the ICP measurement. The results showed that ADORA2B expressed in the nerve bundle, smooth muscle, and endothelium in penile tissue of control mice. Western Blot and quantitative PCR results indicated that the expression levels of ADORA2B protein and mRNA were significantly reduced in penile tissues of diabetic rats. Functional studies showed that the erectile response induced by electrical stimulation was remarkably decreased in diabetic rats, compared with age-matched control rats. However, at 60 min after BAY 60-6583 treatment, the erectile function was improved in diabetic rats, suggesting that enhancement of ADORA2B signaling may improve erectile function in diabetic ED. This preclinical study has revealed a previously unrecognized therapeutic possibility of BAY 60-6583 as an effective and mechanism-based drug to treat diabetic ED. In conclusion, we propose that impaired A2B adenosine signaling is one of the pathological mechanisms of diabetic ED.

Cloning and characterization of squalene synthase gene from Poria cocos and its up-regulation by methyl jasmonate.

Squalene synthase (SQS) catalyzes the condensation of two molecules of farnesyl diphosphate to give presqualene diphosphate and the subsequent rearrangement to form squalene. The gene encoding squalene synthase was cloned from Poria cocos by degenerate PCR and inverse PCR. The open reading frame of the gene is 1,497 bp, which encodes 499 amino acid residues. A phylogenetic analysis revealed that P. cocos SQS belonged to the fungus group, and was more closely related to the SQS of Ganoderma lucidum than other fungi. The treatment of P. cocos with methyl jasmonate (MeJA) significantly enhanced the transcriptional level of P. cocos sqs gene and the content of squalene in P. cocos. The transcriptional level of sqs gene was approximately fourfold higher than the control sample and the squalene content reached 128.62 µg/g, when the concentration of MeJA was 300 µM after 72 h induction.

No causal association between insomnia and bladder cancer: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Previous observational studies have indicated a potential link between insomnia and bladder cancer, yet the underlying causal relationship remains uncertain. The current study employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate this association. METHODS: A two-sample MR analysis was conducted utilizing publicly available summary data from genome-wide association studies (GWAS) on insomnia and bladder cancer. Various regression methods including the inverse variance weighted (IVW), weighted median, MR-Egger, weighted mode, and simple mode methods were employed for the MR analysis. The presence of pleiotropy and heterogeneity in the MR results was also assessed. Furthermore, additional sensitivity tests were performed to mitigate potential biases. RESULTS: No significant causal relationship was detected between insomnia and bladder cancer using IVW method (OR = 0.761, 95% CI 0.996-1.005; P = 0.76). Similarly, the IVW model did not reveal any causal effect of bladder cancer on the risk of insomnia (OR = 1.47, 95% CI 0.772-2.799; P = 0.24). Consistent results were obtained from the other four methods employed. There was no evidence of horizontal pleiotropy or heterogeneity in our MR analysis (P > 0.05). The sensitivity analyses further supported the reliability of the estimated causal effects. CONCLUSIONS: This study presents no evidence for a causal relationship between insomnia and bladder cancer.

Establishment and validation of a novel disulfidptosis-related immune checkpoint gene signature in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal tumors and is associated with a unfavorable prognosis. Disulfidptosis is a recently identified form of cell death mediated by disulfide bonds. Numerous studies have highlighted the significance of immune checkpoint genes (ICGs) in ccRCC. Nevertheless, the involvement of disulfidptosis-related immune checkpoint genes (DRICGs) in ccRCC remains poorly understood. METHODS: The mRNA expression profiles and clinicopathological data of ccRCC patients were obtained from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. The associations between disulfidptosis-related genes (DRGs) and immune checkpoint genes (ICGs) were assessed to identify DRICGs. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were conducted to construct a risk signature. RESULTS: A total of 39 differentially expressed immune-related candidate genes were identified. A prognostic signature was constructed utilizing nine DRICGs (CD276, CD80, CD86, HLA-E, LAG3, PDCD1LG2, PVR, TIGIT, and TNFRSF4) and validated using GEO data. The risk model functioned as an independent prognostic indicator for ccRCC, while the associated nomogram provided a reliable scoring system for ccRCC. Gene set enrichment analysis indicated enrichment of phospholipase D, antigen processing and presentation, and ascorbate and aldarate metabolism-related signaling pathways in the high-risk group. Furthermore, the DRICGs exhibited correlations with the infiltration of various immune cells. It is noteworthy that patients with ccRCC categorized into distinct risk groups based on this model displayed varying sensitivities to potential therapeutic agents. CONCLUSIONS: The novel DRICG-based risk signature is a reliable indicator for the prognosis of ccRCC patients. Moreover, it also aids in drug selection and correlates with the tumour immune microenvironment in ccRCC.

Adenosine signaling: good or bad in erectile function?

The erectile status of penile tissue is governed largely by the tone of cavernosal smooth muscle cells, which is determined by the balance of vascular relaxants and constrictors. Vascular relaxants play a key role in regulating the tone of cavernosal smooth muscle and thus the initiation and maintenance of penile erection. Early studies drew attention to the potential role of adenosine signaling in this process. However, the serendipitous discovery of the effect of sildenafil on erectile physiology drew more attention toward nitric oxide (NO) as a vasodilator in the process of penile erection, and a recently discovered, unexpected erectile phenotype of adenosine deaminase-deficient mice reemphasizes the importance of adenosine as a key regulatory of erectile status. Adenosine, like NO, is a potent and short-lived vasorelaxant that functions via cyclic nucleotide second messenger signaling to promote smooth muscle relaxation. Recent studies reviewed here show that adenosine functions to relax the corpus cavernosum and promote penile erection. Excess adenosine in penile tissue contributes to the disorder called priapism, and impaired adenosine signaling is associated with erectile dysfunction. More recent research summarized in this review reveals that adenosine functions as a key endogenous vasodilator in the initiation and maintenance of normal penile erection. This new insight highlights adenosine signaling pathways operating in penile tissue as significant therapeutic targets for the treatment of erectile disorders.

A simple method to isolate structurally and chemically intact brain vascular basement membrane for neural regeneration following traumatic brain injury.

BACKGROUND: The brain vascular basement membrane (brain-VBM) is an important component of the brain extracellular matrix, and the three-dimensional structure of the cerebrovascular network nested with many cell-adhesive proteins may provide guidance for brain tissue regeneration. However, the potential of ability of brain-VBM to promote neural tissue regeneration has not been examined due to the technical difficulty of isolating intact brain-VBM. METHODS: The present study developed a simple, effective method to isolate structurally and compositionally intact brain-VBM. Structural and component properties of the brain-VBM were characterized to confirm the technique. Seed cells were cocultured with brain-VBM in vitro to analyze biocompatibility and neurite extension. An experimental rat model of focal traumatic brain injury (TBI) induced by controlled cortical impact were conducted to further test the tissue regeneration ability of brain-VBM. RESULTS: Brain-VBM isolated using genipin showed significantly improved mechanical properties, was easy to handle, supported high cell viability, exhibited strong cell adhesive properties, and promoted neurite extension and outgrowth. Further testing of the isolated brain-VBM transplanted at lesion sites in an experimental rat model of focal TBI demonstrated considerable promise for reconstructing a complete blood vessel network that filled in the lesion cavity and promoting repopulation of neural progenitor cells and neurons. CONCLUSION: The technique allows isolation of intact brain-VBM as a 3D microvascular scaffold to support brain tissue regeneration following TBI and shows considerable promise for the production of naturally-derived biomaterials for neural tissue engineering.

Effects of ECM proteins (laminin, fibronectin, and type IV collagen) on the biological behavior of Schwann cells and their roles in the process of remyelination after peripheral nerve injury.

Introduction: It is important to note that complete myelination and formation of myelinated fibers are essential for functional nerve regeneration after peripheral nerve injury (PNI). However, suboptimal myelin regeneration is common and can hinder ideal nerve regeneration. Therefore, it is important to closely monitor and support myelin regeneration in patients with PNI to achieve optimal outcomes. Methods: This study analyzed the effects of three extracellular matrix (ECM) proteins on Schwann cells (SCs) in the nerve regeneration environment, including their adhesion, proliferation, and migration. The study also explored the use of composite sodium alginate hydrogel neural scaffolds with ECM components and investigated the effects of ECM proteins on remyelination following peripheral nerve injury. Results: The results showed that laminin (LN), fibronectin (FN), and collagen Ⅳ (type IV Col) promoted the early adhesion of SCs in 2-dimensional culture but the ratios of early cell adhesion were quite different and the maintenance of cells' morphology by different ECM proteins were significantly different. In transwell experiment, the ability of LN and FN to induce the migration of SCs was obviously higher than that of type IV Col. An vitro co-culture model of SCs and dorsal root ganglia (DRG) neurons showed that LN promoted the transition of SCs to a myelinated state and the maturation of the myelin sheath, and increased the thickness of neurofilaments. Animal experiments showed that LN had superior effects in promoting myelin sheath formation, axon repair, and reaching an ideal G-ratio after injury compared to FN and Col IV. The situation of gastrocnemius atrophy was significantly better in the LN group. Notably, the thickness of the regenerated myelin sheaths in the type IV Col group was the thickest. Conclusion: In this experiment, we analyzed and compared the effects of LN, FN, and type IV Col on the biological behavior of SCs and their effects on remyelination after PNI and further clarified their unique roles in the process of remyelination. Further research is necessary to explore the underlying mechanisms.

Temperature changes of renal calyx during high-power flexible ureteroscopic Moses holmium laser lithotripsy: a case analysis study.

PURPOSE: The risk of thermal damage increases with the introduction of high-power lasers during holmium laser lithotripsy. This study aimed to quantitatively evaluate the temperature change of renal calyx in the human body and the 3D printed model during high-power flexible ureteroscopic holmium laser lithotripsy and map out the temperature curve. METHODS: The temperature was continuously measured by a medical temperature sensor secured to a flexible ureteroscope. Between December 2021 and December 2022, willing patients with kidney stones undergoing flexible ureteroscopic holmium laser lithotripsy were enrolled. High frequency and high-power settings (24 W, 80 Hz/0.3 J and 32 W, 80 Hz/0.4 J) were performed for each patient with room temperature (25 °C) irrigation. In the 3D printed model, we studied more holmium laser settings (24 W, 80 Hz/0.3 J, 32 W, 80 Hz/0.4 J and 40 W, 80 Hz/0.4 J) with warmed (37 °C) and room temperature (25 °C) irrigation. RESULTS: Twenty-two patients were enrolled in our study. With 30 ml/min or 60 ml/min irrigation, the local temperature of the renal calyx did not reach 43 °C in any patient under 25 °C irrigation after 60 s laser activation. There were similar temperature changes in the 3D printed model with the human body under the irrigation of 25 °C. Under the irrigation of 37 °C, the temperature rise slowed down, but the temperature in the renal calyces was close to or even exceeded the 43 °C at the setting of 32 W, 30 ml/min and 40 W, 30 ml/min after continuing laser activation. CONCLUSION: In the irrigation of 60 ml/min, the temperature in the renal calyces can still be maintained within a safe range after continuous activation of a holmium laser up to 40 W. However, continuous activation of 32 W or higher power holmium laser in the renal calyces for more than 60 s in the limited irrigation of 30 ml/min can cause excessive local temperature, in such situation room temperature perfusion at 25 ℃ may be a relatively safer option.

A2B adenosine receptor contributes to penile erection via PI3K/AKT signaling cascade-mediated eNOS activation.

Normal penile erection is under the control of multiple factors and signaling pathways. Although adenosine signaling is implicated in normal and abnormal penile erection, the exact role and the underlying mechanism for adenosine signaling in penile physiology remain elusive. Here we report that shear stress leads to increased adenosine release from endothelial cells. Subsequently, we determined that ecto-5'-nucleotidase (CD73) is a key enzyme required for the production of elevated adenosine from ATP released by shear-stressed endothelial cells. Mechanistically, we demonstrate that shear stress-mediated elevated adenosine functions through the adenosine A(2B) receptor (A(2B)R) to activate the PI3K/AKT signaling cascade and subsequent increased endothelial nitric oxide synthase (eNOS) phosphorylation. These in vitro studies led us to discover further that adenosine was induced during sustained penile erection and contributes to PI3K/AKT activation and subsequent eNOS phosphorylation via A(2B)R signaling in intact animal. Finally, we demonstrate that lowering adenosine in wild-type mice or genetic deletion of A(2B)R in mutant mice significantly attenuated PI3K/AKT activation, eNOS phosphorylation, and subsequent impaired penile erection featured with the reduction of ratio of maximal intracavernosal pressure to systemic arterial pressure from 0.49 ± 0.03 to 0.41 ± 0.05 and 0.38 ± 0.04, respectively (both P<0.05). Overall, using biochemical, cellular, genetic, and physiological approaches, our findings reveal that adenosine is a novel molecule signaling via A(2B)R activation, contributing to penile erection via PI3K/AKT-dependent eNOS activation. These studies suggest that this signaling pathway may be a novel therapeutic target for erectile disorders.