Cell- and noncell-autonomous AUXIN RESPONSE FACTOR3 controls meristem proliferation and phyllotactic patterns.

In cell-cell communication, noncell-autonomous transcription factors play vital roles in controlling plant stem cell fate. We previously reported that AUXIN RESPONSE FACTOR3 (ARF3), a member of the ARF family with critical roles in floral meristem maintenance and determinacy, has a distinct accumulation pattern that differs from the expression domain of its encoding gene in the shoot apical meristem (SAM). However, the biological meaning of this difference is obscure. Here, we demonstrate that ARF3 expression in Arabidopsis (Arabidopsis thaliana) is mainly activated at the periphery of the SAM by auxin where ARF3 cell autonomously regulates the expression of meristem-organ boundary-specific genes, such as CUP-SHAPED COTYLEDON1-3 (CUC1-3), BLADE ON PETIOLE1-2 (BOP1-2), and TARGETS UNDER ETTIN CONTROL3 (TEC3) to regulate the arrangement of organs in regular pattern, a phenomenon referred to as phyllotaxis. We also show that ARF3 is translocated into the organizing center where it represses cytokinin activity and WUSCHEL expression to regulate meristem activity noncell-autonomously. Therefore, ARF3 acts as a molecular link that mediates the interaction of auxin and cytokinin signaling in the SAM while coordinating the balance between meristem maintenance and organogenesis. Our findings reveal an ARF3-mediated coordination mechanism through cell-cell communication in dynamic SAM maintenance.

Proteins and signaling pathways response to Wenjingtongluo drug-contained serum in IHUVECs: an explorative proteomic study.

Angiogenesis is a dynamic and complex process leading to the development of new vessels from pre-existing vessels, which played a major role in pathological processes in many diseases. The present study aimed to investigate the effect of drug-contained serum of Traditional Chinese medicine (TCM) Wenjingtongluo decoction (WJLTD) on antiangiogenesis in Immortalized Human Umbilical Vascular Endothelial cells (IHUVECs), and elucidate the possible mechanisms based on proteomic analysis. Cells were treated with the drug-contained serum of the Drug-contained Serum (DS) of WJLTD and the blank serum (BS). The antiangiogenesis capacity of DS was evaluated using wound healing assay, Transwell, and tube formation assay. We performed three biological replicates to compare large-scale differential protein expression between two groups by tandem mass tag (TMT) labeling technology based on liquid chromatography-mass spectrometry analysis (LC-MS/MS). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the general characterization of overall enriched proteins. For validation of the results of TMT, the candidate proteins were verified by parallel reaction monitoring (PRM) analysis. The results showed that 4% DS could inhibit the migration process of IHUVECs according to wound healing assay and Transwell. And tube formation ability was also dramatically inhibited (p<0.001). TMT analysis revealed 148 differentially expressed proteins between two groups that were identified and quantified. The further validation results of the two candidate proteins, Ferritin heavy chain (FTH1) and Ferritin light chain (FTL) from the Ferroptosis pathway, which played an important role in DS treatment, were consistent with those of LC-MS/MS. In conclusion, this is the first proteomics-based study to report the mechanism underlying DS treatment for angiogenesis. Further functional verification of the potential signaling pathways and the enriched proteins is warranted.

Low-cost and efficient confocal imaging method for arabidopsis flower.

For an extensive period of time apical meristem (SAM) has been considered as a mysterious organ, due to its small, hidden and dynamic structure. Confocal imaging, combined with fluorescent reporters, enables researchers to unveil the mechanisms underlying cellular activities, such as gene expression, cell division, growth patterns and cell-cell communications. Recently, a series of protocols were developed for confocal imaging of inflorescence meristem (IM) and floral meristem (FM). However, the requirement of high configuration, such as the need of a water-dipping lens without coverslip and the specialized turrets associated with fixed-stage microscopes, impedes the wide adoption of these methods. We exploited an improved object slide and matching method aiming to decrease the configuration requirement. Following this protocol, various dry microscope lenses can be selected with flexibility for building 3D images of IM and FM.

Cost-effectiveness analysis of nivolumab versus placebo for relapsed malignant mesothelioma.

BACKGROUND: Although nivolumab has shown clinical benefits for relapsed malignant mesothelioma, its cost-effectiveness requires further investigation. AIM: This study aimed to evaluate the cost-effectiveness of nivolumab compared to placebo for relapsed malignant mesotheliomas from the perspective of the Chinese healthcare system. METHOD: A three-state Markov model was developed based on data from the phase 3 randomized CONFIRM clinical trial. The drug cost and utility values for the health state were obtained from the relevant literature. The measured outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). Probabilistic and one-way sensitivity analyses (OWSA) were performed to assess the uncertainty of the model. RESULTS: Patients receiving nivolumab gained more health benefits (0.65 QALYs vs. 0.43 QALYs). The cost was higher ($25,806.08 vs. $9,310.74) than for patients in the placebo group, resulting in an ICER of $75,805.11/QALY, which was above the willingness-to-pay (WTP) threshold of three times per capita GDP ($35,864.61) in China. The result of OWSA indicated that the cost of nivolumab, the utility of the disease progression, and the discount rate were the most significant factors. Probabilistic sensitivity analysis suggested that the probability that nivolumab was not cost-effective as was 100.00% above the specified WTP threshold. CONCLUSION: From the perspective of the Chinese healthcare system, nivolumab was not as cost-effective as placebo for relapsed malignant mesothelioma.

Combining blood pressure variability and heart rate variability to analyze the autonomic nervous function of rotenone induced Parkinson's rat model.

BACKGROUND: Parkinson's patients have significant autonomic dysfunction, early detect the disorder is a major challenge. To assess the autonomic function in the rat model of rotenone induced Parkinson's disease (PD), Blood pressure and ECG signal acquisition are very important. NEW METHOD: We used telemetry to record the electrocardiogram and blood pressure signals from awake rats, with linear and nonlinear analysis techniques calculate the heart rate variability (HRV) and blood pressure variability (BPV). we applied nonlinear analysis methods like sample entropy and detrended fluctuation analysis to analyze blood pressure signals. Particularly, this is the first attempt to apply nonlinear analysis to the blood pressure evaluate in rotenone induced PD model rat. RESULTS: HRV in the time and frequency domains indicated sympathetic-parasympathetic imbalance in PD model rats. Linear BPV analysis didn't reflect changes in vascular function and blood pressure regulation in PD model rats. Nonlinear analysis revealed differences in BPV, with lower sample entropy results and increased detrended fluctuation analysis results in the PD group rats. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: our experiments demonstrate the ability to evaluate autonomic dysfunction in models of Parkinson's disease by combining the analysis of BPV with HRV, consistent with autonomic impairment in PD patients. Nonlinear analysis by blood pressure signal may help in early detection of the PD. It indicates that the fluctuation of blood pressure in the rats in the rotenone model group tends to be regular and predictable, contributes to understand the PD pathophysiological mechanisms and to find strategies for early diagnosis.