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.

In Asia, about 1%-19.1% of the population suffer from urolithiasis. However, due to variations in socio-economic status and geographic locations, the prevalence and incidence have changed in different countries or regions over the years. The research for risk factors of urinary tract stones is of predominant importance. In this review, we find the prevalence of urolithiasis is 5%-19.1% in West Asia, Southeast Asia, South Asia, as well as some developed countries (South Korea and Japan), whereas, it is only 1%-8% in most part of East Asia and North Asia. The recurrence rate ranges from 21% to 53% after 3-5 years. Calcium oxalate (75%-90%) is the most frequent component of calculi, followed by uric acid (5%-20%), calcium phosphate (6%-13%), struvite (2%-15%), apatite (1%) and cystine (0.5%-1%). The incidence of urolithiasis reaches its peak in population aged over 30 years. Males are more likely to suffer from urinary calculi. Because of different dietary habits or genetic background, differences of prevalence among races or nationalities also exist. Genetic mutation of specific locus may contribute to the formation of different kinds of calculi. Dietary habits (westernized dietary habits and less fluid intake), as well as climatic factors (hot temperature and many hours of exposure to sunshine) play a crucial role in the development of stones. Other diseases, especially metabolic syndrome, may also contribute to urinary tract stones.

Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation of lipid peroxides, provides a novel avenue for delving into the intersection of cellular metabolism, oxidative stress, and disease pathology. We have witnessed a mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological and pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, and traumatic tissue injuries. By unraveling the intricate underpinnings of the molecular machinery, pivotal contributors, intricate signaling conduits, and regulatory networks governing ferroptosis, researchers aim to bridge the gap between the intricacies of this unique mode of cellular death and its multifaceted implications for health and disease. In light of the rapidly advancing landscape of ferroptosis research, we present a comprehensive review aiming at the extensive implications of ferroptosis in the origins and progress of human diseases. This review concludes with a careful analysis of potential treatment approaches carefully designed to either inhibit or promote ferroptosis. Additionally, we have succinctly summarized the potential therapeutic targets and compounds that hold promise in targeting ferroptosis within various diseases. This pivotal facet underscores the burgeoning possibilities for manipulating ferroptosis as a therapeutic strategy. In summary, this review enriched the insights of both investigators and practitioners, while fostering an elevated comprehension of ferroptosis and its latent translational utilities. By revealing the basic processes and investigating treatment possibilities, this review provides a crucial resource for scientists and medical practitioners, aiding in a deep understanding of ferroptosis and its effects in various disease situations.

The relationship of gut microbiota and calcium oxalate stone has been limited investigated, especially with no study of gut microbiota and short chain fatty acids (SCFAs) in nephrolithiasis. We provided Sprague Dawley rats of renal calcium oxalate stones with antibiotics and examined the renal crystals deposition. We also performed a case‐control study by analyzing 16S rRNA microbial profiling, shotgun metagenomics and SCFAs in 153 fecal samples from non‐kidney stone (NS) controls, patients with occasional renal calcium oxalate stones (OS) and patients with recurrent stones (RS). Antibiotics reduced bacterial load in feces and could promote the formation of renal calcium crystals in model rats. In addition, both OS and RS patients exhibited higher fecal microbial diversity than NS controls. Several SCFAs‐producing gut bacteria, as well as metabolic pathways associated with SCFAs production, were considerably lower in the gut microbiota among the kidney stone patients compared with the NS controls. Representation of genes involved in oxalate degradation showed no significance difference among groups. However, fecal acetic acid concentration was the highest in RS patients with high level of urinary oxalate, which was positively correlated with genes involvement in oxalate synthesis. Administration of SCFAs reduced renal crystals. These results shed new light on bacteria and SCFAs, which may promote the development of treatment strategy in nephrolithiasis.

Purpose: We evaluated the effects of α-blockers, antimuscarinics, or a combination of both in reducing ureteral stent-related symptoms. Methods: The relevant studies were identified by searching MEDLINE, EMBASE and Cochrane Library Database from January 2000 to May 2014. Randomized controlled trials evaluating effects of α-blocker, antimuscarinic, and combination therapy for stent-related symptoms were included. Two reviewers independently screened studies and extracted data. Results: A total of 13 articles were identified including 1408 patients. There were statistically significant differences in urinary symptom (−6.37; P<0.0001) and body pain index score (−7.03; P=0.0008) of the Ureteral Stent Symptom Questionnaire (USSQ), total International Prostate Symptom Score (IPSS) (−4.16; P=0.0006), Visual Analogue Pain Scale (VAPS) score (−2.48; P<0.00001), and quality of life (QoL) (−1.42; P=0.0009) in favor of the α-blocker group. Antimuscarinics alone vs the control group showed significant improvement in total IPSS (mean difference [MD]: −3.76; 95% confidence interval [CI], −5.08 to −2.43; P<0.00001) and QoL (MD: −0.82; 95% CI, −1.31 to −0.32; P=0.001). Compared with α-blockers monotherapy, combination therapy has significant lower total IPSS (MD: −3.74; 95% CI, −4.94 to −2.54; P<0.00001), VAPS (MD: −0.50; 95% CI, −0.89 to −0.11; P=0.01), and QoL (MD: −0.93; 95% CI, −1.30 to −0.55; P<0.00001). Conclusions: Our data showed the beneficial effect of α-blockers alone and antimuscarinics alone in reducing stent-related symptoms. Furthermore, we suggested significant advantages of combination therapy of α-blocker and antimuscarinic compared with α-blocker monotherapy. However, more high quality, randomized controlled trials are warranted to better address this issue, however.