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Privacy of user is becoming increasingly significant in constructing efficient multiagent energy management systems for multimicrogrid (MMG). As an emerging privacy-protection method, federated learning (FL) has been used to prevent data breaches in the MMG-related field. However, with the ever-growing participants, the underlying communication burden existing in FL is evident. Besides, since the neural network layers collectively determine an agent's performance, the possible difference in layer convergence speeds would cause the inconsistency problem, that is, the FL may degrade the convergence rate of those fast-convergent layers, which weakens the overall performance of the agent. To address these issues, a communication-efficient FL (CEFL) algorithm is proposed in this study. Considering the cooperative relationship among layers, a layer evaluation (LE) mechanism is developed in CEFL to evaluate layer contribution through the Shapley value (SV), a profit distribution approach for coalitions. In this way, only partial layers with the highest contributions are selected to be uploaded to the server. In addition, instead of average parameters aggregation, a communication-efficient parameter aggregation method is proposed in CEFL to update the parameters of the global model (GM), in which an aggregation model (AM) is developed to receive parameters for aggregation. The performance of the proposed CEFL is verified by the numerical analysis of MMGs with 3-8 MGs participating. Furthermore, experiments investigate the influence of the hyperparameter in the CEFL and also demonstrate performance improvements, compared with the other four state-of-the-art algorithms.

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Delaying an electromagnetic (EM) wave pulse on a thin screen for a significant time before releasing it is highly desired in many applications, such as optical camouflage, information storage, and wave-matter interaction boosting. However, available approaches to achieve this goal either require thick and complex systems or suffer from low efficiencies and a short delay time. This paper proposes an ultra-thin meta-platform that can significantly delay an EM-wave pulse after reflection. Specifically, our meta-platform consists of three meta-surfaces integrated together, of which two are responsible for efficiently coupling incident EM-wave pulse into surface waves (SWs) and vice versa, and the third one supports SWs exhibiting significantly reduced group velocity. We employ theoretical model analyses, full-wave simulations, and microwave experiments to validate the proposed concept. Our experiments demonstrate a 13 ns delay of an EM pulse centered at 12.975 GHz, enabled by a λ/8-thick and 38-λ-long meta-device with an efficiency of 32% (or 70%) with (or without) material loss taken into account. A larger delay time can be enabled by devices with larger sizes considering that the SWs group velocity of our device can be further reduced via dispersion engineering. These findings establish a new road for delaying an EM-wave pulse with ultra-thin screens, which may lead to many promising applications in integration optics.

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Research efforts on electromagnetic interference (EMI) shielding materials have begun to converge on green and sustainable biomass materials. These materials offer numerous advantages such as being lightweight, porous, and hierarchical. Due to their porous nature, interfacial compatibility, and electrical conductivity, biomass materials hold significant potential as EMI shielding materials. Despite concerted efforts on the EMI shielding of biomass materials have been reported, this research area is still relatively new compared to traditional EMI shielding materials. In particular, a more comprehensive study and summary of the factors influencing biomass EMI shielding materials including the pore structure adjustment, preparation process, and micro-control would be valuable. The preparation methods and characteristics of wood, bamboo, cellulose and lignin in EMI shielding field are critically discussed in this paper, and similar biomass EMI materials are summarized and analyzed. The composite methods and fillers of various biomass materials were reviewed. this paper also highlights the mechanism of EMI shielding as well as existing prospects and challenges for development trends in this field.

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A metronomic, low-dose schedule of decitabine and Venetoclax was safe and effective in myeloid malignancies with few dose reductions or interruptions in an older diverse population. Median OS for AML and TP53 mutated patients was 16.1 and 11.3 months respectively.

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Controlled manufacturing and long-term stability are key challenges in the development and translation of nanomedicines. This is exemplified by the mRNA-nanoparticle vaccines against COVID-19, which require (ultra-)cold temperatures for storage and shipment. Various cryogenic protocols have been explored to prolong nanomedicine shelf-life. However, freezing typically induces high mechanical stress on nanoparticles, resulting in aggregation or destabilization, thereby limiting their performance and application. Hence, evaluating the impact of freezing and storing on nanoparticle properties already early-on during preclinical development is crucial. In the present study, we used prototypic π electron-stabilized polymeric micelles based on mPEG-b-p(HPMAm-Bz) block copolymers to macro- and microscopically study the effect of different cryoprotective excipients on nanoformulation properties like size and size distribution, as well as on freezing-induced aggregation phenomena via in-situ freezing microscopy. We show that sucrose, unlike trehalose, efficiently cryoprotected paclitaxel-loaded micelles, and we exemplify the impact of formulation composition for efficient cryoprotection. We finally establish microfluidic mixing to formulate paclitaxel-loaded micelles with sucrose as a cryoprotective excipient in a single production step and demonstrate their stability for 6 months at -20 °C. The pharmaceutical properties and preclinical performance (in terms of tolerability and tumor growth inhibition in a patient-derived triple-negative breast cancer xenograft mouse model) of paclitaxel-loaded micelles were successfully cryopreserved. Together, our efforts promote future pharmaceutical development and translation of π electron-stabilized polymeric micelles, and they illustrate the importance of considering manufacturing and storage stability issues early-on during nanomedicine development.

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Neural stimulation and modulation at high spatial resolution are crucial for mediating neuronal signaling and plasticity, aiding in a better understanding of neuronal dysfunction and neurodegenerative diseases. However, developing a biocompatible and precisely controllable technique for accurate and effective stimulation and modulation of neurons at the subcellular level is highly challenging. Here, we report an optomechanical method for neural stimulation and modulation with subcellular precision using optically controlled bio-darts. The bio-dart is obtained from the tip of sunflower pollen grain and can generate transient pressure on the cell membrane with submicrometer spatial resolution when propelled by optical scattering force controlled with an optical fiber probe, which results in precision neural stimulation via precisely activation of membrane mechanosensitive ion channel. Importantly, controllable modulation of a single neuronal cell, even down to subcellular neuronal structures such as dendrites, axons, and soma, can be achieved. This bio-dart can also serve as a drug delivery tool for multifunctional neural stimulation and modulation. Remarkably, our optomechanical bio-darts can also be used for in vivo neural stimulation in larval zebrafish. This strategy provides a novel approach for neural stimulation and modulation with sub-cellular precision, paving the way for high-precision neuronal plasticity and neuromodulation.

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, with limited therapeutic options. Here, we evaluated the role of regulator of chromosome condensation 1 (RCC1) in PDAC. RCC1 functions as a guanine exchange factor for GTP-binding nuclear protein Ran (Ran) GTPase and is involved in nucleocytoplasmic transport. RCC1 RNA expression is elevated in PDAC tissues compared to normal pancreatic tissues and correlates with poor prognosis. RCC1 silencing by RNAi and CRISPR-Cas9 knockout (KO) results in reduced proliferation in 2-D and 3-D cell cultures. RCC1 knockdown (KD) reduced migration and clonogenicity, enhanced apoptosis, and altered cell cycle progression in human PDAC and murine cells from LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) tumors. Mechanistically, RCC1 KO shows widespread transcriptomic alterations including regulation of PTK7, a co-receptor of the Wnt signaling pathway. RCC1 KD disrupted subcellular Ran localization and the Ran gradient. Nuclear and cytosolic proteomics revealed altered subcellular proteome localization in Rcc1 KD KPC-tumor-derived cells and several altered metabolic biosynthesis pathways. In vivo, RCC1 KO cells show reduced tumor growth potential when injected as sub-cutaneous xenografts. Finally, RCC1 KD sensitized PDAC cells to gemcitabine chemotherapy treatment. This study reveals the role of RCC1 in pancreatic cancer as a novel molecular vulnerability that could be exploited to enhance therapeutic response.

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Enrichment of photosensitizers (PSs) on cancer cell membranes via bioorthogonal reactions is considered to be a very promising therapeutic modality. However, azide-modified sugars-based metabolic labeling processes usually lack targeting and the labeling speed is relatively slow. Moreover, it has been rarely reported that membrane-anchoring pure type-I PSs can induce cancer cell pyroptosis. Here, we report an alkaline phosphatase (ALP) and cholecystokinin-2 receptor (CCK2R) dual-targeting peptide named DBCO-pYCCK6, which can selectively and rapidly self-assemble on cancer cell membrane, and then bioorthogonal enrich type-I aggregation-induced emission luminogens (AIEgen) PSs (SAIE-N3) on the cell membrane. Upon light irradiation, the membrane-anchoring SAIE-N3 could effectively generate type-I reactive oxygen species (ROS) to induce gasdermin E (GSDME)-mediated pyroptosis. In vivo experiments demonstrated that the bioorthogonal combination strategy of peptide and AIEgen PSs could significantly inhibit tumor growth, which is accompanied by CD8+ cytotoxic T cell infiltration. This work provides a novel self-assembly peptide-mediated bioorthogonal reaction strategy to bridge the supramolecular self-assembly and AIE field through strain-promoted azide-alkyne cycloaddition (SPAAC) and elucidates that pure type-I membrane-anchoring PSs can be used for cancer therapy via GSDME-mediated pyroptosis.

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Molecular ultrasound imaging with actively targeted microbubbles (MB) proved promising in preclinical studies but its clinical translation is limited. To achieve this, it is essential that the actively targeted MB can be produced with high batch-to-batch reproducibility with a controllable and defined number of binding ligands on the surface. In this regard, poly (n-butyl cyanoacrylate) (PBCA)-based polymeric MB have been used for US molecular imaging, however, ligand coupling was mostly done via hydrolysis and carbodiimide chemistry, which is a multi-step procedure with poor reproducibility and low MB yield. Herein, we developed a single-step coupling procedure resulting in high MB yields with minimal batch-to-batch variation. Actively targeted PBCA-MB were generated using an aminolysis protocol, wherein amine-containing cRGD was added to the MB using lithium methoxide as a catalyst. We confirmed the successful conjugation of cRGD on the MB surface, while preserving their structure and acoustic signal. Compared to the conventional hydrolysis protocol, aminolysis resulted in higher MB yields and better reproducibility of coupling efficiency. Optical imaging revealed that under flow conditions, cRGD- and rhodamine-labelled MB, generated by aminolysis, specifically bind to tumor necrosis factor-alpha (TNF-α) activated endothelial cells in vitro. Furthermore, US molecular imaging demonstrated a markedly higher binding of the cRGD-MB than of control MB in TNF-α activated mouse aortas and 4T1 tumors in mice. Thus, using the aminolysis based conjugation approach, important refinements on the production of cRGD-MB could be achieved that will facilitate the production of clinical-scale formulations with excellent binding and ultrasound imaging performance.

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Mutations in MAPT, the microtubule-associated protein tau gene, give rise to cases of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) with abundant filamentous tau inclusions in brain cells. Individuals with pathological MAPT variants exhibit behavioural changes, cognitive impairment and signs of parkinsonism. Missense mutations of residue P301, which are the most common MAPT mutations associated with FTDP-17, give rise to the assembly of mutant four-repeat tau into filamentous inclusions, in the absence of extracellular deposits. Here we report the cryo-EM structures of tau filaments from five individuals belonging to three unrelated families with mutation P301L and from one individual belonging to a family with mutation P301T. A novel three-lobed tau fold resembling the two-layered tau fold of Pick's disease was present in all cases with the P301L tau mutation. Two different tau folds were found in the case with mutation P301T, the less abundant of which was a variant of the three-lobed fold. The major P301T tau fold was V-shaped, with partial similarity to the four-layered tau folds of corticobasal degeneration and argyrophilic grain disease. These findings suggest that FTDP-17 with mutations in P301 should be considered distinct inherited tauopathies and that model systems with these mutations should be used with caution in the study of sporadic tauopathies.

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A facile and efficient protocol for P(O)-O bond formation was discovered through NaIO4/air-initiated phosphorylation of alcohols with H-phosphine oxides in water. This reaction showed good functional group tolerance and a broad substrate scope, providing an alternative method for constructing P(O)-O bonds. Mechanistic studies suggested that a phosphoryl radical-involving process from H-phosphine oxides facilitated the phosphorylation of alcohols under air.

Assuntos

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With the rapid development of information and communication industries, the usage of electromagnetic waves has caused the hazard of human health and misfunction of devices. The adsorption and shielding of electromagnetic waves have been achieved in various materials. The unique adjustable spatial structure makes metal-organic frameworks (MOFs) promising for electromagnetic shielding and adsorbing. As MOFs research advances, various large-scale MOF-based materials have been developed. For instance, MOFs spatial structure has been expanded from 2D to 3D to load more ligands. Progress in synthetic methods for MOFs and their derivatives is advancing, with priority on large-scale preparation and green synthesis. This review summarizes the methods for synthesizing MOFs and their derivatives, and explores the effects of MOFs spatial structure on electromagnetic interference (EMI) shielding and electromagnetic wave absorption capabilities. At the same time, detailed examples are used to focus on the applications of five different MOFs composites in electromagnetic shielding and electromagnetic wave absorption. Finally, the current challenges and prospects of MOFs in the electromagnetic field are introduced, providing a useful reference for the preparation and design of MOFs and their composites for electromagnetic wave processing applications.

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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to its low surgical eligibility and resistance to chemotherapy. Abundant stroma is characteristic of PDAC, and cancer-associated fibroblasts (CAFs) are a major stromal constituent, contributing to chemoresistance. Because neoadjuvant chemotherapy (NAC) is included in PDAC treatment as a standard regimen, the role of CAFs in NAC resistance must be studied. Although type IV collagen (COLIV) is present in the tumor of PDAC, the association between COLIV and disease advancement of NAC-treated PDAC is unclear. METHODS: Using a cohort of NAC-treated patients with PDAC, we examined clinicopathological data and conducted immunohistochemical analysis of COLIV in tissue specimens prepared from surgically resected pancreas. RESULTS AND CONCLUSIONS: Our analysis revealed that ~50% of the cases were positive for COLIV in the stroma and diffuse COLIV staining was an independent poor prognosis factor alongside high serum CA19-9 before NAC treatment (>37 U/mL) and postsurgical residual tumors. Based on these findings, we propose that stromal COLIV staining can be used to predict prognosis in NAC-treated patients with PDAC after surgery. Additionally, these findings suggest a possibility that stromal COLIV staining indicates resistance to anticancer drugs and/or contributes to malignancy in PDAC.

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During the development of Zn-air batteries, designing an affordable, efficient and stable electrocatalyst for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) presents a great challenge. Fe2O3 exhibits ORR and OER activities, but when used as a cathode material in Zn-air batteries, its activity requires further improvement. To achieve this goal, Ni is doped into Fe2O3 hexagonal nanorods, derived from a metal-organic framework (MOF) precursor, and further modified by N-doped carbon nanotubes. In ORR, its half-wave potential achieves 0.946 and 0.716 V in alkaline and neutral electrolytes, respectively. In OER, it requires 388 mV to obtain 10 mA cm-2 in an alkaline electrolyte. As illustrated by theoretical calculation, Ni-doping raises the d-band center of Fe2O3, which enhances its adsorption towards relevant oxygen species in electrocatalysis. This improves its ORR and OER activities. Based on these merits, the Zn-air battery is assembled with an alkaline electrolyte. At 10 mA cm-2, its specific capacity and energy density reach 819.8 mA h g-1 and 960.1 W h kg-1, respectively. This battery remains stable after a long time of charge and discharge. In neutral electrolytes, its promising discharge performance is also well retained. This work develops an effective approach to improve ORR and OER activities of Fe2O3-based cathode materials in Zn-air batteries.

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OBJECTIVE: To summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion (OLIF), and put forward preventive measures. METHODS: From October 2015 to December 2019, 23 patients who underwent reoperation after OLIF in four spine surgery centers were retrospectively analyzed. There were 9 males and 14 females with an average age of (61.89±8.80) years old ranging from 44 to 81 years old. The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases, discogenic low back pain in 1 case, degenerative lumbar spondylolisthesis in 6 cases, lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases. Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation. There were 17 cases of single fusion segment, 2 of 2 fusion segments, 4 of 3 fusion segments. All the cases underwent reoperation within 3 months after the initial surgery. The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy, cage adjustment and neurolysis in 2 cases, arthroplasty and neurolysis under endoscope in 1 case, posterior laminectomy and neurolysis in 1 case, pedicle screw adjustment in 1 case, exploration and decompression under percutaneous endoscopic in 1 case, interbody fusion cage and pedicle screw revision in 1 case. Visual analogue scale (VAS) and Oswestry disability index (ODI) index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up. During the follow-up process, the phenomenon of fusion cage settlement or re-displacement, as well as the condition of intervertebral fusion, were observed. The changes in intervertebral space height before the first operation, after the first operation, before the second operation, 3 to 5 days after the second operation, 6 months after the second operation, and at the latest follow-up were measured and compared. RESULTS: There was no skin necrosis and infection. All patients were followed up from 12 to 48 months with an average of (28.1±7.3) months. Nerve root injury symptoms were relieved within 3 to 6 months. No cage transverse shifting and no dislodgement, loosening or breakage of the instrumentation was observed in any patient during the follow-up period. Though the intervertebral disc height was obviously increased at the first postoperative, there was a rapid loss in the early stage, and still partially lost after reoperation. The VAS for back pain recovered from (6.20±1.69) points preoperatively to (1.60±0.71) points postoperatively(P<0.05). The ODI recovered from (40.60±7.01)% preoperatively to (9.14±2.66)% postoperatively(P<0.05). CONCLUSION: There is a risk of reoperation due to failure after OLIF surgery. The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone, intraoperative endplate injury, significant subsidence of the fusion cage after surgery, postoperative fusion cage displacement, nerve damage, etc. As long as it is discovered in a timely manner and handled properly, further surgery after OLIF surgery can achieve better clinical results, but prevention still needs to be strengthened.

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The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch-clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety-like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3-d subacute restraint stress (SRS), a well-validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS-induced anxiety-related behaviors, whereas hM3Dq-mediated chemogenetic or SRS-induced activation of vHPC astrocytes enhances anxiety-like behaviors, which are reversed by intra-vHPC application of the ionotropic glutamate N-methyl-d-aspartate receptor antagonists. Furthermore, intra-vHPC or systemic application of the N-methyl-d-aspartate receptor antagonist memantine, a U.S. FDA-approved drug for Alzheimer's disease, fully rescues SRS-induced anxiety-like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety-related disorders.

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Therapeutics for eradicating hepatitis B virus (HBV) infection are still limited and current nucleos(t)ide analogs (NAs) and interferon are effective in controlling viral replication and improving liver health, but they cannot completely eradicate the hepatitis B virus and only a very small number of patients are cured of it. The TCR-like antibodies recognizing viral peptides presented on human leukocyte antigens (HLA) provide possible tools for targeting and eliminating HBV-infected hepatocytes. Here, we generated three TCR-like antibodies targeting three different HLA-A2.1-presented peptides derived from HBV core and surface proteins. Bispecific antibodies (BsAbs) were developed by fuzing variable fragments of these TCR-like mAbs with an anti-CD3ϵ antibody. Our data demonstrate that the BsAbs could act as T cell engagers, effectively redirecting and activating T cells to target HBV-infected hepatocytes in vitro and in vivo. In HBV-persistent mice expressing human HLA-A2.1, two infusions of BsAbs induced marked and sustained suppression in serum HBsAg levels and also reduced the numbers of HBV-positive hepatocytes. These findings highlighted the therapeutic potential of TCR-like BsAbs as a new strategy to cure hepatitis B.

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OBJECTIVES: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). Its most common immunophenotype is CD4+/CD7-/CD25+, although unusual immunophenotypes can occur and may lead to misdiagnosis. METHODS: The immunophenotypes, cytogenetics, molecular features, clinical presentations, treatment, and prognosis of 131 patients with ATLL were retrospectively studied in a large tertiary medical center in the United States. RESULTS: All cases showed loss of CD7 expression. While 82.4% of cases demonstrated CD4+, 17.6% exhibited unusual phenotypes, including CD4+/CD8+ (6.9%), CD4-/CD8- (2.3%), CD5- (3.1%), CD2-, and CD3-. The most common cytogenetics abnormalities included polysomy 3 (34.6%), translocation 1 (23.1%), and abnormalities found on chromosome 11 (30.8%) and chromosome 14 (26.9%). The common gene mutations identified by the next-generation sequencing study were TP53 (16.7%), TBL1XR1 (16.7%), EP300 (14.3%), and NOTCH1 (14.3%). TBL1XR1 mutation is associated with genetic instabilities. There was no significant difference between the clinical presentations of these 2 groups. CONCLUSIONS: Adult T-cell leukemia/lymphoma exhibits versatile immunophenotypic, cytogenetic, and molecular features. Simultaneous involvement of blood, lymph nodes, and other organs, along with hypercalcemia in a patient from an endemic area, necessitates HTLV-1 testing to avoid underdiagnosis of this dismal disease that might need aggressive chemotherapy followed by bone marrow transplant.

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RATIONALE AND OBJECTIVES: The optimal prognostic assessment for patients with hepatocellular carcinoma (HCC) after drug-eluting bead transarterial chemoembolization (DEB-TACE) remains unclear. This study aimed to propose a novel staging system in comparison with the current staging systems for HCC following DEB-TACE. MATERIALS AND METHODS: From four centers, patients with HCC undergoing DEB-TACE as the initial therapy were retrospectively included and classified into training and validation sets. Multivariable regression was used to determine the independent prognostic factors in the training set. A novel staging system incorporating the independent factors was proposed and externally validated in terms of discrimination and calibration compared to other staging systems in both sets. RESULTS: The training and validation sets included 335 and 99 patients, respectively. Multivariable regression revealed independent factors including alpha-fetoprotein level, aspartate aminotransferase to lymphocyte count ratio index, maximum tumor diameter, Child-Pugh class, and portal vein invasion. The novel prognostic staging system, named PADCA, was proposed and outperformed other staging systems with the highest C-index, area under the curve, Wald test value, clinical benefit, and the lowest Akaike information criterion in the training and validation sets. CONCLUSION: The PADCA staging system has a superior prognostic predictive ability compared to the current staging systems. PADCA can assist clinicians in screening out the patients most likely to derive benefit from DEB-TACE and guiding the formulation of therapy and follow-up strategy.