Testis specific protein, Y-encoded-like 2 activates JAK2/STAT3 pathway in hypothalamic paraventricular nucleus to sustain hypertension.

BACKGROUND: In the hypothalamic paraventricular nucleus (PVN) of spontaneously hypertensive rats (SHRs), the expression of Testis specific protein, Y-encoded-like 2 (TSPYL2) and the phosphorylation level of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) are higher comparing with the normotensive Wistar-Kyoto rats (WKY). But how they are involved in hypertension remains unclear. TSPYL2 may interact with JAK2/STAT3 in PVN to sustain the high blood pressure during hypertension. METHODS: Knockdown of TSPYL2 via adeno-associated virus (AAV) carrying shRNA was conducted through bilateral micro-injection into the PVN of SHR and WKY rats. JAK2/STAT3 inhibition was achieved by intraperitoneally or PVN injection of AG490 into the SHRs. Blood pressure (BP), plasma norepinephrine (NE), PVN inflammatory response, and PVN oxidative stress were measured. RESULTS: TSPYL2 knock-down in the PVN of SHRs but not WKYs led to reduced BP and plasma NE, and deactivation of JAK2/STAT3, decreased expression of pro-inflammatory cytokine IL-1ß, and increased expression of anti-inflammatory cytokine IL-10 in the PVN. Meanwhile, AG490 administrated in both ways reduced the blood pressure in the SHRs and deactivated JAK2/STAT3 but failed to change the expression of TSPYL2 in PVN. AG490 also downregulated expression of IL-1ß and upregulated expression of IL-10. Both knockdown of TSPYL2 and inhibition of JAK2/STAT3 can reduce the oxidative stress in the PVN of SHRs. CONCLUSION: JAK2/STAT3 is regulated by TSPYL2 in the PVN of SHRs, and PVN TSPYL2/JAK2/STAT3 is essential for maintaining high blood pressure in the hypertensive rats, making it a potential therapeutic target for hypertension.

Circadian gene Per3 promotes astroblastoma progression through the P53/BCL2/BAX signalling pathway.

The key circadian genes, Period1(Per1), Period2(Per2), and Period3(Per3), constitute the mammalian Period gene family. The abnormal expression of Per1 and Per2 is closely related to tumor development, but there are few reports on Per3 and tumorigenesis. This study was conducted to determine whether the abnormal expression of Per3 could influence the progression of astroblastoma. The results indicated that the expression level of Per3 was increased in astroblastoma cells, and the high expression of Per3 was correlated with the poor overall survival time of glioma patients. The role of Per3 in astroblastoma cells was then investigated using two approaches: interference and overexpression. The interference of Per3 inhibited astroblastoma cell proliferation by inducing the cell cycle at the S phase. The interference of Per3 inhibited the migration and invasion of astroblastoma cells, while promoted the astroblastoma cell apoptosis and the expression of the apoptosis genes Cleaved-CASP3, P53, and BAX. The overexpression of Per3 promoted proliferation by affecting the S phase distribution of the astroblastoma cell cycle. The overexpression of Per3 promoted the migration and invasion of astroblastoma cells, while inhibited the astroblastoma cell apoptosis and the expression of apoptosis genes Cleaved-CASP3, P53, and BAX. RNA-seq analysis showed that the interference of Per3 in astrocytoma cells resulted in significant changes in the expression levels of 764 genes. Among the differentially expressed genes enriched in apoptosis-related pathways, the interference of Per3 resulted in significant upregulation of MARCKSL1 expression, in contrast to significant downregulation of SFRP4, EPB41L3, and GPC5 expression. Taken together, our results suggest that Per3 appears to be a pro-cancer gene by altering the proliferation, migration, invasion, and apoptosis of astroblastoma cells. As a result, the Per3 gene may be a promising therapeutic target in the treatment of astroblastoma.

Endogenous assessment of late gadolinium enhancement grey zone in patients with non-ischaemic cardiomyopathy with T1ρ and native T1 mapping.

AIMS: This study aims to validate and compare the feasibility of T1ρ and native longitudinal relaxation time (T1) mapping in detection of myocardial fibrosis in patients with non-ischaemic cardiomyopathy, focusing on the performance of both methods in identifying late gadolinium enhancement (LGE) grey zone. METHODS AND RESULTS: Twenty-seven hypertrophic cardiomyopathy (HCM) patients, 16 idiopathic dilated cardiomyopathy (DCM) patients, and 18 healthy controls were prospectively enrolled for native T1 and T1ρ mapping imaging and then all the patients underwent enhancement scan for LGE extent and extracellular volume (ECV) values. In LGE positive patients, the LGE areas were divided into LGE core (6 SDs above remote myocardium) and grey zone (2-6 SDs above remote myocardium) according to the signal intensity of LGE. Both HCM and DCM patients showed significantly higher native T1 values and T1ρ values than controls no matter the presence of LGE (all P < 0.01). There were significant differences in native T1 and T1ρ values among four different types of myocardia (LGE core, grey zone, remote area and control, P < 0.0001). However, the T1ρ values of grey zone were significantly higher than control (P < 0.01), while the native T1 values were not (P = 0.089). T1ρ values were significantly associated with both native T1 values (r = 0.54, P < 0.001) and ECV values (r = 0.54, P < 0.001). CONCLUSION: T1ρ mapping is a feasible method to detect myocardial fibrosis in patients with non-ischaemic cardiomyopathy no matter the presence of LGE. Compared with native T1, T1ρ may serve as a better discriminator in the identification of LGE grey zone.

[Effect of nitrogen,phosphorus and potassium formula fertilizer on growth and chemical composition content of Inula japonica].

Inula japonica was used as the research object, "3414" fertilization experiment were conducted to study the effects of nitrogen,phosphorus and potassium formula fertilizer on the growth and chemical composition content of I. japonica. The characteristics of fertilizer requirement were preliminarily revealed and the study provided fertilization guidance for artificial cultivation of I. japonica. The results showed that different nitrogen,phosphorus and potassium formula fertilizers had significant effects on plant morphology,physiological and biochemical indexes,dry matter accumulation and chemical composition content. The growth indexes and chemical components of I. japonica showed an upward trend with the increase of fertilization amount,especially the nitrogen fertilizer was the most significant. The indicators were analyzed by membership function. After comprehensive evaluation,the optimal nitrogen,phosphorus and potassium formula fertilization level was N3 P2 K2,namely high level nitrogen fertilizer,medium level phosphorus fertilizer and potassium fertilizer. I. japonica is a high fertilizer demand plant,and the rational fertilization scheme is " applying nitrogen fertilizer again and applying phosphorus and potassium fertilizer properly".

A novel immunosensor based on excessively tilted fiber grating coated with gold nanospheres improves the detection limit of Newcastle disease virus.

A novel immunosensor for detecting Newcastle disease virus (NDV) was developed using excessively tilted fiber grating (Ex-TFG) coated with gold nanospheres (AuNs). AuNs were coated on the Ex-TFG surface via Au-S bonds using 3-mercaptopropyltrimethoxysilane (MPTMS), and the activated staphylococcal protein A (SPA) was linked to AuNs by covalent bonds via cysteamine. AuNs greatly enhanced the impact of the analyte on the fiber cladding mode through the local surface Plasmon resonance (LSPR) effect, thus improving the detection limit and sensitivity of the immunosensor. Meanwhile, SPA enhanced the bioactivity of anti-NDV monoclonal antibodies (MAbs), thus promoting the effectiveness of specific binding events on the fiber surface. Immunoassays were performed by monitoring the resonance wavelength shift of the proposed sensor under NDV samples containing different particle amounts. Specificity was assessed, and clinical tests for NDV were performed by contrast experiments. Experimental results showed that the detection limit for NDV was about 5~10 times improved compared to that of reference Ex-TFG without AuN treatment. Moreover, the novel biosensor was reusable and could potentially be applied in clinic.