Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical signals regarding cell activities and metabolism. Typical mechanical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, and extracellular fluid viscosity. Mechanotransduction has been expected to trigger multiple biological processes, such as embryonic development, tissue repair and regeneration. However, prolonged excessive mechanical stimulation can result in pathological processes, such as multi-organ fibrosis, tumorigenesis, and cancer immunotherapy resistance. Although the associations between mechanical cues and normal tissue homeostasis or diseases have been identified, the regulatory mechanisms among different mechanical cues are not yet comprehensively illustrated, and no effective therapies are currently available targeting mechanical cue-related signaling. This review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated evidence. The key effectors responding to mechanical stimulations are listed, such as Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator with PDZ-binding motif (TAZ), and transient receptor potential vanilloid 4 (TRPV4). We also reviewed the key signaling pathways, therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues.

Interstitial cystitis (IC) is a severely debilitating and chronic disorder with unclear etiology and pathophysiology, which makes the diagnosis difficult and treatment challenging. To investigate the role of immunity in IC bladders, we sequenced 135,091 CD45⁺ immune cells from 15 female patients with IC and 9 controls with stress urinary incontinence using single-cell RNA sequencing (scRNA-seq). 22 immune subpopulations were identified in the constructed landscape. Among them, M2-like macrophages, inflammatory CD14⁺ macrophages, and conventional dendritic cells had the most communications with other immune cells. Then, a significant increase of central memory CD4⁺ T cells, regulatory T cells, GZMK⁺CD8⁺ T cells, activated B cells, un-switched memory B cells, and neutrophils, and a significant decrease of CD8⁺ effector T cells, Th17 cells, follicular helper T cells, switched memory B cells, transitional B cells, and macrophages were noted in IC bladders. The enrichment analysis identified a virus-related response during the dynamic change of cell proportion, furthermore, the human polyomavirus-2 was detected with a positive rate of 95% in urine of patients with IC. By integrating the results of scRNA-seq with spatial transcriptomics, we found nearly all immune subpopulations were enriched in the urothelial region or located close to fibroblasts in IC bladders, but they were discovered around urothelium and smooth muscle cells in control bladders. These findings depict the immune landscape for IC and might provide valuable insights into the pathophysiology of IC.

Purpose: Holmium YAG laser lithotripsy (LL) and pneumatic lithotripsy (PL) are the most commonly used procedures in the treatment of ureteral calculi. In a previous meta-analysis examining the treatment effect of the 2 modalities, the authors highlighted the need for large sample size and high quality trials to provide more uncovered outcome. Recently, several randomized controlled trials (RCTs) evaluating the same issue with larger patient number and more complicated data have been published. Therefore, we conducted this meta-analysis to update and synthesize evidence on the efficacy and safety of the 2 procedures in the treatment of ureteral calculi. Methods: The relevant studies were identified by searching Medline, EMBASE and Cochrane Library Database from January 1990 to November 2015. RCTs assessing the efficacy and safety of Holmium YAG laser and PL for ureteral stones were included. Two reviewers independently screened studies and extracted data. Results: A total of 8 studies were identified including 1,555 patients. Compared with PL, Holmium YAG LL significantly reduced the mean operative time (weighted mean difference = -11.52, 95% CI -17.06 to -5.99, p < 0.0001) and increased the early stone-free rate (OR 2.69, 95% CI 1.91-3.78, p < 0.00001) and the delayed stone-free rate (OR 2.12, 95% CI 1.40-3.21, p = 0.0004). However, a higher postoperative ureteral stricture rate (OR 3.38, 95% CI 1.56-7.31, p = 0.002) was observed in LL group over PL group. There was no statistical significance in the ureteral perforation rate (OR 1.19, 95% CI 0.65-2.16, p = 0.58), the stone migration rate (OR 0.64, 95% CI 0.41-1.00, p = 0.05), the postoperative gross hematuria rate (OR 0.71, 95% CI 0.40-1.25, p = 0.23) and the postoperative fever rate (OR 0.73, 95% CI 0.50-1.09, p = 0.12). Conclusions: Our data reconfirmed that Holmium LL for ureteral stones can achieve shorter mean operative time, better early and delayed stone-free rate with larger sample size and more high quality studies. And further trials are unlikely to considerably alter this conclusion. In terms of higher risk of postoperative ureteral stricture in LL group over PL group observed in our review, more high quality, multicenter RCTs with long-term follow-up outcome are warranted to better assess this issue.

Prostate cancer is one of the most common cancers in the elderly population. The standard treatment is radical prostatectomy (RARP). However, urologists do not have consents on the postoperative urine drainage management (suprapubic tube (ST)/ urethral catheter (UC)). Thus, we try to compare ST drainage to UC drainage after robot-assisted radical prostatectomy regarding to comfort, recovery rate and continence using the method of meta-analysis. A systematic search was performed in Dec. 2017 on PubMed, Medline, Embase and Cochrane Library databases. The authors independently reviewed the records to identify studies comparing ST with UC of patients underwent RARP. Meta-analysis was performed using the extracted data from the selected studies. Seven studies, including 3 RCTs, with a total of 946 patients met the inclusion criteria and were included in our meta-analysis. Though there was no significant difference between the ST group and the UC group on postoperative pain (RR1.73, P 0.20), our study showed a significant improvement on bother or discomfort, defined as trouble in hygiene and sleep, caused by catheter when compared two groups at postoperative day (POD) 7 in ST group (RR2.05, P 0.006). There was no significant difference between the ST group and UC group on urinary continence (RR0.98, P 0.74) and emergency department visit (RR0.61, P 0.11). The rates of bladder neck contracture and other complications were very low in both groups. Compared to UC, ST showed a weak advantage. So it might be a good choice to choose ST over RARP.

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.

Mechanical cues play a crucial role in activating myofibroblasts from quiescent fibroblasts during fibrosis, and the stiffness of the extracellular matrix is of significant importance in this process. While intracellular force mediated by myosin II and calcium influx regulated by Piezo1 are the primary mechanisms by which cells sense and respond to mechanical forces, their intercellular mechanical interaction remains to be elucidated. Here, hydrogels with tunable substrate are used to systematically investigate the crosstalk of myosin II and Piezo1 in fibroblast to myofibroblast transition (FMT). The findings reveal that the two distinct signaling pathways are integrated to convert mechanical stiffness signals into biochemical signals during bladder‐specific FMT. Moreover, it is demonstrated that the crosstalk between myosin II and Piezo1 sensing mechanisms synergistically establishes a sustained feed‐forward loop that contributes to chromatin remodeling, induces the expression of downstream target genes, and ultimately exacerbates FMT, in which the intracellular force activates Piezo1 by PI3K/PIP3 pathway‐mediated membrane tension and the Piezo1‐regulated calcium influx enhances intracellular force by the classical FAK/RhoA/ROCK pathway. Finally, the multifunctional Piezo1 in the complex feedback circuit of FMT drives to further identify that targeting Piezo1 as a therapeutic option for ameliorating bladder fibrosis and dysfunction.