CsPAT1, a GRAS transcription factor, promotes lignin accumulation by antagonistic interacting with CsWRKY13 in tea plants.

Lignin is an important component of plant cell walls and plays crucial roles in the essential agronomic traits of tea quality and tenderness. However, the molecular mechanisms underlying the regulation of lignin biosynthesis in tea plants remain unclear. CsWRKY13 acts as a negative regulator of lignin biosynthesis in tea plants. In this study, we identified a GRAS transcription factor, phytochrome A signal transduction 1 (CsPAT1), that interacts with CsWRKY13. Silencing CsPAT1 expression in tea plants and heterologous overexpression in Arabidopsis demonstrated that CsPAT1 positively regulates lignin accumulation. Further investigation revealed that CsWRKY13 directly binds to the promoters of CsPAL and CsC4H and suppresses transcription of CsPAL and CsC4H. CsPAT1 indirectly affects the promoter activities of CsPAL and CsC4H by interacting with CsWRKY13, thereby facilitating lignin biosynthesis in tea plants. Compared with the expression of CsWRKY13 alone, the co-expression of CsPAT1 and CsWRKY13 in Oryza sativa significantly increased lignin biosynthesis. Conversely, compared with the expression of CsPAT1 alone, the co-expression of CsPAT1 and CsWRKY13 in O. sativa significantly reduced lignin accumulation. These results demonstrated the antagonistic regulation of the lignin biosynthesis pathway by CsPAT1 and CsWRKY13. These findings improve our understanding of lignin biosynthesis mechanisms in tea plants and provide insights into the role of the GRAS transcription factor family in lignin accumulation.

Circadian rhythm response and its effect on photosynthetic characteristics of the Lhcb family genes in tea plant.

BACKGROUND: The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. RESULTS: In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. CONCLUSIONS: Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.

Comparison of the imaging and clinical characteristics between Initial and Recurrent Alcoholic Acute Pancreatitis: a retrospective cross-sectional study.

MATERIALS: Patients with alcoholic acute pancreatitis in our hospital were recruited from Jan 2019 to July 2022 and divided into IAAP and RAAP groups. All patients underwent Contrast-Enhanced Computerized Tomography (CECT) or Magnetic Resonance Imaging (MRI) after administration. Imaging manifestations, local complications, severity scores on the Modified CT/MR Severity Index (MCTSI/MMRSI), Extrapancreatic Inflammation on CT/MR (EPIC/M), clinical severity [Bedside Index for Severity in Acute Pancreatitis (BISAP) Acute Physiology and Chronic Health Evaluation (APACHE-II)], and clinical prognosis were compared between the two groups.Results: 166 patients were recruited for this study, including 134 IAAP (male sex 94%) and 32 RAAP patients (male sex 100%). On CECT or MRI, IAAP patients were more likely to develop ascites and Acute Necrosis collection (ANC) than RAAP patients (ascites:87.3%vs56.2%; P = .01; ANC:38%vs18.7%; P < .05). MCTSI/MMRSI and EPIC/M scores were higher in IAAP than in RAAP patients(MCTSI/MMRSI:6.2vs5.2; P < .05; EPIC/M:5.4vs3.8; P < .05).Clinical severity scores (APACHE-II and BISAP), length of stay, and systemic complications [Systemic Inflammatory Response Syndrome (SIRS), respiratory failure] were higher in the IAAP group than in the RAAP group (P < .05). No mortality outcomes were reported in either group while hospitalized.Conclusions: Patients with IAAP had more severe disease than those with RAAP. These results may be helpful for differentiating care paths for IAAP and RAAP, which are essential for management and timely treatment in clinical practice.

Hydrogen sulfide rescues high glucose-induced migration dysfunction in HUVECs by upregulating miR-126-3p.

Diabetes (especially Type II) is one of the primary threats to cardiovascular health. Wound healing defects and vascular dysfunction are common in diabetic patients, and the primary cause of deterioration is sustained high plasma glucose. microRNA, a noncoding RNA, has regulatory functions that are critical to maintaining homeostasis. MicroRNA (miR)-126-3p is a potential diabetes biomarker and a proangiogenic factor, and its plasma level decreases in diabetic patients. Previous studies have revealed the proangiogenic character of the gasotransmitter hydrogen sulfide (H2S). However, little is known about the relationship between H2S and miR-126-3p when the extracellular glucose level is high, let alone their influences on deteriorated endothelial cell migration, a key component of angiogenesis, which is crucial for wound healing. Human umbilical vein endothelial cells (HUVECs) were treated with high glucose (33.3 mmol/L) or normal glucose (5.5 mmol/L) for 48 h. Affymetrix miRNA profiling and real-time PCR were used to validate the miRNA expression. An H2S probe (HSip-1) was used to detect endogenous H2S. Scratch wound-healing assays were used to evaluate HUVEC migration. The protein levels were quantified by Western blot. Both exogenous and endogenous H2S could upregulate the miR-126-3p levels in HUVECs or muscle tissue. High glucose decreased the H2S level and the protein expression of the H2S-producing enzyme cystathionine γ-lyase (CSE) in HUVECs; however, the DNA methyltransferase 1 (DNMT1) protein level was upregulated. CSE overexpression not only increased the miR-126-3p level by decreasing the DNMT1 protein level but also rescued the deteriorated cell migration in HUVECs treated with high glucose. DNMT1 overexpression decreased the miR-126-3p level and inhibited the migration of HUVECs, whereas silencing DNMT1 improved cell migration. High glucose decreased the endogenous H2S and miR-126-3p levels and increased the DNMT1 expression, thus inducing the migration dysfunction of HUVECs. Treatment with exogenous H2S or the overexpression of the endogenously produced enzyme CSE would rescue this migration dysfunction through H2S-DNMT1-miR-126-3p.

MR imaging of hemorrhage associated with acute pancreatitis.

PURPOSE: To study MRI findings of hemorrhage in acute pancreatitis (AP) and correlate the presence and extent of hemorrhage with the MR severity index (MRSI), Acute Physiology And Chronic Health Evaluation (APACHE) II scores, and clinical outcome. MATERIALS AND METHODS: This retrospective study included 539 patients with AP. Hemorrhage was defined as areas of hyperintensity in or outside the pancreas on liver imaging with volume acceleration flexible (LAVA-Flex). The presence of hemorrhage was classified into three areas: within the pancreatic parenchyma, retroperitoneal space, and sub-or intraperitoneal space. Involvement of each area was awarded 1 point resulting in the hemorrhage severity index (HSI) score. The predicted severity of AP was graded by MRSI and APACHE II score. The association between HSI, MRSI, and APACHE II scores was analyzed. The length of hospital stay and organ dysfunction was used as clinical outcome parameters. RESULTS: Among 539 AP patients, 62 (11.5%) had hemorrhage. The prevalence of hemorrhage was 1.1% (2/186), 13.9% (43/310), and 39.5% (17/43) in predicted mild, moderate, and severe AP, respectively, based on MRSI (χ2 = 55.3, p = 0.00); and 7.7% (21/273) and 19.2% (18/94) in predicted mild and severe AP, respectively, based on APACHE II (χ2 = 21.2, p = 0.00). HSI score significantly correlated with MRSI (r = 0.36, p < 0.001) and APACHE II scores (r = 0.21, p = 0.00). The prevalence of organ dysfunction was higher and length of hospital stay was longer in patients with hemorrhage than in those without hemorrhage (p < 0.01). CONCLUSIONS: Hemorrhage in AP is common. The presence of hemorrhage, rather than its extent, correlates with poor clinical outcome.

[The Molecular Switches and Atomic Biological Mechanisms Underlying the Physiological and Pathophysio-logical Effects of Hydrogen Sulfide to Regulate Its "Receptors"].

Hydrogen sulfide (H2S)has emerged as pivotal signaling molecules since it is recognized as the third gasotransmitter together with nitric oxide and carbon monoxide. The development of detecting technologies contributed to the research in H2S biology.H2S plays significant roles in human body systems, such as the cardiovascular system, nervous system, respiratory system etc.. Alterations of H2S concentrations have been connected with many diseases. Hypertension, atherosclerosis, neurodegenerative disorder, asthma and many other diseases are found to be related with abnormal H2S metabolism. It has become a potential drug for therapeutic purposes. Understanding the mechanism of H2S biology, including a molecular switch contained in its "receptor", has deepened the research on how small molecules regulate big molecules, as well as providing new strategy for the therapeutic approaches for varies of diseases.

Hydrogen sulfide promotes angiogenesis by downregulating miR-640 via the VEGFR2/mTOR pathway.

We previously found hydrogen sulfide (H2S) to be a new proangiogenic factor. However, the mechanisms underlying the cardiovascular effect of this small gas molecule remain largely unknown. The aim of the present study was to identify the essential microRNAs (miRNAs) involved in the transduction of H2S signals in vascular endothelial cells (ECs). The expression of miR-640 and its signaling elements, vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia inducible factor 1-α (HIF1A), and mammalian target of rapamycin (mTOR), was measured using quantitative PCR and Western blotting. Overexpression and inhibition of miR-640 were performed to clarify their roles in mediating the effect of H2S. In addition, knockdown of VEGFR2, HIF1A, and mTOR was performed using siRNAs, dominant negative mutants, or inhibitors to examine their roles in the transduction of the H2S signals. miR-640 levels decreased in vascular ECs that were treated with H2S, whereas overexpression of miR-640 blunted the proangiogenic effect of H2S. Knockdown of either VEGFR2 or mTOR blunted the downregulation of miR-640 and the proangiogenic effect induced by H2S. In addition, miR-640 bound to the 3'-UTR of HIF1A mRNA and then inhibited the expression of HIF1A. The inhibition could be recovered by treating cells with H2S. Thus we concluded that miR-640 plays a pivotal role in mediating the proangiogenic effect of H2S; H2S acts through downregulation of the expression of miR-640 and increasing the levels of HIF1A through the VEGFR2-mTOR pathway.

Transcriptome-wide identification of Camellia sinensis WRKY transcription factors in response to temperature stress.

Tea plant [Camellia sinensis (L.) O. Kuntze] is a leaf-type healthy non-alcoholic beverage crop, which has been widely introduced worldwide. Tea is rich in various secondary metabolites, which are important for human health. However, varied climate and complex geography have posed challenges for tea plant survival. The WRKY gene family in plants is a large transcription factor family that is involved in biological processes related to stress defenses, development, and metabolite synthesis. Therefore, identification and analysis of WRKY family transcription factors in tea plant have a profound significance. In the present study, 50 putative C. sinensis WRKY proteins (CsWRKYs) with complete WRKY domain were identified and divided into three Groups (Group I-III) on the basis of phylogenetic analysis results. The distribution of WRKY family transcription factors among plantae, fungi, and protozoa showed that the number of WRKY genes increased in higher plant, whereas the number of these genes did not correspond to the evolutionary relationships of different species. Structural feature and annotation analysis results showed that CsWRKY proteins contained WRKYGQK/WRKYGKK domains and C2H2/C2HC-type zinc-finger structure: D-X18-R-X1-Y-X2-C-X4-7-C-X23-H motif; CsWRKY proteins may be associated with the biological processes of abiotic and biotic stresses, tissue development, and hormone and secondary metabolite biosynthesis. Temperature stresses suggested that the candidate CsWRKY genes were involved in responses to extreme temperatures. The current study established an extensive overview of the WRKY family transcription factors in tea plant. This study also provided a global survey of CsWRKY transcription factors and a foundation of future functional identification and molecular breeding.

Isolation and dynamic expression of four genes involving in shikimic acid pathway in Camellia sinensis 'Baicha 1' during periodic albinism.

Flavonoids are the main flavor components and functional ingredients in tea, and the shikimic acid pathway is considered as one of the most important pathways in flavonoid biosynthesis, but little was known about the function of regulatory genes in the metabolism phenolic compounds in tea plant (Camellia sinensis), especially related genes in shikimic acid pathway. The dynamic changes of catechin (predominant flavonoid) contents were analyzed in this study, and four genes (CsPPT, CsDAHPS, CsSDH and CsCS) involving in shikimic acid pathway in C. sinensis albino cultivar 'Baicha 1' were cloned and characterized. The full-length cDNA sequences of these genes were obtained using reverse transcription-PCR and rapid amplification of cDNA ends. At the albinistic stage, the amounts of all catechins decreased to the lowest levels, when epigallocatechin gallate was the highest, whereas gallocatechin-3-O-gallate the lowest. Gene expression patterns analyzed by qRT-PCR showed that CsPPT and CsDAHPS were highly expressed in flowers and buds, while CsSDH and CsCS showed high expression levels in buds and leaves. It was also found that the transcript abundance of shikimic acid biosynthetic genes followed a tightly regulated biphasic pattern, and was affected by albinism. The transcript levels of CsPPT and CsDAHPS were decreased at albinistic stage followed elevated expression, whereas CsSDH and CsCS were increased only at re-greening stage. Taken together, these findings suggested that these four genes in C. sinensis may play different roles in shikimic acid biosynthesis and these genes may have divergent functions.

Transcriptome-based discovery of AP2/ERF transcription factors related to temperature stress in tea plant (Camellia sinensis).

Tea plant (Camellia sinensis) is an important natural resource for the global supply of non-alcoholic beverage production. The extension of tea plant cultivation is challenged by biotic and abiotic stresses. Transcription factors (TFs) of the APETALA 2 (AP2)/ethylene-responsive factor (ERF) family are involved in growth and anti-stresses through multifaceted transcriptional regulation in plants. This study comprehensively analyzed AP2/ERF family TFs from C. sinensis on the basis of the transcriptome sequencing data of four tea plant cultivars, namely, 'Yunnanshilixiang', 'Chawansanhao', 'Ruchengmaoyecha', and 'Anjibaicha'. A total of 89 putative AP2/ERF transcription factors with full-length AP2 domain were identified from C. sinensis and classified into five subfamilies, namely, AP2, dehydration-responsive-element-binding (DREB), ERF, related to ABI3/VP (RAV), and Soloist. All identified CsAP2/ERF genes presented relatively stable expression levels in the four tea plant cultivars. Many groups also showed cultivar specificity. Five CsAP2/ERF genes from each AP2/ERF subfamily (DREB, ERF, AP2, and RAV) were related to temperature stresses; these results indicated that AP2/ERF TFs may play important roles in abnormal temperature stress response in C. sinensis.

Association of THADA, FOXP4, GPRC6A/RFX6 genes and 8q24 risk alleles with prostate cancer in Northern Chinese men.

PURPOSE: Prostate cancer (PCa) is one of the most common malignancies in males, and multiple genetic studies have confirmed association with susceptibility to PCa. However, the risk conferred in men living in China is unkown. We selected 6 previously identified variants as candidates to define their association with PCa in Chinese men. METHODS: We genotyped 6 single nucleotide polymorphisms (SNPs) (rs1465618, rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) using high resolution melting (HRM) analysis and assessed their association with PCa risk in a case-control study of 481 patients and 480 controls in a Chinese population. In addition, the individual and cumulative contribution for the risk of PCa and clinical covariates were analysed. RESULTS: We found that 5 of the 6 genetic variants were associated with PCa risk. The T allele of rs339331 and the G allele of rs16901966 showed a significant association with PCa susceptibility: OR (95%CI)= 0.78 (0.64-0.94), p<0.009 and OR (95%CI)= 0.66 (0.54-0.81), p<0.0001, as well as A allele of rs1447295 (OR [95%CI]=1.46 (1.17-1.84), p<0.001) and T allele of rs10090154 (OR [95%CI]= 0.58 (0.46-0.74), p<0.0001). rs339331(T) was associated with a 0.71-fold and 1.42-fold increase of PCa risk by dominant model (p=0.007) and recessive model (p=0.007). rs16901966 (G) was associated with a 0.51-fold and 1.98-fold increase of PCa risk by dominant model (p=0.006) and recessive model (p=0.0058). rs10090154 (T) was associated with a 1.89-fold and 0.53-fold increase of PCa risk by dominant model (p=0.000006) and recessive model (p=0.000006). And, rs1983891(C) was associated with a 0.77-fold increase of PCa risk by recessive model (p=0.045). rs1447295 was associated with a 1.57-fold increase of PCa risk by dominant model (p=0.008). rs1465618 showed no significant association with PCa. The cumulative effects test of risk alleles (rs rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) showed an increasing risk to PCa in a frequency-dependent manner (ptrend=0.001), and men with more than 3 risk alleles had the most significant susceptibility to PCa (OR=1.99, p=0.001), compared with those who had one risk allele (OR=1.17, p=0.486). CONCLUSION: Our results provide further support for association of the THADA, FOXP4, GPRC6A/RFX6 and 8q24 genes with Pca in Asian populations. Further work is still required to determine the functional variations and finally clarify the underlying biological mechanisms.

De novo assembly and transcriptome characterization: novel insights into catechins biosynthesis in Camellia sinensis.

BACKGROUND: Tea is a popular natural non-alcoholic beverage consumed worldwide due to its bioactive ingredients, particularly catechins (flavan-3-ols). Catechins not only contribute to tea quality but also serve important functions in the anti-stress regulation of secondary metabolic pathways. However, the percentages of various catechins are different among tea plant [Camellia sinensis (L.) O. Kuntze] cultivars. This study aimed to elucidate the biosynthetic mechanism of catechins. Transcriptomes from leaf tissues of four tea plant cultivars, 'Yunnanshilixiang', 'Chawansanhao', 'Ruchengmaoyecha', and 'Anjibaicha', were sequenced using the high-throughput sequencing platform Illumina HiSeq™ 2000. De novo assemble were also performed. Catechins contents were measured through reversed-phase high-performance liquid chromatography (RP-HPLC), and the biosynthetic pathway was also surveyed. RESULTS: We constructed a unified unigene database. A total of 146,342 pairs of putative orthologs from the four tea plant cultivars, 'Yunnanshilixiang', 'Chawansanhao', 'Ruchengmaoyecha', and 'Anjibaicha' were generated. Approximately 68,890 unigenes (47.1%) were aligned to the sequences of seven public databases with a cut-off E-value of 1E-5. A total of 217 differentially expressed genes were found through RPKM values, and 150 unigenes were assigned to the flavonoid biosynthetic pathway using the integrated function annotation. The (-)-EGC and (-)-EC contents were significantly lower and the (+)-GC and (+)-C contents were abnormally higher in 'Ruchengmaoyecha' than in 'Yunnanshilixiang', 'Chawansanhao', and 'Anjibaicha'. The proportion of catechins was confirmed by selecting critical genes (ANS, ANR, and LAR) for qRT-PCR analysis. CONCLUSIONS: This study provided a global survey of transcriptomes from four tea plant cultivars and serves as an available resource of genetic diversity. The analyses of transcriptome profiles and physiological indicators not only identified the putative genes involved in the flavonoid biosynthetic pathway but also provided some novel insights for the mechanisms of catechins biosynthesis.

Abdominal MRI at 3.0 T: LAVA-Flex compared with conventional fat suppression T1-weighted images.

PURPOSE: To study liver imaging with volume acceleration-flexible (LAVA-Flex) for abdominal magnetic resonance imaging (MRI) at 3.0 T and compare the image quality of abdominal organs between LAVA-Flex and fast spoiled gradient-recalled (FSPGR) T1-weighted imaging. MATERIALS AND METHODS: Our Institutional Review Board approval was obtained in this retrospective study. Sixty-nine subjects had both FSPGR and LAVA-Flex sequences. Two radiologists independently scored the acquisitions for image quality, fat suppression quality, and artifacts and the values obtained were compared with the Wilcoxon signed rank test. According to the signal intensity (SI) measurements, the uniformity of fat suppression, the contrast between muscle and fat and normal liver and liver lesions were compared by the paired t-test. The liver and spleen SI on the fat-only phase were analyzed in the fatty liver patients. RESULTS: Compared with FSPGR imaging, LAVA-Flex images had better and more homogenous fat suppression and lower susceptibility artifact (qualitative scores: 4.70 vs. 4.00, 4.86% vs. 7.14%, 4.60 and 4.10, respectively). The contrast between muscle and fat and between the liver and pathologic lesions was significantly improved on the LAVA-Flex sequence. The contrast value of the fatty liver and spleen was higher than that of the liver and spleen. CONCLUSION: The LAVA-Flex sequence offers superior and more homogenous fat suppression of the abdomen than does the FSPGR sequence. The fat-only phase can be a simple and effective method of assessing fatty liver.

Radiomics models of contrast-enhanced computed tomography for predicting the activity and prognosis of acute pancreatitis.

BACKGROUND: The modified pancreatitis activity scoring system (mPASS) was proposed to assess the activity of acute pancreatitis (AP) while it doesn't include indicators that directly reflect pathophysiology processes and imaging characteristics. OBJECTIVES: To determine the threshold of admission mPASS and investigate radiomics and laboratory parameters to construct a model to predict the activity of AP. METHODS: AP inpatients at institution 1 were randomly divided into training and validation groups based on a 5:5 ratio. AP inpatients at Institution 2 were served as test group. The cutoff value of admission mPASS scores in predicting severe AP was selected to divide patients into high and low level of disease activity group. LASSO was used in screening features. Multivariable logistic regression was used to develop radiomics model. Meaningful laboratory parameters were used to construct combined model. RESULTS: There were 234 (48 years ± 10, 155 men) and 101 (48 years ± 11, 69 men) patients in two institutions. The threshold of admission mPASS score was 112.5 in severe AP prediction. The AUC of the radiomics model was 0.79, 0.72, and 0.76 and that of the combined model incorporating rad-score and white blood cell were 0.84, 0.77, and 0.80 in three groups for activity prediction. The AUC of the combined model in predicting disease without remission was 0.74. CONCLUSIONS: The threshold of admission mPASS was 112.5 in predicting severe AP. The model based on CECT radiomics has the ability to predict AP activity. Its ability to predict disease without remission is comparable to mPASS. CRITICAL RELEVANCE STATEMENT: This work is the first attempt to assess the activity of acute pancreatitis using contrast-enhanced CT radiomics and laboratory parameters. The model provides a new method to predict the activity and prognosis of AP, which could contribute to further management. KEY POINTS: Radiomics features and laboratory parameters are associated with the activity of acute pancreatitis. The combined model provides a new method to predict the activity and prognosis of AP. The ability of the combined model is comparable to the modified Pancreatitis Activity Scoring System.

Genome-wide identification and characterization of PIN-FORMED (PIN) and PIN-LIKES (PILS) gene family reveals their role in adventitious root development in tea nodal cutting (Camellia Sinensis).

Auxin affects all aspects of plant growth and development, including morphogenesis and adaptive responses. Auxin transmembrane transport is promoted by PIN formation (PIN) and a structurally similar PIN-like (PILS) gene family, which jointly controls the directional transport of the auxin between plant cells, and the accumulation of intracellular auxin. At present, there is no study investigating the roles of CslPIN and CslPILS gene family in root development in the tea plant (Camellia sinensis). In this study, 8 CslPIN and 10 CslPILS genes were identified in the tea plant, and their evolutionary relationships, physical and chemical properties, conserved motifs, cis-acting elements, chromosome location, collinearity, and expression characteristics were analyzed. The mechanism of CslPIN and CslPILS in the formation of tea adventitious roots (ARs) was studied by the AR induction system. Through functional verification, the regulation of CslPIN3 gene on root growth and development of tea plant was studied by over-expression of CslPIN3 in Arabidopsis thaliana and in situ hybridization in Camellia sinensis. The results confirmed CslPIN3 was involved in the regulation of root growth and development as well as auxin accumulation. This study provides a better insight into the regulatory mechanism of CslPIN and CslPILS gene family on the formation of AR in tea plant.

Overexpressing CsPSY1 Gene of Tea Plant, Encoding a Phytoene Synthase, Improves α-Carotene and ß-Carotene Contents in Carrot.

Tea plants (Camellia sinensis (L.) O. Kuntze) belong to Theaceae family, in the section Thea. Tea plants are widely distributed in subtropical and tropical regions in the word. α-carotene and ß-carotene in the tea leaves belong to carotenoids, which are associated with the aroma and color of the tea. Phytoene synthase (PSY) is a rate-limiting enzyme in carotenoids biosynthesis. We identified three CsPSY genes in 'Shuchazao', named CsPSY1, CsPSY2, and CsPSY3. Structural analysis of three CsPSY genes showed that CsPSY1 had a longer intro structure. The cis-acting elements of CsPSYs promoter were mainly associated with light-responsiveness, abiotic stress-responsiveness, and hormone-responsiveness. CsPSY1 exhibited expression in all tissues of the tea plants, whereas CsPSY2 and CsPSY3 were trace expression levels in all tissues. The positive expression of CsPSY1 under hormonal and abiotic stresses suggested its role in plant development and defense responses. The amino acid sequence of CsPSY1 was highly conserved in eight tea cultivars. The recombinant vector pCAMBIA1301-CsPSY1 was constructed to stabilize the overexpression of CsPSY1 in carrot. The contents of α-carotene and ß-carotene in transgenic carrot callus were significantly increased. This study provides a foundational basis for further research on the function of CsPSYs and carotenoids accumulation in tea plants.

Long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice.

Statins play an important role in the treatment of diabetic nephropathy. Increasing attention has been given to the relationship between statins and insulin resistance, but many randomized controlled trials confirm that the therapeutic effects of statins on diabetic nephropathy are more beneficial than harmful. However, further confirmation of whether the beneficial effects of chronic statin administration on diabetic nephropathy outweigh the detrimental effects is urgently needed. Here, we find that long-term statin administration may increase insulin resistance, interfere with lipid metabolism, leads to inflammation and fibrosis, and ultimately fuel diabetic nephropathy progression in diabetic mice. Mechanistically, activation of insulin-regulated phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway leads to increased fatty acid synthesis. Furthermore, statins administration increases lipid uptake and inhibits fatty acid oxidation, leading to lipid deposition. Here we show that long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice.

[Prevalence and awareness of hypertension in Gansu Gannan Tibetan adult population].

OBJECTIVE: To investigate the prevalence and awareness status of hypertension in adult Gansu Gannan Tibetan population. METHODS: A total of 6948 adult (aged 18 and over) Tibetan residents were selected by random cluster multistage method. Participants were divided into city, rural dwellers and rural nomads groups. Questionnaires were collected and blood pressure measured from all participants. RESULTS: Prevalence of hypertension in this district was 24.6% (1708/6948), of which city, rural dwellers and nomadic areas were 25.3% (848/3340), 22.7% (628/2765), 27.5% (232/843), respectively. Prevalence of hypertension was significantly higher in city than in rural dwellers group (P<0.05), significantly higher in rural nomads group than in city and rural dwellers groups (all P<0.05). Awareness, treatment and control rates of hypertension in city group were 35.7% (303/848), 25.1% (213/848), 6.9% (59/848), respectively; in rural dwellers group were 28.3% (178/628), 19.3% (121/628), 4.7% (30/628), respectively; in rural nomads group were 16.8% (39/232), 8.6% (20/232), 2.2% (5232), respectively. Rates of awareness, treatment and control were significantly lower in rural dwellers than in city group (all P<0.01), and significantly lower in rural nomads group than in city and rural dwellers groups (all P<0.01). CONCLUSIONS: Prevalence of hypertension in Gansu Gannan Tibetan population aged 18 and over is high. Awareness, treatment and control rates of hypertension are low, especially in rural dwellers and rural nomads residents.

YB-1 Recruits Drosha to Promote Splicing of pri-miR-192 to Mediate the Proangiogenic Effects of H2S.

Aims: The genes targeted by miRNAs have been well studied. However, little is known about the feedback mechanisms to control the biosynthesis of miRNAs that are essential for the miRNA feedback networks in the cells. In this present study, we aimed at examining how hydrogen sulfide (H2S) promotes angiogenesis by regulating miR-192 biosynthesis. Results: H2S promoted in vitro angiogenesis and angiogenesis in Matrigel plugs embedded in mice by upregulating miR-192. Knockdown of the H2S-generating enzyme cystathionine γ-lyase (CSE) suppressed in vitro angiogenesis, and this suppression was rescued by exogenous H2S donor NaHS. Plakophilin 4 (PKP4) served as a target gene of miR-192. H2S up-regulated miR-192 via the VEGFR2/Akt pathway to promote the splicing of primary miR-192 (pri-miR-192), and it resulted in an increase in both the precursor- and mature forms of miR-192. H2S translocated YB-1 into the nuclei to recruit Drosha to bind with pri-miR-192 and promoted its splicing. NaHS treatment promoted angiogenesis in the hindlimb ischemia mouse model and the skin-wound-healing model in diabetic mice, with upregulated miR-192 and downregulated PKP4 on NaHS treatment. In human atherosclerotic plaques, miR-192 levels were positively correlated with the plasma H2S concentrations. Innovation and Conclusion: Our data reveal a role of YB-1 in recruiting Drosha to splice pri-miR-192 to mediate the proangiogenic effect of H2S. CSE/H2S/YB-1/Drosha/miR-192 is a potential therapeutic target pathway for treating diseases, including organ ischemia and diabetic complications. Antioxid. Redox Signal. 36, 760-783. The Clinical Trial Registration number is 2016-224.

Prevalence of Dyslipidemia in Tibetan Monks from Gansu Province, Northwest China.

Tibetan monks have a special way of life and food habits, however, little is known about their dyslipidemia. This study aimed to investigate the prevalence of dyslipidemia and risk factors of this population. A cross-sectional study of dyslipidemia was conducted in 876 Tibetan monks and 912 local residents in the same area. All subjects underwent interviews and physical examinations. The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) of the subjects were analyzed. Compared to local residents, the overall prevalence of dyslipidemia in monks was 29.5%, which was significantly lower (p<0.05). It was increased with higher age and BMI, but reduced with higher educational level (p<0.05). The typical forms of dyslipidemia in monks were elevated TG and low HDL-C, while it was lower HDL-C in residents (p<0.05). Our study demonstrated that monks in Gannan Tibetan autonomous district had a lower prevalence of dyslipidemia. It suggested that the relatively healthy lifestyle and food habits of monks were mainly responsible of the lower prevalence of dyslipidemia.