Non-small cell lung cancer (NSCLC) is characterized by intricate genetic modifications and mechanisms that allow it to evade immune detection, which complicates the pursuit of lasting therapeutic responses. The effectiveness of treatments is greatly affected by the interaction between tumor genetic profiles and the surrounding immune microenvironment, highlighting the need for carefully designed therapeutic combinations. This review provides a comprehensive analysis of oncogenic drivers and signaling pathways (such as the KRAS, BRAF, and CD73/adenosine pathways) that interact with immune checkpoint inhibitors (ICIs), offering practical insights for personalized treatment approaches. The key findings focus on the use of biomarkers to guide the selection of immunotherapy or ICI-based combination therapies (e.g., ICIs plus tyrosine kinase inhibitors or signaling pathway inhibitors). We emphasize the importance of integrating tumor genomics with immune profiling to improve patient survival outcomes. This review aims to optimize treatment strategies by synthesizing insights from recent clinical trials and preclinical research, ultimately improving therapeutic efficacy in NSCLC.

Background Granzyme K (GZMK) is a serine protease known for its perforin-dependent cytotoxicity. However, the non-cytotoxic role of GZMK in lung adenocarcinoma (LUAD) remains largely elusive.Methods Multiomics datasets were integrated to investigate the clinical relevance of GZMK and its association with programmed death-ligand 1 (PD-L1) in LUAD. Recombinant human GZMK (rhGzmK) was applied in tumor-CD8+ T cell co-culture systems, with its effects on PD-L1 expression and CD8+ T-cell function evaluated via flow cytometry. Key signaling proteins were analyzed by Western blotting. To evaluate the therapeutic potential of GZMK inhibition, a selective GZMK inhibitor was combined with anti-programmed cell death protein 1 (anti-PD-1) therapy in both C57BL/6 and human peripheral blood mononuclear cells (huPBMC)-reconstituted NVSG humanized mouse models. Finally, multiplex immunofluorescence analysis was conducted on paired pretreatment and post-treatment specimens from a clinical cohort of patients with LUAD receiving immunotherapy to assess the spatial dynamics of GZMK expression in response to treatment.Results GZMK upregulated PD-L1 expression on tumor cells and enhanced PD-L1/PD-1 binding. Furthermore, GZMK promoted CD8+ T-cell dysfunction through the induction of apoptosis, the promotion of CD8+ T-cell exhaustion and suppression of proliferation. Mechanistically, cleavage of F2R-like trypsin receptor 1 (F2RL1) by GZMK activated the AKT Serine/Threonine Kinase (AKT) /glycogen synthase kinase-3β/β-catenin and Janus kinase 2/signal transducer and activator of transcription 1 (JAK2/STAT1) pathways, triggering nuclear accumulation of β-catenin and phosphorylated STAT1, which ultimately drove PD-L1 transcription. Additionally, F2RL1 signaling upregulated COPS8, stabilizing PD-L1 through inhibition of its ubiquitin-mediated degradation. In vivo, pharmacological inhibition of GZMK synergized with anti-PD-1 therapy to suppress tumor growth and enhance CD8+ T-cell infiltration and function. Clinically, high baseline GZMK expression correlated with an improved response to immunotherapy, and anti-PD-1 treatment modulated the spatial distribution of GZMK within the tumor microenvironment.Conclusion In the absence of perforin, GZMK acquires an immunosuppressive function through F2RL1 activation on tumor cells, which in turn promotes the formation of an immune-suppressive niche. Accordingly, combined targeting of the GZMK/F2RL1 axis and the PD-1/PD-L1 pathway represents a promising synergistic strategy to overcome immune evasion in LUAD.

Gastric perforation, which may be caused by damage to the gastric epithelium, can lead to the entry of food or gastric acid in the stomach into the peritoneum, causing diseases such as peritonitis and sepsis. In severe cases, it can lead to septic shock and pose a threat to life. Developing and preparing a material that has adhesiveness in a wet environment such as the surface of the stomach is a challenge. Therefore, we have successfully prepared a hydrogel membrane with wet adhesiveness. This hydrogel membrane is composed of glutaraldehyde-crosslinked polyvinyl alcohol (PVA) hydrogel modified by 3,4-dihydroxyphenylalanine (DOPA). The side chains of PVA molecules modified with DOPA achieve wet adhesion through the formation of hydrogen bonds between the catechol groups and the surface of the tissue substrate. It is used for suture-free repair of damaged gastric epithelium. According to the results of mechanical experiments, its wet adhesion lap shear strength to gastric tissue reaches 34.8 kPa, and the peeling strength reaches 24.5 kPa. The results of in vitro cell experiments show that the hydrogel has good biocompatibility. The hydrogel prepared by this simple method demonstrates adaptability to the gastric environment, making it promising for applications in gastric wound repair.

Atmospheric humic-like substances (HULIS), a key component of brown carbon (BrC), significantly promote the light absorption of aerosols. However, their linkages to pollution sources and ambient temperature in cold environments remain unresolved. Here, we analyze wintertime urban aerosol samples in Changchun, northeast China, using ultrahigh-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS). HULIS show a high light absorption efficiency (MAE365 = 1.81 +/- 0.24 m2gC-1) and high mass concentration (2.97 +/- 1.54 mu gCm-3), exceeding values reported from other global regions. Through UHPLC-HRMS/MS characterization, we identify 264 compounds at the molecular structure level, accounting for 38.2 %-78.1 % of the total HULIS mass. Compositional analysis demonstrates biomass burning and coal combustion are the main BrC sources during haze events. We screen out 39 strong BrC chromophores, mainly nitrophenols, that contribute 28.9 +/- 10.4 % of the total light absorbance at 365 nm. Low ambient temperatures potentially enhance the accumulation of these strong BrC chromophores in the aerosol particles by suppressing photobleaching processes and altering thermodynamic reaction equilibria. These findings emphasize the potential of BrC to exert a more significant and persistent environmental effect in the cold-region atmosphere.

Background The tolerization of plasmacytoid dendritic cells (pDCs) within the tumor microenvironment facilitates immune evasion, thereby significantly limiting the efficacy of cancer immunotherapy. Metabolic regulators are crucial in determining immune cell fate. However, the specific metabolic modifications influencing tumor-associated pDCs (TA-pDCs) are largely uncharacterized.Methods We isolated TA-pDCs from patients with colon cancer and mouse models for RNA sequencing detection and immunofluorescence staining. Further, in vitro and in vivo models of colon cancer were used to explore the underlying mechanisms of the fatty acid oxidation (FAO) regulatory pathway of TA-pDCs and its immunosuppressive function.Results Peroxisome proliferator-activated receptor gamma pathway promotes FAO in TA-pDCs by upregulating the expression of carnitine palmitoyltransferase-1A (CPT1A). The inhibition of CPT1A significantly reduced the immunosuppressive checkpoint inducible co-stimulator ligand (ICOSL) and increased the levels of the immune-activating protein OX40L and pro-inflammatory cytokines interferon-α and tumor necrosis factor-α. These alterations enhanced CD8+ T-cell functionality and diminished the generation of regulatory T cells, thereby bolstering antitumor immunity. The efficacy of combined immunotherapy using anti-ICOSL and anti-programmed cell death 1-ligand 1 antibodies was markedly improved in murine models of colon cancer.Conclusions These findings elucidate the molecular mechanism of CPT1A-mediated FAO in TA-pDCs and its implications in immune evasion, suggesting a novel therapeutic strategy for colon cancer immunotherapy.

Due to the very important role in physiological process, a simple and sensitive hemin detection method is necessarily required. Biomass-based carbonized polymer dots (CPDs) have been widely studied especially as fluorescence probe owing to the advantages of low toxicity and the variety of fluorescence color, yet there are still challenges in developing their multi-color emission property from the same raw materials. In this work, red, white and blue emissive CPDs derived from chlorophyll have been synthesized via hydrothermal method. Then white-emitted CPDs (white-CPDs) with the Commission International d'Eclairage (CIE) coordinates at (0.34, 0.32) were used to develop a fluorescence quenched sensing system for hemin determination. There is a good linear relationship between (F0-F)/F0 and concentration of hemin in the range of 0.1-0.95 mu M with a detection limit of 0.043 mu M, and the quenching mechanism was considered to be caused by inner filter effect (IFE). Moreover, it has been successfully used for hemin detection in serum and also for visual determination, which indicating great potential in applications of disease diagnoses and trace identification.

RNA helicases are involved in the innate immune response against pathogens, including bacteria and viruses; however, their mechanism in the human airway epithelial cells is still not fully understood. Here, we demonstrated that DEAH (Asp-Glu-Ala-His) box polypeptide 35 (DHX35), a member of the DExD/H (Asp-Glu-x-Asp/His)-box helicase family, boosts antiviral innate immunity in human airway epithelial cells. DHX35 knockdown attenuated the production of interferon-β (IFN-β), IL6, and CXCL10, whereas DHX35 overexpression increased their production. Upon stimulation, DHX35 was constitutively expressed, but it translocated from the nucleus into the cytosol, where it recognized cytosolic poly(I:C) and poly(dA:dT) via its HELICc domain. Mitochondrial antiviral signaling protein (MAVS) acted as an adaptor for DHX35 and interacted with the HELICc domain of DHX35 using amino acids 360-510. Interestingly, DHX35 interacted with retinoic acid-inducible gene 1 (RIG-I), enhanced the binding affinity of RIG-I with poly(I:C) and poly(dA:dT), and formed a signalsome with MAVS to activate interferon regulatory factor 3 (IRF3), NF-κB-p65, and MAPK signaling pathways. These results indicate that DHX35 not only acted as a cytosolic nucleic acid sensor but also synergized with RIG-I to enhance antiviral immunity in human airway epithelial cells. Our results demonstrate a novel molecular mechanism for DHX35 in RIG-I-mediated innate immunity and provide a novel candidate for drug and vaccine design to control viral infections in the human airway.

Chemotherapeutic agents for treating colorectal cancer (CRC) primarily induce apoptosis in tumor cells. The ubiquitin-proteasome system is critical for apoptosis regulation. Deubiquitinating enzymes (DUBs) remove ubiquitin from substrates to reverse ubiquitination. Although over 100 DUB members have been discovered, the biological functions of only a small proportion of DUBs have been characterized. Here, we aimed to systematically identify the DUBs that contribute to the development of CRC. Among the DUBs, ubiquitin-specific protease 36 (USP36) is upregulated in CRC. We showed that the knockdown of USP36 induces intrinsic and extrinsic apoptosis. Through gene silencing and coimmunoprecipitation techniques, we identified survivin and cIAP1 as USP36 targets. Mechanistically, USP36 binds and removes lysine-11-linked ubiquitin chains from cIAP1 and lysine-48-linked ubiquitin chains from survivin to abolish protein degradation. Overexpression of USP36 disrupts the formation of the XIAP-second mitochondria-derived activator of caspase complex and promotes receptor-interacting protein kinase 1 ubiquitination, validating USP36 as an inhibitor to intrinsic and extrinsic apoptosis through deubiquitinating survivin and cIAP1. Therefore, our results suggest that USP36 is involved in CRC progression and is a potential therapeutic target.

Acetamiprid is mainly used to control pests. However, the residues of acetamiprid have resulted in significant negative effects on mammals. Many researchers are working on developing acetamiprid detection methods. In our study, four truncated aptamers were designed based on the secondary structure of the original aptamer. Molecular docking simulation of truncated aptamers confirmed that all of the truncated aptamers bind to acetamiprid, and their binding sites were identified. The affinity, sensitivity, and specificity of these truncated aptamers were measured by a spectrophotometric method with gold nanoparticles (AuNPs). Acetamiprid aptamers with 17-mer (Apt-J2) and 16-mer (Apt-J4) were successfully obtained, which show higher detection sensitivity and satisfactory specificity. Additionally, a spectrophotometric detection route superior to the original aptamer was explored, and the linear ranges were from 1 to 70 mu M and 0.5 to 40 mu M, respectively. The truncated aptamers were applied to the analysis of lake water, indicating that the aptamers have potential for practical analysis.

Chemo/photothermal combination therapy is a promising and practical approach for cancer treatment which calls for certain nanovehicles to achieve the spatiotemporal co-occurrence of photothermal conversion and drug delivery. Herein, we developed a montmorillonite-based Pickering emulsion equipped with a near-infrared photothermal agent (indocyanine green, ICG) and anticarcinogen (paclitaxel, PTX). With both montmorillonite and ICG functioning as interfacial stabilizers, the Pickering emulsion showed good stability and nanoscale droplet size, which were favored for cellular applications. Due to the vast oil-water interface, where the majority of amphiphilic ICG was prone to distribute, the Pickering nanoemulsion could achieve a higher local concentration of ICG than the aqueous solution, therefore leading to a higher local photothermal performance under near-infrared irradiation. The Pickering nanoemulsion exhibited fast cell penetration, which promoted the photothermal therapeutic effect of ICG. Moreover, the inner phase of the Pickering nanoemulsion also facilitated the loading of PTX, further improving its killing efficacy against cancer cells under near-infrared irradiation, because the photothermal conversion of the Pickering nanoemulsion could not only cause heat damage by itself but also promote the loaded PTX to diffuse out and induce cell death. Therefore, this clay-based Pickering nanoemulsion as a nanovehicle could realize the synergy of chemo- and photothermal therapy.

This paper analyzed the chemical characterization of PM2.5 and PM10 in a typical city of Northeast China during the heating period, including trace elements, water-soluble inorganic ions (WSII), organic carbon (OC), and element carbon (EC). The results showed that PM2.5 and PM10 concentrations were 66.55 +/- 28.89 mu g/m(3) and 92.99 +/- 31.00 mu g/m(3). The concentrations of As and Cr in the atmosphere were beyond the current air quality standard in China (6 ng/m(3) for As, 0.025 ng/m(3) for Cr). Secondary inorganic ions (NH4+, NO3-, and SO42-) dominated the WSII, accounting for 40.54% of PM2.5 and 33.80% of PM10. High OC/EC ratios implied a high proportion of secondary organic carbon (SOC). Positive matrix factorization (PMF) was used to identify the sources of PM2.5 and PM10. Six factors were analyzed and identified as secondary aerosol, industry, coal combustion, vehicle emissions, biomass burning, and dust, of which secondary aerosol was the largest contribution to PM2.5 and PM10.

Understanding the metabolic disorders induced by nano-and microplastics in aquatic organisms at the molecular level could help us understand the potential toxicity of nano-and microplastics more thoroughly and provide a fundamental scientific basis for regulating the usage and management of plastic products. In this research, the effect of polypropylene nanoplastics (PP-NPs) and microplastics (PP-MPs) on metabolites in the tilapia liver was comprehensively investigated by internal extractive electrospray ionization mass spectrometry (iEESI-MS). A partial least-squares discriminant analysis (PLS-DA) and a one-component analysis of variance (ANOVA) were used for selecting 46 differential metabolites, including phospholipids, amino acids, peptides, carbohydrates, alkaloids, purines, pyrimidines, and nucleosides. Pathway enrichment analysis showed significant effects on glycerophospholipid metabolism, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis after tilapia were exposed to PP-N/MPs. Dysregulation of these metabolites is mainly reflected in the possible induction of hepatitis, oxidative stress, and other symptoms. The application of iEESI-MS technology without sample pretreatment to the study of metabolic disorders in aquatic organisms under the interference of nano-and microplastics provides a promising analytical method for environmental toxicology research.

Two-dimensional (2D) BiVO4 nanosheets (NSs), featuring distinctive chemical properties and dangling-bond-rich surfaces, are promising for developing high-performance gas sensors. However, the previously reported 2D BiVO4 NSs-based devices suffer from a low responsivity and poor selectivity. Here, catalytic metal (Pt) nanoparticles (NPs) are functionalized on the surface of BiVO4 NSs to improve the sensing ability. Comparative investigations verify the significant enhancement in acetone sensing after Pt modification. The Pt NPs-loaded BiVO4 exhibits a response of 12.5-100 ppm acetone, which is 3.2 times higher than that of pure BiVO4 sensor. Besides, the Pt-BiVO4 sensor possesses better selectivity and lower detection limit. From both the experimental results and density functional theory (DFT) calculation, the effects of Pt modification are elucidated as a synergy of chemical and electronic sensitization. The loading of Pt benefits the thickening of electron depletion layer, and accumulating and activating the acetone molecules, which accelerate the reaction between acetone and chemisorbed oxygen species, resulting in enhanced sensing performance. This work gives deep insights into the effects of noble metal modification on metal oxide-based sensing material and could serve as a guideline for further designing novel high-performance sensing materials.

Liver cancer is one of the most common malignancies, with severe morbidity and mortality. While considerable progress has been made in liver cancer treatment, the 5-year overall survival (OS) of patients has not improved significantly. Reasons include the inadequate capability of early screening and diagnosis, a high incidence of recurrence and metastasis, a high degree of tumor heterogeneity, and an immunosuppressive tumor microenvironment. Therefore, the identification and validation of specific and robust liver cancer biomarkers are of major importance for early screening, timely diagnosis, accurate prognosis, and the prevention of tumor progression. In this review, we highlight some of the latest research progress and potential applications of liver cancer biomarkers, describing hotspots and prospective directions in biomarker discovery.

Cancer cell membranes (CCMs) are widely used as sources of tumor-associated antigens (TAAs) for the development of cancer vaccines. To improve the CCM-associated cancer vaccine efficiency, personalized cancer vaccines and effective delivery systems are required. In this study, we employed surgically harvested cancer tissues to prepare personalized CCMs for use as TAAs. Thioglycolic-acid-grafted poly(2-methyl-2-oxazoline)-block-poly(2-butyl-2-oxazoline-co-2-butenyl-2-oxazoline) (PMBEOx-COOH) was synthesized to load imiquimod (R837) efficiently. The personalized CCMs were then coated onto R837-loaded PMBEOx-COOH nanoparticles (POxTA NPs/R837) to obtain surgically derived CCM-coated POxTA NPs (SCNPs/R837). SCNPs/R837 efficiently travelled to the draining lymph nodes and were taken up and presented by plasmacytoid dendritic cells to elicit enhanced antitumor immune responses. When combined with programmed cell death-1 antibodies, SCNPs/R837 exhibited high efficiency corresponding to antitumor progression. Therefore, SCNP/R837 might represent a promising personalized cancer vaccine with significant potential for cancer immunotherapy.

A simple spectral method with a wider detection range is proposed for the detection of acetamiprid.

The issue of environmental pollutant residues has gained wide public attention all along. Therefore, it is necessary to develop simple, rapid, economical, portable, and sensitive detection techniques, which have become the focus of research in the pollutants detection field. Spectroscopy is one of the most convenient, simple, rapid, and intuitive analytical tools that can provide accurate information, such as ultraviolet spectroscopy, fluorescence spectroscopy, Raman spectroscopy, plasmon resonance spectroscopy, etc. Gold nanoparticles, silver nanoparticles, and their dimers with unique optical properties are commonly used in the construction of spectroscopic probes. As a class of oligonucleotides that can recognize specific target molecules, aptamers also have a strong ability to recognize small-molecule pollutants. The application of aptamer-binding metal nanoparticles in biosensing detection presents significant advantages for instance high sensitivity, good selectivity, and rapid analysis. And many spectroscopic probes constructed by aptamer-binding gold nanoparticles, silver nanoparticles, or their dimers have been successfully demonstrated for detecting pollutants. This review summarizes the progress, advantages, and disadvantages of aptamer sensing techniques constructed by visual colorimetric, fluorescence, Raman, and plasmon resonance spectroscopic probes combining gold/silver nanoparticles or their dimers in the field of pollutants detection, and discusses the prospects and challenges for their future.

Cancer stemness, chemoresistance, and metastasis are related biological events. However, whether they have common molecular mechanisms remains to be determined. Here, we report that imiquimod (IMQ) facilitates the acquisition of stem-cell-like properties and chemoresistance via the upregulation of matrix metalloproteinase 1 (MMP1) and downregulation of microRNA-145 (miR-145). MiR-145-5p was found to suppress MMP1 expression through direct binding, and miR-145-mediated downregulation of MMP1 reversed the effects of IMQ. In addition, IMQ downregulated miR-145 by promoting DNA methylation at its promoter. DNA methyltransferase inhibitors limited IMQ-induced MMP1 expression, stemness, and chemoresistance. Collectively, our results highlight the miR-145-MMP1 axis as a potential coordinator of cancer stemness and chemoresistance. Given the role of MMP1 in the initiation of metastasis, the miR-145-MMP1 axis serves as a promising therapeutic target for improved cancer treatment.

Direct profiling of endogenous biomolecules in tissue samples is considered as a promising approach to investigate metabolic-related toxicity in organisms induced by emerging pollutants. Herein, we report the application of internal extractive electrospray ionization mass spectrometry (iEESI-MS) to direct phospholipid profiling in the liver and spleen tissues of Nile tilapia exposed to perfluorooctanoic acid (PFOA). Combining positive and negative ion detection modes, 130 phospholipid signals were directly detected and identified by iEESI-MS in the tissues of Nile tilapia, including phosphatidyl cholines (PCs), sphingomyelins (SMs), phosphatidic acids (PAs), phosphatidyl ethanolamines (PEs), phosphatidyl glycerols (PGs), phosphatidyl inositols (PIs) and phosphatidyl serines (PSs). With the help of partial least squares discriminant analysis (PLS-DA) and one-way analysis of variance (ANOVA), several phospholipid signals showed a significant difference in the tissue of Nile tilapia between the control group and PFOA exposure groups. In addition, pathway analysis revealed that PFOA has a significant metabolic impact on the glycerophospholipid metabolism in Nile tilapia. Without complex sample preparation, iEESI-MS was applied to direct phospholipid profiling in the liver and spleen tissues of Nile tilapia treated with PFOA, which provided a promising methodology for investigating environmental toxicity and phospholipid-dysregulation caused by emerging pollutants in aquatic organisms.

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor β family, is associated with tumor progression, metastasis, and cell apoptosis. However, controversy persists regarding the role of GDF15 in different tumor types, and its function in glioma stem cells (GSCs) remains unknown. Here, we report that GDF15 promotes the GSC-like phenotype in GSC-like cells (GSCLCs) through the activation of leukemia inhibitor factor (LIF)–STAT3 signaling. Mechanistically, GDF15 was found to upregulate expression of the transcription factor c-Fos, which binds to the LIF promoter, leading to enhanced transcription of LIF in GSCLCs. Furthermore, GDF15 may activate the ERK1/2 signaling pathway in GSCLCs, and the upregulation of LIF expression and the GSC-like phenotype was dependent on ERK1/2 signaling. In addition, the small immunomodulator imiquimod induced GDF15 expression, which in turn activated the LIF–STAT3 pathway and subsequently promoted the GSC-like phenotype in GSCLCs. Thus, our results demonstrate that GDF15 can act as a proliferative and pro-stemness factor for GSCs, and therefore, it may represent a potential therapeutic target in glioma treatment.