Background: Accumulating evidence has suggested an oncogenic effect of diurnal disruption on cancer progression. To test whether targeting circadian rhythm by dietary strategy suppressed lung cancer progression, we adopted 6-h time-restricted feeding (TRF) paradigm to elucidate whether and how TRF impacts lung cancer progression. Methods: This study used multiple lung cancer cell lines, two xenograft mouse models, and a chemical-treated mouse lung cancer model. Stable TIM-knockdown and TIM-overexpressing A549 cells were constructed. Cancer behaviors in vitro were determined by colony formation, EdU proliferation, wound healing, transwell migration, flow cytometer, and CCK8 assays. Immunofluorescence, pathology examinations, and targeted metabolomics were also used in tumor cells and tissues. mCherry-GFP-LC3 plasmid was used to detect autophagic flux. Results: We found for the first time that compared to normal ad libitum feeding, 6-h TRF inhibited lung cancer progression and reprogrammed the rhythms of metabolites or genes involved in glycolysis and the circadian rhythm in tumors. After TRF intervention, only timeless (TIM) gene among five lung cancer-associated clock genes was found to consistently align rhythm of tumor cells to that of tumor tissues. Further, we demonstrated that the anti-tumor effect upon TRF was partially mediated by the rhythmic downregulation of the TIM and the subsequent activation of autophagy. Combining TRF with TIM inhibition further enhanced the anti-tumor effect, comparable to treatment efficacy of chemotherapy in xenograft model. Conclusions: Six-hour TRF inhibits lung cancer progression and reshapes circadian metabolism, which is partially mediated by the rhythmic downregulation of the TIM and the subsequent upregulation of autophagy.

This research examines the association between blood pressure variability (BPV) and renal damage in a cohort of 129 primary aldosteronism (PA) patients, employing ambulatory blood pressure monitoring (ABPM) for comparative analysis with individuals diagnosed with essential hypertension (EH). The study reveals that PA patients exhibited significantly elevated levels of cystatin C and urine microalbumin/creatinine ratio (UACR). Additionally, a higher prevalence of non‐dipping blood pressure patterns in PA patients suggests an increased risk of circadian blood pressure regulation disturbances. Notably, while most BPV indices were comparable between the two groups, the standard deviation of 24‐h weighted diastolic blood pressure was markedly lower in the PA cohort, distinguishing it as a unique variable. Through multiple linear regression analysis, the duration of hypertension, angiotensin II concentrations, and daytime systolic blood pressure standard deviation emerged as significant determinants of estimated glomerular filtration rate (eGFR) in PA patients. Furthermore, UACR was significantly influenced by variables including the 24‐h weighted standard deviation (wSD) of systolic BP, glycosylated hemoglobin levels, nocturnal systolic BP peaks, aldosterone‐renin ratio (ARR), and total cholesterol, with the most pronounced association observed with the 24‐h wSD of systolic BP (β = 0.383).The study also found significant correlations between the 24‐h wSD of systolic BP, ARR, HbA1c, serum potassium levels, and 24‐h urinary microalbumin, underscoring the critical role of the 24‐h wSD of systolic BP (β = 0.267). These findings underscore the imperative of an integrated management strategy for PA, addressing the intricate interconnections among metabolic abnormalities, blood pressure variability, and renal health outcomes.

Aldosterone-producing adenoma (APA) is a significant cause of primary aldosteronism, however, its cellular heterogeneity remains unclear. We performed single-cell RNA sequencing on adrenal tissues from three APA patients and three controls. We identified CAPS⁺ zona glomerulosa (ZG)-like cells in APA with upregulated lipogenesis, oxidative phosphorylation, and mTOR signaling, indicating metabolic reprogramming. Pseudotime analysis revealed disrupted differentiation and aberrant CYP11B1, CYP11B2, and SULT2A1 expression. Oncogenic Myc, Wnt, and G2/M pathways were activated in ZR-like clusters. APA showed immune infiltration (B cells, CD8⁺ T cells, M1 macrophages), angiogenic activation (VWF⁺ endothelial cells), and fibroblast-driven stromal remodeling via Hedgehog signaling. Our study provides a comprehensive single-cell atlas of APA, uncovering key tumorigenic mechanisms and identifying potential biomarkers (e.g., CAPS, VWF, UPK3B) and therapeutic targets, including mTOR and Hedgehog/Wnt pathways. These findings advance the genomic understanding of adrenal tumors and support precision medicine development.

To investigate the role of renal denervation (RDN) on endogenous ouabain (EO) secretion in spontaneously hypertensive rats (SHR). Sixteen 12-week-old male SHR were randomly separated into the renal denervation group (RDNX group) and sham operation group (sham group), and eight age-matched Wistar Kyoto rats (WKY) were served as control group. EO concentrations, the Na+- K+-ATPaseactivity, and the expression of Na+-K+-ATPase were assessed. EO levels in serum, kidneys and hypothalamus of sham group were higher than in RDNX group (p < 0.05). Renal Na+-K+-ATPase activity subjected to denervation surgery showed significantly reduction when compared with the sham groups (p < 0.05). A positive correlation existed between norepinephrine (NE) content and Na+-K+-ATPase activity in the kidney (r2 = 0.579). Renal Na+-K+-ATPase α1 subunit mRNA expression was down-regulated in the RDNX group compared with the sham group (P < 0.05), while renal Na+-K+-ATPase α1 subunit mRNA expression was no statistical significance between the groups (P = 0.63). Immunohistochemical analysis showed that there were significant differences in the renal expression of Na+-K+-ATPasebetween the three groups (P < 0.05). These experiments demonstrate that RDN exerted an anti-hypertensive effect with reduction of EO levels and Na+-K+-ATPase activity and Na+-K+-ATPase α1 subunit expression of kidney in SHR.

Objective: This study aimed to investigate the risk factors associated with renal impairment among patients diagnosed with primary aldosteronism (PA).Methods: This study enrolled 147 PA patients who were initially classified into hypokalemic (n=56) and normokalemic (n=91) groups according to serum potassium levels, followed by subgroup stratification using combined adrenal venous sampling (AVS) and computed tomography (CT) diagnostic data. For comparison, 280 patients diagnosed with essential hypertension (EH) served as the control group. Data on general patient characteristics and biochemical markers from blood and urine samples were collected. The analysis involved comparing these indicators across groups and performing binary logistic regression to identify potential risk factors for renal damage.Results: When compared to the EH group, the PA group had lower serum potassium and heart rate (P < 0.05), but higher diabetes prevalence, standing plasma aldosterone concentration (PAC), serum sodium, albumin-to-creatinine ratio (ACR), and 24-hour urinary potassium excretion (P < 0.05). Among PA patients, the hypokalemic subgroup showed higher systolic/diastolic blood pressures, PAC, serum sodium, 24-hour urinary potassium, microalbumin, and ACR versus the normokalemic subgroup (P < 0.05). Compared with the IHA subgroup, the APA subgroup showed significantly higher standing PAC levels (P < 0.05). The classic APA subgroup exhibited elevated 24-hour urinary microprotein, ACR values, and hypokalemia prevalence relative to non-classic unilateral cases (P < 0.05). However, no significant differences emerged between unilateral and bilateral aldosterone secretion groups for serum potassium, PAC levels, or renal damage markers (P>0.05). Hypokalemia (OR=3.027) and urinary potassium (OR=1.052) predicted proteinuria (P<0.05).Conclusion: This study demonstrates that renal impairment is more pronounced in PA patients than in those with EH. Notably, the classic APA subtype exhibits particularly severe damage, specifically manifested by elevated urinary microalbumin excretion. Furthermore, concomitant hypokalemia in PA patients is associated with more severe renal impairment. Hypokalemia and increased 24-hour urinary potassium excretion emerge as key risk factors for renal damage within this patient population.

This study was conducted to explore the effect of renal denervation (RDN) on the renin–angiotensin–aldosterone system (RAAS) in spontaneously hypertensive rats (SHRs). Our experimental rats were randomly divided into the RDN group conducted by painting 10% phenol on the bilateral renal nerves (RDNX), the shamoperation group simply painting with saline (Sham), and the normotension control group (WKY) following all the animal blood and tissues of kidney, hypothalamus, and adrenal gland collected and examined 2 weeks after RDN operation. We found that the aldosterone (ALD) levels in serum and tissues all decreased in the RDNX group compared with the Sham group (p < .05). Meantime, the expression of angiotensin II type1 receptor (AT1R) mRNA also exhibited significantly reduced by 2.22-fold in the RDNX group compared to the Sham group identical to the expression of AT1R protein in the renal cortex and outer stripe of the outer medulla (OSOM) subjected to denervation surgery, which manifested the lower ATIR protein expression than the Sham group (p < .05). Besides, the expression of angiotensin II (Ang II) protein in the cortex , OSOM, and inner stripe of the outer medulla were all attenuated by RDN in comparison with the Sham group (p < .05). RDN reduced intrarenal RAAS and circulating RAAS to lower blood pressure and repair renal function.