An Implanted Closed-loop Chip System for Heart Rate Control:System Design and Effects in Conscious Rats

Objective： To evaluate the efficiency of an implanted chip system for the control of heart rate （HR）. Methods： The HR was recorded in six conscious Sprague-Dawley （SD） rats. An implanted chip system was designed to regulate the HR by stimulating the right cervical vagus nerve according to the feedback of real time HR. Each rat was subjected to 30-min regulation and 30-min recovery. The change of HR during the regulation period was compared with the control. The ECG was recorded during the experiment for 24 h. Results： The ECG signals were successfully recorded during the experiment. The HR was significantly decreased during the period of regulation compared with control （-79.3 ± 34.5, P 〈 0.01, n = 6） and then recovered to normal after regulation. Conclusion： The described implanted chip system can regulate the HR to a designated set point.

Effects of renal sympathetic denervation on cardiac systolic function after myocardial infarction in rats

This study investigated the therapeutic effects of renal denervation on cardiac systolic function after myocardial infarction （MI） in rats and the mechanism involved. Fifty male SD rats were randomly assigned to the sham group （n = 15）, the MI group （n = 20）, and the MI plus renal denervation group （n = 15）. MI was established through thoracotomic ligation of the anterior descending artery. Renal denervation was achieved by laparotomic stripping of the renal arterial adventitial sympathetic nerve, approximately 3 mm from the abdominal aorta. Left ventricular function and hemodynamics were measured several weeks following MI. The left ventricular systolic function of the MI group was significantly reduced and the systolic blood pressure （SBP） remarkably declined. In rats with MI treated with renal denervation, the left ventricular ejection fraction （EF）, fractional shortening （FS） and SBP markedly improved compared with the MI group. However, heart rate and fibrosis decreased significantly. These findings suggest that renal denervation has therapeutic effects on post-MI cardiac dysfunction. These effects are associated with increased left ventricular ejection fraction （LVEF） and SBP, as well as reduced heart rate and fibrosis. This may represent a new approach to the treatment of post-MI remodeling and subsequent heart failure.

Shiyang River ecosystem problems and countermeasures

With the increase of population and the development of social economy, contradiction between water supply and demand of Shiyang River Basin become more outstanding. Unreasonable exploitation and utilization of water resources cause the serious deterioration of ecological environment. According to the present ecoligical situation, by analyzing some actual problems of the ecosystem of Shiyang River Basin, a series of feasible control countermeasures are proposed. The article provide theoretical basis for the treatment and recovery of the degradation of ecological environment of Shiyang Rive Basin.

FGF4 protects the liver from immune-mediated injury by activating CaMKKβ-PINK1 signal pathway to inhibit hepatocellular apoptosis

Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine;however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca^(2+)/calmodulin-dependent protein kinasekinase 2 (CaMKKβ) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

Author correction to‘FGF4 protects the liver from immune-mediated injury by activating CaMKKβ-PINK1 signal pathway to inhibit hepatocellular apoptosis’[Acta Pharm Sin B 14(2024)1605–1623]

The authors regret that due to the mistake of copying and pasting in the process of assembling figures and negligence in the proofreading,there are picture pasting errors in Fig.8 and Supporting Information Fig.S2,respectively,but the above errors did not affect the conclusion.The author has now revised Fig.8 and Fig.S2 as follows.The authors apologize for any inconvenience caused to the journal and readers.

Exosome miRNAs profiling in serum and prognostic evaluation in patients with multiple myeloma

MicroRNAs(MiRNAs)carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment.Our study aimed at identifying the expression profile of exosomal miRNAs(exo-miRNAs)in the serum of multiple myeloma(MM)patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis.Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing.Differential expression of exo-miRNAs was calculated and target genes of miRNAs were predicted.CytoHubba was applied to identify the hub miRNAs and core target genes.The LASSO Cox regression model was used to develop the prognostic model,and the ESTIMATE immune score was calculated to investigate the correlation between the model and immune status in MM patients.The top six hub differentially expressed serum exo-miRNAs were identified.513 target genes of the six hub exo-miRNAs were confirmed to be differentially expressed in MM cells in the Zhan Myeloma microarray dataset.Functional enrichment analysis indicated that these target genes were mainly involved in mRNA splicing,cellular response to stress,and deubiquitination.13 core exo-miRNA target genes were applied to create a novel prognostic signature to provide risk stratification for MM patients,which is associated with the immune microenvironment of MM patients.Our study comprehensively investigated the exo-miRNA profiles in MM patients.A novel prognostic signature was constructed to facilitate the risk stratification of MM patients with distinct outcomes.