OsTOC1 plays dual roles in the regulation of plant circadian clock by functioning as a direct transcription activator or repressor.

Plant clock function relies on precise timing of gene expression through complex regulatory networks consisting of activators and repressors at the core of oscillators. Although TIMING OF CAB EXPRESSION 1 (TOC1) has been recognized as a repressor involved in shaping oscillations and regulating clock-driven processes, its potential to directly activate gene expression remains unclear. In this study, we find that OsTOC1 primarily acts as a transcriptional repressor for core clock components, including OsLHY and OsGI. Here, we show that OsTOC1 possesses the ability to directly activate the expression of circadian target genes. Through binding to the promoters of OsTGAL3a/b, transient activation of OsTOC1 induces the expression of OsTGAL3a/b, indicating its role as an activator contributing to pathogen resistance. Moreover, TOC1 participates in regulating multiple yield-related traits in rice. These findings suggest that TOC1's function as a transcriptional repressor is not inherent, providing flexibility to circadian regulations, particularly in outputs.

Targeted exome sequencing identifies mutational landscape in a cohort of 1500 Chinese patients with non-small cell lung carcinoma (NSCLC).

BACKGROUND: Non-small cell lung carcinoma (NSCLC) is one of the most common human cancers, comprising approximately 80-85% of all lung carcinomas. An estimated incidence of NSCLC is approximately 2 million new cases per year worldwide. RESULTS: In recent decade, the treatment of NSCLC has made breakthrough progress owing to a large number of targeted therapies which were approved for clinical use. Epidemiology, genetic susceptibility, and molecular profiles in patients are likely to play an important factor in response rates and survival benefits to these targeted treatments and thus warrant further investigation on ethnic differences in NSCLC. In this study, a total number of 1500 Chinese patient samples,1000 formalin fixed paraffin-embedded (FFPE) and 500 blood samples, from patients with NSCLC were analyzed by targeted sequencing to explore mutational landscape in ethnic groups associated with China. CONCLUSIONS: Overall, the data presented here provide a comprehensive analysis of NSCLC mutational landscape in Chinese patients and findings are discussed in the context of similar studies on different ethnic groups.

Identification of miR­124a as a novel diagnostic and prognostic biomarker in non­small cell lung cancer for chemotherapy.

Previous studies have suggested that dysregulation of microRNA (miR) -124a is associated with various types of human cancer. However, there are few studies reporting the level of miR­124a expression in non­small cell lung cancer (NSCLC). The present study investigated the association between miR­124a and NSCLC by analyzing the differential expression of miR­124a in NSCLC using the GEO database, as well as subsequently performing reverse transcription­quantitative polymerase chain reaction analysis on 160 NSCLC biopsies, 32 of which were paired with adjacent normal tissues. The results indicated that mir­124a expression levels were decreased in NSCLC tumor biopsies compared with adjacent normal tissues. The overall survival (OS) in patients with a high expression of miR­124a was prolonged relative to patients with low expression of miR­124a. The expression levels of miR­124a were associated with clinical characteristics, including lymph­node metastasis, tumor differentiation, tumor node metastasis (TNM) stage and diameter. Frequently, lymph­node metastasis, TNM stage, diameter and lack of chemotherapy have been associated with a worse prognosis in patients. In addition, the present study identified that high expression of miR­124awith chemotherapy may increase OS. In conclusion, the current study demonstrated that miR­124a was downregulated in NSCLC, and miR­124a was a potential prognostic tumor biomarker response to chemotherapy.

GABA(A) and GABA(B) receptor-mediated inhibition of sympathetic outflow in the paraventricular nucleus is blunted in chronic heart failure.

1. Alterations in the paraventricular nucleus (PVN) are reported to be involved in sympathetic overactivity in chronic heart failure (CHF). Inhibitory inputs into the PVN contribute to sympathetic outflow. The aim of the present study was to comparatively determine the role of GABA mechanisms in the PVN in the tonic control of cardiovascular activity in anaesthetized sham and CHF rats. 2. The CHF model was induced by coronary artery ligation. Unilateral microinjection of the GABA(A) receptor agonist muscimol (0.1-0.8 nmol/200 nL) or the GABA(B) receptor agonist baclofen (0.25-2.0 nmol/200 nL) into the PVN produced similar, dose-dependent reductions in arterial pressure (AP), heart rate (HR) and renal sympathetic nerve activity (RSNA). This response was significantly blunted in CHF rats. In contrast, microinjection of the GABA(A) receptor antagonist bicuculline (25-200 pmol/200 nL) or the GABA(B) receptor antagonist CGP35348 (0.25-2.0 nmol/200 nL) into the PVN caused larger, dose-dependent increases in AP, HR and RSNA in sham than in CHF rats. 3. Polymerase chain reaction data showed that mRNA expression levels of the GABA(A) receptor alpha(1)-subunit and of the GABA(B1(a)) and GABA(B1(b)) receptor subtypes in the PVN were significantly lower in CHF than in sham rats. 4. The results of the present study suggest that the tonic inhibition mediated by both GABA(A) and GABA(B) receptors in the PVN on sympathetic outflow is blunted in CHF, which may be an important mechanism responsible for sympathetic hyperactivity in CHF.

[Roles of 20-HETE on physiologic and pathologic regulation in organism].

Twenty years ago, some foreign-investigators reported that omega-hydroxylation of arachidonic acid (AA) was catalyzed by cytochrome P-450 enzymes in some tissue to 20-hydroxyeicosatetraenoic acid (20-HETE). As a second messenger, it plays a pivotal role in the regulation of vascular tone, renal function, cerebral blood flow and lung vasodilator. Exogenous administeration of 20-HETE also plays an important role in the regulation of the coronary circulation. Moreover, hypertension, toxemia of pregnancy and other diseases is related to the formation of the 20-HETE. However, there is few domestic report about 20-HETE. Therefore, the domestic investigators should be given attention to 20-HETE adequately in the future. In this paper, roles of 20-HETE on physiologic and pathologic regulation in organism were reviewed.