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The aim of this study was to develop a novel antidepressant with high activity. Based on the findings of molecular docking, eight novel curcumin analogues were evaluated in vitro to check for antidepressant efficacy. Among them, CACN136 had the strongest antidepressant effect. Firstly, CACN136 had a stronger 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) radical ion scavenging ability (IC 50 : 17.500 ± 0.267 μg/mL) compared to ascorbic acid (IC 50 : 38.858 ± 0.263 μg/mL) and curcumin (27.189 ± 0.192 μg/mL). Secondly, only CACN136 demonstrated clear protective effects on cells damaged by glutamate and oxidative stress at all concentrations. Finally, only CACN136 showed ASP + inhibition and was more effective than fluoxetine hydrochloride (FLU) at low concentrations. To further confirm the antidepressant effect of CACN136 in vivo, the CUMS model was established. Following 28 days of oral administration of CUMS mice, CACN136 increased the central area residence time in the open-field test, significantly increased the sucrose preference rate in the sucrose preference test (P < 0.001) and significantly reduced the immobility period in the tail suspension test (P < 0.0001), all of which were more effective than those of FLU. Subsequent research indicated that the antidepressant properties of CACN136 were linked to a decrease in the metabolism of 5-HT and the modulation of oxidative stress levels in vivo. In particular, the activation of the Keap1-Nrf2/BDNF-TrkB signaling pathway by CACN136 resulted in elevated levels of antioxidant enzymes, enhancing the antioxidant capability in mice subjected to CUMS. In conclusion, CACN136 has the potential to treat depression and could be an effective antidepressant., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect., Methods: The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted., Results: The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC (0-t) of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the C max was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration., Conclusion: TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Sheng et al.)

There has been an increase in cardiovascular morbidity and mortality over the past few decades, making cardiovascular disease (CVD) the leading cause of death worldwide. However, the pathogenesis of CVD is multi-factorial, complex, and not fully understood. The gut microbiome has long been recognized to play a critical role in maintaining the physiological and metabolic health of the host. Recent scientific advances have provided evidence that alterations in the gut microbiome and its metabolites have a profound influence on the development and progression of CVD. Among the trillions of microorganisms in the gut, bifidobacteria, which, interestingly, were found through the literature to play a key role not only in regulating gut microbiota function and metabolism, but also in reducing classical risk factors for CVD (e.g., obesity, hyperlipidemia, diabetes) by suppressing oxidative stress, improving immunomodulation, and correcting lipid, glucose, and cholesterol metabolism. This review explores the direct and indirect effects of bifidobacteria on the development of CVD and highlights its potential therapeutic value in hypertension, atherosclerosis, myocardial infarction, and heart failure. By describing the key role of Bifidobacterium in the link between gut microbiology and CVD, we aim to provide a theoretical basis for improving the subsequent clinical applications of Bifidobacterium and for the development of Bifidobacterium nutritional products., (© 2023. The Author(s).)

Thrombotic complications in acute myeloid leukemia (AML) are uncommon due to coagulation dysfunction and thrombocytopenia. We report a unique case of AML presenting as concomitant pulmonary embolism and atypical acute myocardial infarction. A 67-year-old male experienced persistent bilateral chest pain. Despite an unremarkable electrocardiogram, elevated D-dimer and mildly increased troponin T levels prompted further investigation, leading to the diagnosis of simultaneous pulmonary embolism and acute myocardial infarction. The patient underwent percutaneous coronary intervention and received triple antithrombotic therapy. However, antithrombotic therapy was discontinued following a sharp decline in hemoglobin and platelet counts, and the patient subsequently developed persistent fever. AML was diagnosed via bone marrow biopsy. Chemotherapy was not initiated due to the patient's deteriorating condition, and he ultimately succumbed to presumed intracranial bleeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zheng, Luo, Luo, Liu, Zheng and Peng.)

Coronary artery dissection caused by trauma is a rare occurrence that can be life-threatening. Accordingly, its rapid identification and treatment are essential to improve patient outcomes. Here, we present a case of a patient who suffered multiple rib and femur fractures after falling from a height of eighteen meters and subsequently experienced persistent chest pain. After the initial diagnostic workup, the medical team diagnosed the patient's chest pain as rib fractures and failed to consider the potential of a cardiac injury as the underlying cause. No emphasis was placed on monitoring changes in myocardial enzymes and ECG, which could have indicated coronary artery dissection. The dissection was confirmed and treated with a stent only after the subsequent coronary angiography (CAG) and optical coherence tomography (OCT) examinations, gradually relieving the patient's chest pain. In this case report, we discuss the management of fractures complicated by traumatic coronary artery dissection and highlight the benefits of OCT in diagnosing and treating this condition. The case also emphasizes the importance of considering coronary artery injury in patients with chest pain due to trauma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Jiang, Qian, Wei, Cheng, Zheng and Chen.)

The quantification of the extent and dynamics of land-use changes is a key metric employed to assess the progress toward several Sustainable Development Goals (SDGs) that form part of the United Nations 2030 Sustainable Development Agenda. In terms of anthropogenic factors threatening the conservation of heritage properties, such a metric aids in the assessment of achievements toward heritage sustainability solving the problem of insufficient data availability. Therefore, in this study, 589 cultural World Heritage List (WHL) properties from 115 countries were analyzed, encompassing globally distributed and statistically significant samples of "monuments and groups of buildings" (73.2%), "sites" (19.3%), and "cultural landscapes" (7.5%). Land-cover changes in the WHL properties between 2015 and 2020 were automatically extracted from big data collections of high-resolution satellite imagery accessed via Google Earth Engine using intelligent remote sensing classification. Sustainability indexes (SIs) were estimated for the protection zones of each property, and the results were employed, for the first time, to assess the progress of each country toward SDG Target 11.4. Despite the apparent advances in SIs (10.4%), most countries either exhibited steady (20.0%) or declining (69.6%) SIs due to limited cultural investigations and enhanced negative anthropogenic disturbances. This study confirms that land-cover changes are among serious threats for heritage conservation, with heritage in some countries wherein the need to address this threat is most crucial, and the proposed spatiotemporal monitoring approach is recommended., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of their institutions., (© 2023 The Author(s).)

Terrestrial evapotranspiration (ET) refers to a key process in the hydrological cycle by which water is transferred from the Earth's surface to lower atmosphere. With spatiotemporal variations, ET plays a crucial role in the global ecosystem and affects vegetation distribution and productivity, climate, and water resources. China features a complex, diverse natural environment, leading to high spatiotemporal heterogeneity in ET and climatic variables. However, past and future ET trends in China remain largely unexplored. Thus, by using MOD16 products and meteorological datasets, this study examined the spatiotemporal variations of ET in China from 2000 to 2019 and analyzed what is behind changes, and explored future ET trends. Climate variation in China from 2000 to 2019 was statistically significant and had a remarkable impact on ET. Average annual ET increased at a rate of 5.3746 mm yr -1 (P < 0.01) during the study period. The main drivers of the trend are increasing precipitation and wind speed. The increase in ET can also be explained to some extent by increasing temperature, decreasing sunshine duration and relative humidity. The zonation results show that the increase in temperature, wind speed, and precipitation and the decrease in relative humidity had large and positive effects on ET growth, and the decrease in sunshine duration had either promoting or inhibiting effects in different agricultural regions. Pixel-based variations in ET exhibited an overall increasing trend and obvious spatial volatility. The Hurst exponent indicates that the future trend of ET in China is characterized by significant anti-persistence, with widely distributed areas expected to experience a decline in ET. These findings improve the understanding of the role of climate variability in hydrological processes, and the ET variability in question will ultimately affect the climate system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Triple antithrombotic therapy (TAT) consisting of anticoagulant and dual antiplatelet agents is a core treatment for prevention of ischemic events in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing post-percutaneous coronary intervention (PCI), however, due to bleeding risks, the optimal duration of TAT is unclear., Methods: We searched the database and conducted a network meta-analysis of randomized controlled trials (RCTs) to determine the optimal duration of TAT for patients with AF and ACS or undergoing PCI by comparing the probability of ischemic and bleeding outcomes for four different TAT durations., Results: After analyzing data from 12,329 patients, we determined that short-term TAT is advantageous to varying degrees for reducing bleeding events. While long-term TAT has a lower stent thrombosis risk than short-term TAT, the four strategies have comparable outcomes for major adverse cardiovascular events (MACE), stroke, all-cause death, and myocardial infarction events. Based on Surface Under the Cumulative Ranking (SUCRA) values, no treatment duration has an absolute advantage for reducing these ischemic events., Conclusion: Long-term TAT may be reasonable for patients at a high risk for stent thrombosis, but short-term TAT is associated with fewer bleeding complications, and there are no significant differences in most ischemic events across treatment durations. Overall, our results indicate that short-term TAT should be the default strategy unless there is a high risk of stent thrombosis that warrants appropriate prolongation of TAT duration., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To explore the efficacy of community-family management mode under Internet-based mobile terminal (MT) monitoring in stable coronary heart disease (CHD) in the elderly., Methods: A total of 86 patients with stable CHD treated in our hospital from May 2018 to May 2021 were selected as the study objects for the retrospective study and were divided into the control group (routine intervention) and the research group (community-family management mode intervention under Internet MT monitoring) according to the health management modes, with 43 cases each, and the health behaviors and control of CHD were compared between the two groups., Results: No statistical between-group differences in general information were observed ( P > 0.05); 6 months after intervention, the control of laboratory indexes including blood pressure, blood glucose, triglyceride, and total cholesterol in patients was obviously better in the research group than in the control group ( P > 0.05); after intervention, the scores on rehabilitation knowledge level and secondary prevention behavior were obviously higher in the research group than in the control group ( P > 0.05); 6 months after intervention, the scores on physical limitation, anginal stabilization, anginal frequency, disease perception, and treatment satisfaction were obviously higher in the research group than in the control group ( P > 0.05); compared with the control group within 1 year of intervention, the readmission rate of the research group was significantly lower ( P > 0.05); and compared with the control group, the total score of CQQC and scores on physical strength, condition, general life, and social mentality were significantly better in the research group ( P > 0.05)., Conclusion: Community-family management mode under Internet-based MT monitoring is the valid continuation of clinical nursing for elderly patients with stable CHD, which plays an effective role in terms of daily monitoring indexes, stabilizing condition, improving disease cognition, reducing the readmission rate, and improving the prognostic quality of life of patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xiang Li et al.)

Accurate estimation of ground elevation on a large scale is essential and worthwhile in topography, geomorphology, and ecology. The Ice, Cloud and Land Elevation Satellite-2 (ICESat-2) mission, launched in September 2018, offers an opportunity to obtain global elevation data over the earth's surface. This paper aimed to evaluate the performance of ICESat-2 data for ground elevation retrieval. To fulfill this objective, our study first tested the availability of existing noise removal and ground photon identification algorithms on ICESat-2 data. Second, the accuracy of ground elevation data retrieved from ICESat-2 data was validated using airborne LiDAR data. Finally, we explored the influence of various factors (e.g., the signal-to-noise ratio (SNR), slope, vegetation height and vegetation cover) on the estimation accuracy of ground elevation over forest, tundra and bare land areas in interior Alaska. The results indicate that the existing noise removal and ground photon identification algorithms for simulated ICESat-2 data also work well for ICESat-2 data. The overall mean difference and RMSE values between the ground elevations retrieved from the ICESat-2 data and the airborne LiDAR-derived ground elevations are -0.61 m and 1.96 m, respectively. In forest, tundra and bare land scenarios, the mean differences are -0.64 m, -0.61 m and -0.59 m, with RMSE values of 1.89 m, 2.05 m, and 1.76 m, respectively. By analyzing the influence of four error factors on the elevation accuracy, we found that the slope is the most important factor affecting the accuracy of ICESat-2 elevation data. The elevation errors increase rapidly with increasing slope, especially when the slope is greater than 20°. The elevation errors decrease with increasing SNR, but this decrease varies little once the SNR is greater than 10. In forest and tundra areas, the errors in the ground elevation also increase with increasing vegetation height and the amount of vegetation cover.

A simple and sensitive LC-UV method to investigate the pharmacokinetics and biodistribution pattern of baicalin in rabbits was established and validated. Baicalin and the internal standard, rutin, were extracted from biosamples using acetonitrile as protein precipitation after pretreated with ammonium acetate buffer (pH 3.5; 1 M) to obtain a pure chromatographic peak and high extraction recovery. Chromatographic separation was achieved on a reverse-phase C18 column with a gradient elution at flow rate of 1.0 mL/min. UV absorption was set at 278 nm. Chromatographic response was linear over the ranges of 0.05-10.00 μg/mL in plasma and 0.05-300.00 μg/g in tissues with the limits of quantification of 50.0 ng/mL in plasma and tissues, and the limit of detection of baicalin in bio-samples of 15 ng/mL. The RSD of intra-and inter-day for the biosamples were from 4.19% to 10.84% and from 4.37% to 10.93%, respectively. The accuracy of plasma and tissue samples ranged from 81.6% to 95.2% and 80.8% to 98.4%, respectively. The extraction recoveries ranged from 81.5% to 88.3% for plasma, from 73.1% to 93.2% for tissues, respectively. Baicalin was stable in rabbit biosamples. The validated method was successfully applied to the study of the pharmacokinetics and tissue distribution of baicalin after intravenous administration of liposomal and injectable formulations to rabbits. Compared to baicalin injection, the pharmacokinetics and biodistribution behavior of baicalin was altered significantly in rabbits treated with its liposomes and drug concentration in the lungs was greatly increased.

Macrophages and vascular smooth muscle cells (VSMCs) are the major cell types involved in foam cell formation associated with atherosclerosis. The aim of this experiment was to clarify cell-specific regulation of LDL receptor in THP-1 macrophages and human VSMCs under physiological and inflammatory conditions and its potential mechanisms. Inflammatory stress was induced by adding lipopolysaccharide (LPS) to human THP-1 macrophages and human VSMCs. Intracellular total cholesterol, free cholesterol, and cholesterol ester were measured by an enzymic assay. Oil Red O staining was used to visualize lipid droplet accumulation in cells. Total cellular RNA was isolated from cells for detecting LDL receptor, sterol regulatory element binding protein (SREBP)-2 and SREBP cleavage-activating protein (SCAP) mRNA levels using real-time quantitative polymerase chain reaction. LDL receptor, SREBP-2 and SCAP protein expression were examined by Western blotting. The translocation of SCAP from ER to Golgi was detected by confocal microscopy. LDL loading increased intracellular cholesterol level, reducing LDL receptor mRNA level in both THP-1 macrophages and VSMCs under physiological conditions. The IC50 in VSMCs was 11.25 μg/ml, which is much lower than 18.125 μg/ml in THP-1 macrophages. With the increase in concentration of LPS (0-400 ng/ml), the LDL receptor mRNA levels were upregulated in both cells, but the curve of LDL receptor mRNA in VSMCs exhibited a flatter profile than that of THP-1 macrophages. Under the treatment of 200 ng/ml of LPS, the upregulation fold of the LDL receptor mRNA in THP-1 macrophages was much higher than that of VSMCs (0.33 vs 0.04). LDL receptor blocking agent heparin decreased lipid droplets induced by LPS significantly in THP-1 macrophages and VSMCs. LDL loading reduced the SREBP2 and SCAP protein expression under physiological conditions. Exposure to LPS caused overexpression of SREBP2 and SCAP despite a high concentration of LDL in the culture medium, and increased translocation of SCAP from the ER to the Golgi in the presence of 25 μg/ml of LDL. Inflammatory stress disrupts LDL receptor negative feedback regulation induced by intracellular cholesterol in both cell types, to a greater degree in THP-1 macrophages, which could be one reason why THP-1 macrophages are more prone to become foam cells under inflammatory stress.