Background Long-term exposure to ambient fine particulate matter (PM_2.5) is a significant risk factor for cardiometabolic disorders. However, the mechanisms of its interaction with the endogenous circadian system remain incompletely understood. Objective To investigate whether chronic PM_2.5 exposure interferes with the rhythmic expression of the cardiac circadian clock, thereby disrupting downstream antioxidant defenses and metabolic homeostasis, and ultimately driving cardiometabolic dysfunction. Methods Seventy-two male C57BL/6 mice were randomly divided into a PM_2.5 exposure group (PM group) and a filtered air control group (FA group). Whole-body exposure was conducted for 8 weeks in a meteorological environmental animal exposure system. Samples were collected at six distinct zeitgeber time (ZT) points post-exposure. The 24 h ambulatory blood pressure and serum lipid profiles were monitored. Rhythm parameters were derived via cosinor analysis to compare differences in Midline statistic of rhythm (Mesor), amplitude, and phase between the two groups. The rhythmic expression of core circadian clock genes and antioxidant genes in the myocardium was detected by quantitative polymerase chain reaction (qPCR). Myocardial reactive oxygen species (ROS) levels and downstream pathway protein expression were analyzed by immunofluorescence and Western blot (WB), respectively. The expression changes of the clock gene retinoic acid receptor-related orphan receptor α (RORα) were assessed at both the mRNA and protein levels. Finally, Spearman correlation analysis was used to explore the relationships among myocardial RORα expression, lipid profiles, and oxidative stress indicators. Results Compared to the FA group, mice in the PM group exhibited a blunted circadian rhythm in blood pressure, characterized by sustained elevation throughout the day. Chronic PM_2.5 exposure showed a significant interaction with ZT on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (F-interaction=9.11, 5.70, and 6.02, respectively; P<0.05), as well as on serum triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (F-interaction=16.32, 11.12, 15.39, and 28.09, respectively; P<0.05). Cosinor analysis further revealed that the Mesor values of T-CHO, TG, and LDL-C were significantly increased (P<0.05), while that of HDL-C was significantly decreased in the PM group (P<0.05). The oscillation amplitudes of SBP, DBP, and MAP showed a decreasing trend, whereas those of TG and LDL-C were significantly increased (P<0.05). Furthermore, SBP, T-CHO, and HDL-C all exhibited a significant phase delay (P<0.05). Mechanistically, PM_2.5 exposure significantly suppressed the expression of the positive circadian regulator RORα in the myocardium, leading to disordered rhythmic expression of core clock genes (Bmal1, Clock, Per1/2, and Cry1/2). This exposure also inhibited the rhythmic expression of antioxidant genes (GPX1, SOD2, and CAT), resulting in increased ROS generation and elevated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) proteins. Correlation analysis further revealed that myocardial RORα expression level was negatively correlated with T-CHO, TG, and LDL-C (r=−0.55, −0.63, and −0.51, respectively; P<0.001), and positively correlated with HDL-C (r=0.37, P=0.010), and antioxidant genes GPX1, SOD2, and CAT expression (r=0.34, 0.35, and 0.56, respectively; P < 0.001). Conclusion Chronic PM_2.5 exposure induces cardiometabolic dysfunction by suppressing myocardial RORα expression. This suppression disrupts the cardiac circadian clock and the diurnal balance of oxidative stress, triggering oxidative damage and elevating expression of CaMKII/NADPH pathway proteins. Collectively, these alterations precipitate the loss of cardiac metabolic rhythms and subsequent functional impairment.

Objective:To investigate the effect and mechanism of miR-195 regulating FOXK1 gene and PI3K/Akt pathway on stomach adenocarcinoma proliferation, invasion and migration ability.Methods:Public database samples were employed to analyze the expression differences and prognostic significance of miR-195 in stomach adenocarcinoma. After overexpression of mir-195-5p in two cell lines, MGC803 and AGS, altered cell proliferation, invasion, and migration abilities were detected by Alamar Blue, Wound healing, and Transwell assays. The potential target genes and binding sites of miR-195 were predicted by the starBase. Western blot was used to detect the expression levels of foxk1 and phosphorylation sites in the PI3K/Akt pathway of target genes after overexpression of mir-195-5p. A Dual-luciferase reporter assay was used to verify the relationship between mir-195-5p and foxk1. Statistical analyses were performed with IBM SPSS 22 software and R 4.0.3.Results:Our results showed a significant over-expression of miR-195 in the tumor tissues, compared with the paired normal tissues ( P<0.001) , which could inhibit the proliferation and invasion of stomach carcinoma cells and significantly correlated with survival ( P=0.011) . Moreover, our study indicated that miR-195 depressed the expression of FOXK1 and significantly reduced the activation of the PI3K/Akt pathway, which had a negative effect on the proliferation and invasion of stomach carcinoma cells. The phosphorylated Akt (s473 site) expression in the PI3K/Akt pathway was significantly decreased after overexpression of miR-195. Conclusion:Overall, our studies clarify the important function of the miR-195 in the diagnosis and therapy of patients with stomach carcinoma and reveal the FOXK1 and PI3K/Akt pathway regulation by the miR-195, which are of important clinical significance in the differential diagnosis.

Objective To explore the influence of interleukin-2 receptor antagonists(IL-2Ra) on the morbidity and prognosis of new onset diabetes after transplantation(NODAT)in liver transplant recipients. Methods Pre-and post-operative clinical data of 879 nondiabetic patients who underwent a liver transplantation between April 2001 and December 2016 were retrospectively studied. All the enrolled patients were divided into IL-2Ra and non-IL-2Ra groups according to the use of IL-2Ra. Transient-NODAT(T-NODAT)and Persistent-NODAT(P-NODAT)were defined according to whether NODAT would be existed continuously. The impacts of IL-2Ra on the cumulative incidence as well as the risk of NODAT and T-NODAT were analyzed through comparison between patients who used IL-2Ra or not. And influence of IL-2Ra on the long-term survival of NODAT patients was further analyzed. Results Among 879 patients,177(32.24%)from the IL-2Ra group(n=549)developed NODAT and 29.38%(n=52)of the NODAT reversed,while 131(39.70%)from the non-IL-2Ra group(n=330)developed NODAT and 26.72%(n=35)of the NODAT reversed. After adjusting for 18 possible confounding factors,the IL-2Ra group had significantly decreased cumulative incidence of NODAT over the non-IL-2Ra group(adjusted P=0.028). COX regression analyses showed that IL-2Ra was a protective factor against NODAT development(HR 0.774;95% CI 0.616-0.973; P=0.028), while the use of IL-2Ra and the reverse of NODAT did not significantly related. In addition, long-term survival of the NODAT patients were far better in the IL-2Ra group(adjusted P=0.001). Conclusion IL-2Ra significantly reduces the risk of NODAT in liver transplant recipients and is beneficial to the long-term survival of NODAT patients.

Gastric cancer among the world's most common malignant tumor in the fourth, the incidence of the previ-ous decline, but around the world the number of gastric cancer cases occur in China accounted for 42%, ranked the first to east Asia common types of cancer[1] At present,the stomach cancer patients can choose chemical treatment and surgical treatment, but the 5-year survival rate in 50%, cause its one of the leading causes of death are invasion and metastasis of carcinoma tissue [2] Visible, understand the occurrence, invasion and metastasis of gastric cancer related regulation and carries on the early prediction and early intervention, and to develop treatment, improve patient out-come is very beneficial. The study found that high mature gastric cancer cells expressing CXCR4, under the action of chemokines SDF-1 promote the activation of PI3K/Akt pathway in gastric cancer cells,so as to promote antiapoptotic effect of gastric cancer cells. In this paper,the high expression of CXCR4 and chemotactic factor CXCL12 signal shaft impact on PI3K/Akt pathway in gastric cancer cells and expression are reviewed.