Oxidative stress is a primary pathogenic driver in the formation and progression of kidney stones. Consequently, the development of nanomaterials that mitigate oxidative stress has emerged as a promising therapeutic strategy. However, the clinical translation of most nanomedicines remains challenging due to insufficient renal targeting and accumulation. Here, we report a near-infrared (NIR) light-driven polydopamine@polypyrrole nanomotor functionalized with hyaluronic acid (PDA@PPy@HA, PYA) for kidney-specific targeting and enhanced on-demand enrichment. Upon exposure to NIR light, this nanomotor converts photothermal energy into directional propulsion, thereby enhancing its accumulation within the kidneys. In vitro, PYA nanomotor alleviates high-oxalate-induced oxidative stress via effective elimination of reactive oxygen species (ROS) and subsequent restoration of mitochondrial membrane potential, thereby mitigating cellular apoptosis. In vivo studies further confirmed that the NIR-driven propulsion enhanced renal accumulation of the nanomotors. This active targeting strategy resulted in the upregulation of key antioxidant enzymes, including superoxide dismutase (SOD2) and catalase (CAT), alongside the concurrent suppression of the ROS-generating enzyme NOX2 and crystal-adhesion molecules (OPN and CD44). Together, these molecular responses mitigate renal injury and reduce calcium oxalate deposition. Active nanomotors circumvent the limitations of passive biodistribution, enabling a potent platform for kidney stone therapy.

Calcium oxalate crystal-induced kidney injury (COC-KI) is characterized by excessive oxidative stress and inflammation. Nanozymes can partially mitigate COC-KI through superoxide dismutase (SOD)- and catalase (CAT)-like activities, but their therapeutic efficacy is often compromised by the coexisting peroxidase (POD)- and oxidase (OXD)-like activities, which may paradoxically generate reactive oxygen species (ROS). Additionally, the lack of targeted delivery remains another challenge. To overcome these limitations together, metal-organic framework (MOF)-based nanozyme PCN222-Mn (PM), which exhibits prominent SOD- and CAT-like activities with negligible POD/OXD-like activities, was chosen for the treatment of COC-KI. To achieve precise renal targeting, we functionalized PM with hyaluronic acid (HA), yielding PCN222-Mn@HA (PMH). Both in vitro and in vivo studies demonstrated that PMH effectively accumulated in injured renal tubular epithelial cells (RTECs) and provided superior protection against COC-KI. Mechanistic investigation via RNA sequencing revealed that PMH exerted its renoprotective effects primarily by suppressing NF-κB signaling, which in turn downregulated the expression of NLRP3 and MCP-1, thereby inhibiting inflammasome activation and macrophage recruitment. Collectively, this work proposes a novel and effective targeted nanozyme strategy for the treatment of COC-KI.

Clear cell renal cell carcinoma (ccRCC) remains a therapeutic challenge due to tyrosine kinase inhibitor (TKI) resistance and an immunosuppressive tumor microenvironment (TME). To avoid the limitations of systemic nanotherapeutics, which often suffer from inadequate tumor accumulation, we developed a pH-activatable injectable gelatin methacryloyl (GelMA) hydrogel (termed SUN/CuONPs@GelMA) for localized co-delivery of sunitinib and copper oxide nanoparticles. The photocrosslinkable GelMA matrix enables minimally invasive intratumoral administration and sustained drug retention. Unlike ferroptosis, which is frequently migigated by the antioxidant defenses inherent in ccRCC, cuproptosis circumvents this resistance by targeting mitochondrial metabolism. In the weakly acidic TME (pH 5.3-7), CuONP assemblies dissolve to release CuO nanoparticles and Cu2+, triggering dual mechanisms: (1) cuproptosis via mitochondrial proteotoxicity and the depletion of iron-sulfur cluster protein, and (2) Fenton-like reaction-mediated reactive oxygen species (ROS) generation and the release of damage-associated molecular patterns (DAMPs). Concurrently, sunitinib inhibits angiogenesis and synergizes with copper-driven immunomodulation to reprogram macrophages toward tumor-suppressive M1 phenotypes. In vitro and in vivo studies demonstrated potent tumor growth inhibition, migration suppression, and prolonged survival in ccRCC. The SUN/CuONPs@GelMA platform overcomes TKI resistance through the synergy of cuproptosis and immunotherapy. This localized co-delivery strategy provides a multi-mechanistic approach for the treatment of advanced ccRCC. STATEMENT OF SIGNIFICANCE: Systemic treatments for advanced clear cell renal cell carcinoma (ccRCC) are restricted by tyrosine kinase inhibitor (TKI) resistance, systemic toxicity, and an immunosuppressive tumor microenvironment (TME). We herein report a pH-activatable, injectable photocrosslinkable GelMA hydrogel for localized co-delivery of sunitinib and copper nanoparticles, enabling minimally invasive delivery, sustained drug retention, and reduced systemic toxicity. This hydrogel triggers cuproptosis via acidic TME-responsive copper release, and synergizes with sunitinib to reverse TKI resistance, suppress tumor progression and migration, reprogram immunosuppressive macrophages to antitumor phenotypes, and extend preclinical survival. This work establishes a combinatorial ccRCC therapeutic platform, providing a promising translational strategy for advanced ccRCC management.

RNA 5-methylcytosine (m5C) is a dynamic epigenetic mark implicated in tumorigenesis, however, existing editors lack spatiotemporal regulation and reversibility. Here, we develop abscisic acid (ABA)-inducible CRISPR-dCasRx systems for programmable m5C methylation (IDMME) and demethylation (IDMDE). These editors enable site-specific, low off-target m5C modification through ligand-dependent assembly of split effector domains. We further integrate photocaged ABA to achieve light-controlled activation. Application in renal carcinoma models shows that targeted m5C editing modulates transcript function and suppresses tumor growth in vitro and in vivo. This platform provides a versatile, spatiotemporally controllable approach for dissecting RNA epigenetic mechanisms and advancing RNA-based therapeutic strategies.

An imbalance exists between renal tubular epithelial cells (RTECs) injury and repair in kidney stone disease, yet the underlying mechanism remains largely unclear. Here, we found that gasdermin D (GSDMD)-mediated pyroptosis occurred in both patients and mice with calcium oxalate (CaOx) nephrolithiasis, and the expression levels of NOD-like receptor protein 3 (NLRP3) and GSDMD were associated with the severity of kidney stones. Deficiency of GSDMD alleviated renal tubule damage and inflammatory response, ultimately inhibiting renal injury and crystal deposition. Additionally, we found that charged multivesicular body protein 4B (CHMP4B)-dependent cell repair was activated during pyroptosis of RTECs; however, the enhancement was insufficient to offset the damage. Importantly, Ca2+ fluxes during pyroptosis induce activation of the CHMP4B-dependent cell repair machinery. Overexpression of CHMP4B attenuates cell death and reduces the severity of kidney stones. Notably, combining the overexpression of CHMP4B with a GSDMD inhibitor demonstrates heightened efficacy in ameliorating kidney damage and crystal deposition induced by glyoxylate (Gly). Taken together, these results highlight the imbalance between GSDMD-mediated pyroptosis and CHMP4B-dependent cell repair as a driver for CaOx kidney stone formation. Our findings provide new insights and potential therapeutic targets for CaOx kidney stones.

Aim: The aim of the study was to evaluate the safety and efficacy of same-day versus next-day urinary catheter removal following ureteroscopic holmium laser lithotripsy (with routine double-J stent placement) in a day-surgery setting. Methods: In this comparative study, 191 patients undergoing day-care holmium laser lithotripsy were allocated to next-day (n = 94) or same-day (n = 97) extubation groups. Outcomes included catheter retention duration, post-removal complications, voiding function, and recovery parameters. Results: No catheter-related adverse events occurred in either group. No significant differences were observed in first void volume, catheter reinsertion rates, post-catheter removal urination, lower abdominal distension, or urethral pain (p > 0.05). The same-day group demonstrated significantly shorter catheter retention time (p < 0.001) and earlier postoperative ambulation (p < 0.001). Notably, time to spontaneous voiding was prolonged in the same-day group (p = 0.009), though all values remained within physiological ranges. Conclusion: Same-day catheter removal after ureteroscopic holmium laser lithotripsy, even with routine double-J stent placement, safely reduces indwelling time and promotes early mobilization without increasing the risk of urinary retention or exacerbating stent-related discomfort. The protocol is feasible for day-surgery populations.

Objective Kidney stone disease (nephrolithiasis), characterized by calcium oxalate (CaOx) deposition, often leads to chronic kidney disease. Recent studies suggest that copper metabolism and oxidative stress play roles in kidney stone pathogenesis. Cuproptosis, a regulated cell death pathway driven by copper, is hypothesized to be implicated in nephrolithiasis. This study aimed to assess the therapeutic potential of tetrathiomolybdate (TTM), a copper chelator, in reducing copper-induced toxicity and oxidative stress in nephrocalcinosis models. Methods Forty C57BL/6 mice were divided into four groups: control, TTM, glyoxylate-induced CaOx, and glyoxylate with TTM. TTM was administered intraperitoneally for 10 days, and kidney function, copper levels, and crystal deposition were assessed. In vitro, human renal epithelial cells (HK-2) treated with CaOx monohydrate were analyzed for reactive oxygen species levels, protein expression, and gene regulation under the TTM treatment. Results The TTM treatment significantly improved kidney function, reduced copper content, and decreased CaOx crystal deposition in vivo. In vitro, TTM reduced reactive oxygen species, LDH, and malondialdehyde levels in CaOx monohydrate-treated HK-2 cells, while decreasing Cu+ level and reversing altered protein expression associated with cuproptosis. A transcriptomic analysis identified four TTM-regulated copper metabolism-related genes: cyclin D1 (Ccnd1), ceruloplasmin (Cp), lysyl oxidase (Lox), and lox like 2 (Loxl2). Conclusions TTM mitigates copper-induced toxicity and oxidative stress by modulating cuproptosis-related genes, offering a promising therapeutic approach for nephrolithiasis.

The molecular complexity of bladder cancer restricts reliance on single-feature or single-gene targeted therapies, necessitating integrated individualized treatments and multi-gene interventions. In this study, we introduced the CRISPR/dCas9-SAM system to BCa treatment, known for its high specificity, low off-target effects, and reduced genetic toxicity, making it ideal for multiplexed gene activation at minimal cost-just 20 nucleotides per target. However, despite its potential in complex gene therapy and cellular engineering, challenges persist due to safety concerns associated with viral vectors and the risk of off-target effects during in vivo delivery, necessitating the development of new vectors. Herein, we reported pH-sensitive hollow mesoporous silica nanoparticles modified with PLZ4 ligands (PLZ4-Lip@AMSN/CRISPR/dCas9-SAM, PLACS NPs) for precise targeting of bladder tumors and co-delivery of CRISPR/dCas9-SAM system. With good stability and high plasmid loading capacity, they efficiently co-delivered dCas9-VP64, MS2-P65-HSF1, and sgRNA. Compared to Lipofectamine 3000, these nanoparticles exhibited superior lysosomal escape capability, significantly enhancing transfection efficiency in bladder cancer cells. Moreover, PLACS NPs simultaneously activated the expression of four target genes, inhibiting proliferation and migration, and promoting apoptosis in bladder cancer cells. In vivo, they achieved efficient gene editing at tumor sites, significantly inhibiting bladder tumor growth. Real-time imaging revealed their substantial accumulation and prolonged retention at bladder tumor sites without significant liver targeting and major organ damage, showcasing good specificity and biosafety. This study overcomes in vivo delivery challenges of multi-component CRISPR/dCas9 systems, enabling precise gene editing and anti-tumor effects, presenting an innovative strategy for targeted therapy in bladder cancer treatment. STATEMENT OF SIGNIFICANCE: This study introduces a newly-developed approach to address key challenges in bladder cancer gene therapy, namely low gene upregulation efficiency, limited targeting specificity, and inefficient nucleic acid delivery. By integrating the CRISPR/dCas9-SAM system, we achieve highly specific gene activation with minimal off-target effects, enabling the addition of treatment targets with just 20 nucleotides per target. To improve bladder cancer targeting, we developed PLACS NPs, a mesoporous silica nanoparticle system that enhances plasmid delivery, transfection efficiency, and endosomal escape. This system shows good tumor targeting and significant anti-tumor effects in bladder cancer, without significant liver targeting and major organ toxicity, offering promising therapeutic potential and broad clinical applications.

Acute Kidney Injury (AKI) is a significant medical condition characterized by the abrupt decline in kidney function.Low-intensity pulsed ultrasound (LIPUS), a non-invasive therapeutic technique employing low-intensity acoustic wave pulses, has shown promise in promoting tissue repair and regeneration. A novel LIPUS system was developed and evaluated in rat AKI models, focusing on its effects on glomerular filtration rate (GFR), blood urea nitrogen (BUN), serum creatinine (SCr), and the Notch1-Akt-eNOS signaling pathway. The results demonstrated that LIPUS treatment improved GFR, BUN, SCr levels, and renal pathology in AKI rats. In vitro experiments using HUVEC cells revealed that LIPUS stimulation promoted angiogenesis, cell migration mechanically-dependent calcium ion influx, which was partially attenuated by TRPV1 knockdown. RNA sequencing analysis indicated LIPUS-induced activation of the Notch pathway, phosphorylation of Akt and eNOS. Furthermore, inhibition or genetic silencing of Notch1 abolished the beneficial effects of LIPUS on angiogenesis, renal function, and Akt-eNOS phosphorylation in both cells and AKI rats. These findings suggest that LIPUS-induced calcium influx promotes Akt-eNOS phosphorylation, nitric oxide (NO) production, angiogenesis, and improved renal function in AKI via Notch1-Akt-eNOS signaling, positioning LIPUS as a promising therapeutic strategy for AKI by targeting vascular regeneration.

Abstract 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.

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.

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.

Combination therapy is an emerging strategy to overcome multidrug resistance (MDR) in hepatocellular carcinoma (HCC) chemotherapy treatment. However, the passive diffusion in traditional delivery systems greatly retards the approach and penetration of drugs into hepatocellular carcinoma cells and thus hinders the efficacy of combination therapy. Micro/nanomotors with autonomous locomotion in a tiny scale provide the possibility of tackling this issue. Herein, an active drug delivery micromotor platform delicately designed to load drugs with different physicochemical properties and enhance the drug permeability of cells is demonstrated for HCC chemotherapy treatment. The biocompatible micromotor platform Mg/PLGA/CHI comprised magnesium (Mg) coated with two polymer layers made of poly(lactic-co-glycolic acid) (PLGA) and chitosan (CHI), where the hydrophobic and hydrophilic drugs doxorubicin (Dox) and Curcumin (Cur) were loaded, respectively. The autonomous motion of the micromotors with velocity up to 45 μm s-1 greatly enhanced the diffusion of chemotherapeutic drugs and led to higher extracellular and intracellular drug distribution. Moreover, hydrogen produced during the motion eliminated the excess reactive oxygen species (ROS) in the human hepatocellular carcinoma (HepG2) cells. Compared with inert groups, the absorption of Dox and Cur from the active micromotors was about 2.9 and 1.5 times higher in human hepatocellular carcinoma (HepG2) cells. In addition, the anti-tumor activity also obviously improved at the micromotor concentration of 1 mg mL-1 (cell proliferation was reduced by almost 30%). Overall, this work proposes an approach based on loading different chemotherapy agents on an active delivery system to enhance drug permeability and overcome MDR and provides a potentially effective therapeutic strategy for the treatment of HCC.

Helicobacter pylori (H. pylori) infection causes gastric infections and leads to a range of gastric disorders, even becomes a predisposing factor of stomach cancer. Thus, the search for new therapeutic approaches to improve drug resistance and bioavailability of antibiotics has been considered urgent to treat H. pylori. Here we present the first design of an active drug combination therapy and responsive drug release to treat H. pylori based on self-propelled micromotors. This micromotor is consisting of a magnesium/gold (Mg/Au) Janus structure that loaded with amoxicillin and clarithromycin by asymmetrically coating in a pH-sensitive Eudragit (R) L100-55 polymer. The autonomous propulsion of the drug-loaded Mg-micromotors in gastric acid enables them to penetrate the mucus layer, actively deliver amoxicillin and clarithromycin simultaneously then release these drugs in a pH-responsive manner. Notably, the drug loading efficacy and release ratio of therapeutic agents is designed to satisfy the clinical demands. Due to the powerful mucosal penetration, the propelled micromotors exhibits enhanced retention and distribution capability than passive delivery system. Especially, the antimicrobial effi-ciency of the micromotors with combination drug therapy against H. pylori is significantly improved compared to single-drug loaded micromotors. The optimized dosage ratio of two therapeutic agents on the micromotors is determined to be 2:1 of amoxicillin and clarithromycin. With the merits of self-propulsion, good biocompatibility and biodegradability, our proposed combined-drug delivery Mg-based micromotor will offer a promising future for the active treatment of bacterial infections.

BACKGROUND:Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor associated with poor outcomes. Cuproptosis, a new pattern of cell death, relies on mitochondrial respiration and is associated with protein lipoylation. Increasing evidence has demonstrated the potential roles of cuproptosis in several tumor entities. However, the relationship between cuproptosis and ACC remains unclear. METHODS:In total, 10 cuproptosis-related genes (CRGs) of patients with ACC were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and differential expression analysis of CRGs was analyzed. Functional enrichment of the CRGs was performed and protein-protein interaction analysis was utilized to explore the association between the CRGs. Cuproptosis-related risk score (CRRS) was constructed by Lasso Cox regression and validated. RESULTS:In the current study, the alteration and expression patterns of 10 CRGs in TCGA-ACC datasets were analyzed. We identified different expression patterns of CRGs in ACCs, discovered strong associations between CRGs and ACCs, and found that the CRGs were associated with immune infiltration in ACCs. A CRRS was created thereafter to predict overall survival (OS). CRRS = (0.083103718) *FDX1 + (-0.278423862) *LIAS+(0.090985682) *DLAT+(-0.018784047) *PDHA1 + (0.297218951) *MTF1 + (0.310197964) *CDKN2A. Patients were divided into high- and low-risk groups based on their CRRS, and independent prognostic factors were investigated. Finally, CDKN2A and FDX1 were found to be independent prognostic predictors of patients with ACC. CONCLUSIONS:CDKN2A and FDX1 are independent prognostic predictors of patients with ACC. Cuproptosis may play a role in the development of ACC, providing a new perspective on therapeutic strategies related to CRGs for cancer prevention and treatment.

IntroductionWhile phosphodiesterase type 5 inhibitors (PDE5is) and others are used to treat Erectile dysfunction (ED), many patients are either unresponsive or resistant to it. Stem cell therapy (SCT) is a promising alternative approach. Numerous preclinical trials have demonstrated improved erectile function in animal models using SCT, although the number of clinical trials investigating SCT for men with ED is limited. Nonetheless, findings from human clinical trials suggest that SCT may be a useful treatment option.Areas coveredBiomedical literature, including PubMed, ClinicalTrials.gov, and European Union Clinical Trials Registry, were analyzed to summarize and synthesize information on stem cell therapy for ED in this narrative review. The achievements in preclinical and clinical evaluations are presented and critically analyzed.Expert opinionSCT has demonstrated some benefits in improving erectile function, while further studies are urgently needed. Such studies would provide valuable insights into the optimal use of stem cell therapy and its potential as a therapeutic option for ED. Taking advantage of different mechanisms of action involved in various regenerative therapies, combination therapies such as SCT and low-energy shock waves or platelet-rich plasma may provide a more effective therapy and warrant further research.

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. 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. 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. 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.

Intrarenal calcium oxalate (CaOx) crystals induce renal tubular epithelial cell (TEC) inflammatory and oxidative injury. This study is aimed at exploring potential therapeutic lipid components in kidney stones because lipids are involved in the development of several diseases and indicate the risk of kidney stones. Serum specimens were collected from 35 kidney stone patients and 35 normal controls. The lipid components in serum were measured, and differences were analyzed. The documented biological importance was comprehensively reviewed to identify lipids that differed significantly between the two groups to find potential agents associated with kidney stones. CaOx nephrocalcinosis mouse model was established to examine the therapeutic effects of specific lipids on CaOx deposition and CaOx-induced oxidative renal injury. Several lipids with significantly different levels were present in the serum of patients with stones and normal controls. Resolvin D1 (RvD1) (4.93-fold change, P < 0.001) and protectin D1 (PD1) (5.06-fold change, P < 0.001) were significantly decreased in the serum of patients with kidney stones, and an integrative review suggested that these factors might be associated with inflammatory responses, which is a crucial mechanism associated with stone damage. The administration of RvD1 and PD1 significantly inhibited kidney CaOx deposition and suppressed CaOx-induced renal tubular cell inflammatory injury and necrosis in a CaOx nephrocalcinosis mouse model. Furthermore, RvD1 and PD1 facilitated the expression of the oxidative indicator superoxide dismutase 2 (SOD2), inhibited NADPH oxidase 2 (NOX2) expression, and diminished intracellular reactive oxygen species (ROS) levels. This study preliminarily elucidated the role of lipids in kidney stones. The inhibitory effects of RvD1 and PD1 on oxidative damage induced by CaOx deposition provide a promising perspective for kidney stone treatment strategies.

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.