Durable CO2 conversion in the proton-exchange membrane system.

Electrolysis that reduces carbon dioxide (CO2) to useful chemicals can, in principle, contribute to a more sustainable and carbon-neutral future1-6. However, it remains challenging to develop this into a robust process because efficient conversion typically requires alkaline conditions in which CO2 precipitates as carbonate, and this limits carbon utilization and the stability of the system7-12. Strategies such as physical washing, pulsed operation and the use of dipolar membranes can partially alleviate these problems but do not fully resolve them11,13-15. CO2 electrolysis in acid electrolyte, where carbonate does not form, has therefore been explored as an ultimately more workable solution16-18. Herein we develop a proton-exchange membrane system that reduces CO2 to formic acid at a catalyst that is derived from waste lead-acid batteries and in which a lattice carbon activation mechanism contributes. When coupling CO2 reduction with hydrogen oxidation, formic acid is produced with over 93% Faradaic efficiency. The system is compatible with start-up/shut-down processes, achieves nearly 91% single-pass conversion efficiency for CO2 at a current density of 600 mA cm-2 and cell voltage of 2.2 V and is shown to operate continuously for more than 5,200 h. We expect that this exceptional performance, enabled by the use of a robust and efficient catalyst, stable three-phase interface and durable membrane, will help advance the development of carbon-neutral technologies.

Defining the proximal interaction networks of Arf GTPases reveals a mechanism for the regulation of PLD1 and PI4KB.

The Arf GTPase family is involved in a wide range of cellular regulation including membrane trafficking and organelle-structure assembly. Here, we have generated a proximity interaction network for the Arf family using the miniTurboID approach combined with TMT-based quantitative mass spectrometry. Our interactome confirmed known interactions and identified many novel interactors that provide leads for defining Arf pathway cell biological functions. We explored the unexpected finding that phospholipase D1 (PLD1) preferentially interacts with two closely related but poorly studied Arf family GTPases, ARL11 and ARL14, showing that PLD1 is activated by ARL11/14 and may recruit these GTPases to membrane vesicles, and that PLD1 and ARL11 collaborate to promote macrophage phagocytosis. Moreover, ARL5A and ARL5B were found to interact with and recruit phosphatidylinositol 4-kinase beta (PI4KB) at trans-Golgi, thus promoting PI4KB's function in PI4P synthesis and protein secretion.

The microbiome stabilizes circadian rhythms in the gut.

The gut microbiome is well known to impact host physiology and health. Given widespread control of physiology by circadian clocks, we asked how the microbiome interacts with circadian rhythms in the Drosophila gut. The microbiome did not cycle in flies fed ad libitum, and timed feeding (TF) drove limited cycling only in clockless per01 flies. However, TF and loss of the microbiome influenced the composition of the gut cycling transcriptome, independently and together. Moreover, both interventions increased the amplitude of rhythmic gene expression, with effects of TF at least partly due to changes in histone acetylation. Contrary to expectations, timed feeding rendered animals more sensitive to stress. Analysis of microbiome function in circadian physiology revealed that germ-free flies reset more rapidly with shifts in the light:dark cycle. We propose that the microbiome stabilizes cycling in the host gut to prevent rapid fluctuations with changing environmental conditions.

The Arf family GTPases: Regulation of vesicle biogenesis and beyond.

The Arf family proteins are best known for their roles in the vesicle biogenesis. However, they also play fundamental roles in a wide range of cellular regulation besides vesicular trafficking, such as modulation of lipid metabolic enzymes, cytoskeleton remodeling, ciliogenesis, lysosomal, and mitochondrial morphology and functions. Growing studies continue to expand the downstream effector landscape of Arf proteins, especially for the less-studied members, revealing new biological functions, such as amino acid sensing. Experiments with cutting-edge technologies and in vivo functional studies in the last decade help to provide a more comprehensive view of Arf family functions. In this review, we summarize the cellular functions that are regulated by at least two different Arf members with an emphasis on those beyond vesicle biogenesis.

Surface Redox Chemistry Regulates the Reaction Microenvironment for Efficient Hydrogen Peroxide Generation.

Electrosynthesis has emerged as an enticing solution for hydrogen peroxide (H2O2) production. However, efficient H2O2 generation encounters challenges related to the robust gas-liquid-solid interface within electrochemical reactors. In this work, we introduce an effective hydrophobic coating modified by iron (Fe) sites to optimize the reaction microenvironment. This modification aims to mitigate radical corrosion through Fe(II)/Fe(III) redox chemistry, reinforcing the reaction microenvironment at the three-phase interface. Consequently, we achieved a remarkable yield of up to 336.1 mmol h-1 with sustained catalyst operation for an extensive duration of 230 h at 200 mA cm-2 without causing damage to the reaction interface. Additionally, the Faradaic efficiency of H2O2 exceeded 90% across a broad range of test current densities. This surface redox chemistry approach for manipulating the reaction microenvironment not only advances long-term H2O2 electrosynthesis but also holds promise for other gas-starvation electrochemical reactions.

Highly Selective Electrocatalytic CO2 Conversion to Tailored Products through Precise Regulation of Hydrogenation and C-C Coupling.

The electrochemical reduction reaction of carbon dioxide (CO2RR) into valuable products offers notable economic benefits and contributes to environmental sustainability. However, precisely controlling the reaction pathways and selectively converting key intermediates pose considerable challenges. In this study, our theoretical calculations reveal that the active sites with different states of copper atoms (1-3-5-7-9) play a pivotal role in the adsorption behavior of the *CHO critical intermediate. This behavior dictates the subsequent hydrogenation and coupling steps, ultimately influencing the formation of the desired products. Consequently, we designed two model electrocatalysts comprising Cu single atoms and particles supported on CeO2. This design enables controlled *CHO intermediate transformation through either hydrogenation with *H or coupling with *CO, leading to a highly selective CO2RR. Notably, our selective control strategy tunes the Faradaic efficiency from 61.1% for ethylene (C2H4) to 61.2% for methane (CH4). Additionally, the catalyst demonstrated a high current density and remarkable stability, exceeding 500 h of operation. This work not only provides efficient catalysts for selective CO2RR but also offers valuable insights into tailoring surface chemistry and designing catalysts for precise control over catalytic processes to achieve targeted product generation in CO2RR technology.

Characterisation of SARS-CoV-2 variants in Beijing during 2022: an epidemiological and phylogenetic analysis.

BACKGROUND: Due to the national dynamic zero-COVID strategy in China, there were no persistent local transmissions of SARS-CoV-2 in Beijing before December, 2022. However, imported cases have been frequently detected over the past 3 years. With soaring growth in the number of COVID-19 cases in China recently, there are concerns that there might be an emergence of novel SARS-CoV-2 variants. Routine surveillance of viral genomes has been carried out in Beijing over the last 3 years. Spatiotemporal analyses of recent viral genome sequences compared with that of global pooled and local data are crucial for the global response to the ongoing COVID-19 pandemic. METHODS: We routinely collected respiratory samples covering both imported and local cases in Beijing for the last 3 years (of which the present study pertains to samples collected between January and December, 2022), and then randomly selected samples for analysis. Next-generation sequencing was used to generate the SARS-CoV-2 genomes. Phylogenetic and population dynamic analyses were performed using high-quality complete sequences in this study. FINDINGS: We obtained a total of 2994 complete SARS-CoV-2 genome sequences in this study, among which 2881 were high quality and were used for further analysis. From Nov 14 to Dec 20, we sequenced 413 new samples, including 350 local cases and 63 imported cases. All of these genomes belong to the existing 123 Pango lineages, showing there are no persistently dominant variants or novel lineages. Nevertheless, BA.5.2 and BF.7 are currently dominant in Beijing, accounting for 90% of local cases since Nov 14 (315 of 350 local cases sequenced in this study). The effective population size for both BA.5.2 and BF.7 in Beijing increased after Nov 14, 2022. INTERPRETATION: The co-circulation of BF.7 and BA.5.2 has been present in the current outbreak since Nov 14, 2022 in Beijing, and there is no evidence that novel variants emerged. Although our data were only from Beijing, the results could be considered a snapshot of China, due to the frequent population exchange and the presence of circulating strains with high transmissibility. FUNDING: National Key Research and Development Program of China and Strategic Priority Research Program of the Chinese Academy of Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Association of hospital-treated infectious diseases and infection burden with cardiovascular diseases and life expectancy.

BACKGROUND: The association of a broad spectrum of infectious diseases with cardiovascular outcomes remains unclear. OBJECTIVES: We aim to provide the cardiovascular risk profiles associated with a wide range of infectious diseases and explore the extent to which infections reduce life expectancy. METHODS: We ascertained exposure to 900+ infectious diseases before cardiovascular disease (CVD) onset in 453,102 participants from the UK Biobank study. Time-varying Cox proportional hazard models were used. Life table was used to estimate the life expectancy of individuals aged ≥50 with different levels of infection burden (defined as the number of infection episodes over time and the number of co-occurring infections). RESULTS: Infectious diseases were associated with a greater risk of CVD events (adjusted HR [aHR] 1.79 [95% confidence interval {CI} 1.74-1.83]). For type-specific analysis, bacterial infection with sepsis had the strongest risk of CVD events [aHR 4.76 (4.35-5.20)]. For site-specific analysis, heart and circulation infections posed the greatest risk of CVD events [aHR 4.95 (95% CI 3.77-6.50)], whereas noncardiac infections also showed excess risk [1.77 (1.72-1.81)]. Synergistic interactions were observed between infections and genetic risk score. A dose-response relationship was found between infection burden and CVD risks (p-trend <0.001). Infection burden >1 led to a CVD-related life loss at age 50 by 9.3 years [95% CI 8.6-10.3]) for men and 6.6 years [5.5-7.8] for women. CONCLUSIONS: The magnitude of the infection-CVD association showed specificity in sex, pathogen type, infection burden, and infection site. High genetic risk and infection synergistically increased the CVD risk.

Anion/Cation Co-Doping to Improve the Thermoelectric Performance of Sn-Enriched n-Type SnSe Polycrystals with Suppressed Lattice Thermal Conductivity.

Enhancing the thermoelectric performance of n-type polycrystalline SnSe is essential, addressing challenges posed by elevated thermal conductivity and compromised power factor inherent in its intrinsic p-type characteristics. This investigation utilized solid-state reactions and spark plasma sintering techniques for the synthesis of n-type SnSe. A significant improvement in the figure of merit (ZT) is achieved through strategic reduction in Se concentration and optimization of crystal orientation. The co-doping with Br and Ge further improves the material; Br amplifies carrier concentration, enhancing electrical conductivity, while Ge introduces effective phonon scattering centers. In the Br/Ge co-doped SnSe sample, thermal conductivity dropped to 0.38 Wm⁻¹K⁻¹, yielding a remarkable power factor of 662 µW mK- 2 at 773 K, culminating in a ZT of 1.34. This signifies a noteworthy 605% improvement over the pristine sample, underscoring the pivotal role of Ge doping in enhancing n-type material thermoelectric properties. The enhancement is attributed to Br doping introducing additional electronic states near the valence band, and Ge doping modifying the band structure, fostering resonant states near the conduction band. The Br/Ge co-doping further transforms the band structure, influencing electrical conductivity, Seebeck coefficient, and thermal conductivity, advancing the understanding and application of n-type SnSe materials for superior thermoelectric performance.

A nuclear pore complex-associated regulation of SUMOylation in meiosis.

The nuclear pore complex (NPC) provides a permeable barrier between the nucleoplasm and cytoplasm. In a subset of NPC constituents that regulate meiosis in the fission yeast Schizosaccharomyces pombe, we found that nucleoporin Nup132 (homolog of human Nup133) deficiency resulted in transient leakage of nuclear proteins during meiosis I, as observed in the nup132 gene-deleted mutant. The nuclear protein leakage accompanied the liberation of the small ubiquitin-like modifier (SUMO)-specific ubiquitin-like protease 1 (Ulp1) from the NPC. Ulp1 retention at the nuclear pore prevented nuclear protein leakage and restored normal meiosis in a mutant lacking Nup132. Furthermore, using mass spectrometry analysis, we identified DNA topoisomerase 2 (Top2) and RCC1-related protein (Pim1) as the target proteins for SUMOylation. SUMOylation levels of Top2 and Pim1 were altered in meiotic cells lacking Nup132. HyperSUMOylated Top2 increased the binding affinity at the centromeres of nup132 gene-deleted meiotic cells. The Top2-12KR sumoylation mutant was less localized to the centromeric regions. Our results suggest that SUMOylation of chromatin-binding proteins is regulated by the NPC-bound SUMO-specific protease and is important for the progression of meiosis.

Synergistic effects of ceftazidime/avibactam combined with meropenem in a murine model of infection with KPC-producing Klebsiella pneumoniae.

OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.

Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. METHODS: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. RESULTS: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs. CONCLUSIONS: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

Alginate oligosaccharide assimilation by gut microorganisms and the potential role in gut inflammation alleviation.

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.

Total Three-Dimensional-Guided Laparoscopic Radical Resection for Left Perihilar Cholangiocarcinoma.

BACKGROUND: The application of three-dimensional (3D) reconstruction has been extensively adopted in hepatectomy navigation,1 yet its utilization in laparoscopic radical resection of perihilar cholangiocarcinoma (pHCCA) remains underexplored. VIDEO: A 54-year-old male patient, classified as Child-Pugh B, presented a small neoplasm situated at the left hepatic duct proximate to the right hepatic and common hepatic ducts. An enhanced abdominal computed tomographic scan identified a solitary lesion measuring 2.8 × 2.4 cm. 3D reconstruction exposed tumor invasion into the left hepatic artery and left portal vein. Given the lesion's unique location, a pure laparoscopic left hepatectomy and caudate lobectomy were executed using a no-touch en block technique post patient consent. Concurrently, extrahepatic bile duct resection, radical lymphadenectomy with skeletonization, and biliary reconstruction were performed. RESULTS: The 3D reconstruction-guided laparoscopic left hepatectomy and caudate lobectomy were successfully completed in 425 min with minimal blood loss (50 mL). The histological grading was T2bN0M0 (stage II). The patient was discharged on the sixth postoperative day without complications, and postoperative treatment included mono-drug chemotherapy with capecitabine. No recurrence was observed at the 6-month follow-up. CONCLUSION: Our experience suggests that 3D reconstruction-guided laparoscopic radical resection may offer increased precision and efficiency in selected pHCCA patients. This approach can potentially yield outcomes comparable with or superior to open surgery, given standardized lymph node dissection by skeletonization, use of the no-touch en block technique, appropriate digestive tract reconstruction, and reduced bleeding and liver damage.

Laparoscopic Left Hepatectomy for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Minimally invasive surgery for intrahepatic cholangiocarcinoma (ICC) remains challenging, especially in advanced patients. PATIENT AND METHOD: A 66-year-old male was diagnosed with stage II ICC after a comprehensive evaluation and was scheduled for laparoscopic exploration and left hepatectomy. RESULTS: The pure laparoscopic left hepatectomy was completed in 240 min, employing a no-touch en bloc technique and lymphadenectomy skeletonization. The patient was discharged 6 days after the operation without any complications and received gemcitabine and cisplatin treatment postoperatively. There was no recurrence during 14 months of follow-up. CONCLUSIONS: Our experience demonstrates that when utilizing the no-touch en bloc technique, standardized lymphadenectomy through skeletonization, and effective control of bleeding, surgeons with extensive expertise in laparoscopic hepatectomy can achieve results comparable to open surgery.

Prognostic Significance of Tumor Necrosis in Patients with Gallbladder Carcinoma Undergoing Curative-Intent Resection.

BACKGROUND: Tumor necrosis has been indicated to correlate with dismal survival outcomes of a variety of solid tumors. However, the significance and prognostic value of tumor necrosis remain unclear in gallbladder carcinoma. The aim of this research is to explore the relationships between necrosis with long-term survival and tumor-related biological characteristics of patients with gallbladder carcinoma. PATIENTS AND METHODS: Patients with gallbladder carcinoma who accepted curative-intent resection in West China Hospital of Sichuan University (China) between January 2010 and December 2021 were retrospectively analyzed. Tumor necrosis was determined by staining the patient's original tissue sections with hematoxylin and eosin. Based on the presence of tumor necrosis, the pathologic features and survival outcomes were compared. RESULTS: This study enrolled 213 patients with gallbladder carcinoma who underwent curative-intent surgery, of whom 89 had tumor necrosis. Comparative analyses indicated that patients with tumor necrosis had more aggressive clinicopathological features, such as larger tumor size (p = 0.002), poorer tumor differentiation (p = 0.029), more frequent vascular invasion (p < 0.001), presence of lymph node metastasis (p = 0.014), and higher tumor status (p = 0.01), and experienced poorer survival. Univariate and multivariate analyses revealed that tumor necrosis was an independent prognostic factor for overall survival (multivariate: HR 1.651, p = 0.026) and disease-free survival (multivariate: HR 1.589, p = 0.040). CONCLUSIONS: Tumor necrosis can be considered as an independent predictive factor for overall survival and disease-free survival among individuals with gallbladder carcinoma, which was a valuable pathologic parameter.

Magnon-Skyrmion Hybrid Quantum Systems: Tailoring Interactions via Magnons.

Coherent and dissipative interactions between different quantum systems are essential for the construction of hybrid quantum systems and the investigation of novel quantum phenomena. Here, we propose and analyze a magnon-skyrmion hybrid quantum system, consisting of a micromagnet and nearby magnetic skyrmions. We predict a strong-coupling mechanism between the magnonic mode of the micromagnet and the quantized helicity degree of freedom of the skyrmion. We show that with this hybrid setup it is possible to induce magnon-mediated nonreciprocal interactions and responses between distant skyrmion qubits or between skyrmion qubits and other quantum systems like superconducting qubits. This work provides a quantum platform for the investigation of diverse quantum effects and quantum information processing with magnetic microstructures.

Hippo pathway regulation by phosphatidylinositol transfer protein and phosphoinositides.

The Hippo pathway plays a key role in development, organ size control and tissue homeostasis, and its dysregulation contributes to cancer. The LATS tumor suppressor kinases phosphorylate and inhibit the YAP/TAZ transcriptional co-activators to suppress gene expression and cell growth. Through a screen of marine natural products, we identified microcolin B (MCB) as a Hippo activator that preferentially kills YAP-dependent cancer cells. Structure-activity optimization yielded more potent MCB analogs, which led to the identification of phosphatidylinositol transfer proteins α and ß (PITPα/ß) as the direct molecular targets. We established a critical role of PITPα/ß in regulating LATS and YAP. Moreover, we showed that PITPα/ß influence the Hippo pathway via plasma membrane phosphatidylinositol-4-phosphate. This study uncovers a previously unrecognized role of PITPα/ß in Hippo pathway regulation and as potential cancer therapeutic targets.

Secondhand Smoke Exposure and Risk of Dementia in Nonsmokers: A Population-Based Cohort Study.

BACKGROUND: Large population-based prospective studies are necessary to provide clarification on the associations of panoramic secondhand smoking burden, including prenatal and postnatal secondhand smoke (SHS) exposure, with the risk of developing dementia. METHODS: Our study comprised a sample of 353,756 dementia-free individuals from the UK Biobank who were nonsmokers had data on the exposure of maternal smoking as well as SHS exposure in daily life, which was quantified in terms of hours per week (h/week) and whether they lived with household smokers. Multivariable Cox regression models were utilized to analyze the independent and joint associations of maternal smoking and daily life SHS exposure with dementia risk. RESULTS: During a median follow-up of 11.8 years, 4,113 participants developed dementia. Compared with those who lived in the environment without smokers, multivariable-adjusted hazard ratios (HRs) (95% CIs) were 1.11 (1.02, 1.20) and 1.31 (1.13, 1.52) for those who exposed to SHS for >0 but ≤4 h/week and >4 h/week, respectively, and was 1.25 (1.13, 1.39) for those who lived with smokers in the household. A positive history of maternal smoking was associated with a modestly higher risk of dementia (HR = 1.07; 95% CI: 1.01, 1.15). Furthermore, compared with participants with neither history of maternal smoking nor exposure to SHS, a particularly higher risk of dementia was observed among those with both exposures (HR = 1.48; 95% CI: 1.18, 1.86). Additionally, the HR (95% CI) was 1.32 (1.10, 1.59) when comparing participants with a history of maternal smoking who lived with smokers in their households with those who had neither exposures. CONCLUSIONS: Having a history of maternal smoking, longer exposure to SHS, and living with smokers in the household were each associated with an increased risk of developing dementia. Individuals who were simultaneously exposed to maternal smoking and SHS or lived with household smokers had a particularly higher dementia risk.