Phosphatidylserine-functional polydimethylsiloxane substrates regulate macrophage M2 polarization via modulus-dependent NF-κB/PPARγ pathway.

Macrophages, highly plastic innate immune cells, critically influence the success of implantable devices by responding to biochemical and physical cues. However, the mechanisms underlying their synergistic regulation of macrophage polarization on implant surfaces remain poorly understood. Therefore, we constructed anti-inflammatory phosphatidylserine (PS) modified polydimethylsiloxane (PDMS) substrates with low, medium, and high modulus (1-100 kPa) to investigate the combined effects and underlying mechanisms of substrate modulus and biochemical signal on macrophage polarization. The introduction of PS on the PDMS surface not only significantly enhanced the polarization of M0 to M2 but also potently suppressed lipopolysaccharide (LPS)-induced M1 activation, with this effect further potentiated by a reduction in substrate modulus. In vivo subcutaneous implantation experiments also corroborated the synergistic effect of PS functionalization and low modulus PDMS in inhibiting M1 activation and promoting M2 polarization. Notably, reduced modulus led to decreased integrin αV/ß3 clustering and cytoskeletal protein aggregation, ultimately diminishing YAP activation and nuclear translocation. Concomitantly, this disruption of the Piezo1-cytoskeletal protein positive feedback loop resulted in reduced p65/IκB phosphorylation and inflammation, while concurrently promoting PPARγ expression. Overall, our findings underscore the pivotal role of substrate modulus in modulating PS-mediated biomaterial-cell interactions, synergistically potentiating PS-induced M2 macrophage polarization, thus paving the way for the design of advanced immunomodulatory biomaterials.

Nitrogen-Doped 3D-Graphene Advances Near-Infrared Photodetector for Logic Circuits and Image Sensors Overcoming 2D Limitations.

The limitations of two-dimensional (2D) graphene in broadband photodetector are overcome by integrating nitrogen (N) doping into three-dimensional (3D) structures within silicon (Si) via plasma-assisted chemical vapor deposition (PACVD) technology. This contributes to the construction of vertical Schottky heterojunction broad-spectrum photodetectors and applications in logic devices and image sensors. The natural nanoscale resonant cavity structure of 3D-graphene enhances photon capture efficiency, thereby increasing photocarrier generation. N-doping can fine-tune the electronic structure, advancing the Schottky barrier height and reducing dark current. The as-fabricated photodetector exhibits exceptional self-driven photoresponse, especially at 1550 nm, with an excellent photoresponsivity (79.6 A/W), specific detectivity (1013 Jones), and rapid response of 130 µs. Moreover, it enables logic circuits, high-resolution pattern image recognition, and broadband spectra recording across the visible to near-infrared range (400-1550 nm). This research will provide new views and technical support for the development and widespread application of high-performance semiconductor-based graphene broadband detectors.

Thyroid hormone T4 mitigates traumatic brain injury in mice by dynamically remodeling cell type specific genes, pathways, and networks in hippocampus and frontal cortex.

The complex pathology of mild traumatic brain injury (mTBI) is a main contributor to the difficulties in achieving a successful therapeutic regimen. Thyroxine (T4) administration has been shown to prevent the cognitive impairments induced by mTBI in mice but the mechanism is poorly understood. To understand the underlying mechanism, we carried out a single cell transcriptomic study to investigate the spatiotemporal effects of T4 on individual cell types in the hippocampus and frontal cortex at three post-injury stages in a mouse model of mTBI. We found that T4 treatment altered the proportions and transcriptomes of numerous cell types across tissues and timepoints, particularly oligodendrocytes, astrocytes, and microglia, which are crucial for injury repair. T4 also reversed the expression of mTBI-affected genes such as Ttr, mt-Rnr2, Ggn12, Malat1, Gnaq, and Myo3a, as well as numerous pathways such as cell/energy/iron metabolism, immune response, nervous system, and cytoskeleton-related pathways. Cell-type specific network modeling revealed that T4 mitigated select mTBI-perturbed dynamic shifts in subnetworks related to cell cycle, stress response, and RNA processing in oligodendrocytes. Cross cell-type ligand-receptor networks revealed the roles of App, Hmgb1, Fn1, and Tnf in mTBI, with the latter two ligands having been previously identified as TBI network hubs. mTBI and/or T4 signature genes were enriched for human genome-wide association study (GWAS) candidate genes for cognitive, psychiatric and neurodegenerative disorders related to mTBI. Our systems-level single cell analysis elucidated the temporal and spatial dynamic reprogramming of cell-type specific genes, pathways, and networks, as well as cell-cell communications as the mechanisms through which T4 mitigates cognitive dysfunction induced by mTBI.

Start-up of glycerol-driven denitrifying phosphorus removal from wastewater: The effects of the microaerobic environment.

Glycerol, an abundant by-product of biodiesel production, represented a promising carbon source for enhancing nutrient removal from low C/N ratio wastewater. This study discovered a novel approach to initiate glycerol-driven denitrifying phosphorus removal (DPR) in situ by creating a short-term microaerobic environment within the aerobic zone. This approach facilitated the in-situ conversion of glycerol, which was subsequently utilized by denitrifying phosphate accumulating organisms (DPAOs) for DPR. The feasibility and stability of glycerol-driven DPR were validated in a continuous-flow pilot-scale reactor. Anaerobic phosphorus release increased from 1.0 mg/L/h to 2.5 mg/L/h, with fermentation bacteria and related functional genes showing significant increases. The stable stage exhibited 92.8% phosphorus removal efficiency and 55.5% DPR percentage. The microaerobic environment enhanced fermentation bacteria enrichment, crucial for glycerol-driven DPR stability. The collaborative interaction between fermentation bacteria and phosphate accumulating organisms (PAOs) played a key role in sustaining glycerol-driven DPR stability. These findings provide a robust theoretical foundation for applying glycerol-driven DPR in established wastewater treatment plants.

Cu2(OH)3NO3/γ-Al2O3 catalyzes Fenton-like oxidation for the advanced treatment of effluent organic matter (EfOM) in fermentation pharmaceutical wastewater: The synergy of Cu2(OH)3NO3 and γ-Al2O3.

The secondary effluent of fermentation pharmaceutical wastewater exhibits high chromaticity, elevated salinity, and abundant refractory effluent organic matter (EfOM), presenting significant treatment challenges and environmental threats. Herein, Cu2(OH)3NO3/γ-Al2O3 was fabricated through ultrasound-assisted impregnation and calcination to catalyze the Fenton-like oxidation for degrading organic pollutants in this secondary effluent. Under neutral conditions, with 400.00 mg/L H2O2, 8 g/L catalyst, and at 30 ℃, the EfOM and CODCr removal efficiencies can reach 96.90 % and 51.56 %, respectively. The Cu2(OH)3NO3/γ-Al2O3 catalyst possesses ideal reusability, maintaining CODCr, chromaticity, and EfOM removal efficiencies at 44.44 %-64.59 %, 85.45 %-93.45 %, and 61.00 %-95.00 % over 220 h in a continuous-flow catalytic oxidation system operated at room temperatures (15-25 ℃). Electron paramagnetic resonance results and density functional theory calculations indicate that •OOH may be the predominant reactive oxygen species, facilitated by the easier elongation of the OH bond in H2O2 compared to the OO bond. The adjusted electronic structure endows Cu2(OH)3NO3/γ-Al2O3 composite sites with superior catalytic selectivity for H2O2 activation compared to Cu2(OH)3NO3 single crystal sites, with γ-Al2O3 additionally facilitating H2O2 activation through electron donation. This research highlights the efficacy of Cu2(OH)3NO3/γ-Al2O3 in the advanced treatment of complex industrial wastewater, elucidating its catalytic mechanisms and potential applications.

Evaluation of various carbon sources on ammonium assimilation and denitrifying phosphorus removal in a modified anaerobic-anoxic-oxic process from low-strength wastewater.

A pilot-scale continuous-flow modified anaerobic-anoxic-oxic (MAAO) process examined the impact of external carbon sources (acetate, glucose, acetate/propionate) on ammonium assimilation, denitrifying phosphorus removal (DPR), and microbial community. Acetate exhibited superior efficacy in promoting the combined process of ammonia assimilation and DPR, enhancing both to 50.0 % and 60.0 %, respectively. Proteobacteria and Bacteroidota facilitated ammonium assimilation, while denitrifying phosphorus-accumulating organisms (DPAOs) played a key role in nitrogen (N) and phosphorus (P) removal. Denitrifying glycogen-accumulating organisms (DGAOs) aided N removal in the anoxic zone, ensuring stable N and P removal and recovery. Acetate/propionate significantly enhanced DPR (77.7 %) and endogenous denitrification (37.9 %). Glucose favored heterotrophic denitrification (29.6 %) but had minimal impact on ammonium assimilation. These findings provide valuable insights for wastewater treatment plants (WWTPs) seeking efficient N and P removal and recovery from low-strength wastewater.

The Synergistic Effect on the Mimetic Optical Structure of Feline Eyes toward Household Health Monitoring of Acute and Chronic Diseases.

A breakthrough in the performance of bionic optical structures will only be achieved if we can obtain an in-depth understanding of the synergy mechanisms operating in natural optical structures and find ways to imitate them. In this work, inspired by feline eyes, an optical substrate that takes advantage of a synergistic effect that occurs between resonant and reflective structures was designed. The synergistic effect between the reflective and resonant components leads to a Raman enhancement factor (EF) of 1.16 × 107, which is much greater than that achieved using the reflective/resonant cavities on their own. Finite-difference time-domain (FDTD) simulations and experimental results together confirm that the mechanism of this synergistic effect is achieved by realizing multiple reflections and repeated absorptions of light, generating a strong local electric field. Thus, a 2-3 order of magnitude increase in sensitivity could be achieved. More importantly, with the homemade centrifugal device, above optical substrates were further used to develop a rapidly highly sensitive household health monitoring system (detection time <3 min). It can thus be used to give early warning of acute diseases with high risk (e.g., acute myocardial infarction (AMI) and cerebral peduncle). Due to the good reusability and storability (9% and 8% reduction in EF after washing 30 times and 9 months of storage, respectively) of the substrates, the substrates thus reduce detection costs (to ∼$1), making them much cheaper to use than the current gold-standard methods (e.g., ∼$16 for gout detection).

Highly Sensitive Fiber Crossbar Sensors Enabled by Second-Order Synergistic Effect of Air Capacitance and Equipotential Body.

Fiber crossbars, an emerging electronic device, have become the most promising basic unit for advanced smart textiles. The demand for highly sensitive fiber crossbar sensors (FCSs) in wearable electronics is increased. However, the unique structure of FCSs presents challenges in replicating existing sensitivity enhancement strategies. Aiming at the sensitivity of fiber crossbar sensors, a second-order synergistic strategy is proposed that combines air capacitance and equipotential bodies, resulting in a remarkable sensitivity enhancement of over 20 times for FCSs. This strategy offers a promising avenue for the design and fabrication of FCSs that do not depend on intricate microstructures. Furthermore, the integrative structure of core-sheath fibers ensures a robust interface, leading to a low hysteresis of only 2.33% and exceptional stability. The outstanding capacitive response performance of FCSs allows them to effectively capture weak signals such as pulses and sounds. This capability opens up possibilities for the application of FCSs in personalized health management, as demonstrated by wireless monitoring systems based on pulse signals.

Integration of ammonium assimilation with denitrifying phosphorus removal for efficient nutrient management in wastewater treatment.

Nutrient removal from sewage is transitioning to nutrient recovery. However, biological treatment technologies to remove and recover nutrients from domestic sewage are still under investigation. This study delved into the integration of ammonium assimilation with denitrifying phosphorus removal (DPR) as a method for efficient nutrient management in sewage treatment. Results indicated this approach eliminated over 80 % of the nitrogen in the influent, simultaneously recovering over 60 % of the nitrogen as the activated sludge through ammonia assimilation, and glycerol facilitated this process. The nitrification/denitrifying phosphorus removal ensured the stability of both nitrogen and phosphorus removal. The phosphorus removal rate exceeded 96 %, and the DPR rate reached over 90 %. Network analysis highlighted a stable community structure with Proteobacteria and Bacteroidota driving ammonium assimilation. The synergistic effect of fermentation bacteria, denitrifying glycogen-accumulating organisms, and denitrifying phosphorus-accumulating organisms contributed to the stability of nitrogen and phosphorus removal. This approach offers a promising method for sustainable nutrient management in sewage treatment.

Humanin ameliorates TBI-related cognitive impairment by attenuating mitochondrial dysfunction and inflammation.

Traumatic brain injury (TBI) often results in a reduction of the capacity of cells to sustain energy demands, thus, compromising neuronal function and plasticity. Here we show that the mitochondrial activator humanin (HN) counteracts a TBI-related reduction in mitochondrial bioenergetics, including oxygen consumption rate. HN normalized the disruptive action of TBI on memory function, and restored levels of synaptic proteins (synapsin 1 and p-CREB). HN also counteracted TBI-related elevations of pro-inflammatory cytokines in plasma (TNF-α, INF-y, IL 17, IL 5, MCP 5, GCSF, RANNETS, sTNFRI) as well as in the hippocampus (gp-130 and p-STAT3). Gp-130 is an integral part of cytokine receptor impinging on STAT3 (Tyr-705) signaling. Furthermore, HN reduced astrocyte proliferation in TBI. The overall evidence suggests that HN plays an integral role in normalizing fundamental aspects of TBI pathology which are central to energy balance, brain function, and plasticity.

Tracing the Flu Symptom Progression via a Smart Face Mask.

Respiration and body temperature are largely influenced by the highly contagious influenza virus, which poses persistent global public health challenges. Here, we present a wireless all-in-one sensory face mask (WISE mask) made of ultrasensitive fibrous temperature sensors. The WISE mask shows exceptional thermosensitivity, excellent breathability, and wearing comfort. It offers highly sensitive body temperature monitoring and respiratory detection capabilities. Capitalizing on the advances in the Internet of Things and artificial intelligence, the WISE mask is further demonstrated by customized flexible circuitry, deep learning algorithms, and a user-friendly interface to continuously recognize the abnormalities of both the respiration and body temperature. The WISE mask represents a compelling approach to tracing flu symptom progression in a cost-effective and convenient manner, serving as a powerful solution for personalized health monitoring and point-of-care systems in the face of ongoing influenza-related public health concerns.

Softness enhanced macrophage-mediated therapy of inhaled apoptotic-cell-inspired nanosystems for acute lung injury.

Engineered nanosystems offer a promising strategy for macrophage-targeted therapies for various diseases, and their physicochemical parameters including surface-active ligands, size and shape are widely investigated for improving their therapeutic efficacy. However, little is known about the synergistic effect of elasticity and surface-active ligands. Here, two kinds of anti-inflammatory N-acetylcysteine (NAC)-loaded macrophage-targeting apoptotic-cell-inspired phosphatidylserine (PS)-containing nano-liposomes (PSLipos) were constructed, which had similar size and morphology but different Young's modulus (E) (H, ~ 100 kPa > Emacrophage vs. L, ~ 2 kPa < Emacrophage). Interestingly, these PSLipos-NAC showed similar drug loading and encapsulation efficiency, and in vitro slow-release behavior of NAC, but modulus-dependent interactions with macrophages. Softer PSLipos-L-NAC could resist macrophage capture, but remarkably prolong their targeting effect period on macrophages via durable binding to macrophage surface, and subsequently more effectively suppress inflammatory response in macrophages and then hasten inflammatory lung epithelial cell wound healing. Especially, pulmonary administration of PSLipos-L-NAC could significantly reduce the inflammatory response of M1-like macrophages in lung tissue and promote lung injury repair in a bleomycin-induced acute lung injury (ALI) mouse model, providing a potential therapeutic approach for ALI. The results strongly suggest that softness may enhance ligand-directed macrophage-mediated therapeutic efficacy of nanosystems, which will shed new light on the design of engineered nanotherapeutics.

Angioplasty for Supra-Aortic Arterial Lesions from Takayasu Arteritis: Efficacy of Cutting Balloon Angioplasty Versus Conventional Balloon Angioplasty.

BACKGROUND: This retrospective study aimed to evaluate the safety and efficacy of cutting balloon angioplasty and conventional balloon angioplasty in supra-aortic arterial lesions caused by Takayasu arteritis. METHODS: A total of 46 patients with supra-aortic arterial lesions between January 2011 and December 2018 were included. Cutting balloon angioplasty was applied for 17 patients with 24 supra-aortic arterial lesions (group A), while 29 patients with 36 supra-aortic arterial lesions received conventional balloon angioplasty (group B). The preoperative clinical manifestation, operation result, and postoperative outcomes were recorded and compared in the 2 groups. RESULTS: Dizziness, visual disturbance, and unequal/absent pulses were the most common manifestations. The technical success of revascularization was 93.5% (43/46) in patients and 93.3% (56/60) in lesions. The stent implantation rate in group A was significantly lower than that in group B (4.2% vs. 50% in lesions, P < 0.05). Restenosis was the most common complication in both groups. Although the early (≤30 days) and late (>30 days) complications in group A were less than those in group B, there was no significant difference between the 2 groups (P > 0.05). Moreover, the primary-assisted patency of cutting balloon angioplasty and conventional balloon angioplasty at 1, 2, and 5 years were 66.7%, 62.5%, and 62.5% and 61.1%, 58.2%, and 49.8%, there was no significant difference between the 2 groups (P > 0.05), respectively. CONCLUSIONS: Compared with conventional balloon angioplasty, cutting balloon angioplasty could be considered a safe and effective alternative for supra-aortic arterial lesions caused by Takayasu arteritis, demonstrating better patency and clinical benefit.

A network pharmacology approach and experimental validation to investigate the anticancer mechanism and potential active targets of ethanol extract of Wei-Tong-Xin against colorectal cancer through induction of apoptosis via PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Wei-Tong-Xin (WTX), derives from the Chinese herbal decoction (CHD) of Wan-Ying-Yuan in ancient China, has been shown to be effective therapeutic herbal decoction for treating gastrointestinal diseases. Present studies have demonstrated that WTX had potential to alleviate the symptoms of gastrointestinal inflammation, gastric ulcer and improve gastric motility. AIM OF THE STUDY: The study primarily focused on exploring the therapeutic effect and possible pharmacological mechanism of WTX on colorectal cancer (CRC) based on network pharmacology, in vitro and in vivo experiments. MATERIALS AND METHODS: Firstly, colorectal cancer and WTX associated with targets were searched from GeneCards database and TCM Systems Pharmacology Database and Analysis Platform (TCMSP) respectively. The protein-protein interaction (PPI) network also was constructed to screening key targets. In addition, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were applied to predict the underlying biological function and mechanism involving in the anti-colorectal cancer effect of WTX. Next, CCK-8, colony formation and transwell assays were performed to verify the influence of proliferation and metastasizing ability of HCT116 cells after treated with WTX. Cell cycle, apoptosis and reactive oxygen species (ROS) were analysis by flow cytometry. Hoechst 33258 staining was conducted to observe nuclear morphology changes. Protein expression of apoptosis and PI3K/AKT signaling as well as mRNA expression of ferroptosis and apoptosis were determined by Western Blotting and RT-qPCR. The effects of WTX and LY294002 combination on the PI3K/Akt/mTOR signaling pathway were measured by Western Blotting. Finally, the xenograft tumor mouse model was established by subcutaneous injection of CT26 cells to measure tumors volume and weight. Hematoxylin and eosin (HE) staining and immunohistochemical analysis were used to observe the pathological changes and the protein expression in tumor tissues. RESULTS: There were 286 potential treatment targets from 130 bioactive compounds in WTX, 1349 CRC-related targets were identified. Eleven core targets (TP53, AKT1, STAT3, JUN, TNF, HSP90AA1, IL-6, MAPK3, CASP3, EGFR, MYC) were found by PPI network analysis constructed of 142 common targets. The results of KEGG enrichment displayed PI3K/AKT signaling pathway as core pathway. After the treatment of WTX, the inhibitory of viability, metastases and cell cycle arrest at G2/M phase were observed in HCT116 cells. Moreover, WTX induced an increase in the expression of apoptosis proteins (Bak, cytochrome c, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3) and the levels of ROS and MDA, a decrease in the expression of PI3K/AKT signaling related proteins (PI3K, p-PI3K, p-AKT/AKT and p-mTOR/mTOR) and the level of SOD. WTX treatment significantly reduced the tumor weight, increased cleaved caspase-3 positive area and decreased that of ki67 in xenograft mouse model. CONCLUSION: Through a network pharmacology approach and in vitro experiments, we predicted and verified the effect of WTX on colorectal cancer cells mainly depended on the regulation of intrinsic apoptosis via PI3K/AKT signaling pathway, and further animal experiments proved that WTX has a good anti-colon cancer effect in vivo.

Performance and mechanism of modified biological nutrient removal process in treating low carbon-to-nitrogen ratio wastewater.

For solving the challenge of difficult nutrient removal, high running cost and CO2 emission at low carbon-to-nitrogen (C:N) ratio, Bi-Bio-Selector for nitrogen and phosphorus removal (BBSNP) process was developed. Under parallel operation conditions, full-scale BBSNP was less influence by low C:N ratio (3.5-2) than Anaerobic-anoxic-aerobic (AAO) and achieved better nitrogen removal performance. The mechanism of performance advantage in BBSNP was analyzed by mass balance and high throughout sequencing. It demonstrated BBSNP developed unique microbial community at C:N ratio of 2. Higher abundance of Saccharibacteria, Ferruginibacter, Ottowia, Dokdonella, Candidatus_Nitrotoga and Nitrospira in BBSNP was responsible for better chemical oxygen demand (COD) utilization efficiency, denitrification, denitrifying phosphorus removal and nitrification. Meanwhile, under low C:N ratio, BBSNP could save 10% organic carbon and 15% oxygen requirement, reduce 53% running cost and 21% CO2 emission, which had practical value in relieving energy crisis and carbon emission of wastewater treatment plants (WWTPs).

Schisandra chinensis Lignans Exert Antidepressant Effects by Promoting BV2 Microglia Polarization toward the M2 Phenotype through the Activation of the Cannabinoid Receptor Type-2-Signal Transducer and Activator of Transcription 6 Pathway.

Based on the current results, they showed that Schisandra chinensis lignans (SCL) ameliorated depressive-like behaviors in chronic unpredictable mild stress (CUMS) mice, alleviated neuroinflammation, and improved neuronal injury. This study aimed to explore whether SCL exerted antidepressant effects through inhibiting neuroinflammation, in turn improving neuronal injury. In vitro studies revealed that SCL blocked lipopolysaccharide-increased BV2 microglial M1 but promoted the M2 phenotype. The BV2-N2a interaction model suggested that increasing the M2 phenotype of BV2 played neuroprotective effects. The current studies demonstrated that SCL up-regulated the expression of CUMS- and LPS-decreased cannabinoid receptor type-2 (CB2R) mRNA. In vitro studies showed that the transfection of BV2 with siCrn2 blocked the SCL-increased M2 phenotype via the inactivating signal transducer and activator of transcription 6 (STAT6) pathway, further decreasing the viability of N2a cells. Finally, the possible pharmacodynamic compounds, γ-schisandrin and schisantherin A, were indicated by AutoDuck analysis. Overall, our study showed that SCL promoted microglia polarization toward the M2 phenotype, in turn exerting neuroprotective effects by activating CB2R-STAT6 signaling further to play antidepressant roles.

Species richness and asynchrony maintain the stability of primary productivity against seasonal climatic variability.

The stability of grassland communities informs us about the ability of grasslands to provide reliable services despite environmental fluctuations. There is large evidence that higher plant diversity and asynchrony among species stabilizes grassland primary productivity against interannual climate variability. Whether biodiversity and asynchrony among species and functional groups stabilize grassland productivity against seasonal climate variability remains unknown. Here, using 29-year monitoring of a temperate grassland, we found lower community temporal stability with higher seasonal climate variability (temperature and precipitation). This was due to a combination of processes including related species richness, species asynchrony, functional group asynchrony and dominant species stability. Among those processes, functional group asynchrony had the strongest contribution to community compensatory dynamics and community stability. Based on a long-term study spanning 29 years, our results indicate that biodiversity and compensatory dynamics a key for the stable provision of grassland function against increasing seasonal climate variability.

Establishment of a Novel Prognostic Prediction Model for Gastric Cancer Based on Necroptosis-Related Genes.

Background: Necroptosis plays a crucial role in the progression of multiple types of cancer. However, the role of necroptosis in gastric cancer (GC) remains unclear. The aim of this study is to establish a necroptosis-related prediction model, which could provide information for treatment monitoring. Methods: The TCGA-STAD cohort was employed to establish a prognostic prediction signature and the GEO dataset was employed for external validation. The correlation between the risk score and the immune landscape, tumor mutational burden (TMB), microsatellite instability (MSI), as well as therapeutic responses of different therapies were analyzed. Results: We constructed a prognostic model based on necroptosis-associated genes (NAGs), and its favorable predictive ability was confirmed in an external cohort. The risk score was confirmed as an independent determinant, and a nomogram was further established for prognosis. A high score implies higher tumor immune microenvironment (TIME) scores and more significant TIME cell infiltration. High-risk patients presented with lower TMB, and low-TMB patients had worse overall survival (OS). Meanwhile, Low-risk scores are characterized by MSI-high (MSI-H), lower Tumor Immune Dysfunction and Exclusion (TIDE) score, and higher immunogenicity in immunophenoscore (IPS) analysis. Conclusion: The developed NAG score provides a novel and effective method for predicting the outcome of GC as well as potential targets for further research.