Triaryl Carbenium Ion Pair Mediated Electrocatalytic Benzylic C-H Oxygenation in Air.

The selective oxidation of benzylic C-H bonds is a pivotal transformation in organic synthesis. Undoubtedly, achieving efficient and highly selective aerobic oxidation of methylarenes to benzaldehydes has been highly challenging due to the propensity of benzaldehyde to undergo overoxidation under typical aerobic conditions. Herein, we propose an innovative approach to address this issue by leveraging electrocatalytic processes, facilitated by ion-pair mediators [Ph3C]+[B(C6F5)4]-. By harnessing the power of electrochemistry, we successfully demonstrated the effectiveness of our strategy, which enables the selective oxidation of benzylic C-H bonds in benzylic molecules and toluene derivatives. Notably, our approach exhibited high efficiency, excellent selectivity, and compatibility with various functional groups, underscoring the broad applicability of our methodology.

Preferential Adsorption of Ethylene Oxide on Fe and Chlorine on Ni Enabled Scalable Electrosynthesis of Ethylene Chlorohydrin.

Industrial manufacturing of ethylene chlorohydrin (ECH) critically requires excess corrosive hydrochloric acid or hypochlorous acid with dealing with massive by-products and wastes. Here we report a green and efficient electrosynthesis of ECH from ethylene oxide (EO) with NaCl over a NiFe2 O4 nanosheet anode. Theoretical results suggest that EO and Cl preferentially adsorb on Fe and Ni sites, respectively, collaboratively promoting the ECH synthesis. A Cl radical-mediated ring-opening process is proposed and confirmed, and the key Cl and carbon radical species are identified by high-resolution mass spectrometry. This strategy can enable scalable electrosynthesis of 185.1 mmol of ECH in 1 h with 92.5 % yield at a 55 mA cm-2 current density. Furthermore, a series of other chloro- and bromoethanols with good to high yields and paired synthesis of ECH and 4-amino-3,6-dichloropyridine-2-carboxylicacid via respectively loading and unloading Cl are achieved, showing the promising potential of this strategy.

Harnessing 4D Printing Bioscaffolds for Advanced Orthopedics.

The development of programmable functional biomaterials makes 4D printing add a new dimension, time (t), based on 3D structures (x, y, z), therefore, 4D printed constructs could transform their morphology or function over time in response to environmental stimuli. Nowadays, highly efficient bone defect repair remains challenging in clinics. Combining programmable biomaterials, living cells, and bioactive factors, 4D bioprinting provides greater potential for constructing dynamic, personalized, and precise bone tissue engineering scaffolds by complex structure formation and functional maturation. Therefore, 4D bioprinting has been regarded as the next generation of bone repair technology. This review focuses on 4D printing and its advantages in orthopedics. The applications of different smart biomaterials and 4D printing strategies are briefly introduced. Furthermore, one summarizes the recent advancements of 4D printing in bone tissue engineering, uncovering the addressed and unaddressed medical requirements. In addition, current challenges and future perspectives are further discussed, which will offer more inspiration about the clinical transformation of this emerging 4D bioprinting technology in bone regeneration.

Recent Advances of Poly(ester amide)s-Based Biomaterials.

Biodegradable and biocompatible biomaterials have offered much more opportunities from an engineering standpoint for treating diseases and maintaining health. Poly(ester amide)s (PEAs), as an outstanding family among such biomaterials, have risen overwhelmingly in the past decades. These synthetic polymers have easily and widely available raw materials and a diversity of synthetic approaches, which have attracted considerable attention. More importantly, combining the superiorities of polyamides and polyesters, PEAs have emerged with better functions. They could have improved biodegradability, biocompatibility, and cell-material interactions. The PEAs derived from α-amino acids even allow the introduction of pendant sites for further modification or functionalization. Meanwhile, it is gradually recognized that the chemical structures are closely related to the physiochemical and biological properties of PEAs so that their properties can be precisely controlled. PEAs therefore become significant materials in the biomedical fields. This review will attempt to summarize the recent progress in the development of PEAs with respect to the preparation materials and methods, structure-property relationships along with their latest biomedical accomplishments, especially for drug delivery and tissue engineering.

Metabolic reprogramming by traditional Chinese medicine and its role in effective cancer therapy.

Metabolic reprogramming, characterized by alterations of cellular metabolic patterns, is fundamentally important in supporting the malignant behaviors of cancer cells. It is considered as a promising therapeutic target against cancer. Traditional Chinese medicine (TCM) and its bioactive components have been used in cancer therapy for an extended period, and they are well-known for their multi-target pharmacological functions and fewer side effects. However, the detailed and advanced mechanisms underlying the anticancer activities of TCM remain obscure. In this review, we summarized the critical processes of cancer cell metabolic reprogramming, including glycolysis, mitochondrial oxidative phosphorylation, glutaminolysis, and fatty acid biosynthesis. Moreover, we systemically reviewed the regulatory effects of TCM and its bioactive ingredients on metabolic enzymes and/or signal pathways that may impede cancer progress. A total of 46 kinds of TCMs was reported to exert antitumor effects and/or act as chemosensitizers via regulating metabolic processes of cancer cells, and multiple targets and signaling pathways were revealed to contribute to the metabolic-modulating functions of TCM. In conclusion, TCM has its advantages in ameliorating cancer cell metabolic reprogramming by its poly-pharmacological actions. This review may shed some new light on the explicit recognition of the mechanisms of anticancer actions of TCM, leading to the development of natural antitumor drugs based on reshaping cancer cell metabolism.

A stochastic eco-epidemiological system with patchy structure and transport-related infection.

In this paper, a stochastic eco-epidemiological system with patchy structure and transport-related infection is proposed and the stochastic dynamical behaviors are investigated. Firstly, by constructing suitable Lyapunov functions, it is revealed that there is a unique globally positive solution starting from the positive initial value. Secondly, it is proved that the presented system is stochastically ultimately bounded and the average in time of the second moment of solution is bounded. Thirdly, we prove that the large enough stochastic perturbations may lead the predator population and the diseases in the predator to be extinct while it is persistent in the deterministic system. Finally, some numerical simulations are given to test our theoretical results.

Design and development of spirulina polysaccharide-loaded nanoemulsions with improved the antitumor effects of paclitaxel.

Aims: In this study, we prepared spirulina polysaccharides into spirulina polysaccharide-loaded nanoemulsions (SPS-NEs), and determined the antitumor effect of SPS-NEs, when combined with paclitaxel (PTX).Methods: SPS-NEs were prepared by a phase transformation method. The Characterisation and stability of SPS-NEs was measured. The antitumor effect of SPS-NEs combined with PTX was determined by S180 cells or RAW 264.7 macrophages and S180 tumour-bearing mice.Results: SPS-NEs were spherical and stable, the particle size of SPS-NEs was 84.6 ± 3.31 nm, PDI = 0.235 ± 0.02. PTX + SPS-NEs exhibited a much greater toxicity against RAW 264.7 cells than PTX. PTX + SPS-NEs increased the release of NO, IL-6 and TNF-α, and the expression of p-p65 NF-κB, p-I-κB, TLR4. In addition, PTX + SPS-NEs significantly inhibited tumour growth by 72.82% and increased the secretion of serum IL-2, TNF-α and IFN-γ.Conclusions: SPS-NEs can regulate immunity through TLR4/NF-κB signalling pathways, which enhances the anti-tumour effect of PTX.

Polygala tenuifolia: a source for anti-Alzheimer's disease drugs.

Context: Alzheimer's disease (AD) is a chronic neurodegenerative disease that originates from central nervous system lesions or recessions. Current estimates suggest that this disease affects over 35 million people worldwide. However, lacking effective drugs is the biggest handicap in treating AD. In traditional Chinese medicine (TCM), Polygala tenuifolia Willd. (Polygalaceae) is generally used to treat insomnia, memory dysfunction and neurasthenia.Objective: This review article explores the role of P. tenuifolia and its active components in anti-Alzheimer's disease.Methods: Literature for the last ten years was obtained through a search on PubMed, SciFinder, CNKI, Google Scholar, Web of Science, Science Direct and China Knowledge Resource Integrated with the following keywords: Polygala tenuifolia, polygalasaponin XXXII (PGS 32), tenuifolin, polygalacic acid, senegenin, tenuigenin, Alzheimer's disease.Results: Polygala tenuifolia and its active components have multiplex neuroprotective potential associated with AD, such as anti-Aß aggregation, anti-Tau protein, anti-inflammation, antioxidant, anti-neuronal apoptosis, enhancing central cholinergic system and promote neuronal proliferation.Conclusions: Polygala tenuifolia and its active components exhibit multiple neuroprotective effects. Hence, P. tenuifolia is a potential drug against Alzheimer's disease, especially in terms of prevention.

Electrocatalytic Deuteration of Halides with D2 O as the Deuterium Source over a Copper Nanowire Arrays Cathode.

Precise deuterium incorporation with controllable deuterated sites is extremely desirable. Here, a facile and efficient electrocatalytic deuterodehalogenation of halides using D2 O as the deuteration reagent and copper nanowire arrays (Cu NWAs) electrochemically formed in situ as the cathode was demonstrated. A cross-coupling of carbon and deuterium free radicals might be involved for this ipso-selective deuteration. This method exhibited excellent chemoselectivity and high compatibility with the easily reducible functional groups (C=C, C≡C, C=O, C=N, C≡N). The C-H to C-D transformations were achieved with high yields and deuterium ratios through a one-pot halogenation-deuterodehalogenation process. Efficient deuteration of less-active bromide substrates, specific deuterium incorporation into top-selling pharmaceuticals, and oxidant-free paired anodic synthesis of high-value chemicals with low energy input highlighted the potential practicality.

A validated high-performance liquid chromatography-tandem mass spectrometry method for quantification of gefitinib and its main metabolites in xenograft mouse tumor: Application to a pharmacokinetics study.

Monitoring gefitinib and its metabolites may help to explore the underlying mechanisms of gefitinib resistance. The concentration of gefitinib and its metabolites in tumor tissues could influence its anticancer activities more than that in the plasma. In the present study, a rapid and specific HPLC-MS/MS method was developed and validated to simultaneously determine gefitinib, M387783, M523595, M537194 and M608236 in tumor tissues of H1975 human lung cancer xenografts of nude mice. The established HPLC-MS/MS method was validated for specificity, linearity, accuracy and precision, matrix effect and recovery, carryover and dilution integrity, and analyte stability. The standard curves were linear (r2 ≥ 0.99) over the range of 0.5-100 ng/mL for M608236 and 1-200 ng/mL for gefitinib, M523595 and M537194 as well as M387783. The accuracy ranged from -8.35 to 6.03% relative error; and the precision was <15% relative standard deviation. Recoveries (87.74-99.96%) and matrix effects (86.60-106.40%) were satisfactory in the biological matrix examined. Stability studies showed that the analytes were stable during the assay procedure and storage. Finally, the validated method was successfully applied to study the pharmacokinetics profiles for gefitinib and its metabolites in nonsmall cell lung cancer (NSCLC) xenograft mouse tumors. Meanwhile, MTT assay showed that gefitinib had a more powerful inhibitory effect than its four major metabolites in H1975 NSCLC cells. This validated HPLC-MS/MS method may be applied to help understand the mechanisms of gefitinib resistance in EGFR-mutant nonsmall cell lung cancer.

Tumor-associated myoepithelial cells promote the invasive progression of ductal carcinoma in situ through activation of TGFß signaling.

The normal myoepithelium has a tumor-suppressing nature and inhibits the progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC). Conversely, a growing number of studies have shown that tumor-associated myoepithelial cells have a tumor-promoting effect. Moreover, the exact role of tumor-associated myoepithelial cells in the DCIS-to-IDC development remains undefined. To address this, we explored the role of tumor-associated myoepithelial cells in the DCIS-to-IDC progression. We developed a direct coculture system to study the cell-cell interactions between DCIS cells and tumor-associated myoepithelial cells. Coculture studies indicated that tumor-associated myoepithelial cells promoted the invasive progression of a DCIS cell model in vitro, and mechanistic studies revealed that the interaction with DCIS cells stimulated tumor-associated myoepithelial cells to secrete TGFß1, which subsequently contributed to activating the TGFß/Smads pathway in DCIS cells. We noted that activation of the TGFß signaling pathway promoted the epithelial-mesenchymal transition, basal-like phenotypes, stemness, and invasiveness of DCIS cells. Importantly, xenograft studies further demonstrated that tumor-associated myoepithelial cells enhanced the DCIS-to-IDC progression in vivo Furthermore, we found that TGFß-mediated induction of oncogenic miR-10b-5p expression and down-regulation of RB1CC1, a miR-10b-5p-targeted tumor-suppressor gene, contributed to the invasive progression of DCIS. Our findings provide the first experimental evidence to directly support the paradigm that altered DCIS-associated myoepithelial cells promote the invasive progression of DCIS into IDC via TGFß signaling activation.

Detection of Redox State Evolution during Wound Healing Process Based on a Redox-Sensitive Wound Dressing.

To detect the redox state evolution during wound healing process, a redox-sensitive surface-enhanced Raman scattering (SERS) probe was constructed by attaching anthraquinone as a redox-sensitive molecule onto gold nanoshells, and the redox-sensitive SERS probes were loaded on one surface of a chitosan membrane as a redox-sensitive wound dressing. The redox-sensitive wound dressing covered an acute wound as both a wound dressing and a redox state sensor. The spatiotemporal evolution of the redox states of the healing wound was obtained by collecting the SERS spectra of the SERS probes in situ and noninvasively. The domains with the lowest redox potential moved from the edge to the center of a wound during normal wound healing process, and high concentration of glucose blocked the movement of the domains and the healing process. The redox-sensitive wound dressing and the method of detecting redox states of the wound provide a new path for detection in vivo, which would benefit the understanding and therapy of wound healing and other pathophysiological processes.

Marsdenia tenacissima extract induces apoptosis and suppresses autophagy through ERK activation in lung cancer cells.

BACKGROUND: Marsdenia tenacissima is an herb medicine which has been utilized to treat malignant diseases for decades. The M. tenacissima extract (MTE) shows significant anti-proliferation activity against non-small cell lung cancer (NSCLC) cells, but the underlying mechanisms remain unclear. In this study, we explored the potential anti-proliferation mechanisms of MTE in NSCLC cells in relation to apoptosis as well as autophagy, which are two critical forms to control cancer cell survival and death. METHODS: The proliferation of H1975 and A549 cells was evaluated by MTT assay. Cell apoptosis was assessed by Annexin V and PI staining, Caspase 3 expression and activity. Autophagy flux proteins were detected by Western blot with or without autophagy inducer and inhibitor. Endogenous LC3-II puncta and LysoTracker staining were monitored by confocal microscopy. The formation of autophagic vacuoles was measured by acridine orange staining. ERK is a crucial molecule to interplay with cell autophagy and apoptosis. The role of ERK on cell apoptosis and autophagy influenced by MTE was determined in the presence of MEK/ERK inhibitor U0126. RESULTS: The significant growth inhibition and apoptosis induction were observed in MTE treated NSCLC cells. MTE induced cell apoptosis coexisted with elevated Caspase 3 activity. MTE also impaired autophagic flux by upregulated LC3-II and p62 expression. Autophagy inducer EBSS could not abolish the impaired autophagic flux by MTE, while it was augmented in the presence of autophagy inhibitor Baf A1. The autophagosome-lysosome fusion was blocked by MTE via affecting lysosome function as evidenced by decreased expression of LAMP1 and Cathepsin B. The molecule ERK became hyperactivated after MTE treatment, but the MEK/ERK inhibitor U0126 abrogated autophagy inhibition and apoptosis induction caused by MTE, suggested that ERK signaling pathways partially contributed to cell death caused by MTE. CONCLUSION: Our results demonstrate that MTE caused apoptosis induction as well as autophagy inhibition in NSCLC cells. The activated ERK is partially associated with NSCLC apoptotic and autophagic cell death in response to MTE treatment. The present findings reveal new mechanisms for the anti-tumor activity of MTE against NSCLC.

Redox State Detection of Fruits and Vegetables by a Simple Surface-Enhanced Raman Scattering Method.

In order to detect the redox states of fruits and vegetables simply, a SERS (surface-enhanced Raman scattering) method was developed based on a redox-sensitive probe and a pH-sensitive probe. The two probes were dropped onto the flesh of the fresh incision of fruits and vegetables, respectively. The SERS spectra of redox-sensitive probes were used to indicate their redox states, and the SERS spectra of pH-sensitive probes were used to indicate their pH values to discount the influence of pH on the redox states. The order of redox states (redox potential) of the detected fruits and vegetables is as follows: carrot < Green delicious apple < Xinjiang kuerle fragrant pear < Chinese royal pear < Fuji apple < crystal pear < Golden marshall apple < potato. Compared with traditional methods based on the detection of extracts, the developed method is simple without any pretreatments and consumption of additional chemicals, which would become a popular evaluation methodology of the redox states of fruits and vegetables during their growth and storage stages.

A Methylthio-Functionalized-MOF Photocatalyst with High Performance for Visible-Light-Driven H2 Evolution.

Recently, the emergence of photoactive metal-organic frameworks (MOFs) has given great prospects for their applications as photocatalytic materials in visible-light-driven hydrogen evolution. Herein, a highly photoactive visible-light-driven material for H2 evolution was prepared by introducing methylthio terephthalate into a MOF lattice via solvent-assisted ligand-exchange method. Accordingly, a first methylthio-functionalized porous MOF decorated with Pt co-catalyst for efficient photocatalytic H2 evolution was achieved, which exhibited a high quantum yield (8.90 %) at 420 nm by use sacrificial triethanolamine. This hybrid material exhibited perfect H2 production rate as high as 3814.0 µmol g-1 h-1 , which even is one order of magnitude higher than that of the state-of-the-art Pt/MOF photocatalyst derived from aminoterephthalate.

Metabolic profiling of tenacigenin B, tenacissoside H and tenacissoside I using UHPLC-ESI-Orbitrap MS/MS.

Marsdenia tenacissima, which is widely used as an anticancer herb in traditional Chinese medicine, has been shown to possess anticancer activity. However, its metabolic profile is poorly investigated. Tenacigenin B is the major steroidal skeleton of C-21 steroids in M. tenacissima. Tenacissoside H and Tenacissoside I are detected at relatively high levels in M. tenacissima. Therefore, we studied their metabolic characteristics in human liver microsomes by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry. Fourteen metabolites were tentatively identified by accurate mass measurement and MS/MS fragmentation behavior. It was found that hydroxylation reactions were the major metabolic pathway of Tenacissoside H and Tenacissoside I in human liver microsomes, whereas the metabolic pathway of Tenacigenin B involved dehydrogenation reactions. This is the first time that the metabolic profile of C-21 steroids from M. tenacissima has been explored in human liver microsomes, which is of great significance for subsequent pharmacokinetic and interaction research. Biotransformation in vivo or in vitro may influence the structure of a compound and change its activity. Identification of their fragmentation behaviors and metabolites provides valuable and new information for further understanding the anti-tumor activity of M. tenacissima. Copyright © 2016 John Wiley & Sons, Ltd.

Enhancement of gefitinib-induced growth inhibition by Marsdenia tenacissima extract in non-small cell lung cancer cells expressing wild or mutant EGFR.

BACKGROUND: Non-small cell lung cancer (NSCLC) expressed high levels of epidermal growth factor receptor (EGFR). Gefitinib (Iressa) has demonstrated clinical efficacy in NSCLC patients harboring EGFR mutations or refractory to chemotherapy. However, most of NSCLC patients are with wild type EGFR, and showed limited response to gefitinib. Therefore, to develop new effective therapeutic interventions for NSCLC is still required. Our previous study showed Marsdenia tenacissima extract (MTE) restored gefitinib efficacy in the resistant NSCLC cells, but whether MTE acts in the gefitinib-sensitive NSCLC cells is the same as it in the resistant one is unknown. METHODS: Dose response curves for gefitinib and MTE were generated for two sensitive NSCLC cell lines with mutant or wild type EGFR status. Three different sequential combinations of MTE and gefitinib on cell growth were evaluated using IC50 and Combination Index approaches. The flow cytometric method was used to detect cell apoptosis and cell cycle profile. The impact of MTE combined with gefitinib on cell molecular network response was studied by Western blotting. RESULTS: Unlike in the resistant NSCLC cells, our results revealed that low cytotoxic dose of MTE (8 mg/ml) combined gefitinib with three different schedules synergistically or additively enhanced the growth inhibition of gefitinib. Among which, MTE→MTE+gefitinib treatment was the most effective one. MTE markedly prompted cell cycle arrest and apoptosis caused by gefitinib both in EGFR mutant (HCC827) and wild type of NSCLC cells (H292). The Western blotting results showed that MTE→MTE+gefitinib treatment further enhanced the suppression of gefitinib on cell growth and apoptosis pathway such as ERK1/2 and PI3K/Akt/mTOR. This combination also blocked the activation of EGFR and c-Met which have cross-talk with each other. Unlike in gefitinib-resistant NSCLC cells, MTE alone also demonstrated certain unexpected modulation on EGFR related cell signal pathways in the sensitive cells. CONCLUSION: Our results suggest that MTE is a promising herbal medicine to improve gefitinib efficacy in NSCLC regardless of EGFR status. However, why MTE acted differently between gefitinib-sensitive and -resistant NSCLC cells needs a further research.

PM2.5 pollution modulates the response of ozone formation to VOC emitted from various sources: Insights from machine learning.

Numerous studies have linked ozone (O3) production to its precursors and fine particulate matter (PM2.5), while the complex interaction effects of PM2.5 and volatile organic compounds (VOCs) on O3 remain poorly understood. A systematic approach based on an interpretable machine learning (ML) model was utilized to evaluate the primary driving factors that impact O3 and to elucidate how changes in PM2.5, VOCs from different sources, NOx, and meteorological conditions either promote or inhibit O3 formation through their individual and synergistic effects in a tropical coastal city, Haikou, from 2019 to 2020. The results suggest that under low PM2.5 levels, alongside the linear O3-PM2.5 relationship observed, O3 formation is suppressed by PM2.5 with higher proportions of traffic-derived aerosol. Vehicle VOC emissions contributed maximally to O3 formation at midday, despite the lowest concentration. VOCs from fossil fuel combustion and industry emissions, which have opposing effects on O3, act as inhibitors and promoters by inducing diverse photochemical regimes. As PM2.5 pollution escalates, the impact of these VOCs reverses, becoming more pronounced in shaping O3 variation. Sensitivity analysis reveals that the O3 formation regime is VOC-limited, and effective regional O3 mitigation requires prioritizing substantial VOC reductions to offset enhanced VOC sensitivity induced by the co-reduction in PM2.5, with a focus on industrial and vehicular emissions, and subsequently, fossil fuel combustion once PM2.5 is effectively controlled. This study underscores the potential of the SHAP-based ML approach to decode the intricate O3-NOx-VOCs-PM2.5 interplay, considering both meteorological and atmospheric compositional variations.

SILAC proteomics based on 3D cell spheroids unveils the role of RAC2 in regulating the crosstalk between triple-negative breast cancer cells and tumor-associated macrophages.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and is characterized by a high infiltration of tumor-associated macrophages (TAMs). TAMs contribute significantly to tumor progression by intricately interacting with tumor cells. Deeply investigating the interaction between TNBC cells and TAMs is of great importance for finding potential biomarkers and developing novel therapeutic strategies to further improve the clinical outcomes of TNBC patients. In this study, we confirmed the interplay using both 3D and 2D co-culture models. The stable-isotype labeling by amino acids in cell culture (SILAC)-based quantitative proteomics was conducted on 3D cell spheroids containing TNBC cells and macrophages to identify the potential candidate in regulating the crosstalk between TNBC and TAMs. Ras-related C3 botulinum toxin substrate 2 (RAC2) was identified as a potential molecule for further exploration, given its high expression in TNBC and positive correlation with M2 macrophage infiltration. The suppression of RAC2 inhibited TNBC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Meanwhile, knocking down RAC2 in TNBC cells impaired macrophage recruitment and M2 polarization. Mechanistically, RAC2 exerted its roles in TNBC cells and TAMs by regulating the activation of P65 NF-κB and P38 MAPK, while TAMs further elevated RAC2 expression and P65 NF-κB activation by secreting soluble mediators including IL-10. These findings highlight the significance of RAC2 as a crucial molecule in the crosstalk between TNBC and TAMs, suggesting it could be a promising therapeutic target in TNBC.

Targeting cancer stem cell plasticity in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with limited treatment options. Cancer stem cells (CSCs) are thought to play a crucial role in TNBC progression and resistance to therapy. CSCs are a small subpopulation of cells within tumors that possess self-renewal and differentiation capabilities and are responsible for tumor initiation, maintenance, and metastasis. CSCs exhibit plasticity, allowing them to switch between states and adapt to changing microenvironments. Targeting CSC plasticity has emerged as a promising strategy for TNBC treatment. This review summarizes recent advances in understanding the molecular mechanisms underlying CSC plasticity in TNBC and discusses potential therapeutic approaches targeting CSC plasticity.