Salicylic acid modulates secondary metabolism and enhanced colchicine accumulation in long yellow daylily (Hemerocallis citrina).

Salicylic acid (SA) is an essential phytoregulator that is widely used to promote the synthesis of high-value nutraceuticals in plants. However, its application in daylily, an ornamental plant highly valued in traditional Chinese medicine, has not been reported. Herein, we investigated the exogenous SA-induced physiological, transcriptional and biochemical changes in long yellow daylily (LYD). We found that 2 mg/L foliar SA treatment significantly improved LYD plant growth and yield. Transcriptome sequencing and differentially expressed genes (DEGs) analysis revealed that the phenylpropanoid biosynthesis, isoquinoline alkaloid biosynthesis, sulfur metabolism, plant hormone signal transduction and tyrosine metabolism were significantly induced in SA-treated leaves. Many transcription factors and antioxidant system-related DEGs were induced under the SA treatment. Biochemical analyses showed that the leaf contents of soluble sugar, soluble protein (Cpr), ascorbic acid (AsA) and colchicine were significantly increased by 15.15% (from 30.16 ±â€…1.301 to 34.73 ±â€…0.861 mg/g), 19.54% (from 60.3 ±â€…2.227 to 72.08 ±â€…1.617 mg/g), 30.45% (from 190.1 ±â€…4.56 to 247.98 ±â€…11.652 µg/g) and 73.05% (from 3.08 ±â€…0.157 to 5.33 ±â€…0.462 µg/g), respectively, under the SA treatment. Furthermore, we identified 15 potential candidate genes for enhancing the growth, production and phytochemical content of LYD. Our results provide support for the bioaccumulation of colchicine in yellow daylily and valuable resources for biotechnological-assisted production of this important nutraceutical in Hemerocallis spp.

Functions and mechanisms of RNA m6A regulators in breast cancer (Review).

Breast cancer (BC) is a major malignant tumor in females and the incidence rate of BC has increased worldwide in recent years. N6­methyladenosine (m6A) is a methylation modification that occurs extensively in eukaryotic RNA. The abnormal expression of m6A and related regulatory proteins can activate or inhibit certain signal pathways or oncogenes, thus affecting the proliferation, metastasis and prognosis of BC. Numerous studies have shown that m6A regulator disorder exists in BC, and this disorder can be reversed. Therefore, m6A is predicted as a potential therapeutic target for BC. However, the molecular mechanism of m6A RNA methylation regulating the occurrence and development of BC has not been comprehensively elucidated. In this review article, the functions of various m6A regulators and the specific mechanisms of certain regulators of the progress of BC were summarized. Furthermore, the dual role of RNA methylation in tumor progression was discussed, concluding that RNA methylation can not only lead to tumorigenesis but at times give rise to inhibition of tumor formation. In addition, further comprehensive analysis on mechanisms of m6A regulators in BC is conducive to screening effective potential targets and formulating targeted treatment strategies, which will provide new methods for the prevention and treatment of BC.

Cost-effectiveness of talazoparib for patients with germline BRCA1/2 mutated HER2-negative advanced breast cancer in China and the US.

Breast cancer is one of the tumors with the highest prevalence rate among women in the world, and its BRCA1/2 gene is a common mutation site. Talazoparib, as a targeted PARP inhibitor, can effectively control the occurrence and development of breast cancer with BRCA1/2 gene mutation, and play a therapeutic role. Based on the findings from the Phase III EMBRACE trial (NCT01945775 clinical trial), our analysis reveals that the talazoparib group demonstrated a significant extension in progression-free survival, along with improved response markers and patient-reported outcomes when compared to conventional therapies. This study aims to assess the cost-effectiveness of talazoparib for treating advanced breast cancer with germline BRCA1/2 mutations and HER2 negativity, considering the perspectives of health services in China and the United States. The results obtained will serve as a valuable reference for promoting rational drug utilization and enhancing medical resource efficiency. To evaluate the cost-effectiveness of Talazoparib more scientifically and provide clinicians with chemotherapy options, this paper developed a Markov model based on the EMBRACA clinical trial (clinical Trails.gov No., NCT01945775) to simulate the survival events of breast cancer patients in the Talazoparib group and the standard treatment group. The state transition probability and clinical data of breast cancer patients during treatment were extracted from the phase III EMBRACA clinical trial. The cost data generated during the treatment process comes from local hospital pricing, other references, and expert consultation. This article uses US dollars to calculate the treatment cost and incremental cost-effectiveness ratio. Health outcomes are expressed in Quality Adjusted Life Years (QALYs). In addition, Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. This article establishes a Markov model for single-item sensitivity analysis. The results show that the economic benefits of using Talazoparib as a new treatment strategy in both China and the United States are higher than other drugs, and it is cost-effective. Compared to the control group, the incremental cost incurred by the Talazoparib treatment group in China was $2484.48/QALY, with an incremental QALY of 1.5. However, Talazoparib in the United States holds a dominant position, saving costs of $10,223.43 and increasing QALYs by 1.5. The clinical treatment effect of Talazoparib group in BRCA1/2 mutant advanced breast cancer patients is better than that of the standard treatment group, and the progression free survival period is significantly prolonged. From the perspective of medical and health services in China and the United States, the Talazoparib group is more economical than the standard treatment group in treating patients with BRCA1/2 mutant advanced breast cancer.

Ckip-1 3'UTR alleviates prolonged sleep deprivation induced cardiac dysfunction by activating CaMKK2/AMPK/cTNI pathway.

Sleep deprivation (SD) has emerged as a critical concern impacting human health, leading to significant damage to the cardiovascular system. However, the underlying mechanisms are still unclear, and the development of targeted drugs is lagging. Here, we used mice to explore the effects of prolonged SD on cardiac structure and function. Echocardiography analysis revealed that cardiac function was significantly decreased in mice after five weeks of SD. Real-time quantitative PCR (RT-q-PCR) and Masson staining analysis showed that cardiac remodeling marker gene Anp (atrial natriuretic peptide) and fibrosis were increased, Elisa assay of serum showed that the levels of creatine kinase (CK), creatine kinase-MB (CK-MB), ANP, brain natriuretic peptide (BNP) and cardiac troponin T (cTn-T) were increased after SD, suggesting that cardiac remodeling and injury occurred. Transcript sequencing analysis indicated that genes involved in the regulation of calcium signaling pathway, dilated cardiomyopathy, and cardiac muscle contraction were changed after SD. Accordingly, Western blotting analysis demonstrated that the cardiac-contraction associated CaMKK2/AMPK/cTNI pathway was inhibited. Since our preliminary research has confirmed the vital role of Casein Kinase-2 -Interacting Protein-1 (CKIP-1, also known as PLEKHO1) in cardiac remodeling regulation. Here, we found the levels of the 3' untranslated region of Ckip-1 (Ckip-1 3'UTR) decreased, while the coding sequence of Ckip-1 (Ckip-1 CDS) remained unchanged after SD. Significantly, adenovirus-mediated overexpression of Ckip-1 3'UTR alleviated SD-induced cardiac dysfunction and remodeling by activating CaMKK2/AMPK/cTNI pathway, which proposed the therapeutic potential of Ckip-1 3'UTR in treating SD-induced heart disease.

Role of N6­methyladenosine in the pathogenesis, diagnosis and treatment of prostate cancer (Review).

Prostate cancer (PCa) affects males of all racial and ethnic groups, and leads to higher rates of mortality in those belonging to a lower socioeconomic status due to the late detection of the disease. PCa affects middle­aged males between the ages of 45 and 60 years, and is the highest cause of cancer­associated mortality in Western countries. As the most abundant and common mRNA modification in higher eukaryotes, N6­methyladenosine (m6A) is widely distributed in mammalian cells and influences various aspects of mRNA metabolism. Recent studies have found that abnormal expression levels of various m6A regulators significantly affect the development and progression of various types of cancer, including PCa. The present review discusses the influence of m6A regulatory factors on the pathogenesis and progression of PCa through mRNA modification based on the current state of research on m6A methylation modification in PCa. It is considered that the treatment of PCa with micro­molecular drugs that target the epigenetics of the m6A regulator to correct abnormal m6A modifications is a direction for future research into current diagnostic and therapeutic approaches for PCa.

Physicians' understanding of antibiotic intravenous-to-oral switching-a qualitative study in Suzhou, China.

BACKGROUND: The implementation of antibiotic intravenous-to-oral switch (IVOS) therapy in hospitals can slow down the development of drug resistance, reduce the occurrence of adverse reactions, and bring significant economic benefits. The aim of this study is to investigate the understanding of physicians at the Second Affiliated Hospital of Soochow University in Suzhou, China towards the antibiotic IVOS therapy. METHODS: 15 physicians working in 9 different departments of the Second Affiliated Hospital of Soochow University participated in this study. A semi-structured face-to-face interview was conducted to collect interview information about the antibiotic IVOS therapy. NVivo12 software was used to organize the entire interview content, and the interview data was analyzed and summarized using the Colaizzi seven step method. RESULTS: 60% of participants were not familiar with antibiotic IVOS therapy. Barriers of antibiotic IVOS therapy were included by three key issues: (i) Physicians' potential cognition: 'Iv is always better than oral'; (ii) Subjective infusion intention of patients; and (iii) Limitations of drug selection. 60% of participants expressed welcome for pharmacists to help them perform antibiotic IVOS treatment. And electronic recognition technology may be a feasible method for prompting IVOS conversion that recognized by all participants in the interview. Participants also provided some suggestions for pharmacists and IVOS computer reminders. CONCLUSION: Physicians' in China still have insufficient understanding of antibiotic IVOS therapy. The promotion of antibiotic IVOS therapy in China faces many challenges and obstacles. Strategies such as IVOS therapy computer reminders and clinical pharmacists' medication guidance were worth studying to help physicians develop antibiotic IVOS treatment.

Acetyl-CoA metabolic accumulation promotes hepatocellular carcinoma metastasis via enhancing CXCL1-dependent infiltration of tumor-associated neutrophils.

High levels of acetyl-CoA are considered a key metabolic feature of metastatic cancers. However, the impacts of acetyl-CoA metabolic accumulation on cancer microenvironment remodeling are poorly understood. In this study, using human hepatocellular carcinoma (HCC) tissues and orthotopic xenograft models, we found a close association between high acetyl-CoA levels in HCCs, increased infiltration of tumor-associated neutrophils (TANs) in the cancer microenvironment and HCC metastasis. Cytokine microarray and enzyme-linked immunosorbent assays (ELISA) revealed the crucial role of the chemokine (C-X-C motif) ligand 1(CXCL1). Mechanistically, acetyl-CoA accumulation induces H3 acetylation-dependent upregulation of CXCL1 gene expression. CXCL1 recruits TANs, leads to neutrophil extracellular traps (NETs) formation and promotes HCC metastasis. Collectively, our work linked the accumulation of acetyl-CoA in HCC cells and TANs infiltration, and revealed that the CXCL1-CXC receptor 2 (CXCR2)-TANs-NETs axis is a potential target for HCCs with high acetyl-CoA levels.

Machine learning models using symptoms and clinical variables to predict coronary artery disease on coronary angiography.

Introduction: Coronary angiography (CAG) is invasive and expensive, while numbers of patients suspected of coronary artery disease (CAD) undergoing CAG results have no coronary lesions. Aim: To develop machine learning algorithms using symptoms and clinical variables to predict CAD. Material and methods: This study was conducted as a cross-sectional study of patients undergoing CAG. We randomly chose 2082 patients from 2602 patients suspected of CAD as the training set, and 520 patients as the test set. We utilized LASSO regression to do feature selection. The area under the receiver operating characteristic curve (AUC), confusion matrix of different thresholds, positive predictive value (PPV) and negative predictive value (NPV) were shown. Support vector machine algorithm performances in 10 folds were conducted in the training set for detecting severe CAD, while XGBoost algorithm performances were conducted in the test set for detecting severe CAD. Results: The algorithm of logistic regression achieved an average AUC of 0.77 in the training set during 10-fold validation and an AUC of 0.75 in the test set. When probability predicted by the model was less than 0.1, 11 patients in the test set (520 patients) were screened out, and NPV reached 90.9%. When probability predicted by the model was less than 0.2, 110 patients in the test set were screened out, and reached 83.6%. Meanwhile, when threshold was set to 0.9, PPV reached 97.4%. When the threshold was set to 0.8, PPV reached 91.5%. Conclusions: Machine learning algorithm using data from hospital information systems could assist in severe CAD exclusion and confirmation, and thus help patients avoid unnecessary CAG.

The application of Moore's online learning interactions model in learning outcomes: The SOR (stimulus-organism-response) paradigm perspective.

This study presents an in-depth exploration of the impact of online learning interactions on student learning outcomes. Drawing from the Stimulus-Organism-Response (SOR) paradigm, our study focuses on the effects of online learning interactions on learners' perception usefulness and ease of use, subsequently impacting their learning outcomes. The study employs a quantitative research methodology, gathering data from a sample of 397 students enrolled in various higher education institutions across China. Data collection involved administering structured questionnaires that were designed to quantitatively assess the three components of the SOR model: stimulus (online learning interactions), organism (students' perceptions), and response (learning outcomes). The measurement model assessment and structural model assessment were conducted. Our findings reveal that online learning interactions can effectively enhance learners' perception of online learning (usefulness and ease of use), thereby influencing their learning outcomes. Notably, perceived usefulness negatively mediates the relationship between online learning interactions and learning outcomes, while perceived ease of use positively mediates this relationship. These findings offer both theoretical and practical implications.

Efficacy of Nemiralisib in Chronic Obstructive Pulmonary Disease: A Systematic Review.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a major public health concern. Exacerbation of COPD leads to poor health and frequent episodes of increased systemic and airway inflammation. Immunomodulatory drugs have garnered extensive attention because they may reduce the rate of COPD exacerbation. This review aimed to evaluate the efficacy and safety of nemiralisib in COPD patients. METHODS: Medical databases, including the Cochrane Library, EMBASE, and PubMed, were queried from inception to June 2023 to identify randomized controlled trials (RCTs) on the efficacy of nemiralisib in COPD patients. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Cochrane Collaboration tool was used to assess the risk of bias of the included RCTs. Two authors independently conducted literature screening and data extraction. Key information from the included studies was extracted, tabulated, and compared using a data extraction table. Moreover, the key characteristics, quality, potential bias, and endpoint outcomes of the included studies were summarized. A meta-analysis was conducted when the study outcomes were sufficiently comparable, and the required data were available for extraction. FINDINGS: Initially, 48 references were identified, leading to the inclusion of four trials. No significant difference was found between the nemiralisib and placebo groups in St George's Respiratory Questionnaire score, modified Medical Research Council Dyspnea Scale score, COPD Assessment Test score, time to next on-treatment exacerbation, proportion of patients achieving exacerbation recovery, time to exacerbation recovery, and rescue medication use. Contrastingly, the results demonstrated that nemiralisib may lower oral corticosteroid use during acute exacerbation of COPD. Meanwhile, the efficacy of nemiralisib on the exacerbation rate, as well as several parameters associated with lung function, including forced expiratory volume in 1 second, specific airway conductance, specific imaging airway wall thickness, distal specific imaging airway volume measured at functional residual capacity, specific imaging airway resistance, low attenuation score, and internal airflow lobar distribution in the lower pulmonary region, were conflicting. Attributed to the limited number of included RCTs and insufficient extracted data, it was not feasible to conduct a comprehensive meta-analysis. IMPLICATIONS: Because of insufficient data, this systematic review could not make any definitive statement regarding the efficacy of nemiralisib in COPD patients. In terms of safety, nemiralisib was generally well tolerated. Further trials are required to explore the efficacy of this drug.

Ginsenoside Rh2-Based Multifunctional Liposomes for Advanced Breast Cancer Therapy.

Background: Most solid tumors are not diagnosed and treated until the advanced stage, in which tumors have shaped mature self-protective power, leading to off-target drugs and nanomedicines. In the present studies, we established a more realistic large tumor model to test the antitumor activity of a multifunctional ginsenoside Rh2-based liposome system (Rh2-lipo) on advanced breast cancer. Methods: Both cholesterol and PEG were substituted by Rh2 to prepare the Rh2-lipo using ethanol-water system and characterized. The effects of Rh2-lipo on cell uptake, penetration of the tumor spheroid, cytotoxicity assay was investigated with 4T1 breast cancer cells and L929 fibroblast cells. The 4T1 orthotopic-bearing large tumor model was established to study the targeting effect of Rh2-lipo and inhibitory effect of paclitaxel loaded Rh2-lipo (PTX-Rh2-lipo) on advanced breast tumors. Results: Rh2-lipo exhibit many advantages that address the limitations of current liposome formulations against large tumors, such as enhanced uptake in TAFs and tumor cells, high targeting and penetration capacity, cytotoxicity against TAFs, normalization of the vessel network, and depletion of stromal collagen. In in vivo study, PTX-Rh2-lipo effectively inhibiting the growth of advanced breast tumors and outperformed most reported PTX formulations, including Lipusu® and Abraxane®. Conclusion: Rh2-lipo have improved drug delivery efficiency and antitumor efficacy in advanced breast cancer, which offers a novel promising platform for advanced tumor therapy.

Rational designed Fe-ZIFs@CoP nanoplatforms for photothermal-enhanced ROS-mediated tumor therapy.

Metal-organic frameworks (MOFs), with biocompatible and bio-friendly properties, exhibit intriguing potential for the drug delivery system and imaging-guided synergistic cancer theranostics. Even though tremendous attention has been attracted on MOFs-based therapeutics, which play a crucial role in therapeutic drugs, gene, and biomedical agents delivery of cancer therapy, they are often explored as simple nanocarriers without further "intelligent" functions. Herein, Fe-doped MOFs with CoP nanoparticles loading were rationally designed and synthesized for photothermal enhanced reactive oxygen species (ROS)-mediated treatment. Fe-ZIFs@CoP could generate efficient ROS through the Fenton reaction while depleting glutathione for amplifying oxidative stress. Particularly, due to the photothermal effect of Fe-ZIFs@CoP, the hyperthermia generated by as-synthesized Fe-ZIFs@CoP facilitated the advanced performance of the Fenton effect for a high amount of ROS generation. The promising "all-in-one" synergistic MOFs platform herein reported provides some prospects for future directions in this area.

Insights into the Superrosids phylogeny and flavonoid synthesis from the telomere-to-telomere gap-free genome assembly of Penthorum chinense Pursh.

The completion of the first telomere-to-telomere (T2T) genome assembly of Penthorum chinense Pursh (PC), a prominent medicinal plant in China, represents a significant achievement. This assembly spans a length of 257.5 Mb and consists of nine chromosomes. PC's notably smaller genome size in Saxifragales, compared to that of Paeonia ostii, can be attributed to the low abundance of transposable elements. By utilizing single-copy genes from 30 species, including 28 other Superrosids species, we successfully resolved a previously debated Superrosids phylogeny. Our findings unveiled Saxifragales as the sister group to the core rosids, with both being the sister group to Vitales. Utilizing previously characterized cytochrome P450 (CYP) genes, we predicted the compound classes that most CYP genes of PC are involved in synthesizing, providing insight into PC's potential metabolic diversity. Metabolomic and transcriptomic data revealed that the richest sources of the three most noteworthy medicinal components in PC are young leaves and flowers. We also observed higher activity of upstream genes in the flavonoid synthesis pathway in these plant parts. Additionally, through weighted gene co-expression network analysis, we identified gene regulatory networks associated with the three medicinal components. Overall, these findings deepen our understanding of PC, opening new avenues for further research and exploration.

RNA m6A methylation regulators in liver cancer.

Liver cancer is one of the most common cancers in the world and a primary cause of cancer-related death. In recent years, despite the great development of diagnostic methods and targeted therapies for liver cancer, the incidence and mortality of liver cancer are still on the rise. As a universal post-transcriptional modification, N6-methyladenosine (m6A) modification accomplishes a dynamic and reversible m6A modification process, which is executed by three types of regulators, methyltransferases (called writers), demethylases (called erasers) and m6A-binding proteins (called readers). Many studies have shown that m6A RNA methylation has an important impact on RNA metabolism, whereas its regulation exception is bound up with the occurrence of human malignant tumors. Aberrant methylation of m6A RNA and the expression of related regulatory factors may be of the essence in the pathogenesis and progression of liver cancer, yet the precise molecular mechanism remains unclear. In this paper, we review the current research situations of m6A methylation in liver cancer. Among the rest, we detail the mechanism by which methyltransferases, demethylases and m6A binding proteins regulate the occurrence and development of liver cancer by modifying mRNA. As well as the potential effect of m6A regulators in hepatocarcinogenesis and progression. New ideas and approaches will be given to the prevention and treatment of liver cancer through the following relevant research results.

Joule heating and electroosmotic flow in cellular micro/nano electroporation.

Localized micro/nano-electroporation (MEP/NEP) shows tremendous potential in cell transfection with high cell viability, precise dose control, and good transfection efficacy. In MEP/NEP, micro or nanochannels are used to tailor the electric field distribution. Cells are positioned tightly by a micron or nanochannel, and the cargoes are delivered into the cell via the channel by electrophoresis (EP). Such confined geometries with micro and nanochannels are also widely used in sorting, isolation, and condensing of biomolecules and cells. Theoretical studies on the electrokinetic phenomena in these applications have been well established. However, for MEP/NEP applications, electrokinetic phenomena and their impact on the cell transfection efficiency and cell survival rate have not been studied comprehensively. In this work, we reveal the coupling between electric field, Joule heating, electroosmosis (EO), and EP in MEP/NEP at different channel sizes. A microfluidic biochip is used to investigate the electrokinetic phenomena in MEP/NEP on a single cell level. Bubble formation is observed at a threshold voltage due to Joule heating. The bubble is pushed to the cargo side due to EO and grows at the outlet of the nanochannel. As the voltage increases, the cargo transport efficiency decreases due to more intense EO, particularly for plasmid DNAs (3.5 kbp) with a low EP mobility. An 'electroporation zone' is defined for NEP/MEP systems with different channel sizes to avoid bubble formation and excessive EO velocity that may reduce the cargo delivery efficiency.

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Ferroptosis: a new promising target for hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is the sixed most common malignant tumor in the world. The study for HCC is mired in the predicament confronted with the difficulty of early diagnosis and high drug resistance, the survival rate of patients with HCC being low. Ferroptosis, an iron-dependent cell death, has been discovered in recent years as a cell death means with tremendous potential to fight against cancer. The in-depth researches for iron metabolism, lipid peroxidation and dysregulation of antioxidant defense have brought about tangible progress in the firmament of ferroptosis with more and more results showing close connections between ferroptosis and HCC. The potential role of ferroptosis has been widely used in chemotherapy, immunotherapy, radiotherapy, and nanotherapy, with the development of various new drugs significantly improving the prognosis of patients. Based on the characteristics and mechanisms of ferroptosis, this article further focuses on the main signaling pathways and promising treatments of HCC, envisioning that existing problems in regard with ferroptosis and HCC could be grappled with in the foreseeable future.

Optimized Liposomal Delivery of Bortezomib for Advancing Treatment of Multiple Myeloma.

Bortezomib (BTZ), a boronic acid-derived proteasome inhibitor, is commonly employed in treating multiple myeloma (MM). However, the applications of BTZ are limited due to its poor stability and low bioavailability. Herein, we develop an optimized liposomal formulation of BTZ (L-BTZ) by employing a remote-loading strategy. This formulation uses Tiron, a divalent anionic catechol derivative, as the internal complexing agent. Compared to earlier BTZ-related formulations, this alternative formulation showed significantly greater stability due to the Tiron-BTZ complex's higher pH stability and negative charges, compared to the meglumine-BTZ complex. Significantly, the plasma AUC of L-BTZ was found to be 30 times greater than that of free BTZ, suggesting an extended blood circulation duration. In subsequent therapeutic evaluations using two murine xenograft tumor models of MM, the NCI-H929 and OPM2 models showed tumor growth inhibition (TGI) values of 37% and 57%, respectively. In contrast, free BTZ demonstrated TGI values of 17% and 11% in these models. Further, L-BTZ presented enhanced antitumor efficacy in the Hepa1-6 HCC syngeneic model, indicating its potential broader applicability as an antineoplastic agent. These findings suggest that the optimized L-BTZ formulation offers a significant advancement in BTZ delivery, holding substantial promise for clinical investigation in not merely MM, but other cancer types.

Integrated multi-omic analysis reveals the cytokinin and sucrose metabolism-mediated regulation of flavone glycoside biosynthesis by MeJA exposure in Ficus pandurata Hance.

Ficus pandurata Hance (FPH) holds a rich history as a traditional Chinese botanical remedy, utilized both as a culinary condiment and a medicinal intervention for diverse ailments. This study focuses on enhancing FPH's therapeutic potential by subjecting it to exogenous methyl jasmonate (MeJA) treatment, a strategy aimed at elevating the levels of active constituents to align with clinical and commercial requirements. Employing metabolomics, the impact of MeJA treatment on the lipid and flavonoid profiles of FPH leaves was investigated, revealing a marked increase in flavone glycosides, a subset of flavonoids. Investigation into the regulatory mechanism governing flavone glycoside biosynthesis uncovered elevated expression of structural genes associated with flavonoid production in response to MeJA exposure. Global endogenous hormone analysis pinpointed the selective activation of JA and cytokinin biosynthesis following MeJA treatment. Through a comprehensive integration of transcriptomic and metabolomic data, the cooperative stimulation of glucosyltransferase activity, alongside the JA and cytokinin signaling pathways, orchestrated by MeJA were explored. Furthermore, genes linked to sucrose metabolism exhibited heightened expression, concomitant with a noteworthy surge in antioxidant activity subsequent to MeJA treatment. These findings validate the augmentation of FPH leaf antioxidant capacity through MeJA intervention, while also offering profound insights into the regulatory role of MeJA in flavone glycoside biosynthesis, mediated by the interplay between cytokinin and sucrose metabolism pathways.