Ultrasound-responsive microfibers promoted infected wound healing with neuro-vascularization by segmented sonodynamic therapy and electrical stimulation.

Bacteria-infected wounds pose challenges to healing due to persistent infection and associated damage to nerves and vessels. Although sonodynamic therapy can help kill bacteria, it is limited by the residual oxidative stress, resulting in prolonged inflammation. To tackle these barriers, novel 4 octyl itaconate-coated Li-doped ZnO/PLLA piezoelectric composite microfibers are developed, offering a whole-course "targeted" treatment under ultrasound therapy. The inclusion of Li atoms causes the ZnO lattice distortion and increases the band gap, enhancing the piezoelectric and sonocatalytic properties of the composite microfibers, collaborated by an aligned PLLA conformation design. During the infection and inflammation stages, the piezoelectric microfibers exhibit spatiotemporal-dependent therapeutic effects, swiftly eliminating over 94.2 % of S. aureus within 15 min under sonodynamic therapy. Following this phase, the microfibers capture reactive oxygen species and aid macrophage reprogramming, restoring mitochondrial function, achieving homeostasis, and shortening inflammation cycles. As the wound progresses through the healing stages, bioactive Zn2+ and Li + ions are continuously released, improving cell recruitment, and the piezoelectrical stimulation enhances wound recovery with neuro-vascularization. Compared to commercially available dressings, our microfibers accelerate the closure of rat wounds (Φ = 15 mm) without scarring in 12 days. Overall, this "one stone, four birds" wound management strategy presents a promising avenue for infected wound therapy.

18ß-Glycyrrhetinic acid synergizes with enzalutamide to counteract castration-resistant prostate cancer by inhibiting OATP2B1 uptake of dehydroepiandrosterone sulfate.

Androgen dependence is a key feature of prostate cancer, and androgen deprivation is effective in treating prostate cancer. However, the disease often worsens and develops into castration-resistant prostate cancer after short-term control. The current study aimed to explore the mechanism of the synergistic action of 18ß-glycyrrhetinic acid (18ß-GA) and enzalutamide (ENZ) against prostate cancer. Our findings showed that 18ß-GA significantly inhibited the expression of OATP2B1 and the transport of dehydroepiandrosterone sulfate (DHEAS) in LNCap and 22RV1 cells. It also downregulated the expression of androgen receptor (AR) to some extent. ENZ strongly inhibited AR expression, but it did not affect OATP2B1-mediated uptake of DHEAS. Compared to the effects of 18ß-GA and ENZ alone, the combination of 18ß-GA and ENZ significantly enhanced the inhibitory effects on AR, prostate-specific antigen (PSA) expression, tumor cell proliferation, and migration. The results obtained in castrated model mice matched the findings of in vitro experiments. 18ß-GA significantly reduced the uptake of DHEAS mediated by OATP2B1 in mouse tumor tissues and cooperated with ENZ to further inhibit the expression of AR and PSA, combat the growth of tumor cells, and promote the apoptosis of tumor cells. In conclusion, 18ß-GA considerably decreased the uptake of DHEAS and androgen production in cells by inhibiting the transport function of OATP2B1, while ENZ inhibited the nuclear translocation of AR and reduced the expression of AR. The combination of 18ß-GA and ENZ can simultaneously inhibit androgen production and AR expression and exhibit a synergistic effect against castration and prostate cancer progression.

Mechanochemically accelerated deconstruction of chemically recyclable plastics.

Plastics redesign for circularity has primarily focused on monomer chemistries enabling faster deconstruction rates concomitant with high monomer yields. Yet, during deconstruction, polymer chains interact with their reaction medium, which remains underexplored in polymer reactivity. Here, we show that, when plastics are deconstructed in reaction media that promote swelling, initial rates are accelerated by over sixfold beyond those in small-molecule analogs. This unexpected acceleration is primarily tied to mechanochemical activation of strained polymer chains; however, changes in the activity of water under polymer confinement and bond activation in solvent-separated ion pairs are also important. Together, deconstruction times can be shortened by seven times by codesigning plastics and their deconstruction processes.

Metal-Free Wet Chemistry for the Fast Gram-Scale Synthesis of γ-Graphyne and its Derivatives.

γ-Graphyne (GY), an emerging carbon allotrope, is envisioned to offer various alluring properties and broad applicability. While significant progress has been made in the synthesis of GY over recent decades, its widespread application hinges on developing efficient, scalable, and accessible synthetic methods for the production of GY and its derivatives. Here we report a facile metal-free nucleophilic crosslinking method using wet chemistry for fast gram-scale production of GY and its derivatives. This synthesis method involves the aromatic nucleophilic substitution reactions between fluoro-(hetero)arenes and alkynyl silanes in the presence of a catalytic amount of tetrabutylammonium fluoride, where the fluoride plays a crucial role in removing protective groups from alkynyl silanes and generating reactive alkynylides. Our comprehensive analysis of the as-prepared GY reveals a layered structure, characterized by the presence of the C(sp)-C(sp2) bond. The synthetic strategy shows remarkable tolerance to various functional groups and enables the preparation of diverse F-/N-rich GY derivatives, using electron-deficient fluoro-substituted (hetero)arenes as precursors. The feasibility of producing GY and derivatives from fluorinated (hetero)arenes through the metal-free, scalable, and cost-effective approach paves the way for broad applications of GY and may inspire the development of new carbon materials.

Exosomal miR-142-3p from M1-polarized macrophages suppresses cell growth and immune escape in glioblastoma through regulating HMGB1-mediated PD-1/PD-L1 checkpoint.

Glioblastoma (GBM) is one of the most prevalent cancerous brain tumors. Former studies have reported that exosomes derived from M1-polarized macrophages (M1 exosomes) inhibit tumor occurrence and development through delivery of tumor suppressor genes. Also, microRNA-142-3p (miR-142-3p) has been verified to function as a tumor suppressor. GBM cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8), colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay; cell apoptosis was determined by flow cytometry analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Mechanism investigations were conducted for analyzing the molecular mechanism by which miR-142-3p and M1 exosomes affect GBM progression. Upregulation of miR-142-3p expression was detected in M1-polarized macrophages and M1 exosomes. M1 exosomes inhibit GBM cell proliferation and trigger cell apoptosis. Functionally, miR-142-3p silencing promotes the proliferation and inhibits the apoptosis of GBM cells treated with M1 exosomes. As for molecular mechanism, miR-142-3p inhibits GBM cell growth via targeting high-mobility group box 1 (HMGB1). In addition, miR-142-3p/HMGB1 axis affects GBM cell immune escape through modulation of programmed death-1/programmed death ligand-1 (PD-1/PD-L1) checkpoint. Our study demonstrated that exosomal miR-142-3p from M1-polarized macrophages suppresses cell growth and immune escape in GBM through regulating HMGB1-mediated PD-1/PD-L1 checkpoint.

Combining with E-nose, GC-MS, GC-IMS and chemometrics to explore volatile characteristics during the different stages of Zanthoxylum bungeanum maxim fruits.

To explore the volatile characteristics of Z. bungeanum fruits during different developmental stages, the dynamical changes of volatile organic compounds (VOCs) were detected by E-nose, GC-MS and GC-IMS, respectively. The results showed that terpenes, alcohols, esters and aldehydes played the important roles in the aroma formation of Z. bungeanum. Meanwhile, these VOCs also exhibited the high abundance levels among five growth stages of Z. bungeanum. According to the analysis of odor activity value (OAV) and relative odor activity value (ROAV), 37 VOCs can be recognized as the important aroma compounds. Thereinto, ß-myrcene and linalool were the most key aroma compounds. Multi-factor analysis exhibited that the combination of GC-MS and GC-IMS was a better strategy to clarify the volatile characteristics comprehensively. Using the above combined VOC datasets, six positively correlated modules and 32 hub VOCs were finally identified by weighted correlation network analysis among five growth stages of Z. bungeanum.

Responsive Protection of Magnesium Alloys From Multicorrosive Media by Constructing Nanofluidic Channels in Self-Repairing Coatings.

Low-density magnesium (Mg) alloys are excellent engineering materials, and can significantly reduce energy consumption by replacing existing steel and aluminum materials. However, Mg species are susceptible to corrosion, especially in harsh environments (high-temperature or acidic), severely limiting the range of practical applications. Here, 2D covalent organic framework (COF) is synthesized with pore diameters ranging from 1.5 to 2.9 nm to obtain ultrafast nanofluidic channels. Loaded with silver (Ag+) ions, 2-mercaptobenzimidazole (2-MB) inhibitors are immobilized in the COF channels through the silver bridges. Based on the strong metal-complexing capability, Ag+ ions precipitated with various corrosive media (Cl-, Br-, I-, SO3 2-, S2-, S2O3 2- SO4 2-, CO3 2-, PO4 3-); meanwhile, the 2-MB inhibitors are rapidly released through the nanofluidic channels, forming a passivation film as a corrosion barrier to protect the Mg substrate. After integration with commercial polyethersulfone (PES), the COF-based coating exhibits high repairing capability achieving 100% damage restoration within 7 h, outperforming all existing coatings of Mg alloys. Notably, the coating shows almost complete protection of Mg alloys after being treated in respective 473 K, acidic (pH ≈4.0), and alkaline (pH ≈10.0) environments.

Combustion-explosion suppression and environmental protection of typical sulfur-containing hazardous chemicals.

Sulfur, as a crucial chemical raw, poses increased combustion-explosion risks when mixed with other hazardous substances due to its dual nature as both an oxidant and a reducing agent. Additionally, sulfur-induced combustion and explosions can result in environmental pollution. Combustion-explosion suppression technology plays a crucial role in industrial production by effectively preventing hazardous chemical explosion incidents. This research investigates the combustion-explosion suppression of black powder, a common hazardous chemical containing sulfur, by utilizing two solid-based blast suppressants, NH4H2PO4 and NaHCO3. On this basis, examining changes in the oxidation states of sulfur and explaining the mechanisms of combustion-explosion suppression through the examination of combustion-explosion products. Additionally, numerical calculations are employed to analyze the evolution patterns of gaseous and solid-phase products throughout the entire combustion-explosion process. Research indicates that NaHCO3 exhibits a more effective combustion-explosion suppression effect on black powder compared to NH4H2PO4, which attributed to the valence state transformation of sulfur and the reduction of carbon oxidation. Furthermore, with the enhancement of combustion-explosion suppression effect, K2S, which a pollutes the environment, is gradually transform converted into potassium fertilizer K2SO4, which benefits plants. These results offer new insights into the research of combustion-explosion suppression of sulfur-containing substances and environmental protection strategies.

Long-Term Outcomes of ESD for Early Esophageal Adenocarcinoma: A Real-World study in China.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a preferred method for early esophageal cancer, yet its application to esophageal adenocarcinoma (EAC), especially in the Eastern population with its relative rarity, lacks sufficient literature. This study evaluates ESD's long-term outcomes for EAC, focusing on non-curative resections and diagnostic accuracy. METHODS: A retrospective study (2012-2022) included 68 patients undergoing ESD for early EAC at Jiangsu Province Hospital. Primary outcomes encompassed ESD efficacy, en bloc resection, R0 resection, curative resection rates, and follow-up. Secondary outcomes involved non-curative ESD, T1a/T1b stage comparison, and diagnostic consistency. RESULTS: Postoperative staging revealed T1a (n=53) and T1b (n=15) tumors. En bloc resection rate was 97.1%, R0 resection rate was 79.4%, and non-curative rate was 30.9%. T1a had significantly higher R0 rate and curative resection rate. Among non-curative ESDs, 33.3% underwent esophagectomy, 42.9% had surveillance endoscopies, 19.1% repeated curative ESD, and 4.7% were lost to follow-up. Average follow-up was 63.76±28.47 months. Six cases had recurrence, three had residual lesions, and six deaths occurred, unrelated to ESD. No significant difference in survival or recurrence rates between curative and non-curative ESD groups was observed. ESD led to a histologic diagnosis change in 70.6% of cases, all upstaged. CONCLUSIONS: ESD is effective for EAC, with higher curative rates for T1a than T1b. Non-curative ESD cases may benefit from conservative approaches. Long-term follow-up underscores poor consistency between residual lesions and positive margins. ESD serves as a valuable diagnostic staging tool, particularly for T1b patients, considering the low accuracy of EUS and preoperative biopsy.

Grain Boundary Filling Empowers (002)-Textured Zn Metal Anodes with Superior Stability.

Aqueous Zn battery is promising for grid-level energy storage due to its high safety and low cost, but dendrite growth and side reactions at the Zn metal anode hinder its development. Designing Zn with (002) orientation improves the stability of the Zn anode, yet grain boundaries remain susceptible to corrosion and dendrite growth. Addressing these intergranular issues is crucial for enhancing the electrochemical performance of (002)-textured Zn. Here, a strategy based on grain boundary wetting to fill intergranular regions and mitigate these issues is reported. By systematically investigating boundary fillers and filling conditions, In metal is chosen as the filler, and one-step annealing is used to synergistically convert commercial Zn foils into single (002)-textured Zn while filling In into the boundaries. The inter-crystalline-modified (002)-textured Zn (IM(002) Zn) effectively inhibits corrosion and dendrite growth, resulting in excellent stability in batteries. This work offers new insights into Zn anode protection and the development of high-energy Zn batteries.

Enhancing Fire Safety and Softness: Efficacy of Ethanolamine Polyphosphate as a Fire Retardant for Textiles.

The rising awareness of fire safety among consumers has driven the demand for fire retardants (FRs) that are both cost-effective and efficient across various industries, particularly in textiles. Traditional FRs often compromise fabric softness, resulting in undesirable tactile texture and stiffness changes. While the external addition of softeners can mitigate the stiffness, it may introduce issues such as a greasy texture and increased flammability. This study introduces ethanolamine polyphosphate (EAPP), an innovative organic polyphosphate, as an effective fire retardant that preserves the softness of textiles. Comprehensive evaluations are conducted on EAPP-treated textiles, revealing significant improvements in fire retardancy without compromising fabric quality. EAPP treatment (15 wt.% aqueous solutions) increases the limiting oxygen index (LOI) of pure cotton textiles from 17% to 36% and significantly reduces the peak heat release rate (pHRR) and total smoke rate (TSR) as measured by cone calorimetry. Unlike conventional FR products that form FR-salt crystal particles on the fabric surface after drying, EAPP forms a smooth FR protective layer on the fabric, enhancing mechanical fastness and maintaining tactile qualities. These findings highlight EAPP's potential as a non-washing durable, spray-on fire retardant solution for textiles, combining safety with user comfort.

HiSC4D: Human-Centered Interaction and 4D Scene Capture in Large-Scale Space Using Wearable IMUs and LiDAR.

We introduce HiSC4D, a novel Human-centered interaction and 4D Scene Capture method, aimed at accurately and efficiently creating a dynamic digital world, containing large-scale indoor-outdoor scenes, diverse human motions, rich human-human interactions, and human-environment interactions. By utilizing body-mounted IMUs and a head-mounted LiDAR, HiSC4D can capture egocentric human motions in unconstrained space without the need for external devices and pre-built maps. This affords great flexibility and accessibility for human-centered interaction and 4D scene capturing in various environments. Taking into account that IMUs can capture human spatially unrestricted poses but are prone to drifting for long-period using, and while LiDAR is stable for global localization but rough for local positions and orientations, HiSC4D employs a joint optimization method, harmonizing all sensors and utilizing environment cues, yielding promising results for long-term capture in large scenes. To promote research of egocentric human interaction in large scenes and facilitate downstream tasks, we also present a dataset, containing 8 sequences in 4 large scenes (200 to 5,000 m2 ), providing 36k frames of accurate 4D human motions with SMPL annotations and dynamic scenes, 31k frames of cropped human point clouds, and scene mesh of the environment. A variety of scenarios, such as the basketball gym and commercial street, alongside challenging human motions, such as daily greeting, one-on-one basketball playing, and tour guiding, demonstrate the effectiveness and the generalization ability of HiSC4D. The dataset and code will be publicly available for research purposes.

An n-doping cross-linkable quinoidal compound as a new type of electron transport material for fully stretchable inverted organic solar cells.

The photocatalytic activity and inherent brittleness of ZnO, which is commonly used as an electron transport layer (ETL) in inverted organic solar cells (OSCs), have impeded advancements in device stability and the development of fully stretchable OSCs. In this study, we have developed an intrinsically stretchable ETL for inverted OSCs through a side-chain cross-linking strategy. Specifically, cross-linking between bromine atoms on the side chains of a quinoidal compound and the amino groups in polyethylenimine resulted in a film, designated QBr-PEI-50, with high electrical conductivity (0.049 S/m) and excellent stretchability (crack-onset strain >45%). When used as the ETL in inverted OSCs, QBr-PEI-50 was markedly superior to ZnO in terms of device performance and stability, yielding a power conversion efficiency (PCE) of 18.27% and a T80 lifetime exceeding 10000 h. Moreover, incorporation of QBr-PEI-50 in fully stretchable inverted OSCs yielded a PCE of 14.01%, and 80% of the initial PCE was maintained after 21% strain, showcasing its potential for wearable electronics.

A pan-cancer analysis of Wnt family member 7B in human cancers.

Background: Previous studies have highlighted the crucial role of Wnt7B in the development of various cancers, including breast, pancreatic, and gastric cancers. However, research into the involvement of Wnt7B is often confined to specific tumor types, with a noticeable lack of comprehensive studies spanning multiple cancer forms. The potential of Wnt7B as a diagnostic or prognostic cancer biomarker has not been fully explored. Methods: In this study, we combined bioinformatics and immunohistochemistry analyses to examine the expression patterns and functions of Wnt7B in cancerous and adjacent noncancerous tissues across a range of tumors. Results: Our data indicate that Wnt7B may serve as a novel prognostic biomarker and therapeutic target in certain cancers. Conclusion: We found significant upregulation of Wnt7B expression levels in the majority of cancer cases examined. Furthermore, Wnt7B can influence cancer prognosis by modulating the tumor microenvironment, immune cell infiltration, and tumor stemness, among other factors. Additionally, we examined the associations between anticancer drug sensitivity and Wnt7B expression, which could aid in the development of more precise clinical therapies.

Angelica sinensis polysaccharides ameliorate 5-FU-induced stress anemia via promoting extramedullary erythroblastic island central macrophage-mediated erythroid differentiation.

BACKGROUND: Chronic anemia, especially chemotherapy-induced anemia, is a common and intractable symptom. Puzzlingly, the conventional anemic treatment may lead to various side effects, and the mechanism of stress anemia remains unclear. METHODS: Here, peripheral blood, histopathological and transmission electron microscopical examination, colony forming test, flow cytometry, and qRT-PCR assay were used to investigate the effects of Angelia sinensis polysaccharide (ASP), one main active ingredient of Chinese herb medicine Angelica sinensis, on ameliorating 5-fluorouracil (5-FU)-induced stress anemia. RESULTS: We found that intraperitoneal injection to a C57BL/6J mouse ASP 100 mg/kg per day for consecutive 10 days or 14 days, remarkably accelerated the recovery of RBC, hemoglobin, and hematocrit in blood. ASP alleviated 5-FU-caused impairment of bone marrow cell and BFU-E enumeration. Meanwhile, ASP antagonized 5-FU promoting extramedullary erythropoiesis in the spleen, inducing splenomegaly due to stress erythroblastic islands, and occurrence of megakaryocytes and hematopoietic precursors in splenic colonies. ASP increased splenic stress BFU-E enumeration, driving BFU-E differentiation towards Pro-E and end-stage erythroblasts. Furthermore, ASP increased the number of F4/80+VCAM-1+ splenic erythroblastic island central macrophages, upregulating genetic expression of EPOR, Emp, VCAM-1, Hmox-1, Trf, TfR1, Fpn1, Spi-C, DNase2a, Tim4, MertK, and Klf1 in splenocytes. CONCLUSIONS: Our findings indicate that the possible mechanism of chemotherapy-induced anemia is related to stress erythroid maturation arrest. Whereas, ASP may promote stress erythroid differentiation via elevated EPO sensitivity in extramedullary hematopoietic organs and enhanced macrophage-mediated adhesion, iron homeostasis and transfer, and nuclear engulfment, which may represent a promising therapeutic strategy.

LFHP-1c improves cognitive function after TBI in mice by reducing oxidative stress through the PGAM5-NRF2-KEAP1 ternary complex.

Traumatic brain injury (TBI) is a leading cause of disability and death. Thus, timely and effective secondary brain injury intervention is crucial, with potential to improve the prognosis of TBI. Oxidative stress contributes to post-traumatic secondary cognitive impairment, and the reduction of post-traumatic oxidative stress effectively enhances cognitive function. Phosphoglycerate-mutating enzyme 5 (PGAM5), a member of the phosphoglycerate transporter enzyme family, is upregulated in TBI and induces mitochondrial autophagy. This further exacerbates damage following TBI. The present study focused on the small molecule drug, LFHP-1c, which is a novel inhibitor of PGAM5. The present study used an in vivo mouse model incorporating a controlled cortical impact-induced TBI, to examine the impact of LFHP-1c on oxidative stress and cognitive function. The present study aimed to determine the impact of LFHP-1c on the PGAM5-Kelch-like ECH-associated protein 1 (KEAP1)- nuclear factor erythroid 2-related factor 2 (NRF2) ternary complex within the TBI context. Results of the present study indicated that LFHP-1c suppresses PGAM5 expression and inhibits the development of the PGAM5-KEAP1-NRF2 ternary complex, thereby promoting the release of NRF2 and KEAP1. This in turn promotes the entry of NRF2 into the nucleus following TBI, leading to increased expression of anti-oxidative stress downstream factors, such as heme oxygenase-1, glutathione peroxidase 1 and superoxide dismutase 1. In addition, LFHP-1c also released KEAP1, leading to mitochondrial Rho GTPase 2 degradation and reducing perinuclear aggregation of mitochondria in the cell, which reduced oxidative stress and ultimately improved cognitive function after TBI.

Factors Influencing Bone Resorption after Augmentation Mentoplasty with Implants: A Retrospective Study Using Three-Dimensional Imaging.

BACKGROUND: Augmentation mentoplasty with implants is an extremely rewarding procedure. Bone resorption is almost unavoidable. The high-risk factors for chin bone resorption have not been explored in the past. This study aimed to analyze and evaluate the factors influencing bone resorption after augmentation mentoplasty with implants using three-dimensional imaging. METHODS: We retrospectively analyzed preoperative craniofacial Computed Tomography scan data from 105 patients who underwent mandibular implantation surgery and 108 patients who did not. We also examined the extent to which different factors influenced the occurrence of bone resorption in the chin area. RESULTS: Patients with silicone gel implants are more prone to bone resorption than those with Medpor implants. Patients who experienced bone resorption had thicker mentalis muscles than those who did not experience bone resorption (6.35 ± 1. mm vs. 5.73 ± 1.25 mm, P < 0.05), and thinner cortical bone (3.25 ± 1.65 mm vs. 5.22 ± 2.04 mm, P < 0.05). Additionally, implants placed above the mandibular bone were more likely to induce bone resorption than those placed below it. CONCLUSIONS: This study is the first to systematically reveal the impact of implant type, placement position, mentalis muscle thickness, and cortical bone thickness on bone resorption after chin augmentation surgery. For patients with thicker mentalis muscles and thinner cortical bones, greater attention should be paid to the occurrence of bone resorption. Choosing silicone implants or placing the implants higher on the mandible can help reduce the occurrence of bone resorption. This study can assist clinicians in selecting appropriate treatment methods, thereby reducing post-implantation bone resorption. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266.

HPV-YAP1 oncogenic alliance drives malignant transformation of fallopian tube epithelial cells.

High grade serous ovarian carcinoma (HGSOC) is the most common and aggressive ovarian malignancy. Accumulating evidence indicates that HGSOC may originate from human fallopian tube epithelial cells (FTECs), although the exact pathogen(s) and/or molecular mechanism underlying the malignant transformation of FTECs is unclear. Here we show that human papillomavirus (HPV), which could reach FTECs via retrograde menstruation or sperm-carrying, interacts with the yes-associated protein 1 (YAP1) to drive the malignant transformation of FTECs. HPV prevents FTECs from natural replicative and YAP1-induced senescence, thereby promoting YAP1-induced malignant transformation of FTECs. HPV also stimulates proliferation and drives metastasis of YAP1-transformed FTECs. YAP1, in turn, stimulates the expression of the putative HPV receptors and suppresses the innate immune system to facilitate HPV acquisition. These findings provide critical clues for developing new strategies to prevent and treat HGSOC.