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Background and Aim This study investigated the dose-dependent cardioprotective effects of Pterocarpus indicus extract (P.indicus; LD: 27, MD: 54, HD: 108 mg/kg) against isoproterenol (ISO)-induced myocardial ischemia in rats, focusing on oxidative stress, apoptosis, inflammation, and fibrosis. Experimental procedure Rats were pretreated for 14 days and divided into control, ISO, propranolol, and P.indicus (LD, MD, HD) groups. Myocardial injury was assessed via ECG, histopathology, serum biomarkers (CK-MB, LDH, cTnT, IL-6, IL-1β, TNF-α), oxidative markers (SOD, MDA, GSH-Px), and apoptosis-related proteins (Bax, Bcl-2, Caspase-3). Nrf2/HO-1 expression was analyzed by western blot. Phytochemical profiling was performed via UPLC-MS/MS and HPLC. Pharmacokinetics, safety, and therapeutic-regimen efficacy were also evaluated. Results P.indicus at MD and HD significantly attenuated ISO-induced ECG abnormalities, histopathological damage, serum injury markers, inflammatory cytokines, and fibrosis (all P < 0.01). Treatment suppressed oxidative stress (restored SOD/GSH-Px, reduced MDA) via Nrf2/HO-1 activation and inhibited apoptosis via Bax/Bcl-2/Caspase-3 modulation. The efficacy of MD (EC50 ∼50 mg/kg) was confirmed by dose-response analysis. Pharmacological inhibition established that both Nrf2 activation and caspase-3 inhibition are necessary for P.indicus’s effects. PK studies showed systemic exposure to key compounds (quercetin-3-O-glucoside, ferulic acid, linoleic acid), and a 14-day safety assessment revealed no hepatorenal toxicity. Post-injury therapeutic administration also conferred significant protection. Conclusion P. indicus extract confers dose-dependent cardioprotection against ISO-induced myocardial injury through dual modulation of the Nrf2/HO-1 and Bax/Bcl-2/Caspase-3 pathways, with the medium dose (54 mg/kg) identified as optimally effective and well-tolerated. Graphical Abstract

Transforming growth factor—β (TGFβ) signaling drives aneurysm progression in multiple disorders, including Marfan syndrome (MFS), and therapies that inhibit this signaling cascade are in clinical trials. TGFβ can stimulate multiple intracellular signaling pathways, but it is unclear which of these pathways drives aortic disease and, when inhibited, which result in disease amelioration. Here we show that extracellular signal—regulated kinase (ERK) 1 and 2 and Smad2 are activated in a mouse model of MFS, and both are inhibited by therapies directed against TGFβ. Whereas selective inhibition of ERK1/2 activation ameliorated aortic growth, Smad4 deficiency exacerbated aortic disease and caused premature death in MFS mice. Smad4-deficient MFS mice uniquely showed activation of Jun N-terminal kinase—1 (JNK1), and a JNK antagonist ameliorated aortic growth in MFS mice that lacked or retained full Smad4 expression. Thus, noncanonical (Smad-independent) TGFβ signaling is a prominent driver of aortic disease in MFS mice, and inhibition of the ERK1/2 or JNK1 pathways is a potential therapeutic strategy for the disease.

Angiotensin II (AngII) mediates progression of aortic aneurysm, but the relative contribution of its type 1 (AT1) and type 2 (AT2) receptors remains unknown. We show that loss of AT2 expression accelerates the aberrant growth and rupture of the aorta in a mouse model of Marfan syndrome (MFS). The selective AT1 receptor blocker (ARB) losartan abrogated aneurysm progression in the mice; full protection required intact AT2 signaling. The angiotensin-converting enzyme inhibitor (ACEi) enalapril, which limits signaling through both receptors, was less effective. Both drugs attenuated canonical transforming growth factor—β (TGFβ) signaling in the aorta, but losartan uniquely inhibited TGFβ-mediated activation of extracellular signal—regulated kinase (ERK), by allowing continued signaling through AT2. These data highlight the protective nature of AT2 signaling and potentially inform the choice of therapies in MFS and related disorders.

Bart Loeys and colleagues identify mutations or deletions of TGFB2 in individuals with thoracic aortic aneurysm and other features of Loeys-Dietz syndrome. TGFB2 encodes the transforming growth factor-β2 ligand. Loeys-Dietz syndrome (LDS) associates with a tissue signature for high transforming growth factor (TGF)-β signaling but is often caused by heterozygous mutations in genes encoding positive effectors of TGF-β signaling, including either subunit of the TGF-β receptor or SMAD3, thereby engendering controversy regarding the mechanism of disease. Here, we report heterozygous mutations or deletions in the gene encoding the TGF-β2 ligand for a phenotype within the LDS spectrum and show upregulation of TGF-β signaling in aortic tissue from affected individuals. Furthermore, haploinsufficient Tgfb2 +/− mice have aortic root aneurysm and biochemical evidence of increased canonical and noncanonical TGF-β signaling. Mice that harbor both a mutant Marfan syndrome (MFS) allele ( Fbn1 C1039G/+ ) and Tgfb2 haploinsufficiency show increased TGF-β signaling and phenotypic worsening in association with normalization of TGF-β2 expression and high expression of TGF-β1. Taken together, these data support the hypothesis that compensatory autocrine and/or paracrine events contribute to the pathogenesis of TGF-β–mediated vasculopathies.

Background Polyphyllins are significant medicinal compounds found in Paris species, with different polyphyllins fulfilling distinct medicinal roles. Although some genes involved in polyphyllin synthesis have been identified, further exploration of the genes in the polyphyllin synthesis pathway is necessary due to the extensive genome of Paris species. The content and composition of polyphyllins vary among different Paris species, and the variations in specific polyphyllin levels across these plants make them promising candidates for identifying metabolites and genes associated with the biosynthesis of specific polyphyllins. Results In this study, we investigate the global metabolic and transcriptomic profiles of three types of Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz, one Paris fargesii Franch, and one Paris forrestii (Takht.) H. Li. The rhizome of P. polyphylla is rich in polyphyllin I and II, while P. forrestii is abundant in polyphyllin III, and P. fargesii contains high levels of polyphyllin VI, VII and H. The three Paris species exhibit distinct metabolomic and transcriptomic profiles. Through an integrated analysis of metabolic and transcriptomic data, along with a phylogenetic analysis of genes related to polyphyllin synthesis in Pari s, we annotated a total of six 2,3-oxidosqualene cyclases (OSCs), 120 cytochrome P450s (CYPs), and 138 UDP glycosyltransferases (UGTs). Phylogenetic tree analysis of the obtained data assisted in refining the candidate gene pool for OSC , CYP , and UGT . Subsequently, we identified 6, 12, and 26 candidate genes for OSC , CYP , and UGT , respectively. Finally, by combining the analyses of metabolic and genetic differences, we identified a total of 17 candidate genes, including 2 CAS , 4 CYP , and 11 UGT . Conclusions P. fargesii and P. forrestii are candidate medicinal plants for the development and application of specific polyphyllins. Transcripts from the UGT91 subfamily in Paris may play dual roles, contributing to both the synthesis of polyphyllin II and the catabolism of polyphyllin V and VI. The homologous genes of PpUGT73CE1 may regulate the synthesis of polyphyllin VI in P. fargesii . This study provides new insights into the investigation of biosynthetic pathways in medicinal plants that lack gene clusters.

Green Stormwater Infrastructure (GSI), as a nature-based solution, has gained widespread recognition for its role in mitigating urban flood risks and enhancing resilience. Equitable spatial distribution of GSI remains a pressing challenge, critical to harmonizing urban hydrological systems and maintaining ecological balance. However, the complexity of matching GSI supply with urban demand has limited comprehensive spatial assessments. This study introduces a quantitative framework to identify priority zones for GSI deployment and to evaluate supply–demand dynamics in the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) using a coupled coordination simulation model. Clustering and proximity matrix analysis were applied to map spatial relationships across districts and to reveal underlying mismatches. Findings demonstrate significant spatial heterogeneity: over 90% of districts show imbalanced supply–demand coupling. Four spatial clusters were identified based on levels of GSI disparity. Economically advanced urban areas such as Guangzhou and Shenzhen showed high demand, while peripheral regions like Zhaoqing and Huizhou were characterized by oversupply and misaligned allocation. These results provide a systematic understanding of GSI distribution patterns, highlight priority intervention areas, and offer practical guidance for large-scale, equitable GSI planning.

The Zhu III Depression, situated in the northern Pearl River Mouth Basin, features a complex fault system composed of NE–SW-, nearly E–W-, and NW–SE-oriented faults. However, there is limited research on NW-trending faults, especially regarding their formation mechanisms. Through structural analysis of 3D seismic profiles, we have revealed the geometric and kinematic characteristics of NW-trending faults and categorized them into three types based on their formation mechanisms: extensional fault, dextral transtensional fault, and sinistral strike–slip fault. The extensional faults predominantly developed as boundary faults during the rifting I period, caused by tectonic inversion of the NW–NWW-trending basement faults since early Eocene. The transtensional fault resulted from the dextral strike–slip motion of the NE-trending basin-controlling faults since late Eocene, under the regional dextral extension stress setting. The sinistral strike–slip faults have been dominant during the post-rifting period since early Oligocene. This is due to the sinistral shearing action related to the southeastward lateral extrusion of the Indochina Block and slab pull southward by subduction of the proto-SCS. The NW-trending faults controlled the development of local tectonics and structures, the depocenter migration during the rifting period, and the trapping, migration, and preservation of oil and gas.

Background: While the exact mechanisms are not fully understood, there are significant links between sleep quality, anxiety, depressive symptoms, and cognitive emotion regulation. This research examines how sleep quality affects anxiety and depressive symptoms, as well as the potential of cognitive emotion regulation strategies (CERS) to moderate the impact of sleep quality on these symptoms. Methods: The Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), the Cognitive Emotion Regulation Questionnaire (CERQ), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder Scale-7 (GAD-7) were all completed online by students from two colleges in China’s Xizang region. Results: The study included 4325 subjects. The prevalence of poor sleep quality, anxiety symptoms, and depression symptoms was 45.69%, 36.81%, and 51.86%, respectively. We observed significant direct effects on poor sleep and severity of anxiety/depression: c’1 = 0.586 (0. 544–0.628), and c’2 = 0.728 (0.683–0.773). Adaptive CERS only had a mediating effect on the relationship between sleep quality and depression symptoms, with a1b3 = −0.005 (−0.011–−0.001). The link between poor sleep quality and the intensity of anxiety and depression was significantly affected by the indirect effects of maladaptive CERS: effect a2b2 = 0.126 (0.106–0.147), and effect a2b4 = 0.145 (0.123–0.167). Conclusions: Individuals who experience poor sleep quality are more likely to have increased levels of anxiety and depression. However, enhancing sleep quality led to a decrease in anxiety and depression levels. Adaptive CERS did not predict anxiety, but they did predict depression. Multiple maladaptive CERS could increase levels of anxiety and depression. To prevent mental stress, it is crucial to examine sleep problems among college students, understand their cognitive strategies, promote the adoption of adaptive CERS, and reduce the reliance on maladaptive CERS.

Bawei Chenxiang Wan (BCW), a well-known traditional Chinese Tibetan medicine formula, is effective for the treatment of acute and chronic cardiovascular diseases. In the present study, we investigated the effect of BCW in cardiac hypertrophy and underlying mechanisms. The dose of 0.2, 0.4, and 0.8 g/kg BCW treated cardiac hypertrophy in SD rat model induced by isoprenaline (ISO). Our results showed that BCW (0.4 g/kg) could repress cardiac hypertrophy, indicated by macro morphology, heart weight to body weight ratio (HW/BW), left ventricle heart weight to body weight ratio (LVW/BW), hypertrophy markers, heart function, pathological structure, cross-sectional area (CSA) of myocardial cells, and the myocardial enzymes. Furthermore, we declared the mechanism of BCW anti-hypertrophy effect was associated with activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator–activated receptor-α (PPAR-α) signals, which regulate carnitine palmitoyltransferase1β (CPT-1β) and glucose transport-4 (GLUT-4) to ameliorate glycolipid metabolism. Moreover, BCW also elevated mitochondrial DNA-encoded genes of NADH dehydrogenase subunit 1 (ND1 ), cytochrome b ( Cytb ), and mitochondrially encoded cytochrome coxidase I ( mt-co1 ) expression, which was associated with mitochondria function and oxidative phosphorylation. Subsequently, knocking down AMPK by siRNA significantly can reverse the anti-hypertrophy effect of BCW indicated by hypertrophy markers and cell surface of cardiomyocytes. In conclusion, BCW prevents ISO-induced cardiomyocyte hypertrophy by activating AMPK/PPAR-α to alleviate the disturbance in energy metabolism. Therefore, BCW can be used as an alternative drug for the treatment of cardiac hypertrophy.

IntroductionNewcastle disease virus (NDV) is prevalent worldwide with an extensive host range. Among birds infected with velogenic NDV strains, chickens experience high pathogenicity and mortality, whereas ducks mostly experience mild symptoms or are asymptomatic. Ducks have a unique, innate immune system hypothesized to induce antiviral responses. Circular RNAs (circRNAs) are among the most abundant and conserved eukaryotic transcripts. These participate in innate immunity and host antiviral response progression.MethodsIn this study, circRNA expression profile differences post-NDV infection in duck embryo fibroblast (DEF) cells were analyzed using circRNA transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to reveal significant enrichment of differentially expressed (DE) circRNAs. The circRNA-miRNA-mRNA interaction networks were used to predict the related functions of circRNAs. Moreover, circ-FBXW7 was selected to determine its effect on NDV infection in DEFs.ResultsNDV infection altered circRNA expression profiles in DEF cells, and 57 significantly differentially expressed circRNAs were identified post-NDV infection. DEF responded to NDV by forming circRNAs to regulate apoptosis-, cell growth-, and protein degradation-related pathways via GO and KEGG enrichment analyses. circRNA-miRNA-mRNA interaction networks demonstrated that DEF cells combat NDV infection by regulating cellular pathways or apoptosis through circRNA-targeted mRNAs and miRNAs. circ-FBXW7 overexpression and knockdown inhibited and promoted viral replication, respectively. DEF cells mainly regulated cell cycle alterations or altered cellular sensing to combat NDV infection.ConclusionThese results demonstrate that DEF cells exert antiviral responses by forming circRNAs, providing novel insights into waterfowl antiviral responses.