Effect and mechanism analysis of surface hydrogenation and fluorination on the electronic properties of th-GeC2.

A two-dimensional (2D) tetrahex-GeC2 nanosheet demonstrates excellent electronic properties such as a finite direct band gap and high carrier mobilities, as predicted from theoretical calculations. To further expand its potential applications, various strategies can be employed to tailor its electronic properties. These strategies include alloying, strain application, and edge and surface functionalization. This work specifically focuses on the impact of surface functionalization with hydrogen and fluorine adsorption on the 2D tetrahex-GeC2 nanostructures. It was discovered that the electronic properties of these nanostructures undergo significant alterations through surface functionalization by adjusting the adsorption sites and coverage of H/F species. The underlying mechanisms responsible for these property changes have been thoroughly analyzed and discussed in detail. Our calculations, based on density functional theory, reveal that the band gap of tetrahex-GeC2 widens as the surface coverage of H atoms increases. Conversely, the band gap narrows in the case of F adsorption. Additionally, the indirect-direct band gap transition can be triggered through surface functionalization. Such modifications in the electronic band structure are primarily due to the disappearance of the π bond when the C atom is converted from sp2 to sp3 hybridization through the adsorption of surface functionalized species. Furthermore, the results indicate that surface adsorption can regulate the effective mass of carriers, electron affinity, and work function in the 2D tetrahex-GeC2 nanostructure.

Caltrop-like Small-Molecule Antidotes That Neutralize Unfractionated Heparin and Low-Molecular-Weight Heparin In Vivo.

Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs) are widely applied for surgical procedures and extracorporeal therapies, which, however, suffer bleeding risk. Protamine, the only clinically approved antidote, can completely neutralize UFH, but only partially neutralizes LMWHs, and also has a number of safety drawbacks. Here, we show that caltrop-like multicationic small molecules can completely neutralize both UFH and LMWHs. In vitro and ex vivo assays with plasma and whole blood and in vivo assays with mice and rats support that the lead compound is not only superior to protamine by displaying higher neutralization activity and broader therapeutic windows but also biocompatible. The effective neutralization dose and the maximum tolerated dose of the lead compound are determined to be 0.4 and 25 mg/kg in mice, respectively, suggesting good promise for further preclinical studies.

Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor.

Cellular senescence is acknowledged as a key contributor to organismal ageing and late-life disease. Though popular, the study of senescence in vitro can be complicated by the prolonged and asynchronous timing of cells committing to it and by its paracrine effects. To address these issues, we repurposed a small molecule inhibitor, inflachromene (ICM), to induce senescence to human primary cells. Within 6 days of treatment with ICM, senescence hallmarks, including the nuclear eviction of HMGB1 and -B2, are uniformly induced across IMR90 cell populations. By generating and comparing various high throughput datasets from ICM-induced and replicative senescence, we uncovered a high similarity of the two states. Notably though, ICM suppresses the pro-inflammatory secretome associated with senescence, thus alleviating most paracrine effects. In summary, ICM rapidly and synchronously induces a senescent-like phenotype thereby allowing the study of its core regulatory program without confounding heterogeneity.

2D TiS2-Nanosheet-Coated Concave Gold Arrays with Triple-Coupled Resonances as Sensitive SERS Substrates.

Herein, a hybrid substrate for surface-enhanced Raman scattering (SERS) is fabricated, which couples localized surface plasmon resonance (LSPR), charge transfer (CT) resonance, and molecular resonance. Exfoliated 2D TiS2 nanosheets with semimetallic properties accelerate the CT with the tested analytes, inducing a remarkable chemical mechanism enhancement. In addition, the LSPR effect is coupled with a concave gold array located underneath the thin TiS2 nanosheet, providing a strong electromagnetic enhancement. The concave gold array is prepared by etching silicone nanospheres assembled on larger polystyrene nanospheres, followed by depositing a gold layer. The LSPR intensity near the gold layer can be adjusted by changing the layer thickness to couple the molecular and CT resonances, in order to maximize the SERS enhancement. The best SERS performance is recorded on TiS2-nanosheet-coated plasmonic substrates, with a detectable methylene blue concentration down to 10-13 m and an enhancement factor of 2.1 × 109 and this concentration is several orders of magnitude lower than that of the TiS2 nanosheet (10-11 m) and plasmonic substrates (10-9 m). The present hybrid substrate with triple-coupled resonance further shows significant advantages in the label-free monitoring of curcumin (a widely applied drug for treating multiple cancers and inflammations) in serum and urine.

Polypyrrole regulates Active Sites in Co-based Catalyst in Direct Borohydride Fuel Cells.

Direct borohydride fuel cells (DBFCs) convert borohydride (NaBH4) chemical energy into clean electricity. However, catalytic active site deactivation in NaBH4 solution limits their performance and stability. We propose a strategy to regulate active sites in Co-based catalysts using polypyrrole modification (Co-PX catalyst) to enhance electrochemical borohydride oxidation reaction (eBOR). As an anode catalyst, the synthesized Co-PX catalyst exhibits excellent eBOR performance in DBFCs, with current density of 280 mA ⋅ cm-2 and power density of 151 mW ⋅ cm-2, nearly twice that of the unmodified catalyst. The Co-PX catalyst shows no degradation after 120-hour operation, unlike the rapidly degrading control. In-situ electrochemical attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIRS) and density functional theory (DFT) suggest that polypyrrole-modified carbon support regulate the charge distribution, increasing oxidation state and optimizing adsorption/desorption of intermediates. A possible reaction pathway is proposed. This work presents a promising strategy for efficient polymer-modulated catalysts in advanced DBFCs.

K6-linked ubiquitylation marks formaldehyde-induced RNA-protein crosslinks for resolution.

Reactive aldehydes are produced by normal cellular metabolism or after alcohol consumption, and they accumulate in human tissues if aldehyde clearance mechanisms are impaired. Their toxicity has been attributed to the damage they cause to genomic DNA and the subsequent inhibition of transcription and replication. However, whether interference with other cellular processes contributes to aldehyde toxicity has not been investigated. We demonstrate that formaldehyde induces RNA-protein crosslinks (RPCs) that stall the ribosome and inhibit translation in human cells. RPCs in the messenger RNA (mRNA) are recognized by the translating ribosomes, marked by atypical K6-linked ubiquitylation catalyzed by the RING-in-between-RING (RBR) E3 ligase RNF14, and subsequently resolved by the ubiquitin- and ATP-dependent unfoldase VCP. Our findings uncover an evolutionary conserved formaldehyde-induced stress response pathway that protects cells against RPC accumulation in the cytoplasm, and they suggest that RPCs contribute to the cellular and tissue toxicity of reactive aldehydes.

The impacts of thermal heterogeneity across microhabitats on post-settlement selection of intertidal mussels.

Rapid genetic selection is critical for allowing natural populations to adapt to different thermal environments such as those that occur across intertidal microhabitats with high degrees of thermal heterogeneity. To address the question of how thermal regimes influence selection and adaptation in the intertidal black mussel Mytilisepta virgata, we continuously recorded environmental temperatures in both tidal pools and emergent rock microhabitats and then assessed genetic differentiation, gene expression patterns, RNA editing level, and cardiac performance. Our results showed that the subpopulations in the tidal pool and on emergent rocks had different genetic structures and exhibited different physiological and molecular responses to high-temperature stress. These results indicate that environmental heterogeneity across microhabitats is important for driving genetic differentiation and shed light on the importance of post-settlement selection for adaptively modifying the genetic composition and thermal responses of these intertidal mussels.

Unveiling novel perspectives on niche differentiation and plasticity in rhizosphere phosphorus forms of submerged macrophytes with different stoichiometric homeostasis.

Stoichiometric homeostasis is the ability of organisms to maintain their element composition through various physiological mechanisms, regardless of changes in nutrient availability. Phosphorus (P) is a critical limiting element for eutrophication. Submerged macrophytes with different stoichiometric homeostasis regulated sediment P pollution by nutrient resorption, but whether and how P homeostasis and resorption in submerged macrophytes changed under variable plant community structure was unclear. Increasing evidence suggests that rhizosphere microbes drive niche overlap and differentiation for different P forms to constitute submerged macrophyte community structure. However, a greater understanding of how this occurs is required. This study examined the process underlying the metabolism of different rhizosphere P forms of submerged macrophytes under different cultivation patterns by analyzing physicochemical data, basic plant traits, microbial communities, and transcriptomics. The results indicate that alkaline phosphatase serves as a key factor in revealing the existence of a link between plant traits (path coefficient = 0.335, p < 0.05) and interactions with rhizosphere microbial communities (average path coefficient = 0.362, p < 0.05). Moreover, this study demonstrates that microbial communities further influence the niche plasticity of P by mediating plant root P metabolism genes (path coefficient = 0.354, p < 0.05) and rhizosphere microbial phosphorus storage (average path coefficient = 0.605, p < 0.01). This research not only contributes to a deeper comprehension of stoichiometric homeostasis and nutrient dynamics but also provides valuable insights into potential strategies for managing and restoring submerged macrophyte-dominated ecosystems in the face of changing nutrient conditions.

Exploring the adaptability of the secondary structure of mRNA to temperature in intertidal snails based on SHAPE experiments.

RNA-based thermal regulation is an important strategy for organisms to cope with temperature changes. Inhabiting the intertidal rocky shore, a key interface of the ocean, atmosphere and terrestrial environments, intertidal species have developed variable thermal adaptation mechanisms; however, adaptions at the RNA level remain largely uninvestigated. To examine the relationship between mRNA structural stability and species distribution, in the present study, the secondary structure of cytosolic malate dehydrogenase (cMDH) mRNA of Echinolittorina malaccana, Echinolittorina radiata and Littorina brevicula was determined using selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE), and the change in folding free energy of formation (ΔGfold) was calculated. The results showed that ΔGfold increased as the temperature increased. The difference in ΔGfold (ΔΔGfold) between two specific temperatures (25 versus 0°C, 37 versus 0°C and 57 versus 0°C) differed among the three species, and the ΔΔGfold value of E. malaccana was significantly lower than those of E. radiata and L. brevicula. The number of stems of cMDH mRNA of the snails decreased with increasing temperature, and the breakpoint temperature of E. malaccana was the highest among these. The number of loops was also reduced with increasing temperature, while the length of the loop structure increased accordingly. Consequently, these structural changes can potentially affect the translational efficiency of mRNA. These results imply that there were interspecific differences in the thermal stability of RNA secondary structures in intertidal snails, and these differences may be related to snail distribution.

A model description of beta oscillations in the external globus pallidus.

The external globus pallidus (GPe), a subcortical nucleus located in the indirect pathway of the basal ganglia, is widely considered to have tight associations with abnormal beta oscillations (13-30 Hz) observed in Parkinson's disease (PD). Despite that many mechanisms have been put forward to explain the emergence of these beta oscillations, however, it is still unclear the functional contributions of the GPe, especially, whether the GPe itself can generate beta oscillations. To investigate the role played by the GPe in producing beta oscillations, we employ a well described firing rate model of the GPe neural population. Through extensive simulations, we find that the transmission delay within the GPe-GPe pathway contributes significantly to inducing beta oscillations, and the impacts of the time constant and connection strength of the GPe-GPe pathway on generating beta oscillations are non-negligible. Moreover, the GPe firing patterns can be significantly modulated by the time constant and connection strength of the GPe-GPe pathway, as well as the transmission delay within the GPe-GPe pathway. Interestingly, both increasing and decreasing the transmission delay can push the GPe firing pattern from beta oscillations to other firing patterns, including oscillation and non-oscillation firing patterns. These findings suggest that if the transmission delays within the GPe are at least 9.8 ms, beta oscillations can be produced originally in the GPe neural population, which also may be the origin of PD-related beta oscillations and should be regarded as a promising target for treatments for PD.

Multistep Dissolution of Lamellar Crystals Generates Superthin Amorphous Ni(OH)2 Catalyst for UOR.

Urea oxidation reaction (UOR) is an ideal replacement of the conventional anodic oxygen evolution reaction (OER) for efficient hydrogen production due to the favorable thermodynamics. However, the UOR activity is severely limited by the high oxidation potential of Ni-based catalysts to form Ni3+ , which is considered as the active site for UOR. Herein, by using in situ cryoTEM, cryo-electron tomography, and in situ Raman, combined with theoretical calculations, a multistep dissolution process of nickel molybdate hydrate is reported, whereby NiMoO4 ·xH2 O nanosheets exfoliate from the bulk NiMoO4 ·H2 O nanorods due to the dissolution of Mo species and crystalline water, and further dissolution results in superthin and amorphous nickel (II) hydroxide (ANH) flocculus catalyst. Owing to the superthin and amorphous structure, the ANH catalyst can be oxidized to NiOOH at a much lower potential than conventional Ni(OH)2 and finally exhibits more than an order of magnitude higher current density (640 mA cm-2 ), 30 times higher mass activity, 27 times higher TOF than those of Ni(OH)2 catalyst. The multistep dissolution mechanism provides an effective methodology for the preparation of highly active amorphous catalysts.

Effectiveness analysis of multiple epidemic prevention measures in the context of COVID-19 using the SVIRD model and ensemble Kalman filter.

The ability to accurately forecast the spread of coronavirus disease 2019 (COVID-19) is of great importance to the resumption of societal normality. Existing methods of epidemic forecasting often ignore the comprehensive analysis of multiple epidemic prevention measures. This paper aims to analyze various epidemic prevention measures through a compound framework. Here, a susceptible-vaccinated-infected-recovered-deceased (SVIRD) model is constructed to consider the effects of population mobility among origin and destination, vaccination, and positive retest populations. And we further use real-time observations to correct the model trajectory with the help of data assimilation. Seven prevention measures are used to analyze the short-term trend of active cases. The results of the synthetic scene recommended that four measures-improving the vaccination protection rate (IVPR), reducing the number of contacts per person per day (RNCP), selecting the region with less infected people as origin A (SES-O) and limiting population flow entering from A to B per day (LAIP-OD)-are the most effective in the short-term, with maximum reductions of 75%, 53%, 35% and 31%, respectively, in active cases after 150 days. The results of the real-world experiment with Hong Kong as the origin and Shenzhen as the destination indicate that when the daily vaccination rate increased from 5% to 9.5%, the number of active cases decreased by only 7.35%. The results demonstrate that reducing the number of contacts per person per day after productive life resumes is more effective than increasing vaccination rates.

Acetylation of citrate synthase inhibits Bombyx mori nucleopolyhedrovirus propagation by affecting energy metabolism.

Many studies have confirmed that virus infection cause changes in the expression level and post-translational modifications of tricarboxylic acid cycle (TCA) enzymes. In a previous study, we found that the acetylation level of lysine 336 of Bombyx mori citrate synthase (BmCS) was remarkably unregulated after Bombyx mori nucleopolyhedrovirus (BmNPV) infection. In the present study, we found that BmN cells infected with BmNPV could up-regulate BmCS transient expression and promote the acetylation modification of BmCS. Transient expression vectors for over-expression of wild-type Bmcs and K336 acetylation mimic mutant (K336Q) were constructed to analyze enzyme activity, revealing that acetylation of K336 significantly reduced its activity. The obtained results indicated that BmCS knock-down or K336 acetylation similarly suppressed BmN cellular ATP production and mitochondrial membrane potential. Furthermore, the acetylation of K336 and the reduction of BmCS expression contributed to weakening the replication lever of the BmNPV proliferation and the generation of progeny viruses. In sum, our study on the single lysine 336 acetylation and knock-down of Bmcs revealed the potential mechanism for inhibiting the proliferation of BmNPV, which may provide novel insights for the development of antiviral strategies.

A miniaturized electrochemical device based on the nitrogen, carbon-codoped bimetal for real-time monitoring of acetaminophen and dopamine in urine.

In-situ real-time detection of drug metabolites and biomolecules in hospitalized patients' urine helps the doctors to monitor their physiological indicators and regulate the use of drug doses. In this work, nitrogen-doped carbon-supported bimetal was prepared into the screen-printed electrodes (SPEs) and applied for real-time monitoring of acetaminophen (AC) and dopamine (DA) in urine. Via one-step pyrolysis of the core-shell cubic precursor (Cu3[Co(CN)6]2@Co3[Co(CN)6]2, CuCo@CoCo), the nitrogen-doped carbon-supported bimetal (CuCo-NC) was formed. The bimetal composites presented twice higher catalytic activity than the counterparts with single metal. In addition, the nanocomposites exhibited strong conductivity after pyrolysis, promoting electron transport efficiency as indicated by impedance measurements. Accordingly, the CuCo-NC based sensor offered excellent sensitivity with the detection limits down to 50 nM and 30 nM at the detection range of 0.1-400 µM and 0.2-200 µM for detection of AC and DA, respectively. Finally, in combination with a miniaturized electrochemical device, the sensor was applied for in-situ real-time monitoring of AC and DA in the urinary bag for up to 12h. As compared with other techniques such as high-performance liquid chromatography, UV-spectrophotometry and fluorescence spectrometer, the biosensor demonstrated the advantages of real-time monitoring, easy operation and excellent portability. However, the multi-component detection and self-calibration function need to be further developed. This method paves a way for the continuous monitoring of drug metabolites and biomolecules of hospitalized patients.

Acetylation of fructose-bisphosphate aldolase-mediated glycolysis is essential for Bombyx mori nucleopolyhedrovirus infection.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a baculovirus that infects silkworms, and its interaction with silkworm has been considered an important model in the field of insect virology. Accumulating evidence indicates that most viruses promote glycolytic metabolism in host cells to favor infection. However, similar reports are lacking in insects, especially in the area of post-translational modifications of proteins. In this study, we found that BmNPV infection induced the acetylation of fructose-bisphosphate aldolase (ALDO) on lysine 42 (K42) to promote its enzyme activity. To explore the underlying mechanisms, site-directed mutagenesis of deacetylated mimic (K/R) was performed. The results demonstrated that K42 acetylation promoted viral proliferation by exacerbating the glycolytic flux induced by BmNPV infection, which resulted in increased ATP, glucose uptake and lactate accumulation. Inhibiting glycolysis with 2-deoxygucose (2DG) revealed that glycolysis was essential for optimal BmNPV infection. Finally, we showed that BmNPV-infected cells enhanced the transcription of glycolysis-related genes, including Glut1, Hk2 and Ldh. In parallel, K42 acetylation of ALDO also promoted the expression of these genes. Therefore, acetylation of ALDO could be considered a regulator of BmNPV-induced glycolysis. These finding provide insights into the interaction between silkworm and BmNPV.

Maternal High-Fat Diet Aggravates Allergic Asthma in Offspring via Modulating CD4+ T-Cell Differentiation.

Maternal improper nutrition has been reported to trigger respiratory disorders in offspring. Here, we characterized the effects of high-fat environment in the fetal period on mice and human cord blood CD4+ T-lymphocytes, and investigated their roles in susceptibility to asthma. Mice born to mothers that consumed a high-fat diet (HFD) throughout the gestation period were sensitized by ovalbumin to establish an experimental asthma model. To further extrapolate to humans, we collected cord blood from neonates of hypercholesterolemic (HC) mothers (n = 18) and control mothers (n = 20). In mice, aggravated airway hyperresponsiveness and inflammation revealed that maternal high-fat diet could lead to exacerbated allergic asthma in adult offspring. It was partially due to augmented activation and proliferation of CD4+ T-cells, where upregulated klf2 mRNA levels may be potentially involved. Notably, naïve HFD CD4+ T-cells had enhanced TH2-based immune response both in vivo and in vitro, resulting from DNA hypomethylation of the Il-4 promoter region. Moreover, in human, TH2 cytokines transcripts were enhanced in CD4+ T-cells of the HC group, which was associated with an increased risk of developing allergic diseases at 3 years old. Together, our study indicated that early life improper nutrition-triggered epigenetic changes in T-cells may contribute to long-lasting alterations in allergic diseases.

Investigating the association of environmental exposures and all-cause mortality in the UK Biobank using sparse principal component analysis.

Multicollinearity refers to the presence of collinearity between multiple variables and renders the results of statistical inference erroneous (Type II error). This is particularly important in environmental health research where multicollinearity can hinder inference. To address this, correlated variables are often excluded from the analysis, limiting the discovery of new associations. An alternative approach to address this problem is the use of principal component analysis. This method, combines and projects a group of correlated variables onto a new orthogonal space. While this resolves the multicollinearity problem, it poses another challenge in relation to interpretability of results. Standard hypothesis testing methods can be used to evaluate the association of projected predictors, called principal components, with the outcomes of interest, however, there is no established way to trace the significance of principal components back to individual variables. To address this problem, we investigated the use of sparse principal component analysis which enforces a parsimonious projection. We hypothesise that this parsimony could facilitate the interpretability of findings. To this end, we investigated the association of 20 environmental predictors with all-cause mortality adjusting for demographic, socioeconomic, physiological, and behavioural factors. The study was conducted in a cohort of 379,690 individuals in the UK. During an average follow-up of 8.05 years (3,055,166 total person-years), 14,996 deaths were observed. We used Cox regression models to estimate the hazard ratio (HR) and 95% confidence intervals (CI). The Cox models were fitted to the standardised environmental predictors (a) without any transformation (b) transformed with PCA, and (c) transformed with SPCA. The comparison of findings underlined the potential of SPCA for conducting inference in scenarios where multicollinearity can increase the risk of Type II error. Our analysis unravelled a significant association between average noise pollution and increased risk of all-cause mortality. Specifically, those in the upper deciles of noise exposure have between 5 and 10% increased risk of all-cause mortality compared to the lowest decile.

Noninvasive Diagnosis of Gastric Cancer Based on Breath Analysis with a Tubular Surface-Enhanced Raman Scattering Sensor.

SERS-based breath analysis as an emerging technique has attracted increasing attention in cancer screening. Here, eight aldehydes and ketones in the human breath are reported as the VOC biomarkers identified by gas chromatography-mass spectrometry (GC-MS) and applied further for the noninvasive diagnosis of gastric cancer (GC) with a tubular SERS sensor. The tubular SERS sensor is prepared with a glass capillary loaded with ZIF-67-coated silver particles (Ag@ZIF-67), which offers Raman enhancement from the plasmonic nanoparticles and gas enrichment from the metal-organic framework (MOF) shells. The composite materials are modified with 4-aminothiophenol (4-ATP) to capture different aldehyde and ketone compounds. The tubular sensor is served simultaneously as a gas flow channel and a detection chamber, bringing a higher gas capture efficiency than the planar SERS sensor. As a proof-of-concept, the tubular SERS sensor is successfully employed to screen gastric cancer patients with an accuracy of 89.83%, based on the noninvasive, rapid, and easily operated breath analysis. The results demonstrate that the established breath analysis method provides an excellent alternative for the screening of GC and other diseases.

Acetylation of late expression factor 4 is crucial for the transcription and proliferation of Bombyx mori nucleopolyhedrovirus.

Late expression factor 4 (LEF4), RNA polymerase subunit of Bombyx mori nucleopolyhedrovirus (BmNPV), plays an enzymatic role to enhance the capping of pre-mRNA of late and very late genes. Lysine acetylation is a post-translational modification process having many important functions associated with the regulation of a gene expression. Our previous study on lysine acetylome in BmNPV infected BmN cells showed that LEF 4 was acetylated at lysine 76 (K76). However, it is still unclear whether the modification of K76 residue contributes to the modulation of viral gene transcription. To elucidate the role played by acetylation or deacetylation of LEF4 K76 in the transcription of viral genes, we constructed acetylation mimicking and deacetylation mimicking mutant virus, K76Q and K76R, respectively. We then transfected BmN cells with these mutants and analyzed the level of pre-mRNA at different times. The K76R showed a significant decrease in the mRNA transcription level of vp39 and p10 genes at 48 and 72 h post-transfection, while K76Q did not show any significant changes compared with lef4-Wt. We further detected the virus titer of lef4-Wt, K76Q [et] K76R, and it was found that K76R impaired the virus infectivity ability at 72 and 96 h, while K76Q did not affect the virus infectivity. Moreover, the yeast two hybrid technique (Y2H) showed that both mutants (K76Q [et] K76R) affected the association of LEF 4 with the P47 protein. Taken together, these results indicated that acetylation modification of K76 is important for the proper transcription of late and very late genes, and the effectiveness of viral infection. Keywords: BmNPV lef4 gene; lysine acetylation, late genes transcription; BmNPV p47 gene; infectivity.

Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an increasingly important cause of morbidity, disability, and mortality worldwide. We aimed to estimate global, regional, and national COPD prevalence and risk factors to guide policy and population interventions. METHODS: For this systematic review and modelling study, we searched MEDLINE, Embase, Global Health, and CINAHL, for population-based studies on COPD prevalence published between Jan 1, 1990, and Dec 31, 2019. We included data reported using the two main case definitions: the Global Initiative for Chronic Obstructive Lung Disease fixed ratio (GOLD; FEV1/FVC<0·7) and the lower limit of normal (LLN; FEV1/FVC