Multi-organ proteomic landscape of COVID-19 autopsies.

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.

Targeted protein degradation reveals RNA Pol II heterogeneity and functional diversity.

RNA polymerase II (RNA Pol II) subunits are thought to be involved in various transcription-associated processes, but it is unclear whether they play different regulatory roles in modulating gene expression. Here, we performed nascent and mature transcript sequencing after the acute degradation of 12 mammalian RNA Pol II subunits and profiled their genomic binding sites and protein interactomes to dissect their molecular functions. We found that RNA Pol II subunits contribute differently to RNA Pol II cellular localization and transcription processes and preferentially regulate RNA processing (such as RNA splicing and 3' end maturation). Genes sensitive to the depletion of different RNA Pol II subunits tend to be involved in diverse biological functions and show different RNA half-lives. Sequences, associated protein factors, and RNA structures are correlated with RNA Pol II subunit-mediated differential gene expression. These findings collectively suggest that the heterogeneity of RNA Pol II and different genes appear to depend on some of the subunits.

Amyloid fibrils in FTLD-TDP are composed of TMEM106B and not TDP-43.

Frontotemporal lobar degeneration (FTLD) is the third most common neurodegenerative condition after Alzheimer's and Parkinson's diseases1. FTLD typically presents in 45 to 64 year olds with behavioural changes or progressive decline of language skills2. The subtype FTLD-TDP is characterized by certain clinical symptoms and pathological neuronal inclusions with TAR DNA-binding protein (TDP-43) immunoreactivity3. Here we extracted amyloid fibrils from brains of four patients representing four of the five FTLD-TDP subclasses, and determined their structures by cryo-electron microscopy. Unexpectedly, all amyloid fibrils examined were composed of a 135-residue carboxy-terminal fragment of transmembrane protein 106B (TMEM106B), a lysosomal membrane protein previously implicated as a genetic risk factor for FTLD-TDP4. In addition to TMEM106B fibrils, we detected abundant non-fibrillar aggregated TDP-43 by immunogold labelling. Our observations confirm that FTLD-TDP is associated with amyloid fibrils, and that the fibrils are formed by TMEM106B rather than TDP-43.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Engineered Living Materials For Sustainability.

Recent advances in synthetic biology and materials science have given rise to a new form of materials, namely engineered living materials (ELMs), which are composed of living matter or cell communities embedded in self-regenerating matrices of their own or artificial scaffolds. Like natural materials such as bone, wood, and skin, ELMs, which possess the functional capabilities of living organisms, can grow, self-organize, and self-repair when needed. They also spontaneously perform programmed biological functions upon sensing external cues. Currently, ELMs show promise for green energy production, bioremediation, disease treatment, and fabricating advanced smart materials. This review first introduces the dynamic features of natural living systems and their potential for developing novel materials. We then summarize the recent research progress on living materials and emerging design strategies from both synthetic biology and materials science perspectives. Finally, we discuss the positive impacts of living materials on promoting sustainability and key future research directions.

Proteome Landscapes of Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

Liver cancer is among the top leading causes of cancer mortality worldwide. Particularly, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA) have been extensively investigated from the aspect of tumor biology. However, a comprehensive and systematic understanding of the molecular characteristics of HCC and CCA remains absent. Here, we characterized the proteome landscapes of HCC and CCA using the data-independent acquisition (DIA) mass spectrometry (MS) method. By comparing the quantitative proteomes of HCC and CCA, we found several differences between the two cancer types. In particular, we found an abnormal lipid metabolism in HCC and activated extracellular matrix-related pathways in CCA. We next developed a three-protein classifier to distinguish CCA from HCC, achieving an area under the curve (AUC) of 0.92, and an accuracy of 90% in an independent validation cohort of 51 patients. The distinct molecular characteristics of HCC and CCA presented in this study provide new insights into the tumor biology of these two major important primary liver cancers. Our findings may help develop more efficient diagnostic approaches and new targeted drug treatments.

Proteomics Investigation of Diverse Serological Patterns in COVID-19.

Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.

Space-Confined Growth of Ultrathin P-Type GeTe Nanosheets for Broadband Photodetectors.

As p-type phase-change degenerate semiconductors, crystalline and amorphous germanium telluride (GeTe) exhibit metallic and semiconducting properties, respectively. However, the massive structural defects and strong interface scattering in amorphous GeTe films significantly reduce their performance. In this work, two-dimensional (2D) p-type GeTe nanosheets are synthesized via a specially designed space-confined chemical vapor deposition (CVD) method, with the thickness of the GeTe nanosheets reduced to 1.9 nm. The space-confined CVD method improves the crystallinity of ultrathin GeTe by lowering the partial pressure of the reactant gas, resulting in GeTe nanosheets with excellent p-type semiconductor properties, such as a satisfactory on/off ratio of 105. Temperature-dependent electrical measurements demonstrate that variable-range hopping and optical-phonon-assisted hopping mechanisms dominate transport behavior at low and high temperatures, respectively. GeTe devices exhibit significantly high responsivity (6589 and 2.2 A W-1 at 633 and 980 nm, respectively) and detectivity (1.67 × 1011 and 1.3 × 108 Jones at 633 and 980 nm, respectively), making them feasible for broadband photodetectors in the visible to near-infrared range. Furthermore, the fabricated GeTe/WS2 diode exhibits a rectification ratio of 103 at zero gate voltage. These satisfactory p-type semiconductor properties demonstrate that ultrathin GeTe exhibits enormous potential for applications in optoelectronic interconnection circuits.

Strengthened Interficial Adhesive Fracture Energy by Young's Modulus Matching Degree Strategy in Carbon-Based HTM Free MAPbI3 Perovskite Solar Cell with Enhanced Mechanical Compatibility.

Carbon-based hole transport layer-free perovskite solar cells (PSCs) based on methylammonium lead triiodide (MAPbI3 ) have become one of the research focus due to low cost, easy preparation, and good optoelectronic properties. However, instability of perovskite under vacancy defects and stress-strain makes it difficult to achieve high-efficiency and stable power output. Here, a soft-structured long-chain 2D pentanamine iodide (abbreviated as "PI") is used to improve perovskite quality and interfacial mechanical compatibility. PI containing CH3 (CH2 )4 NH3 + and I- ions not only passivate defects at grain boundaries, but also effectively alleviate residual stress during high temperature annealing via decreasing Young's modulus of perovskite film. Most importantly, PI effectively increases matching degree of Young's modulus between MAPbI3 (47.1 GPa) and carbon (6.7 GPa), and strengthens adhesive fracture energy (Gc ) between perovskite and carbon, which is helpful for outward release of nascent interfacial stress generated under service conditions. Consequently, photoelectric conversion efficiency (PCE) of optimal device is enhanced from 10.85% to 13.76% and operational stability is also significantly improved. 83.1% output is maintained after aging for 720 h at room temperature and 25-60% relative humidity (RH). This strategy of regulation from chemistry and physics provides a strategy for efficient and stable carbon-based PSCs.

Inhibitory effects of phthalate esters (PAEs) and phthalate monoesters towards human carboxylesterases (CESs).

Phthalate esters (PAEs), accompanied by phthalate monoesters as hydrolysis metabolites in humans, have been widely used as plasticizers and exhibited disruptive effects on the endocrine and metabolic systems. The present study aims to investigate the inhibition behavior of PAEs and phthalate monoesters on the activity of the important hydrolytic enzymes, carboxylesterases (CESs), to elucidate the toxicity mechanism from a new perspective. The results showed significant inhibition on CES1 and CES2 by most PAEs, but not by phthalate monoesters, above which the activity of CES1 was strongly inhibited by DCHP, DEHP, DiOP, DiPP, DNP, DPP and BBZP, with inhibition ratios exceeding 80%. Kinetic analyses and in vitro-in vivo extrapolation were conducted, revealing that PAEs have the potential to disrupt the metabolism of endogenous substances catalyzed by CES1 in vivo. Molecular docking results revealed that hydrogen bonds and hydrophobic contacts formed by ester bonds contributed to the interaction of PAEs towards CES1. These findings will be beneficial for understanding the adverse effect of PAEs and phthalate monoesters.

Use of 3D Echocardiography Facilitates Analysis of Thrombolytic Efficacy in Patients With Persistent Atrial Fibrillation.

ABSTRACT: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation. During follow-up after 9-24 weeks of rivaroxaban treatment, patients were divided into "effective group" (n = 143) and "ineffective group" (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAAD mean ), angle between left atrial appendage and left atrium (LAA-A), velocity of blood flow in left atrial appendage (LAA-v), and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF, and LAA-v values were greater and LAD and LAAD mean values were lower in the effective ( P < 0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A, and LAA-v with anticoagulant efficacy ( P < 0.05). The efficacy of rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A, and LAA-v. Multivariate logistic regression analysis further revealed LAEF [odds ratio (OR) 1.7, 95% confidence interval (CI), 0.45-16.9, P = 0.008], 3D-EF (OR 6.4, 95% CI, 1.06-16.9, P = 0.039) and left ventricular global longitudinal strain (OR 18.0, 95% CI, 1.38-35.68, P = 0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of rivaroxaban as an anticoagulation agent.

Structural basis of tolvaptan binding to the vasopressin V2 receptor.

The vasopressin V2 receptor (V2R) is a validated therapeutic target for autosomal dominant polycystic kidney disease (ADPKD), with tolvaptan being the first FDA-approved antagonist. Herein, we used Gaussian accelerated molecular dynamics simulations to investigate the spontaneous binding of tolvaptan to both active and inactive V2R conformations at the atomic-level. Overall, the binding process consists of two stages. Tolvaptan binds initially to extracellular loops 2 and 3 (ECL2/3) before overcoming an energy barrier to enter the pocket. Our simulations result highlighted key residues (e.g., R181, Y205, F287, F178) involved in this process, which were experimentally confirmed by site-directed mutagenesis. This work provides structural insights into tolvaptan-V2R interactions, potentially aiding the design of novel antagonists for V2R and other G protein-coupled receptors.

Antimicrobial peptide cecropin B functions in pathogen resistance of Mythimna separata.

Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata. The gene encoding M. separata cecropin B (MscecropinB) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata. It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis (Bt). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata, and resulted in an increased sensitivity to B. bassiana and Bt. The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt.

[Changes in the disease burden of male urinary and reproductive system tumors in China from 1990 to 2019: Analysis with a prediction of the future trend].

OBJECTIVE: To analyze the changes in the disease burden of prostate, testis, kidney and bladder cancers among urinary and reproductive system tumors in Chinese men from 1990 to 2019 with a prediction of the future trend. METHODS: We retrieved the data on the incidence, mortality and disease burden of prostate, testis, kidney and bladder cancers in Chinese men between 1990 and 2019 from the database of Global Burden of Disease Study 2019. Using the Joinpoint regression model, we analyzed the trend of changes in the disease burden, and predicted the prevalence of the tumors with the ARIMA model. RESULTS: From 1990 to 2019, the standardized incidence and prevalence of prostate, testis, kidney and bladder cancers were on the rise in Chinese men, and those of testis cancer increased most significantly, by 326.79% and 1070.93% respectively. The disease burden of PCa was the highest, with standardized incidence, prevalence and mortality ratios of 17.34/100 000, 117.65/100 000 and 7.79/100 000 respectively in 2019. The standardized mortality and disability-adjusted life years (DALY) of kidney cancer were increased by 103.59% and 103.17% respectively. The highest incidence, mortality and DALY of prostate, kidney and bladder cancers in 2019 were found in 90－94 years old males, the highest prevalence rates of prostate, kidney and bladder cancers in the 70－89-year-olds, and the highest prevalence of testis cancer in the 25－49-year-olds. ARIMA model prediction showed that the standardized incidence rates of prostate, testis, kidney and bladder cancers in Chinese men kept rising from 2020 to 2029. CONCLUSION: The disease burden of prostate, testis, kidney and bladder cancers in Chinese men is on the rise, and their standardized incidence rates will be even higher by 2029, with a significant increase in the disease burden in young men, which suggests the need of more attention to the prevention and treatment of genitourinary system tumors in young males.

[Research progress in prevention and treatment of vascular calcification with traditional Chinese medicine].

Vascular calcification is a pathological stage involved in the occurrence and development of cardiovascular diseases, seriously threatening human life and health. At present, few drugs can completely reverse or cure vascular calcification in clinical practice. The pathogenesis of vascular calcification mainly involves the disturbance of calcium and phosphorus homeostasis, autophagy dysfunction, loss of endogenous calcium inhibition, and the apoptosis, cytokine storm, cell osteoblastic transdifferentiation, and stromal vesicle release induced by endoplasmic reticulum stress. Following the therapeutic concepts of warming channels and dredging vessels, activating blood and resolving stasis, tonifying kidney and invigorating spleen, and removing dampness and eliminating turbid, a large number of traditional Chinese medicine(TCM) active compounds/extracts and TCM prescriptions/Chinese patent medicines have shown satisfactory performance in treating vascular calcification, while the specific mechanisms remain unclear and awaits further investigations. This article systematically summarized the pathogenesis of vascular calcification and the latest research progress of TCM in the prevention and treatment of vascular calcification, providing theoretical support for the clinical application of TCM in the prevention and treatment of vascular calcification.

Operando Stable Palladium Hydride Nanoclusters Anchored on Tungsten Carbides Mediate Reverse Hydrogen Spillover for Hydrogen Evolution.

Proton exchange membrane (PEM) electrolysis holds great promise for green hydrogen production, but suffering from high loading of platinum-group metals (PGM) for large-scale deployment. Anchoring PGM-based materials on supports can not only improve the atomic utilization of active sites but also enhance the intrinsic activity. However, in practical PEM electrolysis, it is still challenging to mediate hydrogen adsorption/desorption pathways with high coverage of hydrogen intermediates over catalyst surface. Here, operando generated stable palladium (Pd) hydride nanoclusters anchored on tungsten carbide (WCx) supports were constructed for hydrogen evolution in PEM electrolysis. Under PEM operando conditions, hydrogen intercalation induces formation of Pd hydrides (PdHx) featuring weakened hydrogen binding energy (HBE), thus triggering reverse hydrogen spillover from WCx (strong HBE) supports to PdHx sites, which have been evidenced by operando characterizations, electrochemical results and theoretical studies. This PdHx-WCx material can be directly utilized as cathode electrocatalysts in PEM electrolysis with ultralow Pd loading of 0.022 mg cm-2, delivering the current density of 1 A cm-2 at the cell voltage of ~1.66 V and continuously running for 200 hours without obvious degradation. This innovative strategy via tuning the operando characteristics to mediate reverse hydrogen spillover provide new insights for designing high-performance supported PGM-based electrocatalysts.

Oxygen Plasma Triggered Co-O-Fe Motif in Prussian Blue Analogue for Efficient and Robust Alkaline Water Oxidation.

In the context of oxygen evolution reaction (OER), the construction of high-valent transition metal sites to trigger the lattice oxygen oxidation mechanism is considered crucial for overcoming the performance limitations of traditional adsorbate evolution mechanism. However, the dynamic evolution of lattice oxygen during the reaction poses significant challenges for the stability of high-valent metal sites, particularly in high-current-density water-splitting systems. Here, we have successfully constructed Co-O-Fe catalytic active motifs in cobalt-iron Prussian blue analogs (CoFe-PBA) through oxygen plasma bombardment, effectively activating lattice oxygen reactivity while sustaining robust stability. Our spectroscopic and theoretical studies reveal that the Co-O-Fe bridged motifs enable a unique double-exchange interaction between Co and Fe atoms, promoting the formation of high-valent Co species as OER active centers while maintaining Fe in a low-valent state, preventing its dissolution. The resultant catalyst (CoFe-PBA-30) requires an overpotential of only 276 mV to achieve 1000 mA cm-2. Furthermore, the assembled alkaline exchange membrane electrolyzer using CoFe-PBA-30 as anode material achieves a high current density of 1 A cm-2 at 1.76 V and continuously operates for 250 hours with negligible degradation. This work provides significant insights for activating lattice oxygen redox without compromising structure stability in practical water electrolyzers.

Homoleptic Al(III) Photosensitizers for Durable CO2 Photoreduction.

Exploiting noble-metal-free systems for high-performance photocatalytic CO2 reduction still presents a key challenge, partially due to the long-standing difficulties in developing potent and durable earth-abundant photosensitizers. Therefore, based on the very cheap aluminum metal, we have deployed a systematic series of homoleptic Al(III) photosensitizers featuring 2-pyridylpyrrolide ligands for CO2 photoreduction. The combined studies of steady-state and time-resolved spectroscopy as well as quantum chemical calculations demonstrate that in anerobic CH3CN solutions at room temperature, visible-light excitation of the Al(III) photosensitizers leads to an efficient population of singlet excited states with nanosecond-scale lifetimes and notable emission quantum yields (10-40%). The results of transient absorption spectroscopy further identified the presence of emissive singlet and unexpectedly nonemissive triplet excited states. More importantly, the introduction of methyl groups at the pyrrolide rings can greatly improve the visible-light absorption, reducing power, and durability of the Al(III) photosensitizers. With triethanolamine, BIH (1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole), and an Fe(II)-quaterpyridine catalyst, the most methylated Al(III) photosensitizer achieves an apparent quantum efficiency of 2.8% at 450 nm for selective (>99%) CO2-to-CO conversion, which is nearly 28 times that of the unmethylated one (0.1%) under identical conditions. The optimal system realizes a maximum turnover number of 10250 and higher robustness than the systems with Ru(II) and Cu(I) benchmark photosensitizers. Quenching experiments using fluorescence spectroscopy elucidate that the photoinduced electron transfer in the Al(III)-sensitized system follows a reductive quenching pathway. The remarkable tunability and cost efficiency of these Al(III) photosensitizers should allow them as promising components in noble-metal-free systems for solar fuel conversion.

Rational application of EGFR-TKI adjuvant therapy in patients with completely resected stage IB-IIIA EGFR-mutant NSCLC: a systematic review and meta-analysis of 11 randomized controlled trials.

PURPOSE: To determine the role and rational application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant therapy in patients with completely resected stage IB-IIIA EGFR-mutant non-small-cell lung cancer (NSCLC). METHOD: Randomized controlled trials (RCTs) that compared the survival outcomes between adjuvant EGFR-TKIs and adjuvant chemotherapy or a placebo, or between different EGFR-TKI treatment durations for resected NSCLC, were eligible for inclusion. Disease-free survival (DFS) and overall survival (OS) with hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated as effective measures using random-effect or fixed-effect models. Subgroup analysis was also performed. RESULTS: Eleven RCTs involving 2102 EGFR-mutant NSCLC patients with or without EGFR-TKI adjuvant therapy were included. For all stage IB-IIIA NSCLC patients, EGFR-TKIs adjuvant therapy could not only significantly improve DFS (HR 0.43, 95% CI 0.30-0.63, P < 0.001) and 2- and 3-year DFS rates, but also improve OS (HR 0.72, 95% CI, 0.54-0.96, P = 0.024), compared with chemotherapy or the placebo. Further subgroup analyses indicated prolonged OS from first-generation EGFR-TKI adjuvant therapy in stage III patients, compared with chemotherapy or the placebo (HR for OS, 0.34; 95% CI, 0.18-0.63; P = 0.001). Of note, osimertinib adjuvant therapy led to the OS benefit expanding from stage III to stage II-III patients, with significantly improved DFS and a lower risk of brain recurrence, compared with the placebo. A 2-year treatment duration with EGFR-TKI adjuvant therapy showed a significantly lower recurrence risk than a ≤ 1-year duration. CONCLUSION: The DFS advantage from first-generation EGFR-TKI adjuvant therapy can translate into an OS benefit in stage III NSCLC patients. Osimertinib might be more suitable for adjuvant therapy than first-generation EGFR-TKIs, because of the lower recurrence rate and the potential OS benefit even in early-stage patients. The optimal treatment duration for EGFR-TKIs at different stages of disease needs to be validated.