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N-Glycan-dependent endoplasmic reticulum quality control (ERQC) primarily mediates protein folding, which determines the fate of the polypeptide. Monoglucose residues on N-glycans determine whether the nascent N-glycosylated proteins enter into and escape from the calnexin (CANX)/calreticulin (CALR) cycle, which is a central system of the ERQC. To reveal the impact of ERQC on glycosylation and protein fate, we performed comprehensive quantitative proteomic and glycoproteomic analyses using cells defective in N-glycan-dependent ERQC. Deficiency of MOGS encoding the ER α-glucosidase I, CANX, or/and CALR broadly affected protein expression and glycosylation. Among the altered glycoproteins, the occupancy of oligomannosidic N-glycans was significantly affected. Besides the expected ER stress, proteins and glycoproteins involved in pathways for lysosome and viral infection are differentially changed in those deficient cells. We demonstrated that lysosomal hydrolases were not correctly modified with mannose-6-phosphates on the N-glycans and were directly secreted to the culture medium in N-glycan-dependent ERQC mutant cells. Overall, the CANX/CALR cycle promotes the correct folding of glycosylated peptides and influences the transport of lysosomal hydrolases.
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We study the small mass limit in mean field theory for an interacting particle system with non-Gaussian Lévy noise. When the Lévy noise has a finite second moment, we obtain the limit equation with convergence rate ε+1/εN, by taking first the mean field limit Nâ∞ and then the small mass limit εâ0. If the order of the two limits is exchanged, the limit equation remains the same but has a different convergence rate ε+1/N. However, when the Lévy noise is α-stable, which has an infinite second moment, we can only obtain the limit equation by taking first the small mass limit and then the mean field limit, with the convergence rate 1/Nα-1+1/Np2+εp/α where p∈(1,α). This provides an effectively limit model for an interacting particle system under a non-Gaussian Lévy fluctuation, with rigorous error estimates.
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In this study, we investigated the influence of pressure and the quantity of Co/CoO catalyst on an artificial photosynthesis process that converts CO2 and H2O into hydrocarbons (CnH2n+2, where n ≤ 18). The adsorption of CO2 and H2O on Co/CoO surfaces proved to be pivotal in this photo-catalytic reaction. Photoexcited carbon dioxide and water molecules ((CO2)* and (H2O)*) generated by illuminating the catalyst surface led to the formation of alkene hydrocarbon molecules with carbon numbers following an approximate Poisson distribution. The optimal pressure was found to be 0.40 MPa. Pressure less than 0.40 MPa resulted in low CO2 adsorption, impeding excitation for photosynthesis. At greater pressure, oil/wax accumulation on Co/CoO surfaces hindered CO2 adsorption, limiting further photosynthesis reactions. The average number of carbon atoms in the hydrocarbons and hydrocarbon yield were correlated. The amount of Co/CoO was also found to affect the hydrocarbon yield. Our study contributes to the understanding of Co/CoO-catalyzed photosynthesis and suggests that an open-flow system could potentially enhance the productivity of long-chain hydrocarbons.
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We theoretically study the conditions under which two laser fields can undergo Coherent Perfect Absorption (CPA) when shined on a single-mode bi-directional optical cavity coupled with two two-level quantum emitters (natural atoms, artificial atoms, quantum dots, qubits, etc.). In addition to being indirectly coupled through the cavity-mediated field, in our Tavis-Cummings model, the two quantum emitters (QEs) are allowed to interact directly via the dipole-dipole interaction (DDI). Under the mean-field approximation and low-excitation assumption, in this work, we particularly focus on the impact of DDI on the existence of CPA in the presence of decoherence mechanisms (spontaneous emission from the QEs and the leakage of photons from the cavity walls). We also present a dressed-state analysis of the problem to discuss the underlying physics related to the allowed polariton state transitions in the Jaynes-Tavis-Cummings ladder. As a key result, we find that in the strong-coupling regime of cavity quantum electrodynamics, the strong DDI and the emitter-cavity detuning can act together to achieve the CPA at two laser frequencies tunable by the inter-atomic separation which are not possible to attain with a single QE in the presence of detuning. Our CPA results are potentially applicable in building quantum memories that are an essential component in long-distance quantum networking.
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In this study, we electroplated Co and Cu on nano-spiked silicon substrates that were treated with femtosecond laser irradiations. With energy-dispersive X-ray (EDX) analysis by a scanning electron microscope (SEM), it was found that both Co and Cu are primarily coated on the spike surfaces without changing the morphology of the nanospikes. We also found that nanoscale bridges were formed, connecting the Co-coated silicon spikes. The formation of these bridges was studied and optimized through a series of time-controlled electroplating and oxidizing processes. The bridges are related to the oxidation of Co in the air. When it is irradiated with visible light, this special structure has shown a capability of interactions with carbon monoxide and carbon dioxide molecules. The electroplated cobalt may be used for gas sensors.
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Cobalto , Nanoestruturas , Cobalto/química , Silício , Galvanoplastia , OxirreduçãoRESUMO
Due to the unique band structure, graphene exhibits a number of exotic electronic properties that have not been observed in other materials. Among them, it has been demonstrated that there exist the one-dimensional valley-polarized topological kink states localized in the vicinity of the domain wall of graphene systems, where a bulk energy gap opens due to the inversion symmetry breaking. Notably, the valley-momentum locking nature makes the topological kink states attractive to the property manipulation in valleytronics. This paper systematically reviews both the theoretical research and experimental progress on topological kink states in monolayer graphene, bilayer graphene and graphene-like classical wave systems. Besides, various applications of topological kink states, including the valley filter, current partition, current manipulation, Majorana zero modes and etc, are also introduced.
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In this work, we devise a stochastic version of contact Hamiltonian systems and show that the phase flows of these systems preserve contact structures. Moreover, we provide a sufficient condition under which these stochastic contact Hamiltonian systems are completely integrable. This establishes an appropriate framework for investigating stochastic contact Hamiltonian systems.
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We develop an information-theoretic framework to quantify information upper bound for the probability distributions of the solutions to the McKean-Vlasov stochastic differential equations. More precisely, we derive the information upper bound in terms of Kullback-Leibler divergence, which characterizes the entropy of the probability distributions of the solutions to McKean-Vlasov stochastic differential equations relative to the joint distributions of mean-field particle systems. The order of information upper bound is also figured out.
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Expression levels of many human genes are under the genetic control of expression quantitative trait loci (eQTLs). Despite technological advances, the precise molecular mechanisms underlying most eQTLs remain elusive. Here, we use deep mRNA sequencing of two CEU individuals to investigate those mechanisms, with particular focus on the role of splicing control loci (sQTLs). We identify a large number of genes that are differentially spliced between the two samples and associate many of those differences with nearby single nucleotide polymorphisms (SNPs). Subsequently, we investigate the potential effect of splicing SNPs on eQTL control in general. We find a significant enrichment of alternative splicing (AS) events within a set of highly confident eQTL targets discovered in previous studies, suggesting a role of AS in regulating overall gene expression levels. Next, we demonstrate high correlation between the levels of mature (exonic) and unprocessed (intronic) RNA, implying that â¼75% of eQTL target variance can be explained by control at the level of transcription, but that the remaining 25% may be regulated co- or post-transcriptionally. We focus on eQTL targets with discordant mRNA and pre-mRNA expression patterns and use four examples: USMG5, MMAB, MRPL43, and OAS1, to dissect the exact downstream effects of the associated genetic variants.
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Regulação da Expressão Gênica , Polimorfismo Genético , Splicing de RNA/genética , Análise de Sequência de RNA , 2',5'-Oligoadenilato Sintetase/genética , 2',5'-Oligoadenilato Sintetase/metabolismo , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Linhagem Celular , Éxons , Ordem dos Genes , Humanos , Íntrons , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Locos de Características Quantitativas/genética , Transcrição GênicaRESUMO
OBJECTIVE: To explore the preliminary experiences of "Waffle cone" technique for the treatment of intracranial aneurysm. METHODS: Retrospective data analyses were performed for patients with intracranial aneurysms embolized by the "Waffle cone" technique from stent-assisted coiling at our hospital from December 2010 to November 2012. RESULTS: Six patients used the "Waffle cone" technique from 138 stent-assisted coiling. All had complex wide-neck bifurcation cerebral aneurysms. And the angles between parental artery and distal vessels were acute. Six rupture aneurysms were at the terminus of basilar artery (BA) (n = 2), right anterior communicating artery (AcomA) (n = 3) and trifurcation middle cerebral artery (MCA) (n = 1). All stents were of Solitaire with specification 4×15 mm (ev3, USA) .Four patients had Raymond classification Class I while another 2 Class II. No perioperative complication occurred. The average follow-up period was 6 months. CONCLUSION: This technique is safe, time-saving, simple and effective for complex, wide-necked bifurcation aneurysms with acute angles between parental artery and distal vessels.Long-term follow-ups are needed to further evaluate its efficacy.
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Embolização Terapêutica/métodos , Aneurisma Intracraniano/terapia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Groundwater pollution source recognition (GPSR) is a prerequisite for subsequent pollution remediation and risk assessment work. The actual observed data are the most important known condition in GPSR, but the observed data can be contaminated with noise in real cases. This may directly affect the recognition results. Therefore, denoising is important. However, in different practical situations, the noise attribute (e.g., noise level) and observed data attribute (e.g., observed frequency) may be different. Therefore, it is necessary to study the applicability of denoising. Current studies have two deficiencies. First, when dealing with complex nonlinear and non-stationary situations, the effect of previous denoising methods needs to be improved. Second, previous attempts to analyze the applicability of denoising in GPSR have not been comprehensive enough because they only consider the influence of the noise attribute, while overlooking the observed data attribute. To resolve these issues, this study adopted the variational mode decomposition (VMD) to perform denoising on the noisy observed data in GPSR for the first time. It further explored the influence of different factors on the denoising effect. The tests were conducted under 12 different scenarios. Then, we expanded the study to include not only the noise attribute (noise level) but also the observed data attribute (observed frequency), thus providing a more comprehensive analysis of the applicability of denoising in GPSR. Additionally, we used a new heuristic optimization algorithm, the collective decision optimization algorithm, to improve the recognition accuracy. Four representative scenarios were adopted to test the ideas. The results showed that the VMD performed well under various scenarios, and the denoising effect diminished as the noise level increased and the observed frequency decreased. The denoising was more effective for GPSR with high noise levels and multiple observed frequencies. The collective decision optimization algorithm had a good inversion accuracy and strong robustness.
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At present, consumers increasingly favored the natural food preservatives with fewer side-effects on health. The green tea catechins and black tea theaflavins attracted considerable interest, and their antibacterial effects were extensively reported in the literature. Epicatechin (EC), a green tea catechin without a gallate moiety, showed no bactericidal activity, whereas the theaflavin (TF), also lacking a gallate moiety, exhibited potent bactericidal activity, and the antibacterial effects of green tea catechins and black tea theaflavins were closely correlated with their abilities to disrupt the bacterial cell membrane. In our present study, the mechanisms of membrane interaction modes and behaviors of TF and EC were explored by molecular dynamics simulations. It was demonstrated that TF exhibited markedly stronger affinity for the POPG bilayer compared to EC. Additionally, the hydrophobic interactions of tropolone/catechol rings with the acyl chain part could significantly contribute to the penetration of TF into the POPG bilayer. It was also found that the resorcinol/pyran rings were the key functional groups in TF for forming hydrogen bonds with the POPG bilayer. We believed that the findings from our current study could offer useful insights to better understand the stronger antibacterial effects of TF compared to EC.
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Biflavonoides , Catequina , Bicamadas Lipídicas , Simulação de Dinâmica Molecular , Catequina/química , Catequina/metabolismo , Catequina/análogos & derivados , Catequina/farmacologia , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Biflavonoides/química , Biflavonoides/metabolismo , Biflavonoides/farmacologia , Ligação de HidrogênioRESUMO
BACKGROUND: Corneal alkali burns can lead to ulceration, perforation, and even corneal blindness due to epithelial defects and extensive cell necrosis, resulting in poor healing outcomes. Previous studies have found that chitosan-based in situ hydrogel loaded with limbal epithelium stem cells (LESCs) has a certain reparative effect on corneal alkali burns. However, the inconsistent pore sizes of the carriers and low cell loading rates have resulted in suboptimal repair outcomes. In this study, 4D bioprinting technology was used to prepare a chitosan-based thermosensitive gel carrier (4D-CTH) with uniform pore size and adjustable shape to improve the transfer capacity of LESCs. METHODS: Prepare solutions of chitosan acetate, carboxymethyl chitosan, and ß-glycerophosphate sodium at specific concentrations, and mix them in certain proportions to create a pore-size uniform scaffold using 4D bioprinting technology. Extract and culture rat LESCs (rLESCs) in vitro, perform immunofluorescence experiments to observe the positivity rate of deltaNp63 cells for cell identification. Conduct a series of experiments to validate the cell compatibility of 4D-CTH, including CCK-8 assay to assess cell toxicity, scratch assay to evaluate the effect of 4D-CTH on rLESCs migration, and Calcein-AM/PI cell staining experiment to examine the impact of 4D-CTH on rLESCs proliferation and morphology. Establish a severe alkali burn model in rat corneas, transplant rLESCs onto the injured cornea using 4D-CTH, periodically observe corneal opacity and neovascularization using a slit lamp, and evaluate epithelial healing by fluorescein sodium staining. Assess the therapeutic effect 4D-CTH-loaded rLESCs on corneal alkali burn through histological evaluation of corneal tissue paraffin sections stained with hematoxylin and eosin, as well as immunofluorescence staining of frozen sections. RESULTS: Using the 4D-CTH, rLESCs were transferred to the alkali burn wounds of rats. Compared with the traditional treatment group (chitosan in situ hydrogel encapsulating rLESCs), the 4D-CTH-rLESC group had significantly higher repair efficiency of corneal injury, such as lower corneal opacity score (1.2 ± 0.4472 vs 0.4 ± 0.5477, p < 0.05) and neovascularization score (5.5 ± 1.118 vs 2.6 ± 0.9618, p < 0.01), and significantly higher corneal epithelial wound healing rate (72.09 ± 3.568% vs 86.60 ± 5.004%, p < 0.01). CONCLUSION: In summary, the corneas of the 4D-CTH-rLESC treatment group were similar to the normal corneas and had a complete corneal structure. These findings suggested that LESCs encapsulated by 4D-CTH significantly accelerated corneal wound healing after alkali burn and can be considered as a rapid and effective method for treating epithelial defects.
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Queimaduras Químicas , Quitosana , Lesões da Córnea , Opacidade da Córnea , Ratos , Animais , Queimaduras Químicas/tratamento farmacológico , Queimaduras Químicas/patologia , Quitosana/química , Álcalis/farmacologia , Álcalis/uso terapêutico , Cicatrização , Córnea , Lesões da Córnea/terapia , Opacidade da Córnea/patologia , Células-Tronco/patologia , Hidrogéis/farmacologiaRESUMO
Groundwater contaminant source identification (GCSI) has practical significance for groundwater remediation and liability. However, when applying the simulation-optimization method to precisely solve GCSI, the optimization model inevitably encounters the problems of high-dimensional unknown variables to identify, which might increase the nonlinearity. In particular, to solve such optimization models, the well-known heuristic optimization algorithms might fall into a local optimum, resulting in low accuracy of inverse results. For this reason, this paper proposes a novel optimization algorithm, namely, the flying foxes optimization (FFO) to solve the optimization model. We perform simultaneous identification of the release history of groundwater pollution sources and hydraulic conductivity and compare the results with those of the traditional genetic algorithm. In addition, to alleviate the massive computational load caused by the frequent invocation of the simulation model when solving the optimization model, we utilized the multilayer perception (MLP) to establish a surrogate model of the simulation model and compared it with the method of backpropagation algorithm (BP). The results show that the average relative error of the results of FFO is 2.12%, significantly outperforming the genetic algorithm (GA); the surrogate model of MLP can replace the simulation model for calculation with fitting accuracy of more than 0.999, which is better than the commonly used surrogate model of BP.
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Quirópteros , Água Subterrânea , Animais , Modelos Teóricos , Simulação por Computador , Algoritmos , Redes Neurais de ComputaçãoRESUMO
Textured surfaces were prepared by embedding microspheres with different thermal conductivities of brass microspheres (BS), 304 stainless steel microspheres (SS), and polyoxymethylene microspheres (PS) on the surface of polymethyl methacrylate (PMMA). The effects of surface texture and filling modification on the dry tribological properties of BS/PMMA, SS/PMMA, and PS/PMMA composites were studied by ring-on-disc contact. Based on the finite element analysis of friction heat, the wear mechanisms of BS/PMMA, SS/PMMA, and PS/PMMA composites were analyzed. The results show that regular surface texture can be achieved by embedding microspheres on the PMMA surface. The friction coefficient and wear depth of the SS/PMMA composite are both the lowest. The worn surfaces of BS/PMMA, SS/PMMA, and PS/PMMA composites are divided into three micro-wear-regions. The wear mechanisms of different micro-wear-regions are different. Finite element analysis shows that thermal conductivity and thermal expansion coefficient affect the wear mechanisms of BS/PMMA, SS/PMMA, and PS/PMMA composites.
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One of the main drivers within the field of bottom-up synthetic biology is to develop artificial chemical machines, perhaps even living systems, that have programmable functionality. Numerous toolkits exist to generate giant unilamellar vesicle-based artificial cells. However, methods able to quantitatively measure their molecular constituents upon formation is an underdeveloped area. We report an artificial cell quality control (AC/QC) protocol using a microfluidic-based single-molecule approach, enabling the absolute quantification of encapsulated biomolecules. While the measured average encapsulation efficiency was 11.4 ± 6.8%, the AC/QC method allowed us to determine encapsulation efficiencies per vesicle, which varied significantly from 2.4 to 41%. We show that it is possible to achieve a desired concentration of biomolecule within each vesicle by commensurate compensation of its concentration in the seed emulsion. However, the variability in encapsulation efficiency suggests caution is necessary when using such vesicles as simplified biological models or standards.
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Células Artificiais , Lipossomas Unilamelares , Lipossomas Unilamelares/química , Microfluídica/métodos , Biologia Sintética , EmulsõesRESUMO
A high-temperature accelerometer plays an important role for ensuring normal operation of equipment in aerospace, such as monitoring and identifying abnormal vibrations of aircraft engines. Phase transitions of piezoelectric crystals, mechanical failure and current leakage of piezoresistive/capacitive materials are the prominent inherent limitations of present high-temperature accelerometers working continuously above 973 K. With the rapid development of aerospace, it is a great challenge to develop a new type of vibration sensor to meet the crucial demands at high temperature. Here we report a high-temperature accelerometer working with a contact resistance mechanism. Based on the improved graphene aerogel (GA) prepared by a modulated treatment process, the accelerometer can operate continuously and stably at 1073 K and intermittently at 1273 K. The developed sensor is lightweight (sensitive element <5 mg) and has high sensitivity (an order of magnitude higher than MEMS accelerometers) and wide frequency response range (up to 5 kHz at 1073 K) with marked stability, repeatability and low nonlinearity error (<1%). These merits are attributed to the excellent and stable mechanical properties of the improved GA in the range of 299-1073 K. The accelerometer could be a promising candidate for high-temperature vibration sensing in space stations, planetary rovers and others.
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Extracellular vesicles (EVs) are membrane-bound vesicles released by living cells. As vesicles for macromolecule transmission and intercellular communication, EVs are broadly applied in clinical diagnosis and biomimetic drug delivery. Milk-derived EVs (MEVs) are an ideal choice for scale-up applications because they exhibit biocompatibility and are easily obtained. Herein, intact glycopeptides in MEVs from bovines, caprines, porcines, and humans were comprehensively analyzed by high-resolution mass spectrometry using the sceHCD, followed by the EThcD fragment method, revealing that protein glycosylation is abundant and heterogeneous in MEVs. The dominant glycans in all MEVs were sialic acid-modified N-linked glycans (over 50%). A couple of species-specific glycans were also characterized, which are potentially markers of different original EVs. Interestingly, the Neu5Gc-modified glycans were enriched in caprine milk-derived EVs (58 ± 2%). Heterogeneity of MEV protein glycosylation was observed for glycosites and glycan compositions, and the structural heterogeneity of protein glycosylation was also identified and validated. The glycosignatures of EV biogenesis- and endocytosis-related proteins (CD63 and MFGE8) were significantly different in these four species. Overall, we comprehensively characterized the glycosylation signature of MEVs from four different species and provided insight into protein glycosylation related to drug target delivery.
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Vesículas Extracelulares , Leite Humano , Humanos , Animais , Bovinos , Suínos , Glicosilação , Leite Humano/metabolismo , Cabras/metabolismo , Vesículas Extracelulares/metabolismo , Polissacarídeos/metabolismoRESUMO
OBJECTIVES: This work aimed to analyse the risk factors for poor outcomes and mortality among patients with anterior large vessel occlusion (LVO) ischaemic stroke, despite successful recanalisation. SETTING AND PARTICIPANTS: This study conducted a secondary analysis among patients who underwent successful recanalisation in the CAPTURE trial. The trial took place between March 2018 and September 2020 at 21 sites in China. The CAPTURE trial enrolled patients who had an acute ischaemic stroke aged 18-80 years with LVO in anterior circulation. INTERVENTIONS: Thrombectomy was immediately performed using Neurohawk or the Solitaire FR after randomisation in CAPTURE trial. Rescue treatment was available for patients with severe residual stenosis caused by atherosclerosis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary goal was to predict poor 90-day survival or mortality within 90 days post-thrombectomy. Univariate analysis, using the χ2 test or Fisher's exact test, was conducted for each selected factor. Subsequently, a multivariable analysis was performed on significant factors (p≤0.10) identified through univariate analysis using the backward selection logistic regression approach. RESULTS: Among the 207 recruited patients, 79 (38.2%) exhibited poor clinical outcomes, and 26 (12.6%) died within 90 days post-thrombectomy. Multivariate analysis revealed that the following factors were significantly associated with poor 90-day survival: age ≥67 years, internal carotid artery (ICA) occlusion (compared with middle cerebral artery (MCA) occlusion), initial National Institutes of Health Stroke Scale (NIHSS) score ≥17 and final modified Thrombolysis in Cerebral Infarction (mTICI) score 2b (compared with mTICI 3). Additionally, the following factors were significantly associated with mortality 90 days post-thrombectomy: initial NIHSS score ≥17, ICA occlusion (compared with MCA occlusion) and recanalisation with more than one pass. CONCLUSIONS: Age, NIHSS score, occlusion site, mTICI score and the number of passes can be independently used to predict poor 90-day survival or mortality within 90 days post-thrombectomy. TRIAL REGISTRATION NUMBER: NCT04995757.
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Arteriopatias Oclusivas , Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Lactente , Arteriopatias Oclusivas/etiologia , Isquemia Encefálica/cirurgia , Isquemia Encefálica/etiologia , Infarto da Artéria Cerebral Média/terapia , AVC Isquêmico/etiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/etiologia , Trombectomia/efeitos adversos , Resultado do TratamentoRESUMO
Background: The difference of patients' baseline characteristics such as sex, age, Eastern Cooperative Oncology Group performance status (ECOG PS), and smoking status may influence the immune response. However, little is known about whether these factors affect the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small-cell lung cancer (NSCLC). Therefore, we performed this systematic review and meta-analysis to investigate the relationship between patients' baseline characteristics and survival benefits in immunotherapy-treated NSCLC. Materials and Methods: We performed a systematic search of PubMed, the Cochrane Library, and Embase for randomized controlled trials (RCTs) of NSCLC immunotherapy. We also searched abstracts and presentations from the proceedings of the American Society of Clinical Oncology and the European Society of Medical Oncology to identify unpublished studies. These studies have available data based on patients' baseline characteristics (such as sex, age, ECOG PS, and smoking status). We take the hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) as the effect index and use the random effect model to pool the results. Results: We included 18 phase II/III RCTs with a total of 14,189 participants. The benefits of ICIs were found for both male (pooled OS-HR 0.77, 95% CI 0.72-0.82, P < 0.05) and female patients (pooled OS-HR 0.77, 95% CI 0.67-0.87, P < 0.05); for both younger (<65 y: pooled OS-HR 0.74, 95% CI 0.68-0.81, P < 0.05) and older patients (≥65 y: pooled OS-HR 0.80, 95% CI 0.75-0.86, P < 0.05); and for both patients with ECOG PS = 0 (pooled OS-HR 0.77, 95% CI 0.71-0.84, P < 0.05) and ECOG PS ≥ 1 (pooled OS-HR 0.76, 95% CI 0.70-0.82, P < 0.05). Moreover, there was no significant difference in the efficacy of ICIs among different sex (P value for interaction = 0.955), age (P value for interaction = 0.17), or ECOG PS (P value for interaction = 0.765). However, in patients with different smoking status, the application of ICIs significantly prolonged the OS of smokers (pooled OS-HR 0.77, 95% CI 0.71-0.83, P < 0.05) but could not significantly improve the OS of never smokers (pooled OS-HR 0.85, 95% CI 0.70-1.03, P > 0.05). Conclusions: ICIs could significantly improve prognosis in patients with advanced NSCLC, regardless of sex, age, or ECOG PS. But among patients with different smoking status, the survival benefits of never smokers treated with ICIs were no better than that of controls. The impact of these factors on immunotherapy should be considered in the future clinical practice and guidelines.