Chemical Design of Activatable Photoacoustic Probes for Precise Biomedical Applications.

Photoacoustic (PA) imaging technology, a three-dimensional hybrid imaging modality that integrates the advantage of optical and acoustic imaging, has great application prospects in molecular imaging due to its high imaging depth and resolution. To endow PA imaging with the ability for real-time molecular visualization and precise biomedical diagnosis, numerous activatable molecular PA probes which can specifically alter their PA intensities upon reacting with the targets or biological events of interest have been developed. This review highlights the recent developments of activatable PA probes for precise biomedical applications including molecular detection of the biotargets and imaging of the biological events. First, the generation mechanism of PA signals will be given, followed by a brief introduction to contrast agents used for PA probe design. Then we will particularly summarize the general design principles for the alteration of PA signals and activatable strategies for developing precise PA probes. Furthermore, we will give a detailed discussion of activatable PA probes in molecular detection and biomedical imaging applications in living systems. At last, the current challenges and outlooks of future PA probes will be discussed. We hope that this review will stimulate new ideas to explore the potentials of activatable PA probes for precise biomedical applications in the future.

"Four-In-One" Design of a Hemicyanine-Based Modular Scaffold for High-Contrast Activatable Molecular Afterglow Imaging.

Afterglow luminescence (long persistent luminescence) holds great potential for nonbackground molecular imaging. However, current afterglow probes are mainly nanoparticles, and afterglow imaging systems based on organic small molecules are still lacking and have rarely been reported. Moreover, the lack of reactive sites and a universal molecular scaffold makes it difficult to design activatable afterglow probes. To address these issues, this study reports a novel kind of hemicyanine-based molecule scaffolds with stimuli-responsive afterglow luminescence, which is dependent on an intramolecular cascade photoreaction between 1O2 and the afterglow molecule to store the photoenergy for delayed luminescence after light cessation. As a proof of concept, three modular activatable molecular afterglow probes (MAPs) with a "four-in-one" molecular design by integrating a stimuli-responsive unit, 1O2-generating unit, 1O2-capturing unit, and luminescent unit into one probe are customized for quantification and imaging of targets including pH, superoxide anions, and aminopeptidase. Notably, MAPs show higher sensitivity in afterglow imaging than in fluorescence imaging because the responsive unit simultaneously controls the initiation of fluorescence (S1 to S0) and 1O2 generation (S1 to T1). Finally, MAPs are applied for high-contrast afterglow imaging of drug-induced hepatotoxicity, which is poorly evaluated in clinics and drug discovery. By reporting the sequential occurrence of oxidative stress and upregulation of aminopeptidase, such activatable afterglow probes allow noninvasive imaging of hepatotoxicity earlier than the serological and histology manifestation, indicating their promise for early diagnosis of hepatotoxicity.

Exercise for myocardial ischemia-reperfusion injury: A systematic review and meta-analysis based on preclinical studies.

The main pathological manifestation of coronary artery disease is myocardial injury caused by ischemia-reperfusion (IR) injury. Regular exercise reduces the risk of death during myocardial IR injury. The aim of this study was to describe the effects of various types of exercise on myocardial IR injury. Four electronic databases PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched from inception until February 2022, to identify studies relevant to the current review, using the method of combining subject and free words. Finally, 16 articles were included in the meta-analysis. Results showed that exercise training decreases the Myocardial infarct size compared to the control group (SMD = -2.6, 95 % CI [-3.53 to -1.67], P < 0.01); increasing the coronary blood flow (MD = 2.93, 95 % CI [2.41 to 3.44], P < 0.01), left ventricular developed pressure (SMD = 2.28, 95 % CI [0.12 to 4.43], P < 0.05), cardiac output (SMD = 1.22, 95 % CI [0.61 to 1.83], P < 0.01) compared to the control group. According to the descriptive analysis results also showed that exercise training increases the left ventricular ejection fraction, superoxide dismutase, manganese superoxide dismutase, glutathione peroxidase, copper-zinc superoxide dismutase, glutathione peroxidase, and decrease the creatine kinase, creatine kinase-MB, lactate dehydrogenase, Malondialdehyde, cardiac troponins T. Exercise can improve myocardial function after myocardial IR injury; however, further research is needed in combination with specific issues such as exercise mode, intensity, duration, and model issues.

Crosstalk between the Gut and Brain in Ischemic Stroke: Mechanistic Insights and Therapeutic Options.

There has been a significant amount of interest in the past two decades in the study of the evolution of the gut microbiota, its internal and external impacts on the gut, and risk factors for cerebrovascular disorders such as cerebral ischemic stroke. The network of bidirectional communication between gut microorganisms and their host is known as the microbiota-gut-brain axis (MGBA). There is mounting evidence that maintaining gut microbiota homeostasis can frequently enhance the effectiveness of ischemic stroke treatment by modulating immune, metabolic, and inflammatory responses through MGBA. To effectively monitor and cure ischemic stroke, restoring a healthy microbial ecology in the gut may be a critical therapeutic focus. This review highlights mechanistic insights on the MGBA in disease pathophysiology. This review summarizes the role of MGBA signaling in the development of stroke risk factors such as aging, hypertension, obesity, diabetes, and atherosclerosis, as well as changes in the microbiota in experimental or clinical populations. In addition, this review also examines dietary changes, the administration of probiotics and prebiotics, and fecal microbiota transplantation as treatment options for ischemic stroke as potential health benefits. It will become more apparent how the MGBA affects human health and disease with continuing advancements in this emerging field of biomedical sciences.

Precipitated Fluorophore-Based Molecular Probe for In Situ Imaging of Aminopeptidase N in Living Cells and Tumors.

Aminopeptidase N (APN) is capable of cleaving N-terminal amino acids from peptides with alanine in the N-terminal position and plays a key role in the growth, migration, and metastasis of cancer. However, reliable in situ information is hard to be obtained with the current APN-responsive molecular probes because the released fluorophores are cytoplasmic soluble and thus rapidly depart from the enzymatic reaction sites and spread out all over the cytoplasm. Here, we report a de novo precipitated fluorophore, HBPQ, which is completely insoluble in water and shows strong yellow solid emission when excited with a 405 nm laser. Owing to the controllable solid fluorescence of HBPQ by the protection-deprotection of phenolic hydroxyl, we further utilized HBPQ to design an APN-responsive fluorogenic probe (HBPQ-A) for the imaging of intracellular APN. Importantly, HBPQ-A can not only perform in situ imaging of APN in different organelles (e.g., lysosomes, mitochondria, endoplasmic reticula, and so forth) but also display a stable and indiffusible fluorescent signal for reliable mapping of the distribution of APN in living cells. In addition, through real-time imaging of APN in 4T1 tumors, we found that the fluorescent signal with high fidelity generated by HBPQ-A could remain constant even after 12 h, which further confirmed its diffusion-resistant ability and long-term reliable imaging ability. We believe that the precipitated fluorophore may have great potential for long-term in situ imaging.

Reactive Oxygen Correlated Chemiluminescent Imaging of a Semiconducting Polymer Nanoplatform for Monitoring Chemodynamic Therapy.

In chemodynamic therapy (CDT), real-time monitoring of reactive oxygen species (ROS) production is critical to reducing the nonspecific damage during CDT and feasibly evaluating the therapeutic response. However, CDT agents that can emit ROS-related signals are rare. Herein, we synthesize a semiconducting polymer nanoplatform (SPN) that can not only produce highly toxic ROS to kill cancer cells but also emit ROS-correlated chemiluminescent signals. Notably, the efficacy of both chemiluminescence and CDT can be significantly enhanced by hemin doping (∼10-fold enhancement for luminescent intensity). Such ROS-dependent chemiluminescence of SPN allows ROS generation within a tumor to be optically monitored during the CDT process. Importantly, SPN establishes an excellent correlation of chemiluminescence intensities with cancer inhibition rates in vitro and in vivo. Thus, our nanoplatform represents the first intelligent strategy that enables chemiluminescence-imaging-monitored CDT, which holds potential in assessing therapeutic responsivity and predicting treatment outcomes in early stages.

Smart Nanozyme Platform with Activity-Correlated Ratiometric Molecular Imaging for Predicting Therapeutic Effects.

Nanozymes with intrinsic enzyme-like characteristics have attracted enormous research interest in biological application. However, there is a lack of facile approach for evaluating the catalytic activity of nanozymes in living system. Herein, we develop a novel manganese-semiconducting polymer-based nanozyme (MSPN) with oxidase-like activity for reporting the catalytic activity of itself in acid-induced cancer therapy via ratiometric near-infrared fluorescence (NIRF)-photoacoustic (PA) molecular imaging. Notably, MSPN possess oxidase-like activity in tumor microenvironment, owing to the mixed-valent MnOx nanoparticles, which can effectively kill cancer cells. Because the semiconducting polymer (PFODBT) is conjugated with oxidase-responsive molecule (ORM), the catalytic activity of nanozyme can be correlated with the ratiometric signals of NIRF (FL695 /FL825 ) and PA (PA680 /PA780 ), which may provide new ideas for predicting anticancer efficacy of nanozymes in living system.

An Acidity-Unlocked Magnetic Nanoplatform Enables Self-Boosting ROS Generation through Upregulation of Lactate for Imaging-Guided Highly Specific Chemodynamic Therapy.

Chemodynamic therapy is an emerging tumor therapeutic strategy. However, the anticancer effects are greatly limited by the strong acidity requirements for effective Fenton-like reaction, and the inevitably "off-target" toxicity. Herein, we develop an acidity-unlocked nanoplatform (FePt@FeOx @TAM-PEG) that can accurately perform the high-efficient and tumor-specific catalysis for anticancer treatment, through dual pathway of cyclic amplification strategy. Notably, the pH-responsive peculiarity of tamoxifen (TAM) drug allows for the catalytic activity of FePt@FeOx to be "turn-on" in acidic tumor microenvironments, while keeping silence in neutral condition. Importantly, the released TAM within cancer cells is able to inhibit mitochondrial complex I, leading to the upregulated lactate content and thereby the accumulated intracellular H+ , which can overcome the intrinsically insufficient acidity of tumor. Through the positive feedback loop, large amount of active FePt@FeOx nanocatalyzers are released and able to access to the endogenous H2 O2 , exerting the improved Fenton-like reaction within the more acidic condition. Finally, such smart nanoplatform enables self-boosting generation of reactive oxygen species (ROS) and induces strong intracellular oxidative stress, leading to the substantial anticancer outcomes in vivo, which may provide a new insight for tumor-specific cascade catalytic therapy and reducing the "off-target" toxicity to surrounding normal tissues.

Learning from Artemisinin: Bioinspired Design of a Reaction-Based Fluorescent Probe for the Selective Sensing of Labile Heme in Complex Biosystems.

Labile heme (LH) is an important signaling molecule in virtually all organisms. However, specifically detecting LH remains an outstanding challenge. Herein, by learning from the bioactivation mechanism of artemisinin, we have developed the first LH-responsive small-molecule fluorescent probe, HNG, based on a 4-amino-1,8-naphthalimide (NG) fluorophore. HNG showed high selectivity for LH without interference from hemin, protein-interacting heme, and zinc protoporphyrin. Using HNG, the changes of LH levels in live cells were imaged, and a positive correlation of LH level with the degree of hemolysis was uncovered in hemolytic mice. Our study not only presents the first molecular probe for specific LH detection but also provides a strategy to construct probes with high specificity through a bioinspired approach.

Activatable Magnetic/Photoacoustic Nanoplatform for Redox-Unlocked Deep-Tissue Molecular Imaging In Vivo via Prussian Blue Nanoprobe.

Drug-induced hepatic damage has drawn great attention on public health problems. Drugs are biotransformed in the liver by enzymatic processes, accompanied by the production of reactive free radicals, which is the main cause of drug-induced hepatotoxicity. However, the limited penetration of optics makes the use of current luminescence imaging more difficult for acquiring free radicals mapping for lesion location, when applied to whole-body imaging in vivo. In this work, we develop an activatable nanoprobe based on Prussian blue (PB) that can combine magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) for deep-tissue ONOO- imaging. We discover that ONOO- can oxidize FeII within PB into FeIII and meanwhile destroy the crystal structure of PB so that the strong absorption of PB at 710 nm that originated from the electron transferring between FeII and FeIII is greatly diminished. As a result, the reduced photoacoustic imaging (PA) signal of PB is able to function as an indicator for sensing ONOO-. Importantly, after reaction with ONOO-, the reduced size of PB results in the decrease of rotational correlation time (τR), leading to the activatable MRI signal for sensing ONOO-. Finally, we demonstrate that the PB nanoprobe is successfully able to image the variation of ONOO- in drug-induced hepatotoxicity in vivo by PAI and MRI bimodal imaging. Notably, the complementarity of such dual-modality imaging could not only endow our probes with better accuracy and higher penetration depth for visualizing of ONOO- in drug-induced liver injury but also provide anatomical structure to identify the injury area of livers.

Nitric Oxide-Activated "Dual-Key-One-Lock" Nanoprobe for in Vivo Molecular Imaging and High-Specificity Cancer Therapy.

Cancer treatments are confounded by severe toxic effects toward patients. To address these issues, activatable nanoprobes have been designed for specific imaging and destruction of cancer cells under the stimulation of specific cancer-associated biomarkers. Most activatable nanoprobes were usually activated by some single-factor stimulation, but this restricts therapeutic specificity between diseased and normal tissue; therefore, multifactor activation is highly desired. To this end, we herein develop a novel dual-stimuli responsive theranostic nanoprobe for simultaneously activatable cancer imaging and photothermal therapy under the coactivation of "dual-key" stimulation of "nitric oxide (NO)/acidity", so as to further improve the therapeutic specificity. Specifically, we have integrated a weak electron acceptor (benzo[c][1,2,5]thiadiazole-5,6-diamine) into a donor-π-acceptor-π-donor type chromophore. When the weak acceptor was oxidized by NO in acidic conditions to form a stronger acceptor (5H-[1,2,3]triazolo[4,5-f]-2,1,3-benzothiadiazole), the molecule absorption was significantly increased in the near-infrared region, based on the intramolecular charge transfer (ICT) mechanism. Under the dual-key stimulation of NO/acidity within the tumor associated with inflammation, the nanoprobe can correspondingly output dual signals for ratiometric photoacoustic and photothermal imaging of cancer in vivo and do so with enhanced accuracy and specificity. Our novel nanoprobe exhibited higher photoacoustic signal enhancement under dual-factor activation at 9.8 times that of NO and 132 times that of acidity alone, respectively. Moreover, through such dual activation of NO/acidity, the nanoprobe produces more differentiation of hyperthermia between tumor and normal tissues, to afford satisfactory photothermal therapy with minimal toxic side effects. Thus, our work presents a promising strategy for significantly improving the precision and specificity of cancer imaging and therapy.

Oxygen-Embedded Quinoidal Acene Based Semiconducting Chromophore Nanoprobe for Amplified Photoacoustic Imaging and Photothermal Therapy.

Photoacoustic (PA) imaging as a noninvasive biomedical imaging technology exhibits high spatial resolution and deep tissue penetration for in vivo imaging. In order to fully explore the potential of PA imaging in biomedical applications, new contrast agents with improved PA stability and efficiency are in high demand. Herein, we present a new PA agent based on an oxygen-embedded quinoidal nonacene chromophore that is self-assembled into nanoparticles (Nano(O-Nonacene)-PEG), assisted by polyethylene glycol (PEG). Notably, the photothermal conversion efficiency of Nano(O-Nonacene)-PEG is 1.5 fold that of semiconducting polymer nanoparticles (Nano(PCPDTBT)-PEG) and 2.8 fold that of Au nanorods, owing to the low quantum yield of Nano(O-Nonacene)-PEG. Thereby, Nano(O-Nonacene)-PEG possess a greatly elevated PA signal intensity, compared to Nano(PCPDTBT)-PEG and Au nanorods, which have been widely explored for PA imaging. Due to the high resistance to photo bleaching, Nano(O-Nonacene)-PEG exhibits higher PA signal stability, which may be employed for long-term PA imaging. Moreover, when magnetic Zn0.4Fe2.6O4 nanoparticles are incorporated into Nano(O-Nonacene)-PEG, not only are magnetic resonance signals generated but also the photoacoustic efficacy is greatly enhanced. Therefore, Nano(O-Nonacene)-PEG offers distinct properties: (i) the elevated photoacoustic effect allows for high-resolution photoacoustic imaging, (ii) small size (10 nm in diameter) results in efficient tumor-targeting, and (iii) the facile application of efficient photothermal therapy in vivo. The current work offers the possibility of oxygen-embedded quinoidal acene as a promising PA probe for precision phototheranostics.

Effects of 25-hydroxyvitamin D on bone microstructure in T2MD rats.

OBJECTIVE: This study aims to explore the effects of 25-hydroxyvitamin D on the bone microstructure of rats with type 2 diabetes mellitus (T2MD). METHODS: 40 male Wistar rats were randomly selected for T2MD modeling and injected with streptozotocin solution. The rats in the control group (n=19) were fed with common feed. 25-hydroxyvitamin D was injected into rats with successful modeling results (Treatment group, n=15). The remaining rats were considered as the model group (n=16). The enzyme-linked immunosorbent assay was adopted to determine bone gla protein (BGP) and tartrate-resistant acid phosphatase (TRACP), and an X-ray bone densitometer were applied to observe the vertebral sections. RESULTS: The activity levels of blood glucose, triglyceride, total cholesterol and TRACP in the model group were higher than those in the treatment group and the control group (p⟨0.01), while serum calcium, phosphorus, BGP, ALP, and glycosylated hemoglobin, various indicators of rats in the model group were lower than those in the treatment group and the control group (p⟨0.05). CONCLUSIONS: It is feasible to treat rats with T2MD with 25-hydroxyvitamin D, which can maintain the integrity of bone microstructure and increase the bone health.

One independent or many independent? The relationship among self-construal, number of brand endorsers, and brand attitudes.

Introduction: It was common for brands to use different numbers of endorsers in marketing practice. Nevertheless, research on brand endorsers' quantity has not yielded a uniform consensus. The previous research about brand endorsers mainly focuses on the appeal of endorsement, brand category, and endorser characteristics, paying less attention to the impact of cultural factors, particularly self-construal. This study delves into selecting brand endorsers across diverse cultural regions for the same brand. Methods: Drawing on the principles of self-consistency theory and self-construal theory, our research, conducted through three distinct experiments, reveals that consumers tend to hold more favorable opinions about brands endorsed by a single individual. Furthermore, self-consistency emerges as a crucial mediating factor in this phenomenon. Additionally, self-construal is an essential factor among consumers from various cultural backgrounds. Results: Consumers with an independent self-construal exhibit more favorable brand perceptions when it comes to single-endorser brands compared to their counterparts with an interdependent self-construal. Conversely, individuals with an interdependent self-construal demonstrate a more positive disposition towards brands with multiple endorsers than those with an independent self-construal. Discussion: This research not only enriches and extends our theoretical understanding of the impact of the number of brand endorsers on consumer brand attitudes but also provides valuable practical insights for optimizing the selection of brand endorsers for companies.

Potential mechanisms of exercise for relieving inflammatory pain: a literature review of animal studies.

Inflammatory pain (IP) is one of the most prevalent and intractable human conditions, and it leads to progressive dysfunction and reduced quality of life. Additionally, IP is incredibly challenging to treat successfully with drugs or surgery. The development of IP is complex and multifactorial, and peripheral and central sensitization may influence chronicity and treatment resistance in IP. Understanding the mechanisms underlying IP is vital for developing novel therapies. Strong evidence suggests that exercise can be a first-line relief for patients with IP during rehabilitation. However, the mechanisms through which exercise improves IP remain unclear. Here, we reviewed the current animal experimental evidence for an exercise intervention in IP and proposed biological mechanisms for the effects of synaptic plasticity in the anterior cingulate cortex, endocannabinoids, spinal dorsal horn excitability balance, immune cell polarization balance, cytokines, and glial cells. This information will contribute to basic science and strengthen the scientific basis for exercise therapy prescriptions for IP in clinical practice.

[Effects of Ghrelin on hypertension and insulin resistance in fructose-fed rats].

OBJECTIVE: To explore the effects and mechanisms of Ghrelin on hypertension and insulin resistance in fructose-fed rats. METHODS: A total of 32 male Sprague-Dawley (SD) rats were randomized into control (A) and fructose-fed groups (B). Rats in group B were fed with 10% fructose solution for 4 weeks. Then the rats in group A were randomized into intraperitoneal saline (group GA1) or intraperitoneal 50 nmol/kg Ghrelin (group GA2) and those in group B into intraperitoneal saline (group GB1) or intraperitoneal 50 nmol/kg Ghrelin (group GB2) twice daily for 6 weeks. Caudal arterial pressure was measured weekly. Plasma blood glucose, insulin concentration and lipid profile were measured. And insulin resistance (IR) was calculated by the method of homeostasis model assessment (HOMA). Plasma level of 15-F2t-isoprostane was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Ghrelin caused a significant reduction of systolic pressure at Week 3 in group GB2 versus group GB1 (P < 0.05). Maximal effect appeared at Week 5 ((127 ± 5) vs (120 ± 6) mm Hg, P < 0.05, 1 mm Hg = 0.133 kPa), but blood pressure failed to reach normal value. Ghrelin also decreased plasma insulin concentration and HOMA-IR ((9.6 ± 2.6) vs (13.1 ± 3.6) µU/ml, P < 0.05;1.92 ± 0.12 vs 2.78 ± 0.14, P < 0.01). Plasma level of 15-F2t-isoprostane was lower in group GB2 than that in group GB1 ((75 ± 11) vs (102 ± 14) pg/ml, P < 0.01). CONCLUSION: Ghrelin may lower blood pressure, ameliorate insulin resistance and improve insulin sensitivity through inhibiting oxidative stress in fructose-induced rats.

LncRNA AC093850.2 predicts poor outcomes in patients with triple-negative breast cancer and motivates tumor progression by sponging miR-4299.

BACKGROUND: Accumulating evidence displays that non-coding RNAs (ncRNAs) are involved in the progression of triple-negative breast cancer (TNBC). This study aimed to investigate the role of lncRNA AC093850.2 in TNBC. METHODS: The AC093850.2 levels were compared using RT-qPCR in TNBC tissues and corresponding normal tissues. The Kaplan-Meier curve method was conducted to assess the clinical significance of AC093850.2 in TNBC. Bioinformatic analysis was used to predict potential miRNA. Cell proliferation and invasion assays were carried out to explore the function of AC093850.2/miR-4299 in TNBC. RESULTS: lncRNA AC093850.2 expression is raised in TNBC tissues and cell lines, which is related to the shorter overall survival of patients. AC093850.2 is directly bound to miR-4299 in TNBC cells. Downregulation of AC093850.2 reduces tumor cell proliferation, migration, and invasion abilities, while miR-4299 silence attenuated AC093850.2 silencing induced inhibition of cellular activities in TNBC cells. CONCLUSION: In general, the findings suggest that lncRNA AC093850.2 was closely related to the prognosis and progression of TNBC by sponging miR-4299, which might be a prognosis predictor and potential target for treating TNBC patients.

A comprehensive review on traditional and modern research of the genus Bupleurum (Bupleurum L., Apiaceae) in recent 10 years.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Bupleurum (family Apiaceae), comprising approximately 248 accepted species, is widely distributed and used in China, Japan, India, Central Asia, North Africa and some European countries as traditional herbal medicines. Certain species have been reported to have significant therapeutic effects in fever, inflammatory disorders, cancer, gastric ulcer, virus infection and other diseases. AIM OF THE REVIEW: we performed a comprehensive review of the ten-year research progress in phytochemistry, pharmacology, toxicity, along with bibliometrics research of the genus Bupleurum, aiming to identify knowledge gaps for future research. MATERIALS AND METHODS: All the literatures are retrieved from library and electronic sources including Web of Science, PubMed, Elsevier, Google Scholar, CNKI and Baidu Scholar. These papers cover studies of the traditional use, phytochemistry, pharmacology, and toxicology of the genus Bupleurum. RESULTS: There is a long history of using the genus Bupleurum in traditional herbal medicine that dated back to over 2000 years ago. Twenty-five species and 8 varieties with 3 variants within this genus have been reported to be effective to treat fever, pain, liver disease, inflammation, thoracolumbar pain, irregular menstruation and rectal prolapse. The main phytochemicals found in these plants are triterpene saponins, volatile oil, flavonoid, lignans, and polysaccharides. Many of these compounds have also been shown to have anti-inflammatory, anti-tumor, antimicrobial, immunoregulation, neuroregulation, hepatoprotective and antidiabetic activities. Meanwhile, improper usage of Bupleurum may induce cytotoxic effects, and polyacetylenes may be the main poisonous compounds. CONCLUSIONS: This article summarized recent findings about Bupleurum research from many different aspects. While a small number of Bupleurum species have been investigated through modern pharmacology methods, there are still major knowledge gaps due to inadequate studies and ambiguous findings. Future research could focus on more specific phytochemistry studies combined with mechanistic analysis to provide better guidance to utilize Bupleurum as medicinal resources.

Neuroprotection of isookanin against MPTP-induced cell death of SH-SY5Y cells via BCL2/BAX and PI3K/AKT pathways.

BACKGROUND AND PURPOSE: Isookanin, an important antioxidant component in Coreopsis tinctoria Nutt., has shown remarkable hypolipidemic, hypoglycemic, and hypotensive effects. However, the neuroprotective effect of isookanin has not been reported yet. Here, the neuroprotective effects and relevant molecular mechanisms of isookanin are explored for the first time. METHODS: The SH-SY5Y cells were exposed to neurotoxic H2O2, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and Aß25-35, respectively. Cell viability and apoptosis were evaluated by MTT, lactate dehydrogenase (LDH), and TUNEL assays. Intercellular ROS and mitochondrial membrane potential were assessed by DCFH-DA and JC-1 assay. Western blot and qRT-PCR were used to explore the perturbed signaling at the gene and protein levels. Molecular docking analysis and in vitro assay were further applied to confirm potential target. RESULTS: Among the three in vitro models, isookanin showed the best neuroprotection against MPTP-induced damage. Isookanin attenuated the levels of LDH, intracellular ROS, and mitochondrial membrane potential. Isookanin upregulated phosphorylation of AKT and PI3K, and increased BCL2/BAX ratio. Isookanin possessed a powerful affinity toward AKT. Besides, the protective effects of isookanin disappeared when cells were co-treated with an AKT inhibitor (AZD5363). CONCLUSION: Isookanin regulated BCL2/BAX and PI3K/AKT pathways to reduce mitochondrial damage and cellular apoptosis. Isookanin may be a new protector for neurodegenerative diseases.

Waking up "We" or "I"? How Start Temporal Landmarks Influence Arousal Product Preferences.

Start temporal landmark is the beginning of a period of time. Previous research has established that individuals have the need for arousal at the start temporal landmarks but less research has focused on individual differences and the relationship between self and others (independent vs. interdependent). This research examines the influence of individuals' self-construal on the relationship between start temporal landmarks and arousal product preference. Three experiments with 1136 participants were recruited from a university, community, and online store in Southern China. The data were analyzed by Cochran-Mantel-Haenszel on SPSS 26.0 software program. The results showed that self-construal influenced the effect of start temporal landmarks on arousal product preference. Specifically, compared with ordinary temporal landmarks, individuals with interdependent self-construal prefer high arousal products under start temporal landmarks, whereas those with independent self-construal show no significantly different preference for high or low arousal products under the start temporal landmarks. Furthermore, psychological resources play a mediating role. This research extends the theoretical research on self-construal in the field of temporal landmarks and arousal. It also has important practical implications for improving the sales of high arousal products.