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Background: Cardiopulmonary bypass (CPB) can trigger a systemic inflammatory response during the perioperative period, which may lead to the consumption of the contact system and the production of neutrophil extracellular traps (NETs). This study attempted to determine whether the formation of NETs and contact activation are a vivid occurrence during CPB and whether they are related to post-operative atrial fibrillation (AF) and survival. Methods: A prospective observational study was conducted in 97 patients who underwent aortic valve and/or aorta replacement surgery with CPB. Circulating markers of NETs [histone-DNA complex, cell-free double stranded DNA (dsDNA), neutrophil elastase] and the contact system [prekallikrein, high molecular weight kininogen (HMWK), activated factor XII (FXIIa)] were measured at four-time points: before surgery (T0), immediately after surgery (T1), 1 day after surgery (T2), and 3 days after surgery (T3). Results: Elevated levels of circulating NETs markers were observed across post-CPB time. Significantly elevated levels of histone-DNA complex and cell-free dsDNA measured T3 were detected in patients with post-operative AF compared to those without. In logistic regression analysis, levels of histone-DNA complex and cell-free dsDNA measured at T3 were significant markers of risk for occurrence of AF. The levels of cell-free dsDNA measured T2 were significantly higher in non-survivors than in survivors. The level of cell-free dsDNA showed significant prognostic value. Conclusions: NETs markers may be useful for the assessment of risk for post-operative AF and mortality. Conduct of additional research regarding the role of NETs as clinical markers and as a therapeutic target in CPB is anticipated.
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Polychlorinated biphenyls (PCBs) were once used throughout various industries; however, because of their persistence in the environment, exposure remains a global threat to the environment and human health. The Kv1.3 and Kv1.5 channels have been implicated in the immunotoxicity and cardiotoxicity of PCBs, respectively. We determined whether 3,3',4,4'-tetrachlorobiphenyl (PCB77), a dioxin-like PCB, alters human Kv1.3 and Kv1.5 currents using the Xenopus oocyte expression system. Exposure to 10 nM PCB77 for 15 min enhanced the Kv1.3 current by approximately 30.6%, whereas PCB77 did not affect the Kv1.5 current at concentrations up to 10 nM. This increase in the Kv1.3 current was associated with slower activation and inactivation kinetics as well as right-shifting of the steady-state activation curve. Pretreatment with PCB77 significantly suppressed tumor necrosis factor-α and interleukin-10 production in lipopolysaccharide-stimulated Raw264.7 macrophages. Overall, these data suggest that acute exposure to trace concentrations of PCB77 impairs immune function, possibly by enhancing Kv1.3 currents.
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The availability of carbon nanotube (CNT)-based polymer composites allows the development of surface-attached self-sensing crack sensors for the structural health monitoring of reinforced concrete (RC) structures. These sensors are fabricated by integrating CNTs as conductive fillers into polymer matrices such as polyurethane (PU) and can be applied by coating on RC structures before the composite hardens. The principle of crack detection is based on the electrical change characteristics of the CNT-based polymer composites when subjected to a tensile load. In this study, the electrical conductivity and electro-mechanical/environmental characterization of smart skin fabricated with various CNT concentrations were investigated. This was performed to derive the tensile strain sensitivity of the smart skin according to different CNT contents and to verify their environmental impact. The optimal CNT concentration for the crack detection sensor was determined to be 5 wt% CNT. The smart skin was applied to an RC structure to validate its effectiveness as a crack detection sensor. It successfully detected and monitored crack formation and growth in the structure. During repeated cycles of crack width variations, the smart skin also demonstrated excellent reproducibility and electrical stability in response to the progressive occurrence of cracks, thereby reinforcing the reliability of the crack detection sensor. Overall, the presented results describe the crack detection characteristics of smart skin and demonstrate its potential as a structural health monitoring (SHM) sensor.
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Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory and fibrotic response-driven lung disease that is difficult to cure because it manifests excessive profibrotic cytokines (e.g., TGF-ß), activated myofibroblasts, and accumulated extracellular matrix (ECM). In an attempt to develop an inhalation formulation with enhanced antifibrotic efficacy, we sought to fabricate unique aerosolizable inhaled microgels (µGel) that contain nintedanib-poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs; n-PN) and pirfenidone-liposomes (p-LP). The aero-µGel was â¼12 µm, resisted phagocytosis by alveolar macrophages in vitro and in vivo, and protected inner-entrapped n-PN and p-LP. The n-PN/p-LP@aero-µGel caused enhanced/extended antifibrotic efficacy in a bleomycin-induced pulmonary fibrosis mouse presumably due to prolonged lung residence. Consequently, the results obtained by intratracheal aerosol insufflation of our n-PN/p-LP@aero-µGel twice a week were much better than those by as many as seven doses of single or mixed applications of n-PN or p-LP. The antifibrotic/pharmacokinetic results for the n-PN/p-LP@aero-µGel included reduced fibrosis progression, restored lung physiological functions, deactivated myofibroblasts, inhibited TGF-ß progression, and suppressed ECM component production (collagen I and α-SMA) along with prolonged lung retention time. We believe that our n-PN/p-LP@aero-µGel increased the local availability of both nintedanib and pirfenidone due to evasion of alveolar macrophage phagocytosis and prolonged lung retention with reduced systemic distribution. Through this approach, our inhalation formulation subsequently attenuated fibrosis progression and improved lung function. Importantly, these results hold profound implications in the therapeutic potential of our n-PN/p-LP@aero-µGel to serve as a clinically promising platform, providing significant advancements for improved treatment of many respiratory diseases including IFP.
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Traffic accidents caused by road icing are a serious global problem, and conventional de-icing methods like spraying chemicals have several limitations, including excessive manpower management, road damage, and environmental pollution. In this study, the carbon nanotubes reinforced de-icing coating for the road system with a self-heating function was developed as part of the development of a new system to prevent accidents caused by road icing. The electrical characteristics of the fabricated coating were analyzed, and the carbon nanotube coating heating performance experiment was conducted to measure the temperature increments by applying a voltage to the coating at a sub-zero temperature using an environmental chamber. In addition, the coating was installed on the road pavement and the applicability was investigated through a heating test in winter. As a result of the experiment, the coating made with the higher carbon nanotube concentration presented higher heating owing to its higher electrical conductivity. In addition, the coating showed sufficient heating performance, although the maximum temperature by Joule heating decreased for the entire coating at sub-zero temperatures. Finally, field tests demonstrated the potential of electrically conductive coatings for de-icing applications.
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BACKGROUND: Current influenza vaccines deliver satisfactory results in young people but are less effective in the elderly. Development of vaccines for an ever-increasing aging population has been an arduous challenge due to immunosenescence that impairs the immune response in the aged, both quantitatively and qualitatively. RESULTS: To potentially enhance vaccine efficacy in the elderly, we investigated the immunogenicity and cross-protection of influenza hemagglutinin virus-like particles (HA-VLP) incorporated with glycosylphosphatidylinositol (GPI)-anchored cytokine-adjuvants (GPI-GM-CSF and GPI-IL-12) via protein transfer in aged mice. Lung viral replication against homologous and heterologous influenza viruses was significantly reduced in aged mice after vaccination with cytokine incorporated VLPs (HA-VLP-Cyt) in comparison to HA-VLP alone. Enhanced IFN-γ+CD4+ and IFN-γ+CD8+ T cell responses were also observed in aged mice immunized with HA-VLP-Cyt when compared to HA-VLP alone. CONCLUSIONS: Cytokine-adjuvanted influenza HA-VLP vaccine induced enhanced protective response against homologous influenza A virus infection in aged mice. Influenza HA-VLP vaccine with GPI-cytokines also induced enhanced T cell responses correlating with better protection against heterologous infection in the absence of neutralizing antibodies. The results suggest that a vaccination strategy using cytokine-adjuvanted influenza HA-VLPs could be used to enhance protection against influenza A virus in the elderly.
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OBJECTIVE: The prolonged coronavirus disease-2019 (COVID-19) pandemic is likely to cause psychological distress in people. This systematic review aimed to identify the effectiveness of virtual reality (VR)-based psychological intervention among individuals with psychological distress during the COVID-19 crisis. PubMed, Ovid MEDLINE, Cochrane Library, Web of Science, Embase, and PsycINFO databases were searched for articles published until July 2022. METHODS: The available citations were deduplicated and screened by two authors using the title and abstract information. Eligibility criteria were constructed according to the PICOT guidelines. Empirical studies of all designs and comparator groups were included if they appraised the impact of an immersive VR intervention on any standardized measure indicative of psychological distress (stress, anxiety, depression, and post-traumatic symptoms) or improvements in quality of life in participants, including COVID-19 patients, medical staff working with COVID-19 patients, and people who had experienced strict social distancing during the COVID-19 pandemic. RESULTS: The results were discussed using a narrative synthesis because of the heterogeneity between studies. Seven of the studies met the inclusion criteria. There were two randomized controlled trials and five uncontrolled studies on VR interventions. CONCLUSION: All studies reported significant improvement in a wide range of psychological distress during COVID-19, ranging from stress, anxiety, depression, and post-traumatic symptoms to quality of life, supporting the efficacy of VR-based psychological intervention. Our results suggest that VR intervention has potential to ameliorate COVID-19-related psychological distress with efficacy and safety.
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Improving electrical and optical properties is important in manufacturing high-efficiency solar cells. Previous studies focused on individual gettering and texturing methods to improve solar cell material quality and reduce reflection loss, respectively. This study presents a novel method called saw damage gettering with texturing that effectively combines both methods for multicrystalline silicon (mc-Si) wafers manufactured using the diamond wire sawing (DWS) method. Although mc-Si is not the Si material currently used in photovoltaic products, the applicability of this method using the mc-Si wafers as it contains all grain orientations is demonstrated. It utilizes saw damage sites on the wafer surfaces for gettering metal impurities during annealing. Additionally, it can crystallize amorphous silicon on wafer surfaces generated during the sawing process to allow conventional acid-based wet texturing. This texturing method and annealing for 10 min allow for the removal of metal impurities and effectively forms a textured DWS Si wafer. The results show that the open-circuit voltage (ΔVoc = +29 mV), short-circuit current density (ΔJsc = +2.5 mA cm-2 ), and efficiency (Δη = +2.1%) improved in the p-type passivated emitter and rear cells (p-PERC) manufactured using this novel method, as compared to those in the reference solar cells.
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BACKGROUND: Zika virus (ZIKV) is a mosquito-borne flavivirus classified in Flaviviridae family such as dengue (DENV), yellow fever, and West Nile virus. An outbreak of ZIKV infection can pose a major public health risk because the contagion is unpredictable and induces severe pathology such as Guillan-Barre syndrome and neonatal microcephaly. However, an authorized ZIKV vaccine is not yet available, while several vaccine candidates are under development. METHODS: In this study, we constructed a recombinant ZIKV vaccine (Z_EDIII) that includes ZIKV envelope protein domain III using E. coli expression system. Then both humoral and cellular immunity were examined in C57BL/6 (female, 8-weeks-old) mice via Indirect ELISA assay, PRNT, ELISpot and cytokine detection for IFN-γ, TNF-α, and IL-12. In addition, the cross protection against DENV was evaluated in pups from Z_EDIII vaccinated and infected dam. RESULTS: Mice immunized by Z_EDIII produced a significant amount of ZIKV EDIII-specific and neutralizing antibodies. Together with antibodies, effector cytokines, such as IFN-γ, TNF-α, and IL-12 were induced. Moreover, vaccinated females delivered the adaptive immunity to neonates who are protective against ZIKV and DENV challenge. CONCLUSIONS: This study observed Z-EDIII-induced humoral and cellular immunity that protected hosts from both ZIKV and DENV challenges. The result suggests that our ZIKV EDIII recombinant vaccine has potential to provide a new preventive strategy against ZIKV infection.
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Tuberculosis (TB) is one of the leading causes of death worldwide, consistently threatening public health. Conventional tuberculosis treatment requires a long-term treatment regimen and is associated with side effects. The efficacy of antitubercular drugs has decreased with the emergence of drug-resistant TB; therefore, the development of new TB treatment strategies is urgently needed. In this context, we present host-directed therapy (HDT) as an alternative to current tuberculosis therapy. Unlike antitubercular drugs that directly target Mycobacterium tuberculosis (Mtb), the causative agent of TB, HDT is an approach for treating TB that appropriately modulates host immune responses. HDT primarily aims to enhance the antimicrobial activity of the host in order to control Mtb infection and attenuate excessive inflammation in order to minimize tissue damage. Recently, research based on the repositioning of drugs for use in HDT has been in progress. Based on the overall immune responses against Mtb infection and the immune-evasion mechanisms of Mtb, this review examines the repositioned drugs available for HDT and their mechanisms of action.
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Balance disorders and falls are common in the elderly population. Regular balance exercises are an evidence-based physical intervention to prevent falls in older adults, while patient motivation and adherence are important factors for intervention outcome. Exergames are a relatively new, alternative intervention for physical rehabilitation as they improve balance and strength in older adults. The aims of this systematic review and meta-analysis were to assess the (1) effect of motivation factors as per the Capability, Opportunity and Motivation model of Behavior change (COM-B) on the effectiveness of exergame interventions in healthy older adults, (2) effectiveness of exergames to improve balance in older healthy adults and, (3) impact of exergames on cognitive outcomes. Results show that motivation and capability components influence the general outcome of the exergame training. Motivational factors should thus be considered when setting-up an exergame intervention. Furthermore, exergame intervention appears to be a promising training method in comparison to traditional exercise training. However, exergame training in itself might not be sufficient to improve fall risk and cognitive performance.
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Reported herein is the efficient synthesis of tetra- and tri-substituted (Z)-fluoro- and (Z)-chloro-borylalkenes by the Boron-Wittig reaction of ketones and aldehydes with bench-top stable halo-diborylmethanes. The substrate scope is broad and the Boron-Wittig reaction proceeds from a diverse range of ketones and aldehydes including biologically relevant molecules with fluoro- or chloro-diborylmethanes, providing tetra- and tri-substituted (Z)-fluoro- and (Z)-chloro-borylalkenes in good yields with high stereoselectivity. The utilities of the obtained (Z)-fluoro- and (Z)-chloro-borylalkenes are highlighted by further modifications to afford fluoroalkene derivatives or all-carbon substituted alkene.
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Alcenos , Boro , Aldeídos , Carbono , Cetonas , Estrutura Molecular , EstereoisomerismoRESUMO
BACKGROUND: This study explored the relationship between integrase strand transfer inhibitor (INSTI)-based anti-retroviral agents and weight gain over time, and the risk factors for weight gain in Korean people living with human immunodeficiency virus (PLWH). MATERIALS AND METHODS: The study was conducted retrospectively in PLWHs 18 years of age or older who took one of three INSTI-based single-tablet regimens (STRs) (tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat [TDF/F/EVG/c], tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat [TAF/F/EVG/c], and abacavir/lamivudine/dolutegravir [ABC/3TC/DTG]) for more than 2 years at three university-affiliated hospitals in South Korea from May 2014 to December 2020. Analysis was performed in the treatment-naïve and treatment-experienced groups, respectively. RESULTS: Individual INSTI-based STRs were associated with weight gain at the 24-month follow up in both treatment-naïve (n = 179) and treatment-experienced (n = 290) groups. Body mass index (BMI) categories changed over time for TAF/F/EVG/c and ABC/3TC/DTG, with significant increases in the rates of overweight and obesity in treatment-naïve patients, whereas there was no change for TDF/F/EVG/c. TAF/F/EVG/c significantly increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) compared to other regimens over 24 months. In the treatment-naïve group, a baseline CD4+ T cell count <100 cells/mm3, human immunodeficiency virus (HIV) viral load (VL) ≥100,000 copies/mL, no physical exercise, and TAF/F/EVG/c (vs. TDF/F/EVF/c) were risk factors for ≥10% weight gain. In the treatment-experienced group, age <45 years, BMI <25 kg/m², and no physical exercise were risk factors for ≥5% weight gain. CONCLUSION: INSTI-based STR continued to increase body weight at the 24-month follow up in treated and untreated Korean PLWH. Exercise, together with demographic-, HIV-, and anti-retroviral therapy-related factors, influenced weight gain. Therefore, when prescribing an INSTI-based STR, weight gain and metabolic changes should be closely monitored in PLWH with these risk factors.
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To improve cross-protection of influenza vaccination, we tested conjugation of conserved M2e epitopes to the surface of inactivated influenza virus (iPR8-M2e*). Treatment of virus with chemical cross-linker led to diminished hemagglutination activity and failure to induce hemagglutination inhibiting antibodies. Conjugated iPR8-M2e* vaccine was less protective against homologous and heterosubtypic viruses, despite the induction of virus-specific binding IgG antibodies. In alternative approaches to enhance cross-protection, we developed a genetically linked chimeric protein (M2e-B stalk) vaccine with M2e of influenza A and hemagglutinin (HA) stalk of influenza B virus. Vaccination of mice with inactivated influenza A virus supplemented with M2e-B stalk effectively induced hemagglutination inhibiting antibodies, humoral and cellular M2e immune responses, and enhanced heterosubtypic protection. This study demonstrates the importance of HA functional integrity in influenza vaccine efficacy and that supplementation of influenza vaccines with M2e-B stalk protein could be a feasible strategy of improving cross-protection against influenza viruses.
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Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Orthomyxoviridae , Animais , Anticorpos Antivirais , Proteção Cruzada , Hemaglutinação , Humanos , Influenza Humana/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: In France, the increase in COVID-19 vaccine uptake among older adults slowed down between May and June 2021. Using the data from a national survey, we aimed to assess COVID-19 vaccine uptake among French residents aged 65 years and older, particularly at risk of severe form of the infection, and identify factors associated with non-vaccination. METHODS: A cross-sectional online survey collected the immunization status/intention to get the COVID-19 vaccine, reasons for vaccination/non-vaccination and factors potentially associated with vaccine uptake between May 10 and 23, 2021 among a large sample of French residents. Characteristics of participants were compared according to immunization status. Factors potentially associated with non-vaccination were computed into a multivariate logistic regression. RESULTS: Among the 1941 survey participants, 1612 (83%) reported having received at least one dose of COVID-19 vaccine. Among the 329 unvaccinated, 197 (60%) declared having the intention to get vaccinated. Younger age (adjusted odds ratio (aOR) = 1.50; 95% confidence interval (CI), 1.05-2.14), thinking previously having COVID-19 (aOR = 4.01; 95% CI, 2.17-7.40), having suffered economic impact due to the pandemic (aOR = 2.63; 95% CI, 1.71-4.04), reporting an "unsafe" opinion about COVID-19 vaccine safety (aOR = 6.79; 95% CI, 4.50-10.26), reporting an "unsupportive" opinion about vaccination in general (aOR = 4.24; 95% CI, 2.77-6.49) were independent risk factors for non-vaccination. On the other hand, trust in COVID-19 vaccine information delivered by the doctor (aOR = 0.28; 95% CI, 0.16-0.48) and trust in the government's actions (aOR = 0.50; 95% CI, 0.34-0.74) were independent protective factors for non-vaccination. Political affiliation also remained significantly associated with vaccine uptake. CONCLUSIONS: Despite high overall COVID-19 vaccine uptake among the study participants, differences in vaccine uptake according to the level of concerns regarding COVID-19 vaccine safety, socioeconomic profile and trust in the government were observed. Our results reinforce the importance of "reaching out" vaccination strategy that specifically targets the most vulnerable fringe of older adult population.
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COVID-19 , Vacinas , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Transversais , Humanos , VacinaçãoRESUMO
PURPOSE: To propose a two-compartment renal perfusion model for calculating glomerular blood transfer rate ( k G $$ {k}_G $$ ) as a new measure of renal function. THEORY: The renal perfusion signal was divided into preglomerular and postglomerular flows according to flow velocity. By analyzing perfusion signals acquired with and without diffusion gradients, we estimated k G $$ {k}_G $$ , the blood transfer rate from the afferent arterioles into the glomerulus. METHODS: A multislice multidelay diffusion-weighted arterial spin labeling sequence was applied to subjects with no history of renal dysfunctions. In the multiple b-value experiment, images were acquired with seven b-values to validate the bi-exponential decays of the renal perfusion signal and to determine the appropriate b-value for suppressing preglomerular flow. In the caffeine challenge, six subjects were scanned twice on the caffeine day and the control day. The k G $$ {k}_G $$ values of the two dates were compared. RESULTS: The perfusion signal showed a bi-exponential decay with b-values. There was no significant difference in renal blood flow and arterial transit time between caffeine and control days. In contrast, cortical k G $$ {k}_G $$ was significantly higher on the caffeine day (caffeine day: 106 . 0 ± 20 . 3 $$ 106.0\pm 20.3 $$ min - 1 $$ {}^{-1} $$ control day: 78 . 8 ± 22 . 9 $$ 78.8\pm 22.9 $$ min - 1 $$ {}^{-1} $$ ). These results were consistent with those from the literature. CONCLUSION: We showed that the perfusion signal consists of two compartments of preglomerular flow and postglomerular flow. The proposed diffusion-weighted arterial spin labeling could measure the glomerular blood transfer rate ( k G $$ {k}_G $$ ), which was sensitive enough to noninvasively monitor the caffeine-induced vasodilation of afferent arterioles.
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Cafeína , Rim , Artérias , Humanos , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Rim/fisiologia , Circulação Renal/fisiologia , Marcadores de SpinRESUMO
In the construction and machinery industry, heat is a major factor causing damage and destruction. The safety and efficiency of most machines and structures are greatly affected by temperature, and temperature management and control are essential. In this study, a carbon nanotube (CNT) based temperature sensing coating that can be applied to machines and structures having various structural types was fabricated, and characteristics analysis and temperature sensing performance were evaluated. The surface coating, which detects temperature through resistance change is made of a nanocomposite composed of carbon nanotubes (CNT) and epoxy (EP). We investigated the electrical properties by CNT concentration and temperature sensing performance of CNT/EP coating against static and cyclic temperatures. In addition, the applicability of the CNT/EP coating was investigated through a partially heating and cooling experiment. As a result of the experiment, the CNT/EP coating showed higher electrical conductivity as the CNT concentration increased. In addition, the CNT/EP coating exhibits high sensing performance in the high and sub-zero temperature ranges with a negative temperature coefficient of resistance. Therefore, the proposed CNT/EP coatings are promising for use as multi-functional coating materials for the detection of high and freezing temperatures.
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Hemagglutinin (HA) stem-based vaccines have limitations in providing broad and effective protection against cross-group influenza viruses, despite being a promising universal vaccine target. To overcome the limited cross-protection and low efficacy by HA stem vaccination, we genetically engineered a chimeric conjugate of thermostable H1 HA stem and highly conserved M2e repeat (M2e-H1stem), which was expressed at high yields in Escherichia coli. M2e-H1stem protein presented native-like epitopes reactive to antisera of live virus infection. M2e-H1stem protein vaccination of mice induced strong M2e- and HA stem-specific immune responses, conferring broadly effective cross-protection against both antigenically distinct group 1 (H1N1, H5N1, and H9N2 subtypes) and group 2 (H3N2 and H7N9 subtypes) seasonal and pandemic potential influenza viruses. M2e-H1stem vaccination generated CD4+ and CD8+ T cell responses and antibody-dependent cytotoxic cellular and humoral immunity, which contributed to enhancing cross-protection. Furthermore, comparable broad cross-group protection was observed in older aged mice after M2e-H1stem vaccination. This study provides evidence warranting further development of chimeric M2e-stem proteins as a promising universal influenza vaccine candidate in adult and aged populations.