Leptin-mediated suppression of lipoprotein lipase cleavage enhances lipid uptake and facilitates lymph node metastasis in gastric cancer.

BACKGROUND: Lymph node metastasis (LNM) is the primary mode of metastasis in gastric cancer (GC). However, the precise mechanisms underlying this process remain elusive. Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis, yet the role of lipoprotein lipase (LPL), a pivotal enzyme involved in exogenous lipid uptake, remains uncertain in tumor metastasis. Therefore, the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process. METHODS: Intracellular lipid levels were quantified using oil red O staining, BODIPY 493/503 staining, and flow cytometry. Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown. Protein expression levels were assessed through immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assays. The mouse popliteal LNM model was utilized to investigate differences in LNM. Immunoprecipitation and mass spectrometry were employed to examine protein associations. In vitro phosphorylation assays and Phos-tag sodium dodecyl-sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin-like protein 4 (ANGPTL4) phosphorylation. RESULTS: We identified that an elevated intracellular lipid level represents a crucial characteristic of node-positive (N+) GC and further demonstrated that a high-fat diet can expedite LNM. LPL was found to be significantly overexpressed in N+ GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells. Leptin, an obesity-related hormone, intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage. Circulating leptin binding to the leptin receptor could induce the activation of inositol-requiring enzyme-1 (IRE1) kinase, leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL. Moreover, our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid, which then triggered the cyclooxygenase-2/prostaglandin E2 (PGE2) pathway, thereby promoting tumor lymphangiogenesis. CONCLUSIONS: Leptin-induced phosphorylation of ANGPTL4 facilitates LPL-mediated lipid uptake and consequently stimulates the production of PGE2, ultimately facilitating LNM in GC.

Passive laser power stabilization in a broadband noise spectrum via a second-harmonic generator.

An extremely conspicuous passive power noise stabilization is the first, to the best of our knowledge, discovered in a cavity-enhanced second-harmonic generation (SHG) process. Differing from the SHG as a buffer reservoir, the stronger strength of the nonlinear interaction pushes the power noise suppression level to a higher value and exhibits a broadband noise reduction performance due to the mechanism of dynamic pump suppression in the SHG process. The noise is suppressed to near shot noise limit (SNL) among the kHz to MHz frequency range, accompanied by a maximum noise reduction of 35 dB. A comprehensive demonstration indicates that the nonlinear interaction has no function on the phase noise of fundamental and harmonic waves. A theoretical model is also established that is consistent well with the experimental results. The methodology is beneficial to multiple optical metrology experiments.

Mechanism Switch in Surface-Enhanced Raman Scattering: The Role of Nanoparticle Dimensions.

Surface-enhanced Raman scattering (SERS) is renowned for amplifying Raman signals, with electromagnetic mechanism (EM) enhancement arising from localized surface plasmon resonances and chemical mechanism (CM) enhancement as a result of charge transfer interactions. Despite the conventional emphasis on EM as a result of plasmonic effects, recent findings highlight the significance of CM when noble metals appear as smaller entities. However, the threshold size of the noble metal clusters/particles corresponding to the switch in SERS mechanisms is not clear at present. In this work, the VSe2-xOx/Au composites with different Au sizes are employed, in which a clear view of the SERS mechanism switch is observed at the Au size range of 16-21 nm. Our findings not only provide insight into the impact of noble metal size on SERS efficiency but also offer quantitative data to assist researchers in making informed judgments when analyzing SERS mechanisms.

[Resveratrol attenuates neuroinflammation and alleviates emotional dysfunction in mice with sepsis-associated encephalopathy through promoting chaperone-mediated autophagy (CMA)].

Objective To elucidate the role of chaperone-mediated autophagy (CMA) in alleviating emotional dysfunction in mice with sepsis-associated encephalopathy (SAE). Methods The SAE mouse model was established by cecal ligation and perforation (CLP). The severity of sepsis was assessed using the sepsis severity score (MSS). Emotional function in SAE mice was assessed by the open-field test and elevated plus-maze. The expression levels of cognitive heat shock cognate protein 70 (HSC70), lysosomal-associated membrane protein 2A (LAMP2A) and high mobility group box 1 protein B1 (HMGB1) were detected using Western blotting. Co-localization of LAMP2A in the hippocampal neurons was observed by immunofluorescence. The release of inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) was measured using ELISA. Following 12 hours post-CLP, mice were orally administered resveratrol at a dose of 30 mg/kg once daily until day 14. Results The mortality rate of CLP mice was 45.83% 24 days post CLP, and all surviving mice exhibited emotional disturbances. 24 hours after CLP, a significant decrease in HSC70 and LAMP2A expression in hippocampal neurons was observed, indicating impaired CMA activity. Meanwhile, HMGB1 and inflammatory cytokines (IL-6 and TNF-α) levels increased. After resveratrol treatment, an increase of HSC70 and LAMP2A expression, and a decrease of HMGB1 expression and inflammatory cytokine release were observed, suggesting enhanced CMA activity and reduced neuroinflammation. Behavioral tests showed that emotional dysfunction was improved in SAE mice after resveratrol treatment. Conclusion CMA activity of hippocampal neurons in SAE mice is significantly reduced, leading to emotional dysfunction. Resveratrol can alleviate neuroinflammation and emotional dysfunction in SAE mice by promoting CMA and inhibiting the expression of HMGB1 and the release of inflammatory factors.

Factor-GAN: Enhancing stock price prediction and factor investment with Generative Adversarial Networks.

Deep learning, a pivotal branch of artificial intelligence, has increasingly influenced the financial domain with its advanced data processing capabilities. This paper introduces Factor-GAN, an innovative framework that utilizes Generative Adversarial Networks (GAN) technology for factor investing. Leveraging a comprehensive factor database comprising 70 firm characteristics, Factor-GAN integrates deep learning techniques with the multi-factor pricing model, thereby elevating the precision and stability of investment strategies. To explain the economic mechanisms underlying deep learning, we conduct a subsample analysis of the Chinese stock market. The findings reveal that the deep learning-based pricing model significantly enhances return prediction accuracy and factor investment performance in comparison to linear models. Particularly noteworthy is the superior performance of the long-short portfolio under Factor-GAN, demonstrating an annualized return of 23.52% with a Sharpe ratio of 1.29. During the transition from state-owned enterprises (SOEs) to non-SOEs, our study discerns shifts in factor importance, with liquidity and volatility gaining significance while fundamental indicators diminish. Additionally, A-share listed companies display a heightened emphasis on momentum and growth indicators relative to their dual-listed counterparts. This research holds profound implications for the expansion of explainable artificial intelligence research and the exploration of financial technology applications.

Contribution of oxygen vacancies to phase transition and ferroelectricity of Al:HfO2films.

We investigate the effects of oxygen vacancies on the ferroelectric behavior of Al:HfO2films annealed in O2and N2atmosphere. X-ray photoelectron spectroscopy results showed that the O/Hf atomic ratio was 1.88 for N2-annealed samples and 1.96 for O2-annealed samples, implying a neutralization of oxygen vacancies during O2atmosphere annealing. The O2-annealed films exhibited an increasing remanent polarization from 23µC cm-2to 28µC cm-2after 104cycles, with a negligible leakage current density of ∼2µA cm-2, while the remanent polarization decreased from 29µC cm-2to 20µC cm-2after cycling in the N2-annealed films, with its severe leakage current density decreasing from ∼1200µA cm-2to ∼300µA cm-2.A phase transition from the metastable tetragonal (t) phase to the low-temperature stable orthorhombic (o) phase and monoclinic (m) phase was observed during annealing. As a result of the fierce· competition between the t-to-o transition and the t-to-m transition, clear grain boundaries of several ruleless atomic layers were formed in the N2-annealed samples. On the other hand, the transition from the t-phase to the low-temperature stable phase was found to be hindered by the neutralization of oxygen vacancies, with almost continuous grain boundaries observed. The results elucidate the phase transformation caused by oxygen vacancies in the Al:HfO2films, which may be helpful for the preparation of HfO2-based films with excellent ferroelectricity.

Plant regeneration in the new era: from molecular mechanisms to biotechnology applications.

Plants or tissues can be regenerated through various pathways. Like animal regeneration, cell totipotency and pluripotency are the molecular basis of plant regeneration. Detailed systematic studies on Arabidopsis thaliana gradually unravel the fundamental mechanisms and principles underlying plant regeneration. Specifically, plant hormones, cell division, epigenetic remodeling, and transcription factors play crucial roles in reprogramming somatic cells and reestablishing meristematic cells. Recent research on basal non-vascular plants and monocot crops has revealed that plant regeneration differs among species, with various plant species using distinct mechanisms and displaying significant differences in regenerative capacity. Conducting multi-omics studies at the single-cell level, tracking plant regeneration processes in real-time, and deciphering the natural variation in regenerative capacity will ultimately help understand the essence of plant regeneration, improve crop regeneration efficiency, and contribute to future crop design.

Highly Efficient, Noble-Metal-Free, Fully Aqueous CO2 Photoreduction Sensitized by a Robust Organic Dye.

The development of efficient, selective, and durable CO2 photoreduction systems presents a long-standing challenge in full aqueous solutions owing to the presence of scarce CO2 and the fierce competition against H2 evolution, which is even more challenging when noble metals are not utilized. Herein, we present the facile decorations of four phosphonic acid groups on a donor-acceptor-type organic dye to obtain a water-soluble photosensitizer (4P-DPAIPN), which succeeds the excellent photophysical and photoredox properties of its prototype, exhibiting long-lived delayed fluorescence (>10 µs) in aqueous solutions. Combining 4P-DPAIPN with a cationic cobalt porphyrin catalyst has accomplished record-high apparent quantum yields of 9.4-17.4% at 450 nm for CO2-to-CO photoconversion among the precedented systems (maximum 13%) in fully aqueous solutions. Remarkable selectivity of 82-93% and turnover number of 2700 for CO production can also be achieved with this noble-metal-free system, outperforming a benchmarking ruthenium photosensitizer and a commercial organic dye under parallel conditions. Such high performances of 4P-DPAIPN can be well maintained under real sunlight. More impressively, no significant decomposition of 4P-DPAIPN was detected during the long-term photocatalysis. Eventually, the photoinduced electron transfer pathways were proposed.

Advances in antitumor application of ROS enzyme-mimetic catalysts.

The rapid growth of research on enzyme-mimetic catalysts (Enz-Cats) is expected to promote further advances in nanomedicine for biological detection, diagnosis and treatment of disease, especially tumors. ROS-based nanomedicines present fascinating potential in antitumor therapy owing to the rapid development of nanotechnology. In this review, we focus on the applications of Enz-Cats based on ROS in antitumor therapy. Firstly, the definition and category of ROS are introduced, and the key factors enhancing ROS levels are carefully elucidated. Then, the rationally engineered Enz-Cats via different synthetic approaches with high ROS-producing efficiencies are comprehensively discussed. Subsequently, oncotherapy application of Enz-Cats is comprehensively discussed, which integrates diverse synergistic treatment modalities and exhibits high efficiency in ROS generation. Finally, the challenges and future research direction of this field are presented. This review is dedicated to unraveling the enigmas surrounding the interplay of nanomedicine and organisms.

Recent progress on nickel phthalocyanine-based electrocatalysts for CO2 reduction.

The electrocatalytic reduction of CO2 to high-value fuels by renewable electricity is a sustainable strategy, which can substitute for fossil fuels and circumvent climate changes induced by elevated CO2 emission levels, making the rational design of versatile electrocatalysts highly desirable. Among all the electrocatalytic materials used in the CO2 reduction reaction, nickel phthalocyanine (NiPc)-based electrocatalysts have attracted considerable attention recently because of their high CO selectivity and catalytic activity. Herein, we review the latest advances in CO2 electroreduction to CO catalyzed by immobilized NiPc and its derivatives on diverse surfaces. Specific strategies, the structure-performance relationship and the CO2-to-CO reaction mechanism of these NiPc-based electrocatalysts are analyzed. Future opportunities and challenges for this series of powerful heterogeneous electrocatalysts are also highlighted.

Constructing a Built-In Electric Field To Accelerate Water Dissociation for Efficient Alkaline Hydrogen Evolution.

The alkaline hydrogen evolution reaction (HER) is intricately linked to the water dissociation kinetics. The quest for new strategies to accelerate this step is a pivotal aspect of enhancing the HER performance. Herein, we designed and synthesized a heterogeneous nickel phosphide/cobalt phosphide nanowire array grown on nickel foam (Ni2P/CoP/NF) to form a p-n junction structure. The built-in electric field (BEF) in the p-n junction optimizes the binding ability of hydrogen and hydroxyl intermediates, efficiently promoting water dissociation for the alkaline HER. Consequently, Ni2P/CoP/NF exhibits a lower overpotential of 58 and 118 mV at 30 and 100 mA cm-2, respectively, and high stability over 40 h at 300 mA cm-2 for the HER in 1 M KOH. Computational calculations combined with experiment results testify that the BEF presence in the p-n junction of Ni2P/CoP/NF effectively promotes water dissociation, regulates intermediate adsorption/desorption, and boosts electron transport. This study presents a rational design approach for high-performance heterogeneous electrocatalysts.

An integrated strategy for quality control of Pseudobulbus Cremastrae seu Pleiones based on Q-marker.

Pseudobulbus Cremastrae seu Pleiones (PCsP), a traditional Chinese medicine known as ‶Shan-Ci-Gu″, possesses properties for clearing heat, counteracting toxicity, dissipating phlegm, and resolving masses. As a TCM with multiple bases, the dried pseudobulbs of Pleione bulbocodioides (PB), Pleione yunnanensis (PY) and Cremastra appendiculata (CA) are considered to be the official sources of PCsP. Additionally, several unofficial substitutes are also available in the market. To enhance the quality control of PCsP, an integrated strategy based on Q-marker was proposed. Initially, a study of integrating plant metabolomics, target isolation, structure identification, and activity testing afforded five Q-markers, including three new compounds. Furthermore, a quality evaluation method using a single standard to determine multi-components (SSDMC) based on Q-marker was established, which could effectively distinguish PB from CA and the counterfeit herbs. Finally, the transitivity of Q-markers was explored through a representative Chinese compound prescription containing PCsP. The results indicated that the identified Q-markers together with the established analysis methods could be effectively applied for quality control of PCsP and its preparations.

All-optical steering on the proton emission in laser-induced nanoplasmas.

Nanoplasmas induced by intense laser fields have attracted enormous attention due to their accompanied spectacular physical phenomena which are vigorously expected by the community of science and industry. For instance, the energetic electrons and ions produced in laser-driven nanoplasmas are significant for the development of compact beam sources. Nevertheless, effective confinement on the propagating charged particles, which was realized through magnetic field modulation and target structure design in big facilities, are largely absent in the microscopic regime. Here we introduce a reliable scheme to provide control on the emission direction of protons generated from surface ionization in gold nanoparticles driven by intense femtosecond laser fields. The ionization level of the nanosystem provides us a knob to manipulate the characteristics of the collective proton emission. The most probable emission direction can be precisely steered by tuning the excitation strength of the laser pulses. This work opens new avenue for controlling the ion emission in nanoplasmas and can vigorously promote the fields such as development of on-chip beam sources at micro-/nano-scales.

Nitrous oxide (N2O) Emissions at the Air-Water-Sediment Interfaces of Cascade Reservoirs in the Yunnan-Guizhou Plateau: Spatial Patterns and Environmental Controls.

The construction of cascade reservoirs can interfere with the natural hydrologic cycles of basins, causing negative environmental effects such as altering the emission patterns of the Nitrous oxide (N2O), a potent greenhouse gas. To elucidate the impact of cascade reservoirs construction on river N2O emissions, we utilized the thin boundary model and the incubation experiments to estimate the N2O fluxes at the air-water interface and at the water-sediment interface of cascade reservoirs on the Yunnan-Guizhou Plateau, respectively. Additionally, we explored the influence of various factors, with particular emphasis on damming, on N2O emissions and production. Moreover, we identified the main pathways of N2O production and proposed management strategies to mitigate N2O emissions from cascade reservoirs. The findings revealed that N2O fluxes at the air-water interface and the water-sediment interface were 4.73 ± 1.32 µmol · m-2 · d-1 and 15.56 ± 1.98 µmol · m-2 · d-1, respectively. Influenced by temperature, dissolved oxygen (DO), resource substances (active nitrogen substrates and dissolved organic carbon (DOC)) and reservoir properties (scale, hydraulic retention time (HRT), reservoir age, etc.), the N2O concentration and flux exhibited notable spatial heterogeneity, gradually increasing downstream. Temperature has a significant direct impact on N2O flux, as well as indirect effects through DO and resource chemicals. Furthermore, the correlation between dissolved oxygen utilization rate (AOU) and net N2O flux (△N2O) indicated that N2O emissions at the water-air interface were primarily attributable to nitrification, whereas those at the water-sediment interface were predominantly driven by denitrification. These findings not only enhance our comprehension of N2O emissions at various interfaces of cascade reservoirs but also offer theoretical backing for the formulation of management strategies aimed at efficiently mitigating N2O emissions from continuously dammed rivers.

Dehydroepiandrosterone promotes ovarian angiogenesis and improves ovarian function in a rat model of premature ovarian insufficiency by up-regulating HIF-1α/VEGF signalling.

RESEARCH QUESTION: What impact does dehydroepiandrosterone (DHEA) have on ovarian angiogenesis and function in a rat model of with premature ovarian insufficiency (POI), and what are the potential mechanisms of action? DESIGN: DHEA was added to a culture of human microvascular endothelial cells (HMEC-1) to investigate its effects on cell proliferation, migration and tube formation. A rat model of POI was established by intraperitoneal injection of cyclophosphamide, followed by continuous oral administration of DHEA or vehicle for 28 days. Ovarian angiogenesis, follicular growth and granulosa cell survival in ovarian tissues were assessed through haematoxylin and eosin staining, immunohistochemistry and TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick-end labelling (TUNEL). The effect of DHEA on the fertility of rats with POI was evaluated in pregnant animals. The expression levels of characteristic genes and proteins in the hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor (VEGF) pathway was determined using quantitative reverse transcription PCR and western blotting. RESULTS: In-vitro experiments revealed that DHEA stimulated the proliferation, migration and tube formation of HMEC-1. In in-vivo studies, DHEA treatment improved the disruption of the oestrous cycle and hormone imbalances in POI rats. Key genes in the HIF-1α/VEGF pathway exhibited up-regulated expression, promoting ovarian angiogenesis in POI rats, and enhancing follicular development and granulosa cell survival, thereby restoring fertility in rats. CONCLUSIONS: DHEA can potentially restore ovarian function in rats with cyclophosphamide-induced POI by up-regulating HIF-1α/VEGF signalling, which promotes the growth of blood vessels in the ovaries.

Abietane diterpenoids from Caryopteris incana (Thunb.) Miq. And their HIF-2α inhibitory activities in vitro.

Eleven previously undescribed abietane-type diterpenoids, named caryopincanoids A-K (1-11), together with five known compounds, were isolated from the EtOH extract of the aerial parts of Caryopteris incana (Thunb.) Miq. Their structures were elucidated on the basis of comprehensive spectroscopic data, NMR calculations, and ECD calculations. The inhibitory activities of all compounds against HIF-2α gene expression in 786-O cells were tested by luciferase assay. Compounds 7, 9, 15, and 16 showed significant inhibitory effects with IC50 values ranging from 12.73 to 23.80 µM. The preliminary structure-activity relationship of these compounds was also discussed.

Reciprocal conversion between annual and polycarpic perennial flowering behavior in the Brassicaceae.

The development of perennial crops holds great promise for sustainable agriculture and food security. However, the evolution of the transition between perenniality and annuality is poorly understood. Here, using two Brassicaceae species, Crucihimalaya himalaica and Erysimum nevadense, as polycarpic perennial models, we reveal that the transition from polycarpic perennial to biennial and annual flowering behavior is a continuum determined by the dosage of three closely related MADS-box genes. Diversification of the expression patterns, functional strengths, and combinations of these genes endows species with the potential to adopt various life-history strategies. Remarkably, we find that a single gene among these three is sufficient to convert winter-annual or annual Brassicaceae plants into polycarpic perennial flowering plants. Our work delineates a genetic basis for the evolution of diverse life-history strategies in plants and lays the groundwork for the generation of diverse perennial Brassicaceae crops in the future.

A multicenter, randomized, open-label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis.

BACKGROUND AND PURPOSE: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.

Characteristics of advanced anaerobic digestion sludge-based biochar and its application for sewage sludge conditioning.

The utilization of sludge-based biochar, characterized by abundant pore structures, proves advantageous in enhancing sludge dewatering performance. In this study, advanced anaerobic digestion sludge underwent pyrolysis to produce biochar, subsequently employed for sludge conditioning. Results revealed that biochar, obtained at 800 °C, exhibited the highest specific surface area (105.3 m2/g) and pore volume (0.17 cm3/g). As the pyrolysis temperature increased, the sludge's functional groups tended to aromatize. When used to condition sludge, particularly at a 20 % (dry solid) dosage, biochar significantly reduced sludge capillary suction time and floc size. The addition of biochar enhanced the conditioning effect of cationic polyacrylamide by absorbing extracellular polymeric substances, creating water molecule channels, and forming skeletons for sludge flocs. These findings introduce a novel approach to sludge reuse and provide valuable data supporting the use of biochar as a sludge conditioner.

Rare SMARCA4-deficient thoracic tumor: Insights into molecular characterization and optimal therapeutics methods.

INTRODUCTIONS: The 2021 WHO Classification of Thoracic Tumors recognized SMARCA4-deficient undifferentiated thoracic tumors (SMARCA4-dUT) as a distinct entity that shows a striking overlap in demographic and molecular profiles with SMARCA4-deficient non-small lung cancer (SMARCA4-dNSCLC). The implications of SMARCA4 deficiency based on immunohistochemistry remain unclear. We aimed to investigate molecular characteristics of SMARCA4-deficient thoracic tumors (SDTT) and explore optimal therapeutics. METHODS: From June.15, 2018, to Nov.15, 2023, a large cohort including patients diagnosed with SMARCA4-deficient (N = 196) and SMARCA4-intact (N = 438) thoracic tumors confirmed by immunohistochemistry at SYSUCC were screened. Clinicopathologic and molecular characteristics were identified and compared. External SRRSH cohort (N = 34) was combined into a pooled cohort to compare clinical outcome of first-line therapy efficacy. RESULTS: SDTT is male predominance with smoking history, high tumor burden, and adrenal metastases. The relationship between SMARCA4 mutation and protein expression is not completely parallel. The majority of SMARCA4-deficient patients harbor truncating (Class-I) SMARCA4 mutations, whereas class-II alterations and wild-type also exist. Compared with SMARCA4-intact thoracic tumors, patients with SDTT displayed a higher tumor mutation burden (TMB) and associated with a shorter median OS (16.8 months vs. Not reached; P < 0.001). Notably, SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in these differences. SDTT is generally resistant to chemotherapy, while sensitive to chemoimmunotherapy (median PFS: 7.5 vs. 3.5 months, P < 0.001). In particular, patients with SMARCA4 deficient thoracic tumors treated with paclitaxel-based chemoimmunotherapy achieved a longer median PFS than those with pemetrexed-based chemoimmunotherapy (10.0 vs. 7.3 months, P = 0.028). CONCLUSIONS: SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in its characteristics of higher TMB and poor prognosis. Chemoimmunotherapy serves as the optimal option in the current treatment regimen. Paclitaxel-based chemoimmunotherapy performed better than those with pemetrexed-based chemoimmunotherapy.