Forskolin, a labdane-type diterpenoid isolated from Coleus forskohlii, exhibits therapeutic potential for osteoporosis, cardiovascular diseases, and metabolic syndrome. Its rising nutraceutical demand and limited natural availability have driven synthetic biology approaches for sustainable production. Although significant efforts have been devoted to upstream pathway optimization, the improvement of the downstream pathway still faces challenges due to the complex metabolic network and the low catalytic activity of cytochrome P450s (P450s). In this study, we elucidated the biosynthetic network involved in forskolin production, in which three P450s mediate multi-site oxidation, providing critical pathway insights for forskolin biosynthesis. Based on this, we reconstructed an efficient biosynthetic pathway of forskolin in yeast and subsequently optimized its production efficiency through multidimensional engineering strategies including central carbon flux optimization, rate-limiting enzyme engineering, P450 electron transfer chain reinforcement, and fermentation optimization. The final strain achieved the production of 2.7 g/L forskolin in a 5-L bioreactor, which represents the highest titer reported to date. This study establishes a microbial platform for forskolin production and provides advancements in the complex network of plant natural product biosynthesis.

Hypertension is a prevalent disease globally and its prevalence is rising in sub-Saharan Africa. Urban-rural differences in the prevalence of hypertension are under-reported in Nigeria. Though hypertension is known to be related to obesity, the nature of the relationship is still unclear. This study sought to interrogate these and thus enrolled a total of 1,755 subjects (59% females) from five states in the old Eastern Region of Nigeria. Standard protocols and definitions were used to take measurements and diagnose relevant disease states. Appropriate statistical tools were used for data analysis. The results indicate that prehypertension was found in 40.0% of males and 27.5% of females while hypertension was found in 19.1% of males and 18.6% of females. The prevalence of (pre)hypertension among urban and rural males were similar (19%). However, prehypertension was more prevalent among urban females (29.1% Vs 24.3%); while hypertension was more prevalent among rural females (21.9% Vs 17.1%). SBP was found to be positively and significantly correlated with weight, waist circumference, hip circumference, waist-to-height ratio and body mass index in the general population. When disaggregated based on blood pressure phenotypes, the correlations were found to be consistent mostly among normotensive subjects and among females. Among subjects with (pre)hypertension, the correlations varied in strength and direction depending on sex and measure of adiposity used. The urban-rural difference in the prevalence of hypertension and the relationship between hypertension and obesity are not linear.

Cardiac resynchronization therapy - defibrillator (CRT-D) is an effective treatment for ischemic heart failure (HF). But, it is a tricky challenge for left ventricular lead implantation difficulties during CRT-D. We report an ischemic cardiomyopathy patient with complete right bundle branch block (cRBBB) underwent CRT-D. During the implantation, the left anterior fascicular (LAF) region pacing was not ideal, and the implantation of left ventricular lead in lateral posterior or posterior wall was difficult. Then, leads were changed to be implanted into anterior septal region (near the LAF) and posterior septal region (near the LPF) from right ventricle, respectively. Synchronized pacing of LAB and LPB was performed to replace the pacing of left bundle branch region and left ventricular lateral posterior wall. Then, the QRS duration was shortened from 160ms to 100ms. During one month in follow-up, the patient's quality of life was good and the pacing parameters were stable. This case illustrates a technically feasible, hypothesis-generating bailout approach for selected patients when conventional coronary sinus left ventricular lead placement and standard conduction system pacing are unsuccessful.

ObjectiveVenous thromboembolism (VTE) remains a leading cause of maternal morbidity and mortality worldwide. This study evaluated VTE risk stratification among postpartum women following cesarean section, compared the 2023 National Guidelines (NG) with the Caprini score, and assessed pharmacological thromboprophylaxis safety.MethodsA single-center prospective cohort study was conducted on 386 women undergoing cesarean delivery at Nhan Dan Gia Dinh Hospital between February and July 2025. VTE risk was independently assessed using the 2023 NG and Caprini score. Demographic characteristics, operative variables, and short-term inpatient outcomes related to low-molecular-weight heparin (LMWH) or unfractionated heparin prophylaxis were analyzed.ResultsAccording to the 2023 NG, 71.0% of patients were classified as low risk, 15.5% as intermediate risk, and 13.5% as high risk. Major risk factors included emergency cesarean delivery (45.3%), maternal age above 35 years (23.1%), and obesity (20.5%). Using the Caprini score, 45.3% met criteria for pharmacological prophylaxis, representing a 56.2% increase compared with the 2023 NG. Among 110 women receiving thromboprophylaxis, LMWH accounted for 99.1% of treatment. No severe hemorrhagic complications or thrombocytopenia were observed. Adverse events were mild and localized, mainly injection-site ecchymosis.ConclusionThe 2023 NG generated fewer pharmacological prophylaxis indications than the Caprini score in this cohort. LMWH prophylaxis showed favorable short-term inpatient safety after cesarean delivery. Because follow-up was limited to hospitalization and the study was not powered for rare VTE events, these findings should be interpreted as allocation patterns and short-term safety rather than comparative effectiveness.

Abdominal aortic aneurysms (AAA) are potentially life-threatening if they rupture. Xanthine oxidase inhibitors have been suggested to reduce aneurysm growth via urate-lowering and antioxidative mechanisms, though their clinical efficacy remains uncertain. The primary objective of this prospective cohort study was to estimate potential associations between urate-lowering therapies and AAA growth, and secondarily risk of rupture, surgery, all-cause mortality, and major adverse cardiovascular events (MACE), in men aged 65-74.

This population-based cohort study included data from two large cardiovascular screening trials.

The two Danish AAA male cohorts contributed with baseline characteristics, including AAA measurements through ultrasound and computed tomography scans. Participants were followed for five years through linkage with the Danish national health registries. Prescription records defined the exposure of urate-lowering therapies, and participants were categorised as users or non-users. Growth rate was examined using multivariate linear regression, and the secondary outcomes were evaluated using Cox regression.

This study included 998 men, of whom 73 (7.3%) were exposed to urate-lowering therapies, with a mean defined daily dose of 0.377 per day. During 3 993 person-years, an insignificant mean difference of 0.28 mm/year (95%CI: -0.96-1.52, p = .66) in AAA growth was observed between users and non-users. No associations between urate-lowering therapies and risk of surgery, rupture, all-cause mortality, or MACE were observed.

The use of urate-lowering therapies was not associated with a reduction in AAA progression. These findings do not support a clinically meaningful effect of urate-lowering therapies on aneurysm progression in men with AAA.

Traditional ABG is susceptible to interference from acute stress and daily fluctuations, making it difficult to accurately assess true acute blood glucose surges. To bridge this gap, we adopted the Stress Hyperglycemia Ratio (SHR), which reflects true acute hyperglycemia by controlling for baseline glucose status. SHR is associated with critical illness and has been shown to associated with in-hospital mortality. However, there is a lack of studies investigating SHR and its prognostic significance in patients with hypertension.

This study utilized the Medical Information Mart for Intensive Care IV database (MIMIC-IV) to extract patient information. All subjects were divided into four groups based on the quartiles of SHR. Kaplan-Meier (KM) curves were utilized to assess the relationship between SHR and all-cause mortality at 30, 90, 180, and 365 days. The relationship between the SHR index and prognosis was evaluated using restricted cubic spline (RCS) regression and Cox proportional hazards regression. At the same time, subgroup analyses were performed for gender, age, diabetes, myocardial infarction, congestive heart failure, cerebrovascular disease, and paraplegia.

A total of 2,140 participants with essential hypertension were included in the study. The KM curve analysis revealed that elevated levels of the SHR index were significantly associated with an increased risk of all-cause mortality at 30, 90, 180, and 365 days (log-rank P < 0.05). Moreover, multivariate analysis revealed that the SHR index remained significantly associated with mortality risk (P < 0.001). RCS analysis revealed a nonlinear, inverse U-shaped association between SHR and all-cause mortality (P < 0.05). Subgroup analysis showed statistically significant differences in all-cause mortality across gender, age, diabetes, myocardial infarction, heart failure, cerebrovascular disease, and paraplegia.

In critically ill patients with hypertension, a high level of SHR index is associated with all-cause mortality. The SHR index may be a potential prognostic indicator for assessing illness severity in ICU patients with hypertension.

Upper limb motor impairment is a major contributor to long-term disability after stroke. Mirror therapy (MT) promotes motor relearning through visuomotor feedback, whereas transcranial direct current stimulation (tDCS) may facilitate neuroplasticity by modulating cortical excitability. We conducted a systematic review and meta-analysis to evaluate whether MT combined with tDCS provides additional benefits for poststroke upper limb rehabilitation.

We searched PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang for randomized controlled trials (RCTs) published from 2015 to November 2025. Eligible studies enrolled adults with stroke-related upper limb motor deficits and compared MT + tDCS with MT alone or tDCS alone.

Twelve RCTs involving 1024 participants were included. For Fugl-Meyer Assessment for Upper Extremity, MT + tDCS showed superior improvement versus MT alone (3 studies; I-squared statistic (I2) = 21.9%; MD = 12.65, 95% confidence interval [CI] 10.07-15.23) and versus tDCS alone (7 studies; I2 = 93.3%; MD = 7.03, 95% CI 3.76-10.31). For activities of daily living, the effect on Modified Barthel Index versus MT alone was highly heterogeneous and imprecise (2 studies; I2 = 94.7%; MD = 24.19, 95% CI - 144.99 to 193.38), whereas MT + tDCS significantly improved Modified Barthel Index versus tDCS alone (5 studies; I2 = 42.7%; MD = 9.29, 95% CI 6.36-12.22). For hand function, MT + tDCS improved Wolf Motor Function Test versus tDCS alone (3 studies; I2 = 80.3%; MD = 4.90, 95% CI 0.59-9.22). Reported adverse events were generally mild and transient.

MT combined with tDCS appears to provide additional benefits for poststroke upper limb motor recovery, with consistent improvements in Fugl-Meyer Assessment for Upper Extremity and favorable effects on daily functioning and hand performance in key comparisons. However, heterogeneity across protocols and imprecision in some outcomes limit certainty. Larger, rigorously designed RCTs with standardized MT dosing and tDCS parameters and longer follow-up are warranted.

Prior research has conducted a limited number of studies on the efficacy of atenolol in preventing atrial fibrillation following cardiac surgery (CS). Consequently, a comprehensive evaluation and meta-analysis were undertaken to assess the effectiveness and safety of atenolol in patients undergoing CS for the prevention of postoperative atrial fibrillation (POAF). A meta-analysis of randomized controlled trials was performed. Searches were conducted across multiple databases up to December 1, 2024. The primary focus was the incidence of POAF. Risk ratios (RRs) for treatment effects on dichotomous variables were calculated. The data analysis encompassed 6 randomized controlled trials involving a total of 870 patients. The meta-analysis revealed that atenolol significantly reduces the incidence of POAF in adult patients undergoing CS (RR, 0.55; 95% confidence interval [CI]: 0.32-0.93; P = .03) with moderate heterogeneity (I2 = 57%; P = .10). Atenolol did not demonstrate superiority over sotalol in reducing POAF (RR, 2.39; 95% CI: 1.41-4.04; P = .001) with moderate heterogeneity (I2 = 40%; P = .19). Furthermore, no significant difference was observed between atenolol and the control group (comprising propafenone, metoprolol, nebivolol, and digoxin) in the prevention of POAF (RR, 1.28; 95% CI: 0.76-2.16; P = .35) with moderate heterogeneity (I2 = 43%; P = .15). Recent studies suggest that atenolol could be a safe and effective intervention for the prevention of POAF in adult patients undergoing CS.

Premature acute myocardial infarction (PAMI) is a high-risk condition among critically ill patients, accompanied by metabolic and inflammatory disturbances. The glucose-to-albumin ratio (GAR) reflects both stress hyperglycemia and nutritional-inflammatory status, but evidence regarding its prognostic relevance in critically ill patients with PAMI remains limited. This study aimed to investigate the prognostic value of GAR for short-term in-hospital mortality in this population. We conducted a retrospective cohort study using data from the eICU Collaborative Research Database. Patients with PAMI were divided into 2 groups according to the X-tile-derived exploratory cutoff of 5.80. Cox proportional hazards regression models were constructed with stepwise adjustment for potential confounders to assess the association between GAR and 28-day in-hospital mortality. Restricted cubic spline analysis was used to evaluate the dose-response relationship between GAR and mortality. Kaplan-Meier survival curves were generated to compare survival between groups, and subgroup and interaction analyses were performed across major clinical strata. Receiver operating characteristic curve analysis was used to assess the exploratory discriminatory ability and adjunctive prognostic information of GAR. A total of 622 patients with PAMI were included. Patients in the high GAR group (>5.80) had a higher 28-day in-hospital mortality rate than those in the low GAR group (≤5.80; 11.9% vs 1.6%). In fully adjusted Cox regression models, each 1-unit increase in GAR was associated with an increased risk of 28-day in-hospital mortality (hazard ratio 1.19, 95% confidence interval 1.07-1.33; P = .001). Restricted cubic spline analysis showed a significant nonlinear association between GAR and short-term mortality. Subgroup analyses showed no significant interactions between GAR and other covariates for 28-day in-hospital mortality. Receiver operating characteristic analysis suggested that GAR had exploratory discriminatory ability for 28-day in-hospital mortality, with an area under the curve of 0.779 (95% confidence interval 0.718-0.839). The combination of GAR and the Sequential Organ Failure Assessment score further improved overall adjunctive prognostic information. Elevated GAR was associated with increased 28-day in-hospital mortality in critically ill patients with PAMI. GAR may provide adjunctive prognostic information for short-term in-hospital mortality, and its combination with the Sequential Organ Failure Assessment improved the accuracy of prognostic assessment.

Cardiovascular-kidney-metabolic (CKM) syndrome carries high mortality risk. Whether A Body Shape Index (ABSI), Weight-Adjusted Waist Index (WWI), Systemic Inflammation Response Index (SIRI), and Systemic Immune-Inflammation Index (SII) mediate the associations of Dietary Inflammatory Index (DII) and Composite Dietary Antioxidant Index (CDAI) with mortality in this population remains unknown. We included 21,420 adults with CKM from National Health and Nutrition Examination Survey 1999 to 2018 with mortality follow-up through December 31, 2019. DII and CDAI were calculated from 24-hour dietary recalls. Survey-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cardiovascular mortality, modeling DII and CDAI as continuous variables and tertiles. Restricted cubic splines and 2-piecewise Cox models assessed nonlinearity. Mediation analyses evaluated indirect effects through ABSI, WWI, SIRI, and SII. During follow-up, 3532 all-cause and 1103 cardiovascular deaths occurred. In fully adjusted models, higher DII was associated with increased all-cause mortality (HR per 1-unit increase: 1.06, 95% CI: 1.04-1.09) and cardiovascular mortality (HR: 1.06, 95% CI: 1.02-1.10); the highest versus lowest tertile was associated with HRs of 1.27 (95% CI: 1.16-1.39) and 1.27 (95% CI: 1.08-1.49), respectively. Higher CDAI was associated with lower all-cause and cardiovascular mortality; the highest versus lowest tertile showed HRs of 0.84 (95% CI: 0.77-0.93) and 0.78 (95% CI: 0.65-0.93), respectively. Nonlinearity was observed between CDAI and all-cause mortality (P = .017). The percentage mediated by ABSI, WWI, SIRI, and SII ranged from approximately 4% to 9% for the association with all-cause mortality. In adults with CKM, DII and CDAI were independently associated with mortality outcomes, and ABSI, WWI, SIRI, and SII mediated a modest proportion of the association with all-cause mortality. Further studies are needed to confirm these findings.