Polysarcosine (PSar) has been recognized as a promising alternative to poly(ethylene glycol) (PEG) in biomedical fields. The development of efficient methods for synthesizing PSar with complex architectures is therefore essential for creating optimal biomaterials. Herein, we propose a "one-pot" approach for synthesizing PSar molecular bottlebrush (MBB) with abundant active terminal amino groups through the combination of N-carboxyanhydride (NCA) polymerization and monomer-emulsified aqueous ring-opening metathesis polymerization (ME-ROMP). Briefly, the NCA polymerization of Sar-NCA monomer using norbornenyl amino (NB-NH2) as the initiator was first conducted to prepare norbornenyl terminal PSar (NB-PSar). Subsequently, without purification, this NB-PSar macromonomer was employed to synthesize PSar MBBs with precise architecture by ME-ROMP in the CH2Cl2/H2O (v/v = 1/10) mixtures through a grafting-through strategy. Kinetic studies indicated that the entire process could be completed within 20 min with near-quantitative conversion, and worm-like PSar MBBs with varied length and diameter could be easily synthesized by varying the feed ratios. Moreover, the terminal secondary amines of PSar side chains were retained, which could be further utilized for the surface modification of the MBBs. This work provides a one-pot approach for worm-like nanostructured PSar materials, which are expected to hold promising potential for creating advanced biomaterials.

Lipid nanoparticles (LNPs) have been demonstrated as effective mRNA delivery systems, with ionizable lipids (ILs) serving as critical determinants of their in vivo delivery efficacy. However, elucidating the structure-activity relationship of ILs remains a formidable challenge, hindering the rational design of next-generation LNPs with improved efficiency and targeting specificity. Here, we present a straightforward and powerful isomerism strategy for the efficient synthesis of 9 isomeric ILs using a four-component Ugi reaction (Ugi-4CR). Molecular dynamics simulations and small-angle neutron scattering investigations revealed that differences in IL isomerism lead to distinct IL-mRNA intermolecular interactions and varied IL distribution patterns within LNPs, ultimately resulting in variations in the apparent pK a of LNPs. In vivo evaluation demonstrated that isomeric ILs contribute to different transfection profiles across liver cell types following intravenous administration, enhance muscle-selective mRNA delivery after intramuscular administration, and modulate the delivery efficiency of DOTAP-mediated lung-targeted LNPs. The establishment of IL isomerism not only introduces a new molecular design dimension for IL optimization but also lays the foundation for the rational design of ILs for targeted mRNA delivery, thus expanding the potential applications of mRNA therapeutics.

Eliciting mucosal immunity is crucial for protecting against respiratory pathogen infections. However, the intricate structure of mucosal tissues and their immune tolerance environment pose great challenges for the development of mucosal vaccines. To avoid being expelled by the ciliary clearance system, mucosal adhesion materials, such as chitosan, have been applied to efficiently deliver antigens to the immune system. However, the antigen showed poor mucus penetration due to chitosan's strong adhesion to mucin. Herein, we applied hyaluronic acid (HA)-coated nanoparticulate vaccine, named NHCF, containing Pre-F protein of respiratory syncytial virus (RSV) formulated with chitosan. Compared with the vaccine without HA coating (NC), NHC by intranasal administration (I.N.) to mice exhibited an enhanced penetration of the mucus layer, which was confirmed by a respiratory organoid chip. Moreover, when agonists were cofabricated with Pre-F in NHC, compared to CpG or cholera toxin B (CTB), the vaccines with 2,3-cGAMP (NHCF-GAMP) can overcome the mucosal immune tolerance microenvironment and produce the highest titer of IgA in mucosal and IgG in serum. Aside from the arousing humoral immunity, NHCF-GAMP can recruit the most abundant immune cells to nasal-associated lymphoid tissue from circulation. Notably, the mice that received NHCF-GAMP significantly reduced mucosal damage and viral load upon RSV challenge from mucus. Thus, this study demonstrates that a rational design delivery system of antigen and agonist can effectively enhance mucosal vaccine efficacy.

Non-Small-Cell Lung Cancer (NSCLC) often responds poorly to immune checkpoint blockade due to its immunosuppressive, "cold" tumor microenvironment. Activating alternative immune effectors may overcome this limitation. Here we identified lung-enriched gamma delta T cells as a key compartment in NSCLC and developed a lung-targeted lipid nanovaccine to activate them in situ. Analysis of patient transcriptomic data sets reveals that gamma delta T cell and CD1d signatures are associated with improved patient survival in NSCLC. Using this insight, we engineered alpha-galactosylceramide (alpha-GalCer) and poly(I:C)-loaded lipid nanoparticles that preferentially accumulated in the lung after intravenous administration. In orthotopic NSCLC models, the nanovaccine activated gamma delta T cells, enhanced functional CD8+ T cell infiltration, remodeled the immunosuppressive tumor microenvironment, and significantly prolonged survival. Depletion of gamma delta T cells abolished therapeutic benefit, demonstrating that gamma delta T cells represented the important effector population for this strategy. Furthermore, splenectomy attenuated vaccine efficacy, suggesting a contribution of systemic immune crosstalk to vaccine efficacy. Together, these findings establish a gamma delta T cell-centered lung-targeted immunotherapy strategy for treating immune-resistant NSCLC.

Immunosenescence increases susceptibility to varicella-zoster virus (VZV) infection in the elderly while compromising vaccine responsiveness. Although clinical adjuvants such as AS01 have improved vaccine efficacy, challenges associated with saponin-based components and separate antigen-adjuvant formulations persist. Here, we developed a nanovaccine, NP(gEIM), that co-encapsulates VZV glycoprotein E (gE) with the TLR4 agonist MPLA and TLR7/8 agonist IMQ in lipid nanoparticles via flash nanocomplexation (FNC), enabling coordinated co-delivery of antigen and adjuvants. NP(gEIM) efficiently targeted draining lymph nodes and promoted antigen-presenting cell uptake and maturation. In young and aged mice, NP(gEIM) elicited gE-specific antibody responses and Th1-biased cellular immunity comparable to AS01-adjuvanted gE vaccines while exceeding aluminum-adjuvanted vaccines. Moreover, NP(gEIM) enhanced IFN-γ and TNF-α production by antigen-specific CD4+ and CD8+ T cells while reducing immunosuppressive Treg and MDSC populations in aged mice. Notably, NP(gEIM) reshaped the TCR repertoire by promoting selective expansion of putative antigen-responsive T cell clones and altering TCR V/J gene usage and CDR3 length distribution, providing molecular insights into vaccine-induced T cell responses. Collectively, this study presents a nanovaccine strategy enabling coordinated delivery of antigen and dual TLR agonists. By integrating humoral and cellular immunity with TCR repertoire modulation, NP(gEIM) offers a potential strategy for improving vaccine responses in aging populations and developing vaccines against age-associated infectious diseases.

Neutrophil extracellular traps (NETs) may facilitate metastasis of tumor cells through interaction with the CCDC25 located along cell membrane, resulting high mortality of patients. Although cationic materials can destruct NETs and inhibit tumor metastasis, they lack targeting ability in physiological environments. Herein, we designed and synthesized a peptide-dendrimer conjugates, AAPVRnS(5-n)-G2.5, that may target neutrophil elastase (NE), a component of NETs, expose their cationic cores by NE degradation, and finally neutralize DNAs of NETs via charge interaction. It combined a triple strategy: the AAPV tetrapeptide sequence provides targeting ability to NET-enriched regions; the arginine (R) and serine (S) segment ensures DNA binding efficacy as well as biocompatibility; and the PAMAM-G2.5 dendrimer provides multivalent effect and an extended circulation. The characterization shows that AAPVRnS(5-n)- G2.5 has NET targeting and NE responsiveness, and the obtained RnS(5-n)- G2.5 after NE treatment shows an enhanced zeta potential and DNA binding ability. In turn, the cationic RnS(5-n)-G2.5 can destroy NETs, competitively block the binding between NET-DNA and CCDC25, and then inhibit NET-induced tumor cell cytoskeleton remodeling. In vivo, the conjugates prolong the circulation half-life of the materials and promote the enrichment in organs prone to metastasis. In the 4 T1 orthotopic breast cancer mouse model, AAPVR4S1-G2.5 shows the best performance, significantly reducing the level of NETs in the lung and liver, and inhibiting tumor metastasis without causing obvious toxicity. This NET targeted and NE responsive conjugate materials provide an alternative strategy for precise inhibiting tumor metastasis.

Step-growth polymerization of A2+B2 monomer pair provides valuable opportunities for synthesizing polymeric materials with diverse functions along the polymer backbones. Herein, a copper-catalyzed azide-alkyne cycloaddition (CuAAC) click polymerization of alpha, omega-bifunctional macromonomers (MMs) with reaction enhanced reactivity of intermediates (RERI) mechanism was reported to synthesize high-molecular-weight polymers with controlled insertion of multi-functionalities along the polymer backbones. In this CuAAC click polymerization, the polyethylene glycol (PEG), polystyrene (PS), poly(tert-butyl acrylate) (PtBA) homopolymers with molecular weight ranging from 1.0 to 4.0 kDa, were utilized for alpha, omega-bis-alkynyl-terminated MMs (A2-MMs), and 2,2-bis(azidomethyl)propane-1,3-diol was used as the pair B2 monomers. Given the RERI effect of B2 monomer, these A2-MMs can be quantitatively consumed with slightly excess of B2 in the polymerization, producing high-molecular-weight poly(PEG), poly(PS) and poly(PtBA) with multiple functional groups along the backbones. In addition, by taking the CuAAC copolymerization of these A2-MMs, a series of functional multiblock copolymers (MBCPs) with can be facile synthesized. Moreover, the ester groups from A2-MM units endowed poly(A2-MM) products with degradability under mild condition. The multiple hydroxyl groups from B2 units could be further modified by efficient coupling reactions with anhydride, propargyl ester or isocyanide molecules, promoting the fabrication of polymer materials with desired functions.

Abstract Molecular bottlebrushes (MBBs) represent a class of densely grafted macromolecules where polymeric side chains are covalently and compactly tethered to a polymeric backbone. These highly grafted chain architectures create a confined microenvironment induced by steric congestion of the side chains, offering an exceptional platform for investigating polymer behaviors under molecular confinement. The unique topological structure alters the conformation of backbones and side chains from an entangled coil to an extended chain and endows the MBBs with a unimolecular nanoobject structure with a defined length/diameter ratio and an intrinsically ordered intra- and intermolecular structure. The correlation between chain crowdedness, governed by grafting density and side chain structures, and physical properties, e.g., crystallization, glass transition temperature, and viscoelastic behavior, may direct the development of unique polymer materials through reorganization of known polymer chains. In this Perspective, we focus on the relationship between the crowded structure and the physical properties of MBBs, highlighting the crowdedness-derived material properties. We first introduce the unique nanostructure of MBBs, followed by chemistry and physical properties. Finally, we highlight the functions that differ from those of non-topological polymers and discuss their potential application.

Molecular bottlebrushes (MBBs) represent a unique class of graft polymers with densely packed side chains along a linear backbone, offering distinctive properties and broad applicability. However, their conventional synthesis typically involves multistep procedures with intermediate purification, limiting efficiency and scalability. Herein, we report a streamlined one-pot strategy for the well-defined synthesis of MBBs via a seamlessly integrated sequence of copper superoxido complex-enabled atom transfer radical polymerization (ATRP), nucleophilic radical coupling (NRC), and copper-catalyzed azide–alkyne cycloaddition (CuAAC), without any intermediate isolation. This approach enables near-quantitative monomer conversion (>95%) and efficient in-situ generation of alkyne-terminated side chain precursors, which are directly coupled with azide-functionalized polynorbornene backbones to afford MBBs with tunable grafting densities (0.8-2.9 per repeat unit) and low dispersity (Mw/Mn < 1.15). The platform demonstrates broad monomer compatibility, including tert-butyl acrylate, hydroxyethyl acrylate, and trifluoroethyl acrylate, and is successfully scaled up to ten-gram scale without compromising structural control. This one-pot grafting-onto strategy significantly reduces reaction time and material loss, offering a robust, versatile, and scalable route to functional MBBs for diverse applications.

The nucleus pulposus (NP), the core shock-absorbing component of the intervertebral disc (IVD), plays a vital role in the pathogenesis of intervertebral disc degeneration (IVDD). Here, we uncover that degenerative NP tissue under mechanical stress is characterized by upregulated PIEZO1 and accumulation of cell-free DNA (cfDNA). Specific inhibition or knockout of PIEZO1 suppresses the cfDNA-induced NP degeneration. Mechanistically, PIEZO1-mediated calcium overload triggers mitochondrial DNA (mtDNA) leakage, initiating a cascade that culminates in MAFB-dependent activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome pathway. Targeting the PIEZO1-cfDNA-MAFB-NLRP3 axis, we developed a hydrogel nano composite system (HA-F127@MCC950 SiNPs) containing amino-functionalized SiO2 nanoparticles (SiNPs) loaded with pyroptosis antagonist MCC950, embedded within hyaluronic acid (HA) and pluronic F127 (F127). The engineered hydrogel possesses dual effects in cfDNA scavenging and NLRP3 suppression in NP cells (NPCs). Moreover, this approach markedly attenuated NP degeneration progression in rat models of cfDNA-induced and temporary compression model (TCM)-induced IVDD. Collectively, this nucleic acid clearance strategy provides new insights for IVDD treatment.

4079 Background: Borrmann type IV (Borrmann-IV) gastric cancer (GC), or linitis plastica, is marked by diffuse infiltration, early metastasis, and poor prognosis, with limited benefit from conventional therapies. This study evaluated the efficacy and safety of a total neoadjuvant regimen combining immunotherapy and chemotherapy in Borrmann-IV GC. Methods: This trial (NCT06451211) enrolled patients with Borrmagnn-IV gastric cancer without distant metastasis. Participants received a total neoadjuvant regimen consisting of tislelizumab (an anti–PD-1 antibody) combined with platinum-based chemotherapy (oxaliplatin plus capecitabine or S-1) for 6 cycles at 3-week intervals, followed by radical surgical resection. The prespecified primary endpoint was the pathological response rate, defined as tumor regression grade (TRG) 0/1. Results: A total of 56 patients were enrolled, all patients had no distant metastasis confirmed by laparoscopic exploration and ascitic fluid cytology. The median age was 58 years; all patients were pMMR. In the efficacy analysis population (n=47), 41 patients completed 5–6 cycles and 6 patients completed 3–4 cycles of preoperative chemotherapy plus immunotherapy, no patients experienced disease progression leading to tumor metastasis during preoperative treatment. 47 patients underwent radical surgical resection, including 42 total gastrectomy, with an R0 resection rate of 98% (46/47). The prespecified primary endpoint of TRG 0/1 was achieved in 32% of patients (15/47; 95% CI, 21%–48%). Notably, 17% (n = 8) achieved pCR (ypT0N0), and 53% (n =25) were ypN0. Pathological response (TRG 0/1) was significantly higher in Lauren intestinal/mixed versus diffuse types (53% vs. 21%; p < 0.05), while efficacy was comparable between PD-L1 CPS ≥5 and <5 (44% vs. 30%). Grade 3/4 treatment-related adverse events occurred in 32% of patients (n=18), mainly thrombocytopenia and liver function impairment. Surgical morbidity (Clavien–Dindo grade II/III) occurred in 10.6% of surgical patients (5/47), including 1 patient with postoperative bleeding and 3 patients with anastomotic leakage; no perioperative mortality was observed. Conclusions: Total neoadjuvant tislelizumab plus chemotherapy demonstrated promising efficacy and an acceptable safety profile in patients with Borrmann-IV gastric cancer. Lauren classification may serve as a potential predictive biomarker and warrants further study. Clinical trial information: NCT06451211 .

The combination of controlled radical polymerization technique and grafting-from strategy has been widely employed for synthesizing molecular bottlebrushes (MBBs); however, this approach always meets challenges at the high monomer conversion stage due to the intra- and inter-molecular cross-linking caused by inevitable radical-radical coupling. Herein, we report the utilization of copper superoxido complex-enabled atom transfer radical polymerization (ATRP) for the grafting-from synthesis of MBBs with well-defined architectures in high yield. Owing to the use of a low concentration of copper catalyst, the intra- and inter-molecular cross-linking is greatly minimized, leading to the precise synthesis of MBBs with narrow distribution, near-quantitative monomer conversion, and worm-like architecture. Under this premise, we further evaluate the feasibility of this approach for the one-pot preparation of MBBs with block copolymer (BCP) side chains as well as dye-loaded functional MBBs. Overall, this work proposes an efficient grafting-from approach for MBBs with precise architectures and unprecedentedly high yield, which can be utilized for multicomponent MBBs with diverse functions.

Altering the properties of polymer chains under confinement represents fundamental challenges in polymer science. Molecular bottlebrushes (MBs), with their densely grafted architecture, create a unique constrained environment that serves as an ideal model system for exploring the structure-property relationships of confined molecular chains. In this work, we employed a Me6TREN/CuBr-catalyzed CuAAC click chemistry to synthesize precisely defined MBs with ultrahigh grafting densities (up to 6.2 side chains (SCs) per C-C repeating unit) via a reaction-enhanced reactivity of intermediates (RERI)-driven grafting-onto strategy. Using this approach, we prepared 65 MBs bearing tetraphenylethylene (TPE) units, a fluorescent moiety sensitive to mechanical strain, at tailored positions along poly(ethylene glycol) (PEG) SCs, including the interior segment, middle portion, and terminal end of the side chains. By systematically varying grafting density (G dst), molecular weight, composition, and TPE location of SCs, as well as the backbone length, and correlating these with the luminescent behavior in both good and poor solvents, we elucidated the local segmental motion within the SCs. The results demonstrate that the mobility of the interior SC segments decreases initially in a linear manner with an increase of G dst. Beyond a critical threshold, however, the decline in the mobility of segments follows a steeper linear trend. Moreover, the mobility of the SC segments away from the backbone increases significantly, even under dense grafting. This work not only clarifies how molecular parameters influence side-chain dynamics but also provides a theoretical basis for the design of advanced functional materials based on MBs.

The NEOSUMMIT-01 trial previously showed that adding the PD-1 antibody toripalimab to perioperative chemotherapy improved the pathologic response in patients with locally advanced gastric or gastroesophageal junction cancer. Here, we present the event-free survival (EFS) and overall survival (OS) after extended follow-up. A total of 108 patients were enrolled (toripalimab plus chemotherapy, n = 54; chemotherapy alone, n = 54). At the data cutoff date (August 29, 2025), the median follow-up was 43.2 months (interquartile range: 36.6-53.7). The 3-year EFS was 74.7% (95% CI, 63.6% to 87.7%) in the toripalimab plus chemotherapy group and 56.2% (95% CI, 43.3% to 73.0%) in the chemotherapy group, with a hazard ratio (HR) of 0.51 (95% CI, 0.27 to 0.98; P = .044). The 3-year OS was 81.3% (95% CI, 71.4% to 92.4%) versus 72.2% (95% CI, 61.2% to 85.2%), respectively, with an HR of 0.45 (95% CI, 0.21 to 0.95; P = .036). The survival benefits were consistent across most predefined subgroups and were maintained in the analysis excluding patients with dMMR. In conclusion, perioperative toripalimab plus chemotherapy significantly improved 3-year EFS and OS compared with chemotherapy alone, suggesting it as a promising treatment option for patients with locally advanced gastric or gastroesophageal junction cancer.

Excessive accumulation of cell-free DNA (cfDNA) has been identified as a primary pathogenic factor in autoimmune diseases. The circulating deoxyribonuclease (DNase) maintaining cfDNA homeostasis is suppressed, and thus exogenous DNase has been applied to degrade cfDNA for inflammation control. However, in pathological states, cfDNA and cationic endogenous peptide (e.g., LL37) form immune complexes (ICs), which not only weaken DNase efficacy but also facilitate immune cell internalization to induce an inflammatory response. With LL37-DNA as a model IC, here we found that the LL37 occupancy not only sterically hinders cfDNA's access to the catalytic sites but also induces deactivation of DNase via formation of ternary complexes (LL37-DNA-DNase I). This transition critically impairs the activity of DNase I within LL37-rich inflammatory microenvironments. Thus, we postulated that heparin, a clinically approved anionic glycosaminoglycan, could destruct the ICs and liberate cfDNAs, restoring their susceptibility to degradation. Indeed, we found that a combination of heparin and DNase I facilitates the DNA degradation and inhibits the ICs-mediated TLR9 activation in vitro. However, the therapeutic outcome observed in rheumatoid arthritis (RA) model was still suboptimal, attributed to the short plasma half-life of DNase. To validate this, we engineered a DNase nanoparticle (DNase@TANP) capable of sustained release of the enzyme. Consequently, the sequential administration of heparin and DNase@TANP (with a 30-min interval) to RA model demonstrated a synergistic cfDNA degradation efficiency, effectively suppressing Toll-like receptor (TLR) mediated inflammatory pathways and ameliorating joint inflammation. This strategy, leveraging clinically approved agents for cfDNA clearance, establishes a promising therapeutic paradigm for cfDNA-associated autoimmune disorders.

Worm-like micelles are a type of highly anisotropic polymer nanostructure that have found promising applications in materials science. However, to precisely tailor the chemical compositions of worm-like micelles without sacrificing their morphology is challenging. Herein, we demonstrate the feasibility of a kinetically controlled ring-opening metathesis polymerization-induced self-assembly (ROMPISA) approach for preparing worm-like micelles with tunable chemical compositions and surface properties. We first evaluated the effect of the glass transition temperature (T-g) of the core-forming blocks on the morphology of the resultant nano-objects and determined the critical T-g value for the preparation of worm-like nanostructures with an enlarged morphology region. The morphology could be predicted in this ROMPISA analysis by comparing the T-g of the employed core-forming blocks with the critical T-g value. Moreover, worm-like micelles with different surface properties, such as surface potentials, could be facilely synthesized by tailoring the chemical compositions of shell-forming blocks and fixing the core-forming blocks with T-g > 135 degrees C. This work provides a predictable and robust approach for worm-like nanomaterials that could find potential applications in the field of materials science.

282 Background: The NEOSUMMIT-01 trial evaluated the efficacy of adding the PD-1 antibody toripalimab to perioperative chemotherapy in patients with locally advanced, resectable gastric or gastroesophageal junction (GEJ) cancer. Previously, we reported significant improvements in pathological complete or moderate regression (TRG 0/1) rate (44.4% vs 20.4%, P =0.009) and pathological complete response (pCR) rate (22.2% vs 7.4%, P =0.030) with the addition of toripalimab (2023 ASCO Abstract 4001; Nature Medicine 2024). Here, we present the 3-year survival outcomes after extended follow-up. Methods: In this open-label, randomized, phase 2 trial, patients with resectable gastric or GEJ cancer (clinical stage cT3–4a N+ M0) were randomized (1:1) to receive either three preoperative and five postoperative cycles of SOX/XELOX chemotherapy (chemotherapy group), or the same chemotherapy combined with toripalimab, followed by toripalimab monotherapy for 6 months (toripalimab plus chemotherapy group). The primary endpoint was pathological complete or moderate regression rate (TRG 0/1). Secondary endpoints included pathological complete response (pCR), R0 resection rate, objective response rate, disease control rate, event-free survival (EFS), overall survival (OS), and treatment safety. This analysis focuses on 3-year EFS and OS, assessed in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT04250948). Results: Between October 12, 2019, and June 27, 2022, 108 patients were enrolled (toripalimab plus chemotherapy, n = 54; chemotherapy alone, n = 54) and included in the intention-to-treat analysis. As of the clinical cutoff date (August 29, 2025), the median follow-up was 43.2 months (IQR 36.6–53.7). The 3-year EFS was 74.7% (95% CI: 63.6–87.7%) in the toripalimab plus chemotherapy group and 56.2% (95% CI: 43.3–73.0%) in the chemotherapy group, with a hazard ratio (HR) of 0.52 (95% CI: 0.27–1.00; P = 0.047). The 3-year OS was 81.3% (95% CI: 71.4–92.4%) versus 72.2% (95% CI: 61.2–85.2%), respectively, with an HR of 0.45 (95% CI: 0.21–0.95; P = 0.031). Conclusions: Perioperative toripalimab combined with chemotherapy demonstrated significantly improved 3-year EFS and OS compared to chemotherapy alone, suggesting it as a promising treatment option for patients with locally advanced, resectable gastric or GEJ adenocarcinoma. Clinical trial information: NCT04250948 .

BACKGROUND:Adjuvant chemotherapy following D2 gastrectomy constitutes the standard-of-care for resectable gastric or gastroesophageal junction (GEJ) carcinoma. The CAPITAL trial is a multicenter, randomized, phase 3 study, aiming to assess the efficacy and safety of adjuvant oxaliplatin plus S-1 (SOX) versus S-1 alone. METHODS:Patients with histologically confirmed pathological stage II-III gastric or GEJ adenocarcinoma after gastrectomy with D2 lymphadenectomy were randomly assigned (1:1) to receive either the SOX regimen (n = 362) or the S-1 regimen (n = 362). The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov (NCT01795027). FINDINGS:The median follow-up was 74.0 months (interquartile range [IQR], 35.5-89.3). The 5-year overall survival rates were 70.9% (95% confidence interval [CI], 66.0-76.1) in the SOX group and 62.9% (95% CI, 57.8-68.5) in the S-1 group (hazard ratio [HR], 0.74; 95% CI, 0.58-0.95; p = 0.018). The 3- and 5-year disease-free survival rates were 71.2% (95% CI, 66.5-76.3) and 66.2% (95% CI, 61.2-71.6) in the SOX group, as compared with 65.1% (95% CI, 60.2-70.5) and 55.6% (95% CI, 50.4-61.3) in the S-1 group (HR, 0.76; 95% CI, 0.61-0.96). Treatment-related adverse events of grade 3-4 occurred in 87 (25%) of 349 patients in the SOX group and 45 (13%) of 347 patients in the S-1 group. The most common grade 3-4 adverse event was neutropenia, occurring in 44 (13%) of 349 patients in the SOX group and 23 (7%) of 347 patients in the S-1 group. CONCLUSIONS:The addition of adjuvant oxaliplatin to S-1 chemotherapy significantly improved overall survival and disease-free survival in patients with gastric cancer. FUNDING:This research was supported by the National Natural Science Foundation of China (82573092 and 82573387).

This study constructed a synergistic strategy of flexible-rigid dual curing agents based on dynamic bonding to overcome the shortcomings of traditional epoxy resins, such as poor reprocessability, difficulty in balancing strength and toughness, and insufficient functional activity. A flexible PEG-based curing agent NBS-PEGDA (NP) and a rigid cobalt-tryptamine coordination complex TM-Co were co-introduced into fluorinated epoxy resin (FEP) to construct a dual dynamic cross-linked network containing borate ester bonds and Co-N coordination bonds. The results showed that the co-curing system with optimized ratio could simultaneously improve the strength and toughness of the material. The composite material exhibited a tensile strength of 46 MPa and an elongation at break of nearly 100%, along with excellent thermoresponsive shape recovery and reprocessability. The synergistic effect of multiple elements (fluorine, boron, and cobalt) endowed the material with low heat release, low smoke emission, good flame retardancy and dielectric properties. When the ratio of TM-Co to NP was 2:1, the total heat release (THR) of the system was 34% lower than that of pure NP-FEP, and the CO2 and CO emissions were reduced by 30.24% and 13.15%, respectively. This multifunctional fluorinated epoxy composite material had good application potential in high-end electronics and aerospace fields.