Impaired 2',3'-cyclic phosphate tRNA repair causes thermo-sensitive genic male sterility in rice.

Hybrid rice, widely planted in Asia, is pathogen resistant and has superior yields, making it a major contributor to global food security. The two-line hybrid rice system, which utilizes mutants exhibiting photo-/thermo-sensitive genic male sterility (P/TGMS), is the leading hybrid rice breeding technology. Mutations in THERMO-SENSITIVE GENIC MALE STERILE 5 (TMS5) accounts for over 95% of current TGMS lines. We previously found that tms5 carries a mutation in ribonuclease ZS1. Despite its importance for breeding robust rice lines, the mechanism underlying tms5-mediated TGMS remains elusive. Here, we demonstrate that TMS5 is a tRNA 2',3'-cyclic phosphatase. The tms5 mutation leads to accumulation of 2',3'-cyclic phosphate (cP)-ΔCCA-tRNAs (tRNAs without 3' CCA ended with cP), which is exacerbated by high temperatures, and reduction in the abundance of mature tRNAs, particularly alanine tRNAs (tRNA-Alas). Overexpression of tRNA-Alas in the tms5 mutant restores male fertility to 70%. Remarkably, male fertility of tms5 mutant is completely restored at high temperatures by knocking out OsVms1 which encodes the enzyme for cP-ΔCCA-tRNA generation. Our study reveals the mechanism underlying tms5-mediated TGMS in rice and provides mechanistic insight into the further improvement of TGMS in hybrid crop development.

Evolving capabilities of computed tomography imaging for transcatheter valvular heart interventions - new opportunities for precision medicine.

The last decade has witnessed a substantial growth in percutaneous treatment options for heart valve disease. The development in these innovative therapies has been mirrored by advances in multi-detector computed tomography (MDCT). MDCT plays a central role in obtaining detailed pre-procedural anatomical information, helping to inform clinical decisions surrounding procedural planning, improve clinical outcomes and prevent potential complications. Improvements in MDCT image acquisition and processing techniques have led to increased application of advanced analytics in routine clinical care. Workflow implementation of patient-specific computational modeling, fluid dynamics, 3D printing, extended reality, extracellular volume mapping and artificial intelligence are shaping the landscape for delivering patient-specific care. This review will provide an insight of key innovations in the field of MDCT for planning transcatheter heart valve interventions.

Interleukin-10 overexpression in 4T1 cells: A gateway to suppressing mammary carcinoma growth.

Interleukin-10 (IL-10) exerts complex effects on tumor growth, exhibiting both pro- and anti-tumor properties. Recent focus on the anti-inflammatory properties of IL-10 has highlighted its potential anti-tumor properties, particularly through the enhancement of CD8+ T cell activity. However, further research is needed to fully elucidate its other anti-tumor mechanisms. Our study investigates novel anti-tumor mechanisms of IL-10 in a murine mammary carcinoma model (4T1). We found that IL-10 overexpression in mouse 4T1 cells suppressed tumor growth in vivo. This suppression was accompanied by an increase in IFN-γ-secreting CD8+ T cells and a decrease in myeloid-derived suppressor cells (MDSCs) in tumor tissue. In vitro experiments showed that IL-10-rich tumor cell-derived supernatants inhibited myeloid cell differentiation into monocytic and granulocytic MDSCs while reducing MDSCs migration. In addition, IL-10 overexpression downregulated CXCL5 expression in 4T1 cells, resulting in decreased CXCR2+ MDSCs infiltration. Using RAG1-deficient mice and CXCL5 knockdown tumor models, we demonstrated that the anti-tumor effects of IL-10 depend on both CD8+ T cells and reduced MDSC infiltration. IL-10 attenuated the immunosuppressive tumor microenvironment by enhancing CD8+ T cell activity and inhibiting MDSCs infiltration. In human breast cancer, we observed a positive correlation between CXCL5 expression and MDSC infiltration. Our findings reveal a dual mechanism of IL-10-mediated tumor suppression: (1) direct enhancement of CD8+ T cell activity and (2) indirect reduction of immunosuppressive MDSCs through CXCL5 downregulation and inhibition of myeloid cell differentiation. This study provides new insights into the role of IL-10 in anti-tumor immunity and suggests potential strategies for breast cancer immunotherapy by modulating the IL-10-CXCL5-MDSCs axis.

Nanomedicines with Versatile GSH-Responsive Linkers for Cancer Theranostics.

Glutathione (GSH)-responsive nanomedicines have generated significant interest in biochemistry, oncology, and material sciences due to their diverse applications, including chemical and biological sensors, diagnostics, and drug delivery systems. The effectiveness of these smart GSH-responsive nanomedicines depends critically on the choice of GSH-responsive linkers. Despite their crucial role, comprehensive reviews of GSH-responsive linkers are scarce, revealing a gap in the current literature. This review addresses this gap by systematically summarizing various GSH-responsive linkers and exploring their potential applications in cancer treatment. We provide an overview of the mechanisms of action of these linkers and their bioapplications, evaluating their advantages and limitations. The insights presented aim to guide the development of advanced GSH-responsive agents for cancer diagnosis and therapy.

Chemical-Assisted CO2 Water-Alternating-Gas Injection for Enhanced Sweep Efficiency in CO2-EOR.

CO2-enhanced oil recovery (CO2-EOR) is a crucial method for CO2 utilization and sequestration, representing an important zero-carbon or even negative-carbon emission reduction technology. However, the low viscosity of CO2 and reservoir heterogeneity often result in early gas breakthrough, significantly reducing CO2 utilization and sequestration efficiency. A water-alternating-gas (WAG) injection is a technique for mitigating gas breakthrough and viscous fingering in CO2-EOR. However, it encounters challenges related to insufficient mobility control in highly heterogeneous and fractured reservoirs, resulting in gas channeling and low sweep efficiency. Despite the extensive application and research of a WAG injection in oil and gas reservoirs, the most recent comprehensive review dates back to 2018, which focuses on the mechanisms of EOR using conventional WAG. Herein, we give an updated and comprehensive review to incorporate the latest advancements in CO2-WAG flooding techniques for enhanced sweep efficiency, which includes the theory, applications, fluid displacement mechanisms, and control strategies of a CO2-WAG injection. It addresses common challenges, operational issues, and remedial measures in WAG projects by covering studies from experiments, simulations, and pore-scale modeling. This review aims to provide guidance and serve as a reference for the application and research advancement of CO2-EOR techniques in heterogeneous and fractured reservoirs.

Mapping sagittal-plane reference brain atlas of the cynomolgus macaque (Macaca fascicularis) based on consecutive cytoarchitectonic images.

The brain atlas is essential for exploring the anatomical structure and function of the brain. Non-human primates, such as cynomolgus macaque, have received increasing attention due to their genetic similarity to humans. However, current macaque brain atlases only offer coarse sections with intervals along the coronal direction, failing to meet the needs of single-cell resolution studies in functional and multi-omics research of the macaque brain. To address this issue, we utilized fluorescence micro-optical sectioning tomography to obtain sub-micron resolution cytoarchitectonic images of the macaque brain at the sagittal plane. Based on the obtained 8000 image sequences, a reference brain atlas comprising 45 sagittal sections was created, delineating 270 brain regions other than the cortex. Additionally, a website was established to share the reference atlas corresponding image data. This study is expected to provide an essential dataset and tool for scientists studying the macaque brain.

Genipin promotes the apoptosis and autophagy of neuroblastoma cells by suppressing the PI3K/AKT/mTOR pathway.

This study investigated the underlying function and mechanism of genipin in neuroblastoma (NB). Using flow cytometry analysis and cytotoxicity tests, in vitro studies were conducted to assess the effects of genipin on the SK-N-SH cell line. The mechanism of action of genipin was explored through immunofluorescence staining, Western blotting, and caspase-3 activity assays. In addition, we also created a xenograft tumour model to investigate the effects of genipin in vivo. This research confirmed that genipin suppressed cell viability, induced apoptosis, and promoted autophagy, processes that are likely linked to the inhibition of the PI3K/AKT/mTOR signalling pathway. Autophagy inhibition increases the sensitivity of SK-N-SH cells to genipin. Furthermore, combination treatment with a PI3K inhibitor enhanced the therapeutic efficacy of genipin. These results highlight the potential of genipin as a candidate drug for the treatment of NB.

Large-Area Layered Membranes with Precisely Controlled Nano-Confined Channels.

Two-dimensional (2D) nanosheets-based membranes, which have controlled 2D nano-confined channels, are highly desirable for molecular/ionic sieving and confined reactions. However, it is still difficult to develop an efficient method to prepare large-area membranes with high stability, high orientation, and accurately adjustable interlayer spacing. Here, we present a strategy to produce metal ion cross-linked membranes with precisely controlled 2D nano-confined channels and high stability in different solutions using superspreading shear-flow-induced assembly strategy. For example, membranes based on graphene oxide (GO) exhibit interlayer spacing ranging from 8.0±0.1 Što 10.3±0.2 Å, with a precision of down to 1 Å. At the same time, the value of the orientation order parameter (f) of GO membranes is up to 0.95 and GO membranes exhibit superb stability in different solutions. The strategy we present, which can be generalized to the preparation of 2D nano-confined channels based on a variety of 2D materials, will expand the application scope and provide better performances of membranes.

Bushen Huoxue decotion-containing serum prevents chondrocyte pyroptosis in a m6A-dependent manner in facet joint osteoarthritis.

BACKGROUND: Facet joint osteoarthritis (FJOA) is a common lumbar osteoarthritis characterized by degeneration of small joint cartilage. Bushen Huoxue decotion (BSHXD) has good therapeutic effects on OA. Our work aimed to further probe the pharmacological effects of BSHXD-containing serum (BSHXD-CS) on FJOA and define underlying the mechanisms invovled. METHODS: To establish a FJOA cell model, primary rat chondrocytes were treated with LPS. The mRNA and protein expressions were assessed using qRT-PCR and western blot, respectively. The secretion levels of pro-inflammatory cytokines were measured by ELISA. Cell viability was determined by CCK8 assay. The global m6A level was detected by the kit, and NLRP3 mRNA m6A level was determined by Me-RIP assay. The molecular interactions were analyzed by RIP and RNA pull-down assays. RESULTS: BSHXD-CS treatment relieved LPS-induced cell injury, inflammation, NLRP3 inflammasome and pyroptosis in chondrocytes (all p < 0.05). LPS-induced NLRP3 upregulation in chondrocytes was related to its high m6A modification level (p < 0.05). It was also observed that BSHXD-CS reduced LPS-induced m6A modification in chondrocytes via repressing STAT3 (all p < 0.05), suggesting BSHXD-CS could repress NLRP3 expression via m6A-dependent manner. Moreover, DAA, a m6A specific inhibitor, was proved to strengthen the protectively roles of BSHXD-CS on LPS-challenged pytoptosis (all p < 0.05). CONCLUSION: BSHXD-CS inhibited NLRP3 inflammasome activation and pyroptosis in chondrocytes to repress OA progression by reducing RNA m6A modification.

Impacts of Left Atrial Appendage Treatments on Mitral Valve Diseases during Surgical Ablations.

Background: Left atrial appendages (LAAs) play an important role in regulating left atrial function, and much evidence supports the possibility that changes in left atrial structure may cause or worsen mitral regurgitation. This study intended to investigate the outcomes of patients with mitral regurgitation who underwent left atrial appendage closure (resection or endocardial closure) during isolated surgical ablations. Methods: Patients with mild or moderate mitral regurgitation who received isolated surgical ablations for atrial fibrillation (AF) in our center from 2013 to 2022 were referred. During follow-up, each clinical visit was composed of medical interrogation, a 24 h Holter, and echocardiographic evaluation. Death, atrial fibrillation, worsening of mitral regurgitation, and stroke were evaluated as outcomes. Freedom from outcomes whose results were adjusted by inverse probability of treatment weighting for causal effects after acquiring propensity scores. Results: A total of 456 patients were enrolled in this study. During a median follow-up of 48 months, 30 deaths and 11 cases of stroke were observed. After adjustments, no significant differences in terms of death or stroke were observed among the three groups. Patients who underwent resection or endocardial closure during surgical ablations had a higher risk of mitral regurgitation worsening during follow-up (p < 0.05). During the whole follow-up, patients who underwent left atrial appendage interventions showed significantly larger left atrial and mitral annular diameters, as well as lower tethering height than those who had left atrial appendage preserved (all p < 0.05). Conclusions: Mitral regurgitation was more likely to get worse when patients with fundamental mitral diseases underwent LAA interventions during isolated surgical AF ablations. In the absence of LAA, the dilation of the left atrium and mitral annulus may ultimately lead to worsening of regurgitation.

Flexible Positive Temperature Coefficient Composites (PVAc/EVA/GP-CNF) with Room Temperature Curie Point.

Polymeric positive temperature coefficient (PTC) materials with low switching temperature points are crucial for numerous electronic devices, which typically function within the room temperature range (0-40 °C). Ideal polymeric PTC materials for flexible electronic thermal control should possess a room-temperature switching temperature, low room-temperature resistivity, exceptional mechanical flexibility, and adaptive thermal control properties. In this study, a novel PTC material with a room-temperature switching temperature and superb mechanical properties has been designed. A blend of a semi-crystalline polymer EVA with a low melting temperature (Tm) and an amorphous polymer (PVAc) with a low glass transition temperature (Tg) was prepared. Low-cost graphite was chosen as the conductive filler, while CNF was incorporated as a hybrid filler to enhance the material's heating stability. PVAc0.4/EVA0.6/GP-3wt.% CNF exhibited the lowest room temperature resistivity, and its PTC strength (1.1) was comparable to that without CNF addition, with a Curie temperature of 29.4 °C. Room temperature Joule heating tests revealed that PVAc0.4/EVA0.6/GP-3wt.% CNF achieved an equilibrium temperature of approximately 42 °C at 25 V, with a heating power of 3.04 W and a power density of 3.04 W/cm2. The Young's modulus of PVAc0.4/EVA0.6/GP-3wt.% CNF was 9.24 MPa, and the toughness value was 1.68 MJ/m3, indicating that the elasticity and toughness of the composites were enhanced after mixing the fillers, and the mechanical properties of the composites were improved by blending graphite with CNF.

Nickel atom-clusters nanozyme for boosting ferroptosis tumor therapy.

The translation of Fe-based agents for ferroptosis tumor therapy is restricted by the unstable iron valence state, the harsh catalytic environment, and the complex tumor self-protection mechanism. Herein, we developed a stable nickel-based single-atom-metal-clusters (NSAMCs) biocatalyst for efficient tumor ferroptosis therapy. NSAMCs with a nanowire-like nanostructure and hydrophilic functional groups exhibit good water-solubility, colloidal stability, negligible systemic toxicity, and target specificity. In particular, NSAMCs possess excellent peroxidase-like and glutathione oxidase-like activities through the synergistic influence between metal clusters and single atoms. The dual-enzymatic performance enables NSAMCs to synergistically promote efficient ferroptosis of cancer cells through lipid peroxidization aggregation and glutathione peroxidase 4 inactivation. Importantly, NSAMCs highlight the boost of ferroptosis tumor therapy via the synergistic effect between single-atoms and metal clusters, providing a practical and feasible paradigm for further improving the efficiency of ferroptosis tumor treatment.

Association between IL-2 Receptor and Severe Coronary Artery Calcification in Patients with Coronary Artery Disease.

Background: Coronary artery calcification (CAC) is a crucial marker for coronary atherosclerosis, and the extent of CAC is closely linked to the incidence and progression of cardiovascular diseases. The interleukin-2 (IL-2) receptor (IL-2R), which plays a critical role in mediating the proliferation and differentiation of immune cells, may also be involved in the development of CAC. The study aimed to investigate the relationship between IL-2R and CAC, with the goal of providing new insights into cardiovascular diseases. Methods: In this study, we enrolled 606 patients diagnosed with coronary artery disease to assess CAC. Based on coronary artery calcification score (CACS), patients were divided into two groups: the non-severe CAC group (CACS ≤ 400 Agatston units, AU) and the severe CAC group (CACS > 400 AU). Results: The results showed that IL-2R levels were significantly higher in patients with severe CAC compared to those with non-severe CAC (383 vs. 352 pg/mL, p = 0.002). Moreover, the level of IL-2R was positively correlated with the severity of CAC, independent of other clinical risk factors. According to Receiver Operating Characteristic (ROC) curve, the IL-2R prediction model demonstrated a good capability in distinguishing severe CAC with the Area Under the Curve (AUC) value of 0.726. Conclusions: Our study suggests that IL-2R is independently associated with the occurrence of severe CAC in coronary artery disease (CAD) patients. Additionally, IL-2R may play a crucial role in the development of advanced atherosclerosis. Consequently, therapeutic strategies targeting the IL-2/IL-2R pathway may be effective in preventing or treating CAD.

S100A10 promotes cancer metastasis via recruitment of MDSCs within the lungs.

Tumor-derived exosomes bind to organ resident cells, activating S100 molecules during the remodeling of the local immune microenvironment. However, little is known regarding how organ resident cell S100A10 mediates cancer metastatic progression. Here, we provided evidence that S100A10 plays an important role in regulating the lung immune microenvironment and cancer metastasis. S100A10-deficient mice reduced cancer metastasis in the lung. Furthermore, the activation of S100A10 within lung fibroblasts via tumor-derived exosomes increased the expression of CXCL1 and CXCL8 chemokines, accompanied by the myeloid-derived suppressor cells (MDSCs) recruitment. S100A10 inhibitors such as 1-Substituted-4-Aroyl-3-hydroxy-5-Phenyl-1 H-5-pyrrol-2(5 H)-ones inhibit lung metastasis in vivo. Our findings highlight the crucial role of S100A10 in driving MDSC recruitment in order to remodel the lung immune microenvironment and provide potential therapeutic targets to block cancer metastasis to the lung.

MXene-Based Skin-Like Hydrogel Sensor and Machine Learning-Assisted Handwriting Recognition.

Conductive hydrogels are widely used in flexible sensors owing to their adjustable structure, good conductivity, and flexibility. The performance of excellent mechanical properties, high sensitivity, and elastic modulus compatible with human tissues is of great interest in the field of flexible sensors. In this paper, the functional groups of trisodium citrate dihydrate (SC) and MXene form multiple hydrogen bonds in the polymer network to prepare a hydrogel with mechanical properties (Young's modulus (23.5-92 kPa) of similar human tissue (0-100 kPa)), sensitivity (stretched GF is 4.41 and compressed S1 is 5.15 MPa-1), and durability (1000 cycles). The hydrogel is able to sensitively detect deformations caused by strain and stress and can be used in flexible sensors to detect human movement in real time such as fingers, wrists, and walking. In addition, the combination of matrix sensing and machine learning was successfully used for handwriting recognition with an accuracy of 0.9744. The combination of machine learning and flexible sensors shows great potential in areas such as healthcare, information security, and smart homes.

Meta-analysis on axillary lymph node metastasis rate in ductal carcinoma in situ with microinvasion.

OBJECTIVE: To address the question of axillary lymph node staging in ductal carcinoma in situ with microinvasion (DCIS-MI), we retrospectively evaluated axillary lymph nodes metastasis (ALNM) rate in a cohort of postsurgical DCIS-MI patients. By analyzing these data, we aimed to generate clinically relevant insights to inform treatment decision-making for this patient population. METHODS: A systematic search was conducted on PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang Database, Wipe, and China Biomedical Literature Database to identify relevant publications in any language. All the analyses were performed using Stata 16.0 software. RESULTS: Among the 28 studies involving 8279 patients, the pooled analysis revealed an ALNM rate of 8% (95% CI, 7% to 10%) in patients with DCIS-MI. Furthermore, the rates of axillary lymph node macrometastasis, micrometastasis, and ITC in patients with DCIS-MI were 2% (95% CI, 2% to 3%), 3% (95% CI, 2% to 4%), and 2% (95% CI, 1% to 3%), respectively. Moreover, 13 studies investigated the non-sentinel lymph node (Non-SLN) metastasis rate, encompassing a total of 1236 DCIS-MI cases. The pooled analysis identified a Non-SLN metastasis rate of 33% (95% CI, 14% to 55%) in patients with DCIS-MI. CONCLUSION: The SLNB for patients with DCIS-MI is justifiable and could provide a novel therapeutic basis for systemic treatment decisions.

Tough and elastic hydrogels based on robust hydrophobicity-assisted metal ion coordination for flexible wearable devices.

Flexible wearable sensors that combine excellent flexibility, high elasticity, sensing capabilities, and outstanding biocompatibility are gaining increasing attention. In this study, we successfully develop a robust and elastic hydrogel-based flexible wearable sensor by modulating molecular structures combined with metal ion coordination. We leverage three N-acryloyl amino acid monomers, including N-acryloyl glycine (AG), N-acryloyl alanine (AA), and N-acryloyl valine (AV) with different hydrophobic groups adjacent to the carboxyl group, to copolymerize with acrylamide (AM) in the presence of Zr4+ for hydrogel preparation in one step (P(AM3-AG/AA/AV0.06)-Zr0.034+ hydrogels). Our investigation reveals that the P(AM3-AV0.06)-Zr0.034+ hydrogel with the most hydrophobic side group demonstrates superior mechanical properties (1.1 MPa tensile stress, 3566 kJ m-3 toughness and 1.3 kJ m-2 fracture energy) and resilience to multiple tensile (30% strain, 500 cycles) and compression cycling (50% strain, 500 cycles). Moreover, the P(AM3-AV0.06)-Zr0.034+ hydrogel exhibits good biocompatibility and high conductivity (1.1 S m-1) and responsivity (GF = 16.21), and is proved to be suitable as a flexible wearable sensor for comprehensive human activity monitoring.

Biological pretreatment with white rot fungi for preparing hierarchical porous carbon from Banlangen residues with high performance for supercapacitors and dye adsorption.

White rot fungi possess superior infiltrability and biodegradability on lignocellulosic substrates, allowing them to form tailored microstructures which are conducive to efficient carbonization and chemical activation. The present research employed white rot fungus pretreatment as a viable approach for preparing porous carbon from Banlangen residues. The resultant F-A-BLGR-PC prepared by pretreating Banlangen residues with white rot fungi followed by carbonization and activation has a hierarchical porous structure with a high specific surface area of 898 m2 g-1, which is 43.4% greater than that of the unprocessed sample (R-BLGR-PC). When used as an electrode for supercapacitors, the F-A-BLGR-PC demonstrated a high specific capacitance of 308 F g-1 at 0.5 A g-1 in 6 M KOH electrolyte in three-electrode configuration. Moreover, the F-A-BLGR-PC based symmetric supercapacitor device achieved a superb cyclic stability with no obvious capacitance decay after 20,000 cycles at 5 A g-1 in 1 M Na2SO4 electrolyte. Additionally, the F-A-BLGR-PC sample was found to be an ideal adsorbent for removing methyl orange (MO) from water, exhibiting an adsorption ability of 173.4 mg g-1 and a maximum removal rate of 86.6%. This study offers a promising method for the preparation of a porous carbon with a high specific surface area in a biological way using white rot fungi pretreatment, and the derived carbon can not only be applied in energy storage but also in environmental remediation, catalysis, and so on.

Megalin-targeting and ROS-responsive elamipretide-conjugated polymeric prodrug for treatment of acute kidney injury.

Acute kidney injury (AKI) is associated with both kidney function loss and increased mortality. In the pathological progression of ischemia-reperfusion-induced AKI, the surge of reactive oxygen species (ROS) plays a crucial role. To combat this, mitochondrial-targeted antioxidant therapy shows great promise as mitochondria are the primary source of ROS in AKI. However, most strategies aiming to target mitochondria directly result in nanodrugs that are too large to pass through the glomerular system and reach the renal tubules, which are the main site of damage in AKI. This study focused on synthesizing a Megalin receptor-targeted polymeric prodrug, low molecular weight chitosan-thioketal-elamipretide (LMWC/TK/Ela), to mitigate excessive ROS in renal tubular epithelial cells for AKI. This soluble polymeric prodrug has the ability to successfully reach the tubular site by crossing the glomerular barrier. Once there, it can responsively release elamipretide, which possesses excellent antioxidative properties. Therefore, this research offers a novel approach to actively target renal tubular epithelial cells and intracellular mitochondria for the relief of AKI.

The combination of breast cancer PDO and mini-PDX platform for drug screening and individualized treatment.

The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.