Jujubosides are the principal bioactive constituents of the traditional Chinese medicine Ziziphi Spinosae Semen and are well-known for their sedative, anxiolytic, and sleep-promoting activities. These compounds are dammarane-type triterpenoid saponins characterized by a unique aglycone, jujubogenin, featuring a 5,6-spiroketal moiety that forms a rigid D/E/F tricyclic scaffold. However, the enzymatic basis underlying the formation of this distinctive spiroketal structure remains elusive. In this study, we identified and functionally characterized three cytochrome P450 enzymes from wild jujubes and Bacopa monnieri. These enzymes cooperatively catalyze an oxidative cascade in which site-selective oxidations at C-16, C-23, and C-30 drive spiroketal formation, converting dammarenediol II into jujubogenin. We further reconstituted the complete biosynthetic pathway in engineered yeast, enabling the de novo production of jujubogenin. This study establishes a foundational platform for the complete biosynthesis of jujubosides in microbial cell factories.
Jun Tang, Wei Liu, Linhua Zhao et al.· Journal of Agricultural and...· 0 citations
Background Abnormal nocturnal blood pressure (BP) profiles may expose the left atrium to persistent hemodynamic load before overt remodeling occurs. This study evaluated the association between nocturnal systolic blood pressure (SBP) dipping patterns and left atrial reservoir strain (LARS) in untreated adults with office-defined grade 1 essential hypertension. Methods This single-center retrospective cross-sectional study enrolled 315 adults who underwent 24-h ambulatory blood pressure monitoring (ABPM) and transthoracic echocardiography within 7 days. BP dipping patterns were classified as dipper, non-dipper, reverse-dipper, or extreme-dipper. Continuous LARS was the primary outcome; low LARS (<35%) was the operational secondary outcome. The primary model was adjusted for age, sex, body mass index (BMI), 24-h SBP, fasting plasma glucose, natural-log-transformed triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and estimated glomerular filtration rate (eGFR). Results There were 126 dippers (40.0%), 124 non-dippers (39.4%), 45 reverse-dippers (14.3%), and 20 extreme-dippers (6.3%); 300 participants (95.2%) met ambulatory criteria for sustained hypertension, and 100 (31.7%) had low LARS. LARS differed across patterns (P < 0.001). Compared with dippers, non-dippers and reverse-dippers had lower adjusted LARS [β = −3.44, 95% confidence interval (CI) −4.68 to −2.20; β = −5.92, 95% CI −7.80 to −4.04] and higher odds of low LARS [non-dippers odds ratio (OR) = 3.68, 95% CI 1.83–7.39; reverse-dippers OR = 8.12, 95% CI 3.00–21.98; both P < 0.001]. Extreme-dipping was not associated with either outcome. When nighttime SBP replaced 24-h SBP, the associations were attenuated but remained statistically significant; the direction of association did not change in analyses restricted to participants with complete sleep diaries or sustained hypertension. Restricted cubic spline (RCS) analysis suggested nonlinearity. Conclusion Non-dipping and reverse-dipping BP patterns were associated with lower LARS and a higher likelihood of low LARS. Prospective multicenter studies are needed to determine prognostic and incremental clinical value.
Lei Zha, Haoqin Zhu, Jiajia Liu et al.· Frontiers in Cardiovascular...· 0 citations
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