Chemically Cross-Linked Hammerhead Ribozyme as an Efficient RNA Interference Tool.

RNA-cleaving ribozymes are promising candidates as general tools of RNA interference (RNAi) in gene manipulation. However, compared with other RNA systems, such as siRNA and CRISPR technologies, the ribozyme tools are still far from broad applications on RNAi due to their poor performance in the cellular context. In this work, we report an efficient RNAi tool based on chemically modified hammerhead ribozyme (HHR). By the introduction of an intramolecular linkage into the minimal HHR to reconstruct the distal interaction within the tertiary ribozyme structure, this cross-linked HHR exhibits efficient RNA substrate cleavage activities with almost no sequence constraint. Cellular experiments suggest that both exogenous and endogenous RNA expression can be dramatically knocked down by this HHR tool with levels comparable to those of siRNA. Unlike the widely applied protein-recruiting RNA systems (siRNA and CRISPR), this ribozyme tool functions solely on RNA itself with great simplicity, which may provide a new approach for gene manipulation in both fundamental and translational studies.

Pathological Characteristics and Classification of Unstable Coronary Atherosclerotic Plaques.

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart disease, such as acute or chronic myocardial ischemic changes, sometimes make it difficult to locate the ischemic site due to the short death process, the lack of tissue reaction time. In some cases, the deceased died of sudden death on the first-episode, resulting in difficulty for medical examiners to make an accurate diagnosis. However, clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process. This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medical research, including plaque rupture, plaque erosion and calcified nodules, as well as the influencing factors leading to plaque instability, and briefly describes the research progress and technique of the atherosclerotic plaques, in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different pathologic states of coronary atherosclerotic plaques.

Harnessing Catalytic RNA Circuits for Construction of Artificial Signaling Pathways in Mammalian Cells.

Engineering of genetic networks with artificial signaling pathways (ASPs) can reprogram cellular responses and phenotypes under different circumstances for a variety of diagnostic and therapeutic purposes. However, construction of ASPs between originally independent endogenous genes in mammalian cells is highly challenging. Here we report an amplifiable RNA circuit that can theoretically build regulatory connections between any endogenous genes in mammalian cells. We harness the system of catalytic hairpin assembly with combination of controllable CRISPR-Cas9 function to transduce the signals from distinct messenger RNA expression of trigger genes into manipulation of target genes. Through introduction of these RNA-based genetic circuits, mammalian cells are endowed with autonomous capabilities to sense the changes of RNA expression either induced by ligand stimuli or from various cell types and control the cellular responses and fates via apoptosis-related ASPs. Our design provides a generalized platform for construction of ASPs inside the genetic networks of mammalian cells based on differentiated RNA expression.

Accurate Density Prediction of Sesquiterpenoid HEDFs and the Multiproperty Computing Server SesquiterPre.

Accurate and rapid evaluation of density is crucial for evaluating the packing and combustion characteristics of high-energy-density fuels (HEDFs). This parameter is pivotal in the selection of high-performance HEDFs. Our study leveraged a polycyclic compound density data set and quantum chemical (QC) descriptors to establish a correlation with the target properties using the XGBoost algorithm. We utilized a recursive feature elimination method to simplify the model and developed a concise and interpretable density prediction model incorporating only six QC descriptors. The model demonstrated robust performance, achieving coefficients of determination (R 2) of 0.967 and 0.971 for internal and external test sets, respectively, and root-mean-square errors (RMSE) of 0.031 and 0.027 g/cm3, respectively. Compared to the other two mainstream methods, the marginal discrepancy between the predicted and actual molecular densities underscores the model's superior predictive ability and more usefulness for energy density calculation. Furthermore, we developed a web server (SesquiterPre, https://sespre.cmdrg.com/#/) that can simultaneously calculate the density, enthalpy of combustion, and energy density of sesquiterpenoid HEDFs, which greatly facilitates the use of researchers and is of great significance for accelerating the design and screening of novel sesquiterpenoid HEDFs.

Analysis of Factors Influencing Prognosis and Assessment of 60 Cases of Decompensated Cirrhotic Patients with Portal Hypertension.

Objective: To investigate the risk factors for the development of portal hypertension in patients with decompensated cirrhosis and analyze their prognosis. Methods: Patients with decompensated cirrhosis who were admitted to our hospital and Qu fu People's Hospital from June 2022 to June 2023 were included in this study. Among them, there were 45 male and 15 female patients, with a median age of 56 (range: 35-77) years. A comparative analysis was performed between Group A (hepatic venous pressure gradient, HVPG <16 mmHg) and Group B (HVPG ≥16 mmHg) patients, along with various clinical outcomes. Multivariate analysis was conducted to explore the risk factors influencing the occurrence of portal hypertension and adverse prognosis in patients with cirrhosis. Results: In Group A patients with portal hypertension, we observed lower levels of aspartate aminotransferase, laminin, serum hyaluronic acid, type III procollagen N-terminal peptide, total bile acids, and cholylglycine acid compared to Group B. On the other hand, levels of alanine aminotransferase, white blood cells, and serum albumin were higher in Group A than in Group B. These differences between the groups were statistically significant (P < 0.05). Multivariate analysis of the aforementioned risk factors indicated that low white blood cell count, high cholylglycine acid levels, and high serum hyaluronic acid levels were identified as independent risk factors for the occurrence of difficult-to-control complications in decompensated portal hypertension among patients with liver cirrhosis (P < 0.05). Conclusion: Liver cirrhosis patients with portal hypertension and multiple risk factors like low white blood cell count and high liver transaminase levels should be cautious regarding the progression of portal hypertension when combined with splenomegaly, liver fibrosis, and bile stasis, as it often indicates a poor prognosis.