Hepatic Energy Metabolism under the Local Control of the Thyroid Hormone System

The energy homeostasis of the organism is orchestrated by a complex interplay of energy substrate shuttling, breakdown, storage, and distribution. Many of these processes are interconnected via the liver. Thyroid hormones (TH) are well known to provide signals for the regulation of energy homeostasis through direct gene regulation via their nuclear receptors acting as transcription factors. In this comprehensive review, we summarize the effects of nutritional intervention like fasting and diets on the TH system. In parallel, we detail direct effects of TH in liver metabolic pathways with regards to glucose, lipid, and cholesterol metabolism. This overview on hepatic effects of TH provides the basis for understanding the complex regulatory network and its translational potential with regards to currently discussed treatment options of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) involving TH mimetics

Periostin Promotes Colorectal Tumorigenesis through Integrin-FAK-Src Pathway-Mediated YAP/TAZ Activation

肠道炎症与结直肠癌的发生发展密切相关，溃疡性肠炎（Ulcerative colitis）和克罗恩病(Crohn’s disease)患者发展为结直肠癌的风险明显高于正常人群。因此，研究炎症条件下结直肠癌的发生发展机制有望为预防和治疗肠炎相关结直肠癌提供重要的理论依据。细胞外基质蛋白Periostin与多种疾病的发生发展密切相关。大量的研究表明细胞外基质蛋白Periostin能够影响组织再生、炎症、纤维化以及肿瘤的发生发展。2020年1月21日，我校生命科学学院欧阳高亮教授课题组首次阐明了Periostin蛋白在炎症相关肿瘤发生发展中的功能及其作用机制，并可能为肠炎相关肠癌的治疗提供新的靶点。我校生命科学学院博士生马汉栋为该论文的第一作者，欧阳高亮教授和我校医学院刘迎福副教授为该论文的共同通讯作者。Periostin is a multifunctional extracellular matrix protein involved in various inflammatory diseases and tumor metastasis; however, evidence regarding whether and how periostin actively contributes to inflammation-associated tumorigenesis remains elusive. Here, we demonstrate that periostin deficiency significantly inhibits the occurrence of colorectal cancer in azoxymethane/dextran sulfate sodium-treated mice and in ApcMin/+ mice. Moreover, periostin deficiency attenuates the severity of colitis and reduces the proliferation of tumor cells. Mechanistically, stromal fibroblast-derived periostin activates FAK-Src kinases through integrin-mediated outside-in signaling, which results in the activation of YAP/TAZ and, subsequently, IL-6 expression in tumor cells. Conversely, IL-6 induces periostin expression in fibroblasts by activating STAT3, which ultimately facilitates colorectal tumor development. These findings provide the evidence that periostin promotes colorectal tumorigenesis, and identify periostin- and IL-6-mediated tumor-stroma interaction as a promising target for treating colitis-associated colorectal cancer.We thank Prof. Bin Zhao for providing pCMV5-FLAG-YAP WT and pCMV5-FLAG-YAP 5SA plasmids. We thank Prof. Yongyou Zhang for providing technical support. This work was supported by grants from the National Natural Science Foundation of China (81572598, 81772616, and 81972748), the Natural Science Foundation of Fujian Province of China (2019J02002), and the Health-Education Joint Research Program of Fujian Province (WKJ2016-2-16). 该研究工作获得了国家自然科学基金、福建省自然科学基金等资助

Trajectory outlier detection: Algorithms, taxonomies, evaluation, and open challenges

acceptedVersio

In vitro selection of small RNA-cleaving deoxyribozymes that cleave pyrimidine–pyrimidine junctions

Herein, we sought new or improved endoribonucleases based on catalytic DNA molecules known as deoxyribozymes. The current repertoire of RNA-cleaving deoxyribozymes can cleave nearly all of the 16 possible dinucleotide junctions with rates of at least 0.1/min, with the exception of pyrimidine–pyrimidine (pyr–pyr) junctions, which are cleaved 1–3 orders of magnitude slower. We conducted four separate in vitro selection experiments to target each pyr–pyr dinucleotide combination (i.e. CC, UC, CT and UT) within a chimeric RNA/DNA substrate. We used a library of DNA molecules containing only 20 random-sequence nucleotides, so that all possible sequence permutations could be sampled in each experiment. From a total of 245 clones, we identified 22 different sequence families, of which 21 represented novel deoxyribozyme motifs. The fastest deoxyribozymes exhibited kobs values (single-turnover, intermolecular format) of 0.12/min, 0.04/min, 0.13/min and 0.15/min against CC, UC, CT and UT junctions, respectively. These values represent a 6- to 8-fold improvement for CC and UC junctions, and a 1000- to 1600-fold improvement for CT and UT junctions, compared to the best rates reported previously under identical reaction conditions. The same deoxyribozymes exhibited ∼1000-fold lower activity against all RNA substrates, but could potentially be improved through further in vitro evolution and engineering

Influencing factors of extracorporeal membrane oxygenation on outcomes in critically ill children

Objective To summarize the clinical features of extracorporeal membrane oxygenation (ECMO) in pediatric intensive care unit (PICU) in a single center and analyze the influencing factors of clinical outcomes so as to provide experience for pediatric ECMO management. Methods A case-control trial was carried out on 35 children undergoing ECMO support from May 2018 to January 2022 in our department. According to the clinical outcomes, they were divided into survival group (n=22) and death group (n=13). Duration of mechanical ventilation, Pediatric Risk of Mortality Ⅲ (PRISM Ⅲ) score and results of laboratory tests before ECMO support, and incidence rates of comorbidities and/or complications during ECMO support were compared between the 2 groups. Univariate analysis and logistic regression analysis were used to explore the influencing factors of clinical outcomes in children with ECMO support. Results There were no significant differences in age distribution, gender, primary diseases, PICU hospitalization time, hospitalization cost, ECMO support mode, and potential of hydrogen (pH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), blood urea nitrogen (BUN), lactic acid (Lac), partial activated thromboplastin time (APTT) and prothrombin time (PT) before ECMO support between the 2 groups (all P>0.05). Compared with the survival group, the death group had lower body weight (P=0.004), higher PRISM Ⅲ score (P=0.001), longer duration of mechanical ventilation (P=0.009) and lower oxygenation index (OI) (P=0.039) before ECMO, and higher incidence of concomitant and/or combined acute kidney injury (AKI) (P=0.032) and higher use of renal replacement therapy during ECMO (P=0.024). Multivariate logistic regression analysis showed that PRISM Ⅲ score before ECMO support (OR=1.482, 95%CI: 1.043~2.105, P=0.028) and concomitant and/or combined AKI during ECMO (OR=0.055, 95%CI: 0.004~0.676, P=0.023) were independent risk factors for death in critically ill children supported by ECMO. Conclusion PRISM Ⅲ score before ECMO operation and concomitant and/or combined AKI during ECMO are independent risk factors for predicting death in critically ill children with ECMO support

Stability and Cementation of the Surrounding Rock in Roof-Cutting and Pressure-Relief Entry under Mining Influence

The application of roof-cutting and pressure-relief gob-side entry retention plays a critical role in controlling the stability of the surrounding rock at the entry, easing continuity tension and improving resource recovery ratio. The excavation of the 360,803 airway in Xinji No. 1 Mine is affected by intense mining of the 360,805 working face. Hence, to address the stability problem of surrounding rock in the 360,803 airway, rock mass blast weakening theory was used in this study to analyze the blasting stress of columnar charged rock mass and obtain the radiuses of crushed, fractured, and vibration zones under uncoupled charging conditions. The reasonable array pitch, length, and dip angle of boreholes were determined according to the pressure-relief range of the blasting fracture. The migration laws of roof strata were explored based on a mechanical model of overlying roof strata structure on the working face. Subsequently, the horizon, breaking span, and caving sequence of hard roof strata were obtained to determine the roof-cutting height of this entry. On the basis of the theory of key stratum, the number of sequences at the roof caving limit stratum and hanging roof length in the goaf were calculated, the analytical solution to critical coal pillar width was acquired, the evaluation indexes for the stability of entry-protecting coal pillars were determined, and the engineering requirements for the 25 m entry-protecting coal pillars in the 360,803 airway were met. Moreover, various indexes such as roof separation fracture, displacement of surrounding rock, and loose circle of surrounding rock in the gob-side entry were analyzed. The stability and cementation status of surrounding rock in the 360,803 airway were evaluated, and tunneling safety was ensured

Single-trial estimation and analysis of PVEP based on independent component analysis

A novel method based on the extended infomax approach of independent component analysis (ICA) is proposed for the single-trial estimation of multi-channel pattern-reversal visual evoked potential (PVEP). The clinical applications illustrate the encouraging performance of the method. The number of trials needed is reduced to 3, but the estimated VEP complex is clearer than that obtained by conventional ensemble averaging with 50 trials. By analyzing the time course and spatial pattern of the independent components (ICs) of the multi-channel PVEP, one component is found to be reasonably related to the P100 peak

Rapid profiling of fish cell nitrogen metabolism with single-cell Raman spectroscopy: unveiling enzyme’s role in ammonia detoxification

Ammonia is a prevalent aquatic pollutant that disrupts cellular functions and energy metabolism in fish, posing significant environmental and health threats. This research investigates the critical role of arginase 2 (ARG2) in mitigating ammonia toxicity in fish cells and its implications in adapting to nitrogen metabolism under high ammonia exposure. Through a CRISPR-Cas9 engineered ARG2 knockdown (KD) in the Epithelioma Papulosum Cyprini (EPC) cell line, we first investigated the biochemical responses of ARG2 KD and wild-type (WT) EPC cells to ammonia stress (NH4Cl treatment), showing diminished urea production and decreased cell viability in ARG2 KD cells. Subsequently, single-cell Raman spectroscopy analysis revealed that ARG2 KD cells exhibited profound metabolic shifts, including changes in protein, nucleic acids, lipid and sugar levels, showing the adjusting role of ARG2 in the balance of carbohydrate and nitrogen metabolism. Furthermore, the upregulated responses of various amino acids, such as glutamine, arginine, alanine, glutamic acid , glycine, histidine, phenylalanine and valine, in WT cells after NH4Cl treatment diminished in ARG2 KD cells except for the decrease in aspartic acid, indicating a switching effect of ARG2 in nitrogen metabolism under ammonia stress. This study highlights ARG2's essential role in ammonia detoxification and emphasizes ARG2's protective function and its importance in metabolism, shedding light on the adaptive mechanisms fish cells deploy against high ammonia environments. These insights contribute to deep understanding of aquatic organisms' molecular responses to environmental ammonia pollution, offering potential strategies for their protection