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The present study aimed to determine the effects of Tianxiangdan Granule on nuclear factor (NF)-κB p65 and p38 mitogen-activated protein kinase (MAPK) inflammatory signaling pathways, and explored the possible mechanism underlying the effects of Tianxiangdan Granule on prevention and treatment of atherosclerosis. A total of 48 apolipoprotein E-/- mice (age, 8 weeks) were selected and divided into two groups: The normal control group (n=12) and the modeling group (n=36). In the modeling group, mice were fed a high-fat diet and were maintained in an artificial climate box, in order to stimulate the climate and eating habit characteristics of Xinjiang. Every morning, ApoE-/- mice in the modeling group were placed in the artificial climate box at 10:00 am and were taken out at 09:00 pm and placed back in the room temperature environment. The temperature of the artificial climate box was set at 6±2°C, relative humidity was controlled at 25-32.8% and the light-dark cycle was 12 h/day. The purpose of this method was to establish the Huizhuo Tanzu type atherosclerosis model. Following successful generation of the model, mice in the modeling group were randomly divided into three groups: Model group (n=10), Tianxiangdan group (n=10) and atorvastatin group (n=10). After 12 weeks, mice were sacrificed and the serum levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in each group were detected. Furthermore, the expression levels of NF-κB p65 and p38 MAPK in aortic tissue were detected. The results indicated that the concentrations of IL-1β and TNF-α were significantly higher in mice in the model group compared with in the normal control group (P<0.01), whereas the concentrations of IL-1β and TNF-α were lower in the Tianxiangdan and atorvastatin groups compared with in the model group (P<0.01). Furthermore, the protein expression levels of phosphorylated (p)-NF-κB p65 and p-p38 MAPK protein were higher in aortic tissues from the model group compared with in the normal control group (P<0.01), p-NF-κB p65 and p-p38 MAPK protein expression was reduced in the atorvastatin and Tianxiangdan groups compared with in the model group. The present study indicated that the mechanism underlying the effects of Tianxiangdan Granule on the prevention and treatment of atherosclerosis may be as follows: Tianxiangdan Granule may decrease the expression of the inflammatory cytokines IL-1β and TNF-α, and suppress activation of the NF-κB p65 and p38 MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

Motivation Promoters with desirable properties are crucial in biotechnological applications. Generative AI (GenAI) has demonstrated potential in creating novel synthetic promoters with significantly enhanced functionality. However, these methods' reliance on various programming frameworks and specific task-oriented contexts limits their flexibilities. Overcoming these limitations is essential for researchers to fully leverage the power of GenAI to design promoters for their tasks. Results Here, we introduce GPro (Generative AI-empowered toolkit for promoter design), a user-friendly toolkit that integrates a collection of cutting-edge GenAI-empowered approaches for promoter design. This toolkit provides a standardized pipeline covering essential promoter design processes, including training, optimization, and evaluation. Several detailed demos are provided to reproduce state-of-the-art promoter design pipelines. GPro's user-friendly interface makes it accessible to a wide range of users including non-AI experts. It also offers a variety of optional algorithms for each design process, and gives users the flexibility to compare methods and create customized pipelines. Availability and implementation GPro is released as an open-source software under the MIT license. The source code for GPro is available on GitHub for Linux, macOS, and Windows: https://github.com/WangLabTHU/GPro , and is available for download via Zenodo repository at https://zenodo.org/doi/10.5281/zenodo.10681733. [ABSTRACT FROM AUTHOR]

Background: Respiratory variation in the internal jugular vein (IJVV) has not shown promising results in predicting volume responsiveness in ventilated patients with low tidal volume (Vt) in prone position. We aimed to determine whether the baseline respiratory variation in the IJVV value measured by ultrasound might predict fluid responsiveness in patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF) with low Vt. Methods: According to the fluid responsiveness results, the included patients were divided into two groups: those who responded to volume expansion, denoted the responder group, and those who did not respond, denoted the non-responder group. The primary outcome was determination of the value of baseline IJVV in predicting fluid responsiveness (≥15% increases in stroke volume index (SVI) after 7 ml·kg-1 colloid administration) in patients with AIS undergoing PSF during low Vt ventilation. Secondary outcomes were estimation of the diagnostic performance of pulse pressure variation (PPV), stroke volume variation (SVV), and the combination of IJVV and PPV in predicting fluid responsiveness in this surgical setting. The ability of each parameter to predict fluid responsiveness was assessed using a receiver operating characteristic curve. Results: Fifty-six patients were included, 36 (64.29%) of whom were deemed fluid responsive. No significant difference in baseline IJVV was found between responders and non-responders (25.89% vs. 23.66%, p = 0.73), and no correlation was detected between baseline IJVV and the increase in SVI after volume expansion (r = 0.14, p = 0.40). A baseline IJVV greater than 32.00%, SVV greater than 14.30%, PPV greater than 11.00%, and a combination of IJVV and PPV greater than 64.00% had utility in identifying fluid responsiveness, with a sensitivity of 33.33%, 77.78%, 55.56%, and 55.56%, respectively, and a specificity of 80.00%, 50.00%, 65.00%, and 65.00%, respectively. The area under the receiver operating characteristic curve for the baseline values of IJVV, SVV, PPV, and the combination of IJVV and PPV was 0.52 (95% CI, 0.38–0.65, p=0.83), 0.54 (95% CI, 0.40–0.67, p=0.67), 0.58 (95% CI, 0.45–0.71, p=0.31), and 0.57 (95% CI, 0.43–0.71, p=0.37), respectively. Conclusions: Ultrasonic-derived IJVV lacked accuracy in predicting fluid responsiveness in patients with AIS undergoing PSF during low Vt ventilation. In addition, the baseline values of PPV, SVV, and the combination of IJVV and PPV did not predict fluid responsiveness in this surgical setting. Trail registration: This trial was registered at www.chictr.org (ChiCTR2200064947) on 24/10/2022. All data were collected through chart review. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. Heat shock protein 90 alpha family class B member 1 (HSP90AB1) is highly expressed in a variety of cancers and is associated with poor prognosis, however, its role in HNSCC is still poorly understood. This study aimed to explore the function HSP90AB1 played in HNSCC progression. Methods: The expression level of HSP90AB1 in HNSCC was analyzed by bioinformatics analysis and western blotting, and its relationship with clinicopathological parameters was analyzed by bioinformatics analysis and immunohistochemistry. Three stable HSP90AB1 knockdown HNSCC cell lines were constructed by lentiviral transfection. The effect of HSP90AB1 knockdown on the proliferation and migration of HNSCC cells was tested by CCK-8 assay, EdU incorporation assay, colony formation assay, nude mouse xenograft models, transwell migration assay, wound healing assay, and western blotting. The effect of HSP90AB1 knockdown on glycolysis in HNSCC cells was assessed by quantitative real-time PCR and related assay kits. Finally, the levels of Akt and phospho-Akt (Ser473) proteins after HSP90AB1 knockdown were detected by western blotting. Results: HSP90AB1 was highly expressed in HNSCC and associated with T grade, lymph node metastasis, and prognosis. Knockdown of HSP90AB1 inhibited the proliferation, migration, and glycolysis of HNSCC, and reduced the level of phospho-Akt. Conclusion: HSP90AB1 functions as an oncogene in HNSCC, and has the potential to become a prognostic factor and therapeutic target. [ABSTRACT FROM AUTHOR]

Saussurea involucrata has been reported to have potential therapeutic effects against myocardial ischemia. The pharmacological effects of oral natural medicines may be influenced by the participation of gut microbiota. In this study, we aimed to investigate the bidirectional regulation of gut microbiota and the main components of Saussurea involucrata. We first established a quantitative method for the four main components (chlorogenic acid, syringin, acanthoside B, rutin) which were chosen by fingerprint using liquid chromatography tandem mass spectrometry (LC-MS/MS), and found that gut microbiota has a strong metabolic effect on them. Meanwhile, we identified five major rat gut microbiota metabolites (M1–M5) using liquid chromatography tandem time-of-flight mass spectrometry (LC/MSn-IT-TOF). The metabolic properties of metabolites in vitro were preliminarily elucidated by LC-MS/MS for the first time. These five metabolites of Saussurea involucrata may all have potential contributions to the treatment of myocardial ischemia. Furthermore, the four main components (10 μg/mL) can significantly stimulate intestinal bacteria to produce short chain fatty acids in vitro, respectively, which can further contribute to the effect in myocardial ischemia. In this study, the therapeutic effect against myocardial ischemia of Saussurea involucrata was first reported to be related to the intestinal flora, which can be useful in understanding the effective substances of Saussurea involucrata. [ABSTRACT FROM AUTHOR]

Quercetin is a plant-derived polyphenol flavonoid that has been proven to be effective for many diseases. However, the mechanism and in vivo metabolism of quercetin remains to be clarified. It achieves a wide range of biological effects through various metabolites, gut microbiota and its metabolites, systemic mediators produced by inflammation and oxidation, as well as by multiple mechanisms. The all-round disease treatment of quercetin is achieved through the organic combination of multiple channels. Therefore, this article clarifies the metabolic process of quercetin in the body, and explores the new pattern of action of quercetin in the treatment of diseases. [ABSTRACT FROM AUTHOR]

The stepwise chemical reduction of a molecular warped nanographene (WNG) having a negatively curved π‐surface and defined C80H30 composition with Cs metal used as the reducing and complexing agent allowed the isolation of three different reduced states with one, two, and three electrons added to its π‐conjugated system. This provided a unique series of nanosized carbanions with increasing negative charge for in‐depth structural analysis of consequences of controlled electron charging of non‐planar nanographenes, using X‐ray crystallographic and computational tools. The 3D molecular electrostatic potential (MEP) maps identified the negative charge localization at the central part of the WNG surface where selective coordination of Cs+ ions is confirmed crystallographically. In‐depth theoretical investigation revealed a complex response of the WNG to the stepwise electron acquisition. The extended and contorted π‐surface of the WNG undergoes subtle swinging distortions that are accompanied by notable changes in the electronic structure and site‐dependent aromaticity of the resulting carbanions. [ABSTRACT FROM AUTHOR]

The t-DLBCL patients are generally regarded to experience a poor prognosis. However, there is little consensus to guide optimal management strategies for such patients group. The present study aimed to explore the incidence of transformation and the prognosis factors for t-DLBCL patients, thereby providing insights for clinical choices. We retrospectively investigated 46 patients with diffuse large B-cell lymphomas (DLBCL) associated with an indolent small B-cell non-Hodgkin lymphoma (iNHL) from January 2007 to June 2017 in our department. In multivariate analysis, bone marrow (BM) involvement and low level of high-density lipoprotein cholesterol (HDL-C) were considered as two negatively and independently prognostic factors for overall survival (OS) (BM: p=0.007, HR 7.475, 95%CI: 1.744-32.028; HDL-C: p=0.032, HR10.037, 95%CI: 1.226-82.162). International Prognostic Index (IPI) risk group was identified as a single independent prognostic factor of progression-free survival (PFS) (p=0.048, HR 2.895, 95%CI: 1.010-8.297). A novel prognostic scoring system named BH model (BH stands for the intertwined initials of BM situation and the level of HDL-C) was further developed to stratify these patients into two risk groups, which performed well. Combining the BH scoring model and IPI scoring system could better predict the outcomes of these patients. [ABSTRACT FROM AUTHOR]

This paper uses a VAR model to empirically analyze the impact of economic growth, financial development, and urbanization on carbon emissions of the ASEAN countries from 2000 to 2013. The empirical results show that economic growth and carbon emissions, and financial development and carbon emissions have unidirectional Granger causality relationships. Economic growth and urbanization will increase carbon emissions, while financial development will reduce carbon emissions during the initial stage but have little impact on carbon emissions over the long term. Economic growth and urbanization are the main variables to forecast the degree of variance of carbon emissions, while financial development is the least important variable to forecast the degree of variance of carbon emissions. Finally, this study puts forward policy suggestions on improving environmental quality as economic growth, financial development and urbanization occur. [ABSTRACT FROM AUTHOR]

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Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1–M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future. [ABSTRACT FROM AUTHOR]