A point-of-care testing assay for clonorchiasis using a EuNPs-CsTR1 fluorescent probe-based immunoassay.

Clonorchis sinensis is one of the most important fish-borne zoonotic parasitic worms in humans, and is distributed in several countries with more than 15 million people infected globally. However, the lack of a point-of-care testing (POCT) method is still the critical barrier to effectively prevent clonorchiasis. With the application of novel fluorescent nanomaterials, the development of on-site testing methods with high signal enhancement can provide a simple, precise and inexpensive tool for disease detection. In this study, Eu-(III) nanoparticles (EuNPs) were used as indicative probes, combined with C. sinensis tandem repeat sequence 1 (CSTR1) antigen to capture specific antibodies. Afterward, the complex binds to mouse anti-human IgG immobilized on the test line (T-line) producing a fluorescent signal under UV light. The EuNPs-fluorescent immunoassay (EuNPs-FIA) was successfully constructed, allowing sample detection within 10 min. It enabled both qualitative determination with the naked eye under UV light and quantitative detection by scanning the fluorescence intensity on the test line and control line (C-line). A total of 133 clinical human sera (74 negative, 59 clonorchiasis, confirmed by conventional Kato-Katz (KK) methods and PCR via testing fecal samples corresponding to each serum sample) were used in this study. For qualitative analysis, the cut-off value of fluorescence for positive serum was 31.57 by testing 74 known negative human samples. The assay had no cross-reaction with other 9 parasite-infected sera, and could recognize the mixed infection sera of C. sinensis and other parasites. The sensitivity and specificity of EuNPs-FIA were both 100% compared with KK smear method. Taking advantage of its high precision and user-friendly procedure, the established EuNPs-FIA provides a powerful tool for the diagnosis and epidemiological survey of clonorchiasis.

Pain Intensity and Satisfaction of Pain Relief in Discharged Cancer Patients: A Large Sample Study in China.

BACKGROUND: Many studies have focused on the quality of pain management in hospitalized patients with cancer pain, while what happens after discharge remains unclear. AIM: The purpose of this study was to investigate the pain intensity and satisfaction of pain relief among a large sample of Chinese patients with cancer pain after discharge. DESIGN: Cross-sectional, descriptive, correlational research. SETTINGS AND SAMPLE: ABOUT: 1,013 patients were recruited in a tertiary cancer hospital, and their residence addresses were distributed in 6 geographical regions, including 26 provinces, municipalities, and autonomous regions. METHODS: The 1,013 patients with cancer pain were discharged from the wards of a national cancer hospital in China from July 2020 to October 2021. A nurse in the pain clinic followed the patients based on a whole-process information system and collected the data after the cancer pain patients were discharged. The study methods followed the STROBE guidelines. RESULTS: The average age of 1,013 discharged patients was 61.30 (±12.56) years. Moderate and severe background pain (BGP) was reported in 749 patients (73.94%), and more than 3 instances of breakthrough pain (BTP) in the past 24 hours were reported in 541 patients (53.41%). More severe BGP was associated with more frequent BTP (p < .01). In addition, there were 572 patients (56.47%) whose satisfaction with pain relief was lower than 70%. More severe BGP was associated with a lower satisfaction degree (r = -0.796, p < .01). CONCLUSIONS: Pain among discharged Chinese patients with cancer is poorly managed, and there is a low degree of satisfaction with pain relief. Nurses can do more work to assist cancer patients in managing pain more effectively by ensuring they have a plan to report and manage pain after discharge.

In-situ synthesis of ZIF-8 on magnetic pineapple leaf biochar as an efficient and reusable adsorbent for methylene blue removal from wastewater.

The presence of organic dyes in aquatic systems poses a significant threat to ecosystems and human well-being. Due to recycling challenges, traditional commercial activated carbon is not cost-effective. To address this, an imidazolate acid zeolite framework-8 (ZIF-8)-modified magnetic adsorbent (ZMPLB-800) was synthesized through the in-situ formation of ZIF-8 and subsequent carbonization at 800 °C, using magnetic pineapple leaf biochar (MPLB) as a carrier. The porous structure of ZMPLB-800 facilitates the rapid passage of dye molecules, enhancing adsorption performance. ZMPLB-800 exhibited remarkable adsorption capacity for methylene blue (MB) across a pH range of 3-13, with a maximum adsorption capacity of 455.98 mg g-1. Adsorption kinetics and thermodynamics followed the pseudo-second-order kinetic model and Langmuir isotherm model. Mechanisms of MB adsorption included pore filling, hydrogen bonding, electrostatic interactions, π-π interactions, and complexation through surface functional groups. Additionally, ZMPLB-800 demonstrated excellent regeneration performance, recording a removal efficiency exceeding 87% even after five adsorption/desorption cycles. This study provides a novel strategy for treating dye wastewater with MOF composites, laying the foundation for waste biomass utilization.

MS3 Imaging Enables the Simultaneous Analysis of Phospholipid C═C and sn-Position Isomers in Tissues.

Mass spectrometry (MS) imaging of lipids in tissues with high structure specificity is challenging in the effective fragmentation of position-selective structures and the sensitive detection of multiple lipid isomers. Herein, we develop an MS3 imaging method for the simultaneous analysis of phospholipid C═C and sn-position isomers by on-tissue photochemical derivatization, nanospray desorption electrospray ionization (nano-DESI), and a dual-linear ion trap MS system. A novel laser-based sensing probe is developed for the real-time adjustment of the probe-to-surface distance for nano-DESI. This method is validated in mouse brain and kidney sections, showing its capability of sensitive resolving and imaging of the fatty acyl chain composition, the sn-position, and the C═C location of phospholipids in an MS3 scan. MS3 imaging of phospholipids has shown the capability of differentiation of cancerous, fibrosis, and adjacent normal regions in liver cancer tissues.

Chensinin-1b Alleviates DSS-Induced Inflammatory Bowel Disease by Inducing Macrophage Switching from the M1 to the M2 Phenotype.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with an increasing prevalence worldwide. Macrophage polarization is involved in the pathogenesis of IBD. Repolarization of macrophage has thus emerged as a novel therapeutic approach for managing IBD. Chensinin-1b, derived from the skin of Rana chensinensis, is a derivative of a native antimicrobial peptide (AMP). It shows anti-inflammatory effects in sepsis models and can potentially modulate macrophage polarization. The objective of this research was to study the role of chensinin-1b in macrophage polarization and dextran sulfate sodium (DSS)-induced colitis. RAW264.7 macrophages were polarized to the M1 phenotype using lipopolysaccharide (LPS) and simultaneously administered chensinin-1b at various concentrations. The ability of chenisnin-1b to reorient macrophage polarization was assessed by ELISA, qRT-PCR, and flow cytometry analysis. The addition of chensinin-1b significantly restrained the expression of M1-associated proinflammatory cytokines and surface markers, including TNF-α, IL-6, NO, and CD86, and exaggerated the expression of M2-associated anti-inflammatory cytokines and surface markers, including IL-10, TGF-ß1, Arg-1, Fizz1, Chil3, and CD206. Mechanistically, via Western Blotting, we revealed that chensinin-1b induces macrophage polarization from the M1 to the M2 phenotype by inhibiting the phosphorylation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). In mouse models of colitis, intraperitoneal administration of chensinin-1b alleviated symptoms induced by DSS, including weight loss, elevated disease activity index (DAI) scores, colon shortening, colonic tissue damage, and splenomegaly. Consistent with our in vitro data, chensinin-1b induced significant decreases in the expression of M1 phenotype biomarkers and increases in the expression of M2 phenotype biomarkers in the mouse colitis model. Furthermore, chensinin-1b treatment repressesed NF-κB phosphorylation in vivo. Overall, our data showed that chensinin-1b attenuates IBD by repolarizing macrophages from the M1 to the M2 phenotype, suggesting its potential as a therapeutic candidate for IBD.

Multi-omics Analysis of Volatile Flavor Components in Pacific Chub and Spanish Mackerel during Freezing using GC-MS-O.

This study employed gas chromatography-mass spectrometry with olfactory (GC-MS-O) and multi-omics methods to investigate the changes in volatile flavor compounds during the freezing process of Pacific chub mackerel (Scomber japonicus) from Japan and China, and Spanish mackerel (Scomberomorus niphonius). A total of 18 volatile flavor compounds were identified, and significant differences in volatile flavor components were observed among samples frozen for 1 week, 1 year, and 2 years. The results of the Partial least squares regression (PLSR) indicated that the fishy odor was correlated with independent variables such as fatty acids (FA 22:4, FA 28:6, FA 24:4), differentially expressed genes (Gene.2425 (NDUFA5), Gene.38 (GPX1), and Gene.2844 (DAD1)). Classification and regression tree (CART) analysis revealed that the peak area values of fatty acids (FA 22:5, FA 20:4) and fatty acid esters of hydroxy fatty acids (FAHFA 18:0/22:3) were the main differentiating factors for fishy odor perception.

Delayed recovery of surface water chemistry from acidification in subtropical forest region of China.

The three largest acid rain regions of current earth are located in northern and western Europe, eastern North America, and East Asia. Sulfur and nitrate concentrations in headwater streams in Europe and North America decreased as atmospheric sulfur and nitrogen deposition decreased, albeit with a considerable delay. However, how water chemistry responds to the declining sulfur and nitrogen deposition in China is unclear. The regional survey of surface water chemistry during 2010 and 2018 within the Sichuan Basin in southwestern China showed that the recovery of the surface water chemistry was delayed for at least 5 years owing to the release of previously deposited sulfur and nitrogen stored in the soil. After sulfur deposition declined from its peak value, the subregions of purplish soil with low sulfate adsorption capacity still exhibited a net sulfur release in 2010, but this release was no longer evident by 2018. The subregions with the red and yellow soils, which have a high sulfate adsorption capacity, operated as sulfur sinks during 2010 and 2018, indicating a continuous immobilization process through sulfate reduction despite a decrease in sulfur deposition. Additionally, this sulfate reduction countered the release of sulfate caused by sulfur desorption. There was a substantial nitrogen sink within the Sichuan Basin. Nitrogen leaching decreased slowly with the declined nitrogen deposition, except in regions where nitrogen deposition exceeded the critical threshold. Compared to temperate forest regions in Europe, the Sichuan Basin and its surrounding areas have experienced higher decline rates in the leaching of sulfur and nitrogen, highlighting that the subtropical forest region undergoes a faster restoration of surface water chemistry.

Palladium-Catalyzed Regiodivergent Three-Component Alkenylamination of 1,3-Dienes with Alkyl and Aryl Amines.

We report a palladium-catalyzed method for 4,3- or 4,1-selective alkenylamination of terminal dienes. Three-component couplings proceed with alkenyl triflates and several amines, giving vicinal carboamination with a Xantphos-supported catalyst and distal difunctionalization with a phosphoramidite ligand. A number of constitutionally different disubstituted dienes also participate in regiodivergent carboaminations. Experimental evidence indicates that selectivity in the Xantphos reactions is largely influenced by the substrate, whereas the phosphoramidite-promoted process is catalyst controlled, orchestrated by a key π-stacking interaction among the ligand, solvent, and substrate.

Mobility-Modulated Sequential Dissociation Analysis Enables Structural Lipidomics in Mass Spectrometry Imaging.

Spatial lipidomics based on mass spectrometry imaging (MSI) is a powerful tool for fundamental biology studies and biomarker discovery. But the structure-resolving capability of MSI is limited because of the lack of multiplexed tandem mass spectrometry (MS/MS) method, primarily due to the small sample amount available from each pixel and the poor ion usage in MS/MS analysis. Here, we report a mobility-modulated sequential dissociation (MMSD) strategy for multiplex MS/MS imaging of distinct lipids from biological tissues. With ion mobility-enabled data-independent acquisition and automated spectrum deconvolution, MS/MS spectra of a large number of lipid species from each tissue pixel are acquired, at no expense of imaging speed. MMSD imaging is highlighted by MS/MS imaging of 24 structurally distinct lipids in the mouse brain and the revealing of the correlation of a structurally distinct phosphatidylethanolamine isomer (PE 18 : 1_18 : 1) from a human hepatocellular carcinoma (HCC) tissue. Mapping of structurally distinct lipid isomers is now enabled and spatial lipidomics becomes feasible for MSI.

Generative Adversarial Network-based Noncontrast CT Angiography for Aorta and Carotid Arteries.

Background Iodinated contrast agents (ICAs), which are widely used in CT angiography (CTA), may cause adverse effects in humans, and their use is time-consuming and costly. Purpose To develop an ICA-free deep learning imaging model for synthesizing CTA-like images and to assess quantitative and qualitative image quality as well as the diagnostic accuracy of synthetic CTA (Syn-CTA) images. Materials and Methods A generative adversarial network (GAN)-based CTA imaging model was trained, validated, and tested on retrospectively collected pairs of noncontrast CT and CTA images of the neck and abdomen from January 2017 to June 2022, and further validated on an external data set. Syn-CTA image quality was evaluated using quantitative metrics. In addition, two senior radiologists scored the visual quality on a three-point scale (3 = good) and determined the vascular diagnosis. The validity of Syn-CTA images was evaluated by comparing the visual quality scores and diagnostic accuracy of aortic and carotid artery disease between Syn-CTA and real CTA scans. Results CT scans from 1749 patients (median age, 60 years [IQR, 50-68 years]; 1057 male patients) were included in the internal data set: 1137 for training, 400 for validation, and 212 for testing. The external validation set comprised CT scans from 42 patients (median age, 67 years [IQR, 59-74 years]; 37 male patients). Syn-CTA images had high similarity to real CTA images (normalized mean absolute error, 0.011 and 0.013 for internal and external test set, respectively; peak signal-to-noise ratio, 32.07 dB and 31.58 dB; structural similarity, 0.919 and 0.906). The visual quality of Syn-CTA and real CTA images was comparable (internal test set, P = .35; external validation set, P > .99). Syn-CTA showed reasonable to good diagnostic accuracy for vascular diseases (internal test set: accuracy = 94%, macro F1 score = 91%; external validation set: accuracy = 86%, macro F1 score = 83%). Conclusion A GAN-based model that synthesizes neck and abdominal CTA-like images without the use of ICAs shows promise in vascular diagnosis compared with real CTA images. Clinical trial registration no. NCT05471869 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Zhang and Turkbey in this issue.

Nuclear Factor Erythroid 2-Related Factor 2 is Essential for Low-Normobaric Oxygen Treatment-Mediated Blood-Brain Barrier Protection Following Ischemic Stroke.

Cerebral ischemia/reperfusion (I/R) injury increases blood-brain barrier (BBB) permeability, leading to hemorrhagic transformation and brain edema. Normobaric oxygen (NBO) is a routine clinical treatment strategy for this condition. However, its neuroprotective effects remain controversial. This study investigated the effect of different NBO concentrations on I/R injury and explores the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the underlying mechanism. A mouse middle cerebral artery occlusion (MCAO) model, and an oxygen and glucose deprivation (OGD) model featuring mouse brain microvascular endothelial cells (ECs) called bEnd.3, were used to investigate the effect of NBO on I/R injury. A reactive oxygen species (ROS) inducer and Nrf2-knockdown by RNA were used to explore whether the Nrf2 pathway mediates the effect of NBO on cerebrovascular ECs. In the early stage of MCAO, 40% O2 NBO exposure significantly improved blood perfusion in the ischemic area and effectively relieved BBB permeability, cerebral edema, cerebral injury, and neurological function after MCAO. In the OGD model, 40% O2 NBO exposure significantly reduced apoptosis, inhibited ROS generation, reduced ER stress, upregulated the expression of tight junction proteins, and stabilized the permeability of ECs. Blocking the Nrf2 pathway nullified the protective effect of 40% O2 NBO on ECs after OGD. Finally, our study confirmed that low concentrations of NBO have a neuroprotective effect on I/R by activating the Nrf2 pathway in ECs.

Origin of Deformation Twinning in bcc Tungsten and Molybdenum.

Twinning is profuse in bcc transition metals (TMs) except bulk W and Mo. However, W and Mo nanocrystals surprisingly exhibit twinning during room temperature compression, which is completely unexpected as established nucleation mechanisms are not viable in them. Here, we reveal the physical origin of deformation twinning in W and Mo. We employ density functional theory (DFT) and a reduced-constraint slip method to compute the stress-dependent generalized stacking fault enthalpy (GSFH), the thermodynamic quantity to be minimized under constant loading. The simple slipped structures and GSFH lines show that compressive stresses stabilize a two-layer twin embryo, which can grow rapidly via twinning disconnections with negligible energy barriers. Direct atomistic simulations unveil the explicit twinning path in agreement with the DFT GSFH lines. Twinning is thus the preferred deformation mechanism in W and Mo when shear stresses are coupled with high compressive stresses. Furthermore, twinnability can be related to the elastic constants of a stacking fault phase (SFP). The hcp phase may serve as a candidate SFP for the {112}⟨1[over ¯]1[over ¯]1⟩ twinning system in bcc TMs and alloys, which is coincident with the {111}⟨112[over ¯]⟩ twinning in fcc structures.

High-sensitivity non-cooled near-infrared detector based on lithium niobate surface acoustic wave resonators combined with MXene Ti3C2Tx quantum dot thin films.

In this study, we propose the design of a surface acoustic wave (SAW) near-infrared sensor combined with an MXene quantum dot thin film to improve the infrared absorption efficiency at near-infrared wavelengths. A YZ-cut lithium niobate (LiNbO3) SAW resonator is fabricated as an infrared sensing unit with a resonant frequency shift reflecting the change in infrared radiation. It was observed that the responsivity of the near-infrared sensor (with a base frequency of 460 MHz) increased by approximately 88.89%. Thus, the proposed device exhibits high-performance infrared detection. Owing to the passive wireless capability of the device, it has wide applications.

Eimeria granulosa causes spots visible through the serous membrane of small intestine in sheep.

Coccidiosis, also known as Eimeriosis, is a highly prevalent parasitic disease affecting sheep in nearly all sheep-rearing nations across the globe. Currently, there is a scarcity of literature documenting the specific lesions in sheep resulting from coccidia infection. This study aimed to investigate these characteristic lesions through necropsy, microscopic observation, and molecular biological techniques. As a result, Eimeria granulosa was identified as the causative agent, which induced distinct pathological alterations in the small intestine of lambs as observed during necropsy. Notably, E. granulosa manifested as small scattered petechiae and white spots, visible through the serous membrane of the small intestine, akin to the pathology observed in E. necatrix. Therefore, this study provides valuable insights for the accurate diagnosis of coccidiosis in sheep.

Genome-Wide Identification and Expression Analysis of CCO Gene Family in Liriodendron chinense.

Carotenoid cleavage oxygenase (CCO) is an enzyme that can catalyze carotenoids to volatile aromatic substances and participate in the biosynthesis of two important phytohormones, i.e., abscisic acid (ABA) and strigolactone (SL). However, the genome-wide identification and analysis of the CCO gene family in the rare and endangered woody plant Liriodendron chinense has not been reported. Here, we performed a genome-wide analysis of the CCO gene family in the L. chinense genome and examined its expression pattern during different developmental processes and in response to various abiotic stresses. A total of 10 LcCCO genes were identified and divided into 6 subfamilies according to the phylogenetic analysis. Subcellular localization prediction showed that most of the LcCCO proteins were located in the cytoplasm. Gene replication analysis showed that segmental and tandem duplication contributed to the expansion of this gene family in the L. chinense genome. Cis-element prediction showed that cis-elements related to plant hormones, stress and light response were widely distributed in the promoter regions of LcCCO genes. Gene expression profile analysis showed that LcNCED3b was extensively involved in somatic embryogenesis, especially the somatic embryo maturation, as well as in response to heat and cold stress in leaves. Furthermore, qRT-PCR analysis showed that LcNCED3b obviously responded to drought stress in roots and leaves. This study provides a comprehensive overview of the LcCCO gene family and a potential gene target for the optimization of the somatic embryogenesis system and resistance breeding in the valuable forest tree L. chinense.

Chemically-Modified Sepharose 6B Beads for Collection of Circulating Tumor Cells.

The isolation and quantitative characterization of circulating tumor cells (CTCs) are of great importance in cancer diagnosis and prognosis. However, isolating and detecting CTCs in whole blood presents a significant challenge due to the low numbers of CTCs (often ranging from one to five) in samples containing billions of erythrocytes. Recently, point-of-care devices that use antibody trapping coupled with remote immunofluorescence analyses have been described to identify the number and type of CTCs in blood. In this study, we propose a novel method for trapping and quantifying CTCs using Sepharose 6B beads of 45-160 µm size that are engineered with capture antibodies. Specifically, we employed CD44 antibody conjugates (bearing a maleimide group) that are specific to the CTCs of breast cancer to thiol-Sepharose beads 6B. These beads, when mixed with MDAMB231 and Jurkat cells and filtered through a 40 µm filter, can capture ~80% of MDAMB231 cells. Furthermore, the antibody-modified Sepharose 6B can be stored at four degrees Celsius for a period exceeding six months.

Temperature-Tuning Desorption Ionization for Ambient Mass Spectrometry.

In the past decade, mass spectrometry (MS) has been widely used for a broad range of on-site applications. This is largely attributed to the rapid advancement of technologies, such as ambient ionization and mass spectrometer miniaturization. Here, we report the development of the temperature-tuning desorption ionization (TTDI) method for versatile on-site applications using a miniature MS system. A unique feature of TTDI is its dynamic temperature range applicable from 30 to 800 °C, which enables optimal desorption ionization applied for chemical and biological compounds through tuning the temperature at the sampling spot. The versatility of TTDI has been demonstrated through on-site MS analysis of a variety of samples, such as explosives on surfaces, drugs of abuse in biofluids, and screening biomarkers in tissues.

DeepS: Accelerating 3D Mass Spectrometry Imaging via a Deep Neural Network.

Mass spectrometry imaging (MSI) is a powerful methodology that enables the visualization of the spatial distribution of biomolecules, including lipids, peptides, and proteins, from biological tissue sections. While two-dimensional (2D) MSI has been widely reported in various applications, three-dimensional (3D) MSI can enable the mapping of biomolecule distribution in complex biological structures (e.g., organs) with an added dimension. However, traditional 3D MSI techniques are time-consuming since 3D MS images are constructed from 2D MSI analyses of a series of tissue sections. In this study, we propose a 3D MSI workflow, termed DeepS, which uses a 3D sparse sampling network (3D-SSNet) and a sparse sampling strategy to significantly accelerate 3D MSI analyses. Sparsely sampled tissue sections are reconstructed using 3D-SSNet, yielding results comparable to those using full sampling MSI, even at a sampling ratio of 20-30%. The workflow performed well when applied to 3D imaging of a mouse brain with Alzheimer's disease, and combined with transfer learning, it is successfully used for the 3D MSI analyses of more heterogeneous samples, e.g., a mouse brain with glioblastoma and a mouse kidney.

Characterization of the Liriodendron chinense Pentatricopeptide Repeat (PPR) Gene Family and Its Role in Osmotic Stress Response.

The Pentatricopeptide repeat (PPR) superfamily is a large gene family in plants that regulates organelle RNA metabolism, which is important for plant growth and development. However, a genome-wide analysis of the PPR gene family and its response to abiotic stress has not been reported for the relict woody plant Liriodendron chinense. In this paper, we identified 650 PPR genes from the L. chinense genome. A phylogenetic analysis showed that the LcPPR genes could roughly be divided into the P and PLS subfamilies. We found that 598 LcPPR genes were widely distributed across 19 chromosomes. An intraspecies synteny analysis indicated that duplicated genes from segmental duplication contributed to the expansion of the LcPPR gene family in the L. chinense genome. In addition, we verified the relative expression of Lchi03277, Lchi06624, Lchi18566, and Lchi23489 in the roots, stems, and leaves and found that all four genes had the highest expression in the leaves. By simulating a drought treatment and quantitative reverse transcription PCR (qRT-PCR) analysis, we confirmed the drought-responsive transcriptional changes in four LcPPR genes, two of which responded to drought stress independent of endogenous ABA biosynthesis. Thus, our study provides a comprehensive analysis of the L. chinense PPR gene family. It contributes to research into their roles in this valuable tree species' growth, development, and stress resistance.

TRIM28 promotes the escape of gastric cancer cells from immune surveillance by increasing PD-L1 abundance.

Immune checkpoint blockade (ICB) offers a new opportunity for treatment for gastric cancer (G.C.). Understanding the upstream regulation of immune checkpoints is crucial to further improve the efficacy of ICB therapy. Herein, using the CRISPR-Cas9-based genome-wide screening, we identified TRIM28 as one of the most significant regulators of PD-L1, a checkpoint protein, in G.C. cells. Mechanistically, TRIM28 directly binds to and stabilizes PD-L1 by inhibiting PD-L1 ubiquitination and promoting PD-L1 SUMOylation. Furthermore, TRIM28 facilitates K63 polyubiquitination of TBK1, activating TBK1-IRF1 and TBK1-mTOR pathways, resulting in enhanced PD-L1 transcription. It was found that TRIM28 was positively correlated with PD-L1 in G.C. cells. Moreover, high TRIM28 expression suggests poor survival in a cohort of 466 patients with G.C., and this observation is consistent while analyzing data from publicly available databases. Ectopic TRIM28 expression facilitated tumor growth, increased PD-L1 expression, and suppressed T cell activation in mice. Administration of the PD-L1 or TBK1 inhibitor significantly alleviated the TRIM28-induced tumor progression. Furthermore, combining the TBK1 inhibitor with CTLA4 immune checkpoint blockade has synergistic effects on G.C., and provides a novel strategy for G.C. therapy.