Nature-inspired protein mineralization strategies for nanoparticle construction: advancing effective cancer therapy.

Recently, nanotechnology has shown great potential in the field of cancer therapy due to its ability to improve the stability and solubility and reduce side effects of drugs. The biomimetic mineralization strategy based on natural proteins and metal ions provides an innovative approach for the synthesis of nanoparticles. This strategy utilizes the unique properties of natural proteins and the mineralization ability of metal ions to combine nanoparticles through biomimetic mineralization processes, achieving the effective treatment of tumors. The precise control of the mineralization process between proteins and metal ions makes it possible to obtain nanoparticles with the ideal size, shape, and surface characteristics, thereby enhancing their stability and targeting ability in vivo. Herein, initially, we analyze the role of protein molecules in biomineralization and comprehensively review the functions, properties, and applications of various common proteins and metal particles. Subsequently, we systematically review and summarize the application directions of nanoparticles synthesized based on protein biomineralization in tumor treatment. Specifically, we discuss their use as efficient drug delivery carriers and role in mediating monotherapy and synergistic therapy using multiple modes. Also, we specifically review the application of nanomedicine constructed through biomimetic mineralization strategies using natural proteins and metal ions in improving the efficiency of tumor immunotherapy.

An investigation of the molecular characterization of the tripartite motif (TRIM) family and primary validation of TRIM31 in gastric cancer.

Most TRIM family members characterized by the E3-ubiquitin ligases, participate in ubiquitination and tumorigenesis. While there is a dearth of a comprehensive investigation for the entire family in gastric cancer (GC). By combining the TCGA and GEO databases, common TRIM family members (TRIMs) were obtained to investigate gene expression, gene mutations, and clinical prognosis. On the basis of TRIMs, a consensus clustering analysis was conducted, and a risk assessment system and prognostic model were developed. Particularly, TRIM31 with clinical prognostic and diagnostic value was chosen for single-gene bioinformatics analysis, in vitro experimental validation, and immunohistochemical analysis of clinical tissue microarrays. The combined dataset consisted of 66 TRIMs, of which 52 were differentially expressed and 43 were differentially prognostic. Significant survival differences existed between the gene clusters obtained by consensus clustering analysis. Using 4 differentially expressed genes identified by multivariate Cox regression and LASSO regression, a risk scoring system was developed. Higher risk scores were associated with a poorer prognosis, suppressive immune cell infiltration, and drug resistance. Transcriptomic data and clinical sample tissue microarrays confirmed that TRIM31 was highly expressed in GC and associated with a poor prognosis. Pathway enrichment analysis, cell migration and colony formation assay, EdU assay, reactive oxygen species (ROS) assay, and mitochondrial membrane potential assay revealed that TRIM31 may be implicated in cell cycle regulation and oxidative stress-related pathways, contribute to gastric carcinogenesis. This study investigated the whole functional and expression profile and a risk score system based on the TRIM family in GC. Further investigation centered around TRIM31 offers insight into the underlying mechanisms of action exhibited by other members of its family in the context of GC.

[Therapeutic effect of calcaneal beak-like fracture secondary to calcaneal osteomyelitis caused by diabetic foot].

OBJECTIVE: To explore clinical effect of vancomycin calcium sulfate combined with internal fixation on calcaneal beak-like fracture secondary to calcaneal osteomyelitis caused by diabetic foot. METHODS: From April 2018 to October 2021, a retrospective analysis was performed on 5 patients with calcaneal bone osteomyelitis secondary to diabetic foot, including 2 males and 3 females, aged from 48 to 60 years old;diabetes course ranged from 5 to 13 years;the courses of diabetic foot disease ranged from 18 to 52 days;5 patients were grade Ⅲ according to Wagner classification. All patients were treated with debridement, vancomycin bone cement implantation, negative pressure aspiration at stageⅠ, vancomycin calcium sulfate and internal fixation at stageⅡfor calcaneal beak-like fracture. Surgical incision and fracture healing time were recorded, and the recurrence of osteomyelitis was observed. American Orthopedic Foot Andankle Society (AOFAS) score and exudation at 12 months after operation were evaluated. RESULTS: Five patients were successfully completed operation without lower extremity vascular occlusion, and were followed up for 16 to 36 months. The wound healing time after internal fixation ranged from 16 to 26 days, and healing time of fractures ranged from 16 to 27 weeks. AOFAS score ranged from 65 to 91 at 12 months after operation, and 2 patients got excellent result, 2 good and 1 fair. Among them, 1 patient with skin ulcer on the back of foot caused by scalding at 5 months after operation (non-complication), was recovered after treatment;the wound leakage complication occurred in 2 patients, and were recovered after dressing change. No osteomyelitis or fracture occurred in all patients. CONCLUSION: Vancomycin calcium sulfate with internal fixation in treating calcaneal osteomyelitis secondary to calcaneal osteomyelitis caused by diabetic foot could not only control infection, but also promote fracture healing, and obtain good clinical results.

Preparation of the double cross-linking carbon dots-polyvinyl alcohol-carboxymethyl cellulose composite film for food active packaging application.

This paper prepared a new kind of carbon dots-polyvinyl alcohol-carboxymethyl cellulose composite film with antibacterial properties. Carbon dots and citric acid were used as cross-linking agents, and polyvinyl alcohol and carboxymethyl cellulose were used as matrices respectively. The mechanical properties, UV shielding performance, thermal stability, antioxidant capability, and antibacterial activities of the carbon dots-polyvinyl alcohol-carboxymethyl cellulose composite film were researched. The prepared carbon dots-polyvinyl alcohol-carboxymethyl cellulose composite film was applied in the strawberry freshness preservation test. And test results indicated that the carbon dots-polyvinyl alcohol-carboxymethyl cellulose composite film could prevent rotting and extend the shelf life of strawberries. This carbon dots-polyvinyl alcohol-carboxymethyl cellulose composite film could be applied in the food active packaging field.

A near-infrared spectroscopy dataset of coal and coal-measure rock under diverse conditions.

The identification technology for coal and coal-measure rock is required across multiple stages of coal exploration, mining, separation, and tailings management. However, the construction of identification models necessitates substantial data support. To this end, we have established a near-infrared spectral dataset for coal and coal-measure rock, which includes the reflectance spectra of 24 different types of coal and coal-measure rock. For each type of sample, 11 sub-samples of different granularities were created, and reflectance spectra were collected from sub-samples at five different detection azimuths, 18 different detection zeniths, and under eight different light source zenith conditions. The quality and usability of the dataset were verified using quantitative regression and classification machine learning algorithms. Primarily, this dataset is used to train artificial intelligence-based models for identifying coal and coal-measure rock. Still, it can also be utilized for regression studies using the industrial analysis results contained within the dataset.

Development and verification of a manganese metabolism- and immune-related genes signature for prediction of prognosis and immune landscape in gastric cancer.

Background: Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical settings, its efficacy remains limited to a minority of GC patients. Manganese, recognized for its role in the body's anti-tumor immune response, has the potential to enhance the effectiveness of tumor treatment when combined with immune checkpoint inhibitors. Methods: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases was utilized to obtain transcriptome information and clinical data for GC. Unsupervised clustering was employed to stratify samples into distinct subtypes. Manganese metabolism- and immune-related genes (MIRGs) were identified in GC by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. We conducted gene set variation analysis, and assessed the immune landscape, drug sensitivity, immunotherapy efficacy, and somatic mutations. The underlying role of NPR3 in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments. Results: GC patients were classified into four subtypes characterized by significantly different prognoses and tumor microenvironments. Thirteen genes were identified and established as MIRGs, demonstrating exceptional predictive effectiveness in GC patients. Distinct enrichment patterns of molecular functions and pathways were observed among various risk subgroups. Immune infiltration analysis revealed a significantly greater abundance of macrophages and monocytes in the high-risk group. Drug sensitivity analysis identified effective drugs for patients, while patients in the low-risk group could potentially benefit from immunotherapy. NPR3 expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of NPR3 was distributed in endothelial cells. Cellular experiments demonstrated that NPR3 facilitated the proliferation of GC cells. Conclusion: This is the first study to utilize manganese metabolism- and immune-related genes to identify the prognostic MIRGs for GC. The MIRGs not only reliably predicted the clinical outcome of GC patients but also hold the potential to guide future immunotherapy interventions for these patients.

Adhesion between EVs and tumor cells facilitated EV-encapsulated doxorubicin delivery via ICAM1.

Doxorubicin (Dox) is an anti-tumor drug with a broad spectrum, whereas the cardiotoxicity limits its further application. In clinical settings, liposome delivery vehicles are used to reduce Dox cardiotoxicity. Here, we substitute extracellular vesicles (EVs) for liposomes and deeply investigate the mechanism for EV-encapsulated Dox delivery. The results demonstrate that EVs dramatically increase import efficiency and anti-tumor effects of Dox in vitro and in vivo, and the efficiency increase benefits from its unique entry pattern. Dox-loading EVs repeat a "kiss-and-run" motion before EVs internalization. Once EVs touch the cell membrane, Dox disassociates from EVs and directly enters the cytoplasm, leading to higher and faster Dox import than single Dox. This unique entry pattern makes the adhesion between EVs and cell membrane rather than the total amount of EV internalization the key factor for regulating the Dox import. Furthermore, we recognize ICAM1 as the molecule mediating the adhesion between EVs and cell membranes. Interestingly, EV-encapsulated Dox can induce ICAM1 expression by irritating IFN-γ and TNF-α secretion in TME, thereby increasing tumor targeting of Dox-loading EVs. Altogether, EVs and EV-encapsulated Dox synergize via ICAM1, which collectively enhances the curative effects for tumor treatment.

Hypocretenolides: collective total syntheses and activities toward metastatic colon cancer.

A concise and collective synthetic route to hypocretenolides was developed for the first time. This route features one-pot addition-alkylation and intramolecular 1,3-dipolar cycloaddition to efficiently assemble the 5/7/6 ring system. Our syntheses enabled multigram preparation of hypocretenolide which facilitated further biological evaluation. Preliminary CCK-8 cytotoxic results of hypocretenolide indicated its IC50 values within 1 µM against 4 colon cancer cell lines. Wound healing and transwell assays suggested the promising inhibitory activities of hypocretenolide toward the migratory capabilities of colon cancer cells in vitro. The animal results confirmed that hypocretenolide can inhibit metastasis of colon cancer cells.

GSH-Responsive Liposomes with Heat Shock Protein Regulatory Ability for Efficient Photodynamic/Photothermal Combined Therapy of Tumors.

Phototherapy, represented by photodynamic therapy (PDT) and photothermal therapy (PTT), has great potential in tumor treatment. However, the presence of antioxidant glutathione (GSH) and the heat shock proteins (HSPs) expression caused by high temperature can weaken the effects of PDT and PTT. Here, a multifunctional nanocomplex BT&GA@CL is constructed to realize enhanced synergistic PDT/PTT. Cinnamaldehyde liposomes (CLs) formed by cinnamaldehyde dimer self-assembly were loaded with in gambogic acid (GA) and an aggregation-induced emission molecule BT to obtain BT&GA@CL. As a drug carrier, CL can consume glutathione (GSH) and release drugs responsively. The released BT aggregates can simultaneously act as both a photothermal agent and photosensitizer to achieve PDT and PTT under 660 nm laser irradiation. Specifically, GA as an HSP90 inhibitor can attenuate PTT-induced HSP90 protein expression, thereby weakening the tolerance of tumor cells to high temperatures and enhancing PTT. Such a multifunctional nanocomplex simultaneously modulates the content of GSH and HSP90 in tumor cells, thus enhancing both PDT and PTT, ultimately achieving the goal of efficient combined tumor suppression.

Pickering emulsions with high ionic strength resistance stabilized by pea protein isolate-polyglycerol conjugate particles with good biocompatibility.

Among various biopolymers, protein particles are widely used for stabilizing Pickering emulsions, yet their emulsifying ability are easily influenced by the ion concentration, pH, and high temperatures. To address these challenges, this study utilized chemical modification to prepare pea protein isolate-polyglycerol (PPI-PG) conjugates by Schiff-base reaction. Compared with other chemical modifications, this method produces conjugate particles with excellent biocompatibility, capable of promoting cell proliferation by up to 177 %. These conjugates showed improved dispersibility, with diffusion coefficients 3.5 times greater than pure PPI, and the isoelectric points shift from pH 4.6 to pH 1.5, which contribute to the pH stability of emulsions (pH 3-9). Additionally, the anisotropic nature of the conjugate particles, with a three-phase contact angle close to 90°, make particles need more energy for detachment from the oil-water interface, leading to good thermal stability of emulsion (80 °C, 48 h). Notably, after conjugation, these particles rely more on PG chains for dispersibility, which are less affected by ions, resulting in emulsions with high ionic strength resistance (3000 mM). Furthermore, the prepared Pickering emulsion demonstrates remarkable antioxidative properties (only a 10 % decrease), indicating widely potential applications in food, cosmetics, and pharmaceutical sectors.

Endogenous retroviral solo-LTRs in human genome.

Human endogenous retroviruses (HERVs) are derived from the infection and integration of exogenetic retroviruses. HERVs account for 8% of human genome, and the majority of HERVs are solitary LTRs (solo-LTRs) due to homologous recombination. Multiple findings have showed that solo-LTRs could provide an enormous reservoir of transcriptional regulatory sequences involved in diverse biological processes, especially carcinogenesis and cancer development. The link between solo-LTRs and human diseases still remains poorly understood. This review focuses on the regulatory modules of solo-LTRs, which contribute greatly to the diversification and evolution of human genes. More importantly, although inactivating mutations, insertions and deletions have been identified in solo-LTRs, the inherited regulatory elements of solo-LTRs initiate the expression of chimeric lncRNA transcripts, which have been reported to play crucial roles in human health and disease. These findings provide valuable insights into the evolutionary and functional mechanisms underlying the presence of HERVs in human genome. Taken together, in this review, we will present evidences showing the regulatory and encoding capacity of solo-LTRs as well as the significant impact on various aspects of human biology.

Extracellular vesicles derived from M2-like macrophages alleviate acute lung injury in a miR-709-mediated manner.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterised by an uncontrolled inflammatory response, and current treatment strategies have limited efficacy. Although the protective effect of M2-like macrophages (M2φ) and their extracellular vesicles (EVs) has been well-documented in other inflammatory diseases, the role of M2φ-derived EVs (M2φ-EVs) in the pathogenesis of ALI/ARDS remains poorly understood. The present study utilised a mouse model of lipopolysaccharide-induced ALI to first demonstrate a decrease in endogenous M2-like alveolar macrophage-derived EVs. And then, intratracheal instillation of exogenous M2φ-EVs from the mouse alveolar macrophage cell line (MH-S) primarily led to a take up by alveolar macrophages, resulting in reduced lung inflammation and injury. Mechanistically, the M2φ-EVs effectively suppressed the pyroptosis of alveolar macrophages and inhibited the release of excessive cytokines such as IL-6, TNF-α and IL-1ß both in vivo and in vitro, which were closely related to NF-κB/NLRP3 signalling pathway inhibition. Of note, the protective effect of M2φ-EVs was partly mediated by miR-709, as evidenced by the inhibition of miR-709 expression in M2φ-EVs mitigated their protective effect against lipopolysaccharide-induced ALI in mice. In addition, we found that the expression of miR-709 in EVs derived from bronchoalveolar lavage fluid was correlated negatively with disease severity in ARDS patients, indicating its potential as a marker for ARDS severity. Altogether, our study revealed that M2φ-EVs played a protective role in the pathogenesis of ALI/ARDS, partly mediated by miR-709, offering a potential strategy for assessing disease severity and treating ALI/ARDS.

Ultra-stable pickering emulsion stabilized by anisotropic pea protein isolate-fucoidan conjugate particles through Maillard reaction.

Bio-based emulsifiers hold significant importance in various industries, particularly in food, cosmetics, pharmaceuticals and other related fields. In this study, pea protein isolate (PPI) and fucoidan (FUD) were conjugated via the Maillard reaction, which is considered safe and widely used in the preparation of food particle. The PPI-FUD conjugated particles exhibit an anisotropic non-spherical structure, thereby possessing a high detachment energy capable of preventing emulsion coalescence and Ostwald ripening. Compared to emulsions previously prepared in other studies (< 500 mM), the Pickering emulsion stabilized by PPI-FUD conjugate particles demonstrates outstanding ionic strength resistance (up to 5000 mM). Furthermore, when encapsulating curcumin, the Pickering emulsion protects the curcumin from oxidation. Additionally, the formulated emulsions demonstrated the capability to incorporate up to 60 % (v/v) oil phase, revealing remarkable performance in terms of storage stability, pH stability, and thermal stability.

Comprehensive characterization of ERV-K (HML-8) in the chimpanzee genome revealed less genomic activity than humans.

Endogenous retroviruses (ERVs) originate from ancestral germline infections caused by exogenous retroviruses. Throughout evolution, they have become fixed within the genome of the animals into which they were integrated. As ERV elements coevolve with the host, they are normally epigenetically silenced and can become upregulated in a series of physiological and pathological processes. Generally, a detailed ERV profile in the host genome is critical for understanding the evolutionary history and functional performance of the host genome. We previously characterized and cataloged all the ERV-K subtype HML-8 loci in the human genome; however, this has not been done for the chimpanzee, the nearest living relative of humans. In this study, we aimed to catalog and characterize the integration of HML-8 in the chimpanzee genome and compare it with the integration of HML-8 in the human genome. We analyzed the integration of HML-8 and found that HML-8 pervasively invaded the chimpanzee genome. A total of 76 proviral elements were characterized on 23/24 chromosomes, including detailed elements distribution, structure, phylogeny, integration time, and their potential to regulate adjacent genes. The incomplete structure of HML-8 proviral LTRs will undoubtedly affect their activity. Moreover, the results indicated that HML-8 integration occurred before the divergence between humans and chimpanzees. Furthermore, chimpanzees include more HML-8 proviral elements (76 vs. 40) and fewer solo long terminal repeats (LTR) (0 vs. 5) than humans. These results suggested that chimpanzee genome activity is less than the human genome and that humans may have a better ability to shape and screen integrated proviral elements. Our work is informative in both an evolutionary and a functional context for ERVs.

A Catalyst-Like System Enables Efficient Perovskite Solar Cells.

High-quality perovskite films are essential for achieving high performance of optoelectronic devices; However, solution-processed perovskite films are known to suffer from compositional and structural inhomogeneity due to lack of systematic control over the kinetics during the formation. Here, the microscopic homogeneity of perovskite films is successfully enhanced by modulating the conversion reaction kinetics using a catalyst-like system generated by a foaming agent. The chemical and structural evolution during this catalytic conversion is revealed by a multimodal synchrotron toolkit with spatial resolutions spanning many length scales. Combining these insights with computational investigations, a cyclic conversion pathway model is developed that yields exceptional perovskite homogeneity due to enhanced conversion, having a power conversion efficiency of 24.51% for photovoltaic devices. This work establishes a systematic link between processing of precursor and homogeneity of the perovskite films.

Progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of BCHE as a potential biomarker.

Background: Globally, gastric cancer (GC) is a category of prevalent malignant tumors. Its high occurrence and fatality rates represent a severe threat to public health. According to recent research, lipid metabolism (LM) reprogramming impacts immune cells' ordinary function and is critical for the onset and development of cancer. Consequently, the article conducted a sophisticated bioinformatics analysis to explore the potential connection between LM and GC. Methods: We first undertook a differential analysis of the TCGA queue to recognize lipid metabolism-related genes (LRGs) that are differentially expressed. Subsequently, we utilized the LASSO and Cox regression analyses to create a predictive signature and validated it with the GSE15459 cohort. Furthermore, we examined somatic mutations, immune checkpoints, tumor immune dysfunction and exclusion (TIDE), and drug sensitivity analyses to forecast the signature's immunotherapy responses. Results: Kaplan-Meier (K-M) curves exhibited considerably longer OS and PFS (p<0.001) of the low-risk (LR) group. PCA analysis and ROC curves evaluated the model's predictive efficacy. Additionally, GSEA analysis demonstrated that a multitude of carcinogenic and matrix-related pathways were much in the high-risk (HR) group. We then developed a nomogram to enhance its clinical practicality, and we quantitatively analyzed tumor-infiltrating immune cells (TIICs) using the CIBERSORT and ssGSEA algorithms. The low-risk group has a lower likelihood of immune escape and more effective in chemotherapy and immunotherapy. Eventually, we selected BCHE as a potential biomarker for further research and validated its expression. Next, we conducted a series of cell experiments (including CCK-8 assay, Colony formation assay, wound healing assay and Transwell assays) to prove the impact of BCHE on gastric cancer biological behavior. Discussion: Our research illustrated the possible consequences of lipid metabolism in GC, and we identified BCHE as a potential therapeutic target for GC. The LRG-based signature could independently forecast the outcome of GC patients and guide personalized therapy.

Trehalose 6-phosphate synthase gene rdtps1 contributes to thermal acclimation in Rhyzopertha dominica.

BACKGROUND: The lesser grain borer (Rhyzopertha dominica), a worldwide primary pest of stored grain, causes serious economic losses and threatens stored food safety. R. dominica can respond to changes in temperature, especially the adaptability to heat. In this study, transcriptome analysis of R. dominica exposed to different temperatures was performed to elucidate differences in gene expression and the underling molecular mechanism. RESULTS: Isoform-sequencing generated 17,721,200 raw reads and yielded 20,416 full-length transcripts. A total of 18,880 (92.48%) transcripts were annotated. We extracted RNA from R. dominica reared at 5 °C (cold stress), 15 °C (cold stress), 27 °C (ambient temperature) and 40 °C (heat stress) for RNA-seq. Compared to those of control insects reared at 27 °C, 119, 342, and 875 differentially expressed genes (DEGs) were identified at 5 °C, 15 °C, and 40 °C, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that pathways associated with "fatty acid metabolism", "fatty acid biosynthesis", "AMPK signaling pathway", "neuroactive ligand receptor interaction", and "longevity regulating pathway-multiple species" were significantly enriched. The functional annotation revealed that the genes encoding heat shock proteins (HSPs), fatty acid synthase (FAS), phospholipases (PLA), trehalose transporter (TPST), trehalose 6-phosphate synthase (TPS), and vitellogenin (Vg) were most likely involved in temperature regulation, which was also validated by RT-qPCR. Seven candidate genes (rdhsp1, rdfas1, rdpla1, rdtpst1, rdtps1, rdvg1, and rdP450) were silenced in the RNA interference (RNAi) assay. RNAi of each candidate gene suggested that inhibiting rdtps1 expression significantly decreased the trehalose level and survival rate of R. dominica at 40 °C. CONCLUSIONS: These results indicated that trehalose contributes to the high temperature resistance of R. dominica. Our study elucidates the molecular mechanisms underlying heat tolerance and provides a potential target for the pest management in R. dominica.

Association of survival with adjuvant chemotherapy in patients with stage IB gastric cancer: a multicentre, observational, cohort study.

Background: Recurrence following radical resection in patients with stage IB gastric cancer (GC) is not uncommon. However, whether postoperative adjuvant chemotherapy could reduce the risk of recurrence in stage IB GC remains contentious. Methods: We collected data on 2110 consecutive patients with pathologic stage IB (T1N1M0 or T2N0M0) GC who were admitted to 8 hospitals in China from 2009 to 2018. The survival of patients who received adjuvant chemotherapy was compared with that of postoperative observation patients using propensity score matching (PSM). Two survival prediction models were constructed to estimate the predicted net survival gain attributable to adjuvant chemotherapy. Findings: Of the 2110 patients, 1344 received adjuvant chemotherapy and 766 received postoperative observation. Following the 1-to-1 matching, PSM yielded 637 matched pairs. Among matched pairs, adjuvant chemotherapy was not associated with improved survival compared with postoperative observation (OS: hazard ratio [HR], 0.72; 95% CI, 0.52-1.00; DFS: HR, 0.91; 95% CI, 0.64-1.29). Interestingly, in the subgroup analysis, reduced mortality after adjuvant chemotherapy was observed in the subgroups with elevated serum CA19-9 (HR, 0.22; 95% CI, 0.08-0.57; P = 0.001 for multiplicative interaction), positive lymphovascular invasion (HR, 0.32; 95% CI, 0.17-0.62; P < 0.001 for multiplicative interaction), or positive lymph nodes (HR, 0.17; 95% CI, 0.07-0.38; P < 0.001 for multiplicative interaction). The survival prediction models mainly based on variables associated with chemotherapy benefits in the subgroup analysis demonstrated good calibration and discrimination, with relatively high C-indexes. The C-indexes for OS were 0.74 for patients treated with adjuvant chemotherapy and 0.70 for patients treated with postoperative observation. Two nomograms were built from the models that can calculate individualized estimates of expected net survival gain attributable to adjuvant chemotherapy. Interpretation: In this cohort study, pathologic stage IB alone was not associated with survival benefits from adjuvant chemotherapy compared with postoperative observation in patients with early-stage GC. High-risk clinicopathologic features should be considered simultaneously when evaluating patients with stage IB GC for adjuvant chemotherapy. Funding: National Natural Science Foundation of China; the National Key R&D Program of China.

Soft-hard dual nanophases: a facile strategy for polymer strengthening and toughening.

Polymers often face a trade-off between stiffness and extensibility-for example, toughening rigid polymers by incorporating plasticizers or flexible polymers leads to strikingly decreased stiffness. Herein, we circumvent this long-standing tricky dilemma in materials science via constructing soft-hard dual nanophases in polymers. As-fabricated dual-nanophase PLA shows a high yield strength of 69.1 ± 4.4 MPa, a large extensibility of 279.1 ± 25.5%, and a super toughness of 115.2 ± 10.3 MJ m-3, which are 1.2, 48 and 82 times, respectively, those of neat PLA. Combined high stiffness, large ductility, and super toughness are unprecedented for PLA and enable bio-sourced PLA to replace petroleum-based resins such as PP, PET and PC. Besides, soft-hard dual nanophases in polymers are rarely reported due to significant constraints in terms of modifier dispersion/aggregation, interfacial regulation, and processing difficulties. The construction strategy described herein, combining controlled annealing and a well-designed plasticizer, can efficiently construct soft-hard dual nanophases in polymers, which will greatly advance the nanostructure design of polymers. More importantly, the proposed strategy for materials design will be widely applicable to industrial manufacturing in terms of nanophase construction and interfacial optimization due to the simplicity and availability at a large scale. We envision that this work offers an innovative and facile strategy to circumvent the trade-off between stiffness and extensibility and to advance the nanostructure design of high-performance polymers in a manner applicable to industrial manufacturing.