Specific Action Research Articles

Atlantic salmon Salmo salar do not prioritize digestion when energetic budgets are constrained by warming and hypoxia.

During summer, farmed Atlantic salmon (Salmo salar) can experience prolonged periods of warming and low aquatic oxygen levels due to climate change. This often results in a drop in feed intake; however, the physiological mechanism behind this behaviour is unclear. Digestion is a metabolically expensive process that can demand a high proportion of an animal's energy budget and might not be sustainable under future warming scenarios. We investigated the effects of elevated temperature and acute hypoxia on specific dynamic action (SDA; the energetic cost of digestion), and how much of the energy budget (i.e. aerobic scope, AS) was occupied by SDA in juvenile Atlantic salmon. AS was 9% lower in 21°C-acclimated fish compared to fish reared at their optimum temperature (15°C) and was reduced by ~50% by acute hypoxia (50% air saturation) at both temperatures. Furthermore, we observed an increase in peak oxygen uptakerate during digestion which occupied ~13% of the AS at 15°C and ~20% of AS at 21°C, and increased the total cost of digestion at 21°C. The minimum oxygen tolerance threshold in digesting fish was ~42% and ~53% at 15 and 21°C, respectively, and when digesting fish were exposed to acute hypoxia, gut transit was delayed. Thus, these stressors result in a greater proportion of the available energy budget being directed away from digestion. Moderate environmental hypoxia under both optimal and high temperatures severely impedes digestion and should be avoided to limit exacerbating temperature effects on fish growth.

To Catch a Glimpse from Afar: MENA Scholars in US International Conferences

Abstract: As a dauntless practitioner of exulansis , I write this Note from the Field in an attempt to unlearn my practice of keeping silent about the challenges of moving across borders. It is based on a survey I did about the challenges and issues (e.g., securing visas and funds) that Middle Eastern and North African (MENA) scholars/researchers sadly encounter when they decide to participate in US conferences. While offering specific action items to the ATHE organizing committee, I remind my fellow MENA colleagues who have experienced disconnect that their sadness should prompt a vivid upsurge of collective attention to the countless possibilities we organizers and participants still have for cosmopolitan friendship while taking joy and grief all in, at once, from afar.

Municipal Tax Policy in State Emergencies

Abstract A significant part of the revenue supplying municipal budgets in Poland comes from taxes that are subject to municipalities’ constitutionally enshrined powers. This income is mainly generated by contributions connected with the right of property ownership, among others. Apart from a fiscal function, taxes may also stimulate specific processes. Positive stimulation within the scope of tax policy is mainly based on various types of tax preferences. They may be applied as a tool of tax policy which fulfils specific economic and social objectives. These issues have become particularly important during emergencies taking place in the state, such as the COVID-19 pandemic, the migration crisis or the war in Ukraine. In the wake of the recent occurrence of such types of quasi-extraordinary measures, it is reasonable to ask a question about the need to adjust the legal limits of municipal tax powers in this regard. Concurrently, the necessity to maintain balance between support provided to specific categories of entities and the financial needs of municipalities may not escape notice. The Polish experience shows that as a consequence of emergencies, ad hoc solutions of a merely occasional nature have been introduced to the tax law system. Hence a thesis may be formulated according to which it is reasonable to approach this kind of phenomenon in a systemic way, which should be reflected in the introduction of standard and stable tools that could enable municipalities to undertake specific action. The purpose of this study is to verify this assumption, relying, most of all, on the experiences and needs that have emerged in Poland in recent years.

Action Segmentation Through Self-Supervised Video Features and Positional-Encoded Embeddings

Action segmentation consists of temporally segmenting a video and labeling each segmented interval with a specific action label. In this work, we propose a novel action segmentation method that requires no initial video analysis and no annotated data. Our proposal involves extracting features from videos using several pre-trained deep-learning models, including spatiotemporal and self-supervised methods. Data is then transformed using a positional encoder, and finally, a clustering algorithm is applied, where each produced cluster presumably corresponds to a different single and distinguishable action. For self-supervised features, we explored DINO, and for spatiotemporal features, we investigated I3D and SlowFast methods. Moreover, two different clustering algorithms (FINCH and KMeans) were investigated, and we also explored how varying the length of video snippets that generate the feature vectors affected the quality of the segmentation. Experiments show that our method produces competitive results on the Breakfast and INRIA Instructional Videos dataset benchmarks. Our best result was produced using a composition of self-supervised features generated by DINO, FINCH clustering, and positional encoding.

Enhancing Medical Students' Reflective Capacity: Utilizing Reflective Practice Questionnaire as an Action Research Diagnostic Tool.

Introduction Reflection is the intentional evaluation of one's beliefs or understanding in consideration of the available evidence. Reflection has been noted to enhance profound learningand critical thinking and is an essential foundation of experiential learning. The Reflective Practice Questionnaire (RPQ) is a valid and reliable tool for assessing reflective capacity among medical students. It assesses not only reflective capacity but also other psychological constructs relevant to reflective practice, such as job satisfaction, confidence while interacting with patients, stress during patient interaction, desire for improvement, and feelings of uncertainty. The use of RPQ as a diagnostic tool for improving reflective capacity among medical students is scarcely available in the literature. Thus, the present study aimed to utilize the RPQ for identifying discrete action points for training and future improvement in reflective capacity. Materials and methods The present cross-sectional descriptive study was conducted among 300 medical students of a medical college. To identify the clusters or meaningful subgroups within the study population, cluster analysis was done. Inter-correlation between subscales of RPQ was performed by forming Pearson's correlation matrix to understand the dynamics between various subscales of RPQ. Results Five groups were identified in the cluster analysis: typical (25.6%), reflective (27%), non-reflective (16.7%), unconfident (14%), and overconfident (16.7%). This sets the template for specific action points for each group identified above. Reflective capacity was positively correlated with Desire for Improvement (DfI), General Confidence (CG), Communication Confidence (CC), and Job Satisfaction (JS). It was also positively correlated with negative outcomes such as Uncertainty (Unc) and Stress when Interacting with Patients (SiC). Conclusion RPQ can be used as a diagnostic tool in terms of reflective capacity for action research.

Determinants of adherence to insulin and blood glucose monitoring among adolescents and young adults with type 1 diabetes in Qatar: a qualitative study.

Adherence to insulin and blood glucose monitoring (BGM) is insufficient in adolescents and young adults (AYAs) with type 1 diabetes (T1D) worldwide and in Qatar. Little is known about the factors related to being aware of suboptimal adherence and the beliefs related to suboptimal adherence in this group. This qualitative study investigated factors related to awareness of, and beliefs about suboptimal adherence, as well as the existence of specific action plans to combat suboptimal adherence using the I-Change model. The target group was comprised of 20 Arab AYAs (17-24 years of age) with T1D living in Qatar. Participants were interviewed via semi-structured, face-to-face individual interviews, which were audio-recorded, transcribed verbatim, and analyzed using the Framework Method. Suboptimal adherence to insulin, and particularly to BGM, in AYAs with T1D was identified. Some AYAs reported to have little awareness about the consequences of their suboptimal adherence and how this can adversely affect optimal diabetes management. Participants also associated various disadvantages to adherence ( e.g., hypoglycemia, pain, among others) and reported low self-efficacy in being adherent ( e.g., when outside home, in a bad mood, among others). Additionally, goal setting and action-planning often appeared to be lacking. Factors facilitating adherence were receiving support from family and healthcare providers, being motivated, and high self-efficacy. Interventions that increase awareness concerning the risks of suboptimal adherence of AYAs with T1D are needed, that increase motivation to adhere by stressing the advantages, creating support and increasing self-efficacy, and that address action planning and goal parameters.

Are SMART goals fit-for-purpose? Goal planning with mental health service-users in Australian community pharmacies.

Goal planning is an important element in brief health interventions provided in primary healthcare settings, with specific, measurable, achievable, realistic/relevant, and timed (SMART) goals recommended as best practice. This study examined the use of SMART goals by Australian community pharmacists providing a brief goal-oriented wellbeing intervention with service-users experiencing severe and persistent mental illnesses (SPMIs), in particular, which aspects of SMART goal planning were incorporated into the documented goals. Goal data from the PharMIbridge Randomized Controlled Trial (RCT) were used to investigate how community pharmacists operationalized SMART goals, goal quality, and which SMART goal planning format aspects were most utilized. Goals were evaluated using the SMART Goal Evaluation Method (SMART-GEM) tool to determine how closely each documented goal met the SMART criteria. Goals were also categorized into five domains describing their content or purpose. Descriptive analysis was used to describe the SMART-GEM evaluation results, and the Kruskal-Wallis H test was used to compare the evaluation results across the goal domains. All goals (n = 512) co-designed with service-users (n = 156) were classified as poor quality when assessed against the SMART guidelines for goal statements, although most goals contained information regarding a specific behaviour and/or action (71.3% and 86.3%, respectively). Less than 25% of goals identified how goal achievement would be measured, with those related to lifestyle and wellbeing behaviours most likely to include measurement information. Additionally, the majority (93.5%) of goals lacked details regarding monitoring goal progress. Study findings raise questions regarding the applicability of the SMART goal format in brief health interventions provided in primary healthcare settings, particularly for service-users experiencing SPMIs. Further research is recommended to identify which elements of SMART goals are most relevant for brief interventions. Additionally, further investigation is needed regarding the impact of SMART goal training or support tools on goal quality.

Pharmaceutical retail supply chain responses to the COVID-19 pandemic

AbstractIn the wake of the COVID-19 pandemic, the importance of resilient supply chain and operations management in the pharmaceutical industry has intensified. A particular challenge has been the timely adaptation to rapid fluctuations in the business environment to cope with disruptions and ensure the adequate supply of medical equipment and pharmaceuticals. In this study, we perform a simulation-based analysis of pandemic-triggered impacts on pharmaceutical supply chains in Germany with the aim of examining supply chain response to the COVID-19 pandemic. To accomplish this, we build a digital supply chain model using a hybrid approach that combines case study analysis and discrete-event simulation implemented in anyLogistix. Based on the results, we propose a specific response action plan for the pharmaceutical industry that can be deployed in response to severe disruptions and pandemic-like crises. We also offer a resilience framework for the post-pandemic environment as a guideline for strategic decision-making.

Abstract B070: Myc synthetic lethality as a therapeutic strategy for resistance: Insights into the targetability of mitochondrial complex I in Myc-high TNBC

Abstract Patients with advanced triple-negative breast cancer (TNBC) frequently develop chemoresistance, emphasizing an urgent need for novel therapeutic strategies able to eradicate treatment resistant tumor cells. Recent studies have highlighted MYC as a common oncogenic alteration and a driver of stem-like TNBC phenotype, which commonly features high mitochondrial respiratory activity instated through OXPHOS system and chemoresistance. Interestingly, emerging evidence suggests that residual tumors from chemo treatment remain susceptible to OXPHOS inhibition through inhibition of respiratory complex I. Our previous studies have revealed a specific MYC-dependent and tumor suppressive synthetic lethal action for combination of metformin and BH3 mimetics in cells, ex vivo and in vivo models of aggressive breast cancer (PMID: 30728358). Metformin is a systemic and local metabolic modulator, which acts as a weak complex I inhibitor and promoter of AMPK activation. Here, we have explored the role of MYC in OXPHOS regulation, to address the question if metformin specifically and lethally targets MYC-modulated OXPHOS in MYC-high TNBC. We found that a selective c-MYC inhibitor (EN4) leads to a significant decrease in complex I activity despite only a modest drop in complex I mass in endogenously MYC-high TNBC cell lines. Conversely, engineered MYC overexpression in these cells upregulated complex I activity. Our current work explores transcriptomic, proteomic, and functional approaches to the mechanisms through which MYC regulates complex I activity, structure, and dynamics, ultimately hoping to define a biological rationale for therapeutic targeting of OXPHOS in Myc-high TNBC. Citation Format: Antti O Hiltunen, Linda J Id, Juha Klefström. Myc synthetic lethality as a therapeutic strategy for resistance: Insights into the targetability of mitochondrial complex I in Myc-high TNBC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B070.

Tobacco use and dependence among adults residing in an urbanized village, Delhi, India.

Tobacco use is one of the most significant public health concerns globally as it is a risk factor for chronic illnesses. GATS-2 concluded that 28.6% of all adults currently use Tobacco in India and 17.8% in Delhi. It is important to conduct such surveys in local areas to make specific and effective action plans. Community-based cross-sectional study conducted between January 2020-June 2021 in Aliganj, an urbanized village in South Delhi. Four hundred ninety participants were enrolled using simple random sampling. The first author conducted the interview using GATS and Fagerstrom nicotine dependence test. Data was analyzed using SPSS-21. Median age-35 (26.75-75.00), range-15-84 years. Of the 490 participants, 20.0% were current tobacco users (10.6% smokeless, 7.3% smoked, and 2.2% both). Among current smokers, 78.3% had low, 17.4% moderate, and 4.3% had high dependence on nicotine dependence. Among current smokeless tobacco users, 52.4% had, low, 36.5% moderate, and 11.1% had high dependence. Males had significantly higher odds [6.6 (2.9-15.1)] of tobacco use than females. Higher education [0.3 (0.2-0.8)] compared to no formal education had significantly lower odds of using tobacco. Students [0.1 (0.04-0.4)] and homemakers [0.1 (0.01-0.5)] had significantly lower odds of using tobacco as compared to those employed. One in every five adults is a tobacco user in Aliganj. Manufactured cigarettes, bidi, and water pipes were the most common products among smokers. Among smokeless tobacco users, the most common products were chewing tobacco gutka, and khaini. A larger proportion of smokeless tobacco users had high nicotine dependence than smoked tobacco users.

Adolescents and sexual assault: A critical integrative review.

Adolescents are sexually assaulted at remarkably high rates. Adolescents are also unique given the specific dynamics of adolescent sexual assault, their current stage in human development, their limited legal standing and rights, and their experiences navigating postassault services and resources. While literature exists within each of these domains, it is somewhat disconnected and overlooks how adolescents are often relegated to the margins in research and practice. The purpose of this integrative review is to (1) provide a more complete understanding of adolescent sexual assault and survivors'nuanced needs; (2) frame adolescent survivors as a too-often-overlooked oppressed group that researchers and responders must consider and center in their work, lest contribute to their further marginalization; and (3) inspire and orient social justice-minded scholar activists to various action steps to take to center and prioritize adolescents in research and practice. Through our intersectional feminist approach, we offer specific action steps for social justice-minded scholar activists to recenter adolescents in their research and practice.

Aconitine and its derivatives: bioactivities, structure-activity relationships and preliminary molecular mechanisms.

Aconitine (AC), which is the primary bioactive diterpene alkaloid derived from Aconitum L plants, have attracted considerable interest due to its unique structural feature. Additionally, AC demonstrates a range of biological activities, such as its ability to enhance cardiac function, inhibit tumor growth, reduce inflammation, and provide analgesic effects. However, the structure-activity relationships of AC are remain unclear. A clear understanding of these relationships is indeed critical in developing effective biomedical applications with AC. In line with these challenges, this paper summarized the structural characteristics of AC and relevant functional and bioactive properties and the structure-activity relationships presented in biomedical applications. The primary temporal scope of this review was established as the period spanning from 2010 to 2023. Subsequently, the objective of this review was to provide a comprehensive understanding of the specific action mechanism of AC, while also exploring potential novel applications of AC derivatives in the biomedical field, drawing upon their structural characteristics. In conclusion, this review has provided a comprehensive analysis of the challenges and prospects associated with AC in the elucidation of structure-bioactivity relationships. Furthermore, the importance of exploring modern biotechnology approaches to enhance the potential biomedical applications of AC has been emphasized.

Clinical Symptoms of the Systemic Inflammatory Response in Acute Severe Poisoning by Agents Affecting the Central Nervous System

Relevance. Currently, acute poisoning with substances affecting the central nervous system in the general structure of exogenous intoxications accounts for up to 50-60% of cases, of which up to 25% are severe and extremely severe lesions leading to the formation of critical conditions and requiring intensive care (Bonitenko E.Yu. et al., 2018; Luzhnikov E.A. et al., 2016; Bohnert A.S. et al., 2019; Muller D. et al., 2017; Taheri F. et al., 2015). The causes of widespread acute poisoning include the uncontrolled use of various medicines in everyday life, suicidal attempts, as well as the use of narcotic drugs for the purpose of drug intoxication (Rokhlina M.L., 2019; Nordstrom D. L. et al., 2017; Taheri F. et al., 2018). The severity of the condition of patients with acute severe poisoning by drugs affecting the central nervous system is due to pronounced disorders of the functions of various organs and body systems due to the specific action of xenobiotics (Luzhnikov E.A. et al., 2016), as well as developing hypoxia (Livanov G.A. et al., 2014; Hashemian M. et al., 2016), leading to the development of life-threatening complications, which often determines the outcome of chemical trauma.

S288T mutation altering MmpL3 periplasmic domain channel and H-bond network: a novel dual drug resistance mechanism.

Mycobacterial membrane proteins Large 3 (MmpL3) is responsible for the transport of mycobacterial acids out of cell membrane to form cell wall, which is essential for the survival of Mycobacterium tuberculosis (Mtb) and has become a potent anti-tuberculosis target. SQ109 is an ethambutol (EMB) analogue, as a novel anti-tuberculosis drug, can effectively inhibit MmpL3, and has completed phase 2b-3 clinical trials. Drug resistance has always been the bottleneck problem in clinical treatment of tuberculosis. The S288T mutant of MmpL3 shows significant resistance to the inhibitor SQ109, while the specific action mechanism remains unclear. The results show that MmpL3 S288T mutation causes local conformational change with little effect on the global structure. With MmpL3 bound by SQ109 inhibitor, the distance between D710 and R715 increases resulting in H-bond destruction, but their interactions and proton transfer function are still restored. In addition, the rotation of Y44 in the S288T mutant leads to an obvious bend in the periplasmic domain channel and an increased number of contact residues, reducing substrate transport efficiency. This work not only provides a possible dual drug resistance mechanism of MmpL3 S288T mutant but also aids the development of novel anti-tuberculosis inhibitors. In this work, molecular dynamics (MD) and quantum mechanics (QM) simulations both were performed to compare inhibitor (i.e., SQ109) recognition, motion characteristics, and H-bond energy change of MmpL3 after S288T mutation. In addition, the WT_SQ109 complex structure was obtained by molecular docking program (Autodock 4.2); Molecular Mechanics/ Poisson Boltzmann Surface Area (MM-PBSA) and Solvated Interaction Energy (SIE) methods were used to calculate the binding free energies (∆Gbind); Geometric criteria were used to analyze the changes of hydrogen bond networks.

Mode of Antibacterial Action of Tomatidine C3-Diastereoisomers.

Tomatidine (TO) is a natural narrow-spectrum antibiotic acting on the Staphylococcus aureus small colony variant (SCV) with a minimal inhibitory concentration (MIC) of 0.06 µg/mL while it shows no activity against prototypical strains (MIC > 128 µg/mL). To expand the spectrum of activity of TO, the 3β-hydroxyl group was substituted with an ethane-1,2-diamine, resulting in two diastereoisomers, TM-02 (C3-β) and TM-03 (C3-α). These molecules are equally potent against prototypical S. aureus and E. coli strains (MIC 8 and 32 µg/mL, respectively), whereas TM-02 is more potent against SCV (MIC 0.5 µg/mL) and hyperpermeable E. coli strains (MIC 1 µg/mL). The differences in their modes of action were investigated. We used membrane vesicles to confirm the inhibition of the bacterial ATP synthase, the documented target of TO, and measured effects on bacterial cell membranes. Both molecules inhibited E. coli ATP synthase, with Ki values of 1.1 µM and 3.5 µM for TM-02 and TM-03, respectively, and the bactericidal effect of TM-02 was linked to ATP synthase inhibition. Furthermore, TM-02 had no major effect on the membrane fluidity and gradually reduced membrane potential. In contrast, TM-03 caused structural damages to membranes and completely disrupted the membrane potential (>90%). We were successful in broadening the spectrum of activity of TO. C3-β-diastereoisomers may have more specific antibacterial action than C3-α.

Towards a New Generation of Hormone Therapies: Design, Synthesis and Biological Evaluation of Novel 1,2,3-Triazoles as Estrogen-Positive Breast Cancer Therapeutics and Non-Steroidal Aromatase Inhibitors.

Aromatase inhibitors (AIs) show promising features as drugs to treat estrogen-responsive breast cancer as they block aromatase activity, the key enzyme in estrogen synthesis. The current AIs approved by the Food and Drug Administration for breast cancer treatment present severe adverse effects. For these reasons, it is important to develop of new AIs that are more specific and sensitive. In this paper, we report the synthesis and the characterization of new nonsteroidal aromatase AIs containing triazoles moieties for the treatment of hormone-dependent breast cancer in post-menopausal women. A new series of 1,2,3-triazole based molecules were successfully synthetized and their chemical structures were determined from the spectral data (FT-IR, 13C NMR, 1H NMR, mass spectroscopy) and micro-analytical data. Additionally, the physical properties of the newly synthesized derivatives were reported. The novel compounds were also tested for their anticancer activity in both breast cancer (MCF7 and T-47D) and normal breast (MCF 10A) cell lines, evaluating their effect on cell proliferation, migration, and invasion. The results revealed that the compounds exhibited promising and specific anti-cancer action.

Effect of peanut stilbenoids, arachidin-1 and arachidin-3, on Streptococcus mutans growth and acid production

In this study we evaluated the effect of prenylated peanut stilbenoids on the growth, biofilm accumulation and acid production of the dental caries pathogen Streptococcus mutans. Prior research with the non-prenylated stilbenes, resveratrol and piceatannol, has shown that these molecules are active against S. mutans. Here we sought to determine if the addition of a prenyl group to the stilbene backbone increased anti-S. mutans activities. Two prenylated stilbenes, arachidin-1 and arachidin-3, were produced using a peanut hairy root production system. Compared to resveratrol and piceatannol, both arachidin-1 and arachidin-3 led to greater inhibition of S. mutans planktonic growth. This effect also led to reduced biofilm formation, by inhibiting growth, instead of a specific action against biofilm cells. Lastly, sub-MIC concentrations of arachidin-3 reduced the acid production of S. mutans above the ‘critical pH’ that leads to tooth enamel erosion. In summary, stilbenoids have anti-S. mutans activity, and prenylation enhances this activity.

Efficient Bike-sharing Repositioning with Cooperative Multi-Agent Deep Reinforcement Learning

As an emerging mobility-on-demand service, bike-sharing system (BSS) has spread all over the world by providing a flexible, cost-efficient, and environment-friendly transportation mode for citizens. Demand-supply unbalance is one of the main challenges in BSS because of the inefficiency of the existing bike repositioning strategy, which reallocates bikes according to a pre-defined periodic schedule without considering the highly dynamic user demands. While reinforcement learning has been used in some repositioning problems for mitigating demand-supply unbalance, there are significant barriers when extending it to BSS due to the dimension curse of action space resulting from the dynamic number of workers and bikes in the city. In this paper, we study these barriers and address them by proposing a novel bike repositioning system, namely BikeBrain, which consists of a demand prediction model and a spatio-temporal bike repositioning algorithm. Specifically, to obtain accurate and real-time usage demand for efficient bike repositioning, we first present a prediction model ST-NetPre, which directly predicts user demand considering the highly dynamic spatio-temporal characteristics. Furthermore, we propose a spatio-temporal cooperative multi-agent reinforcement learning method (ST-CBR) for learning the worker-based bike repositioning strategy in which each worker in BSS is considered an agent. Especially, ST-CBR adopts the centralized learning and decentralized execution way to achieve effective cooperation among large-scale dynamic agents based on Mean Field Reinforcement Learning (MFRL), while avoiding the huge dimension of action space. For dynamic action space, ST-CBR utilizes a SoftMax selector to select the specific action. Meanwhile, for the benefits and costs of agents’ operation, an efficient reward function is designed to seek an optimal control policy considering both immediate and future rewards. Extensive experiments are conducted based on large-scale real-world datasets, and the results have shown significant improvements of our proposed method over several state-of-the-art baselines on the demand-supply gap and operation cost measures.

B4 suppresses lymphoma progression by inhibiting fibroblast growth factor binding protein 1 through intrinsic apoptosis.

Lymphoma positions as the fifth most common cancer, in the world, reporting remarkable deaths every year. Several promising strategies to counter this disease recently include utilizing small molecules that specifically target the lymphoma cellular proteins to overwhelm its progression. FGFBP1 is a soluble intracellular protein that progresses cancer cell proliferation and is upregulated in several cancers. Therefore, inhibiting FGFBP1 could significantly slow down lymphoma progression through triggering apoptosis. Thus, in this study, a flavonoid B4, isolated from Cajanus cajan, has been investigated for its effects of B4 on lymphoma, specifically as an FGFBP1 inhibitor. B4 could selectively hinder the growth of lymphoma cells by inducing caspase-dependent intrinsic apoptosis through G1/S transition phase cell cycle arrest. RNA sequencing analysis revealed that B4 regulates the genes involved in B-cell proliferation and DNA replication by inhibiting FGFBP1 in vitro. B4 increases the survival rate of lymphoma mice. B4 also represses the growth of patient-derived primary lymphoma cells through FGFBP1 inhibition. Drug affinity responsive target stability experimentations authorize that B4 powerfully binds to FGFBP1. The overexpression of FGFBP1 raises the pharmacological sensitivity of B4, supplementing its specific action on lymphoma cells. This study pioneers the estimation of B4 as a possible anticancer agent for lymphoma treatment. These outcomes highlight its selective inhibitory effects on lymphoma cell growth by downregulating FGFBP1 expression through intrinsic apoptosis, causing mitochondrial and DNA damage, ultimately leading to the inhibition of lymphoma progression. These suggest B4 may be a novel FGFBP1 inhibitor for the lymphoma treatment.

Total Water–Soluble Flavonoids From Lithocarpus litseifolius (Hance) Chun (Sweet Tea) Improve Glucose Homeostasis Through Multitarget Signalling in GDM Mice

Background: The oral safety of Lithocarpus litseifolius (Hance) Chun (sweet tea) that has antihyperglycemic potential has been verified. However, its specific application and action mechanism in the treatment of gestational diabetes mellitus (GDM) are still unclear.Methods: Total water–soluble flavonoids extracted from L. litseifolius (Hance) Chun (sweet tea) were applied to GDM mice. The glucose tolerance, insulin sensitivity, and histopathology of the GDM mice were evaluated through an intraperitoneal glucose tolerance test (IPGTT), an intraperitoneal insulin tolerance test (IPITT), and histochemistry. The possible mechanism was analysed through network pharmacology.Results: Compared with those in GDM model mice (MD group), blood glucose levels indicating both glucose tolerance and insulin sensitivity were improved in GDM mice treated with total water–soluble flavonoids (LLHC group) but were greater than those in normal control mice (NC group). The number of apoptotic liver cells was significantly lower in the LLHC group than in the MD group, but greater than that in the NC group. Multiple targets and signalling pathways that were acted by eight main active ingredients were involved in the process by which total water–soluble flavonoids protect against GDM. The main mechanism involved quercetin (10 targets) and luteolin (8 targets), which acted on the effector target of GAA through six main signalling pathways around the AKT1 core axis.Conclusion: Oral administration of total water–soluble flavonoids can alleviate glucose intolerance and insulin resistance via the inhibition of liver cell apoptosis. The main active ingredients act on GAA through the signalling pathways of the AKT1 core axis.