ABSTRACT
Heterogeneous high-valent cobalt-oxo [≡Co(IV)=O] is a widely focused reactive species in oxidant activation; however, the relationship between the catalyst interfacial defects and ≡Co(IV)=O formation remains poorly understood. Herein, photoexcited oxygen vacancies (OVs) were introduced into Co3O4 (OV-Co3O4) by a UV-induced modification method to facilitate chlorite (ClO2-) activation. Density functional theory calculations indicate that OVs result in low-coordinated Co atom, which can directionally anchor chlorite under the oxygen-atom trapping effect. Chlorite first undergoes homolytic O-Cl cleavage and transfers the dissociated O atom to the low-coordinated Co atom to form reactive ≡Co(IV)=O with a higher spin state. The reactive ≡Co(IV)=O rapidly extracts one electron from ClO2- to form chlorine dioxide (ClO2), accompanied by the Co atom returning a lower spin state. As a result of the oxygen-atom trapping effect, the OV-Co3O4/chlorite system achieved a 3.5 times higher efficiency of sulfamethoxazole degradation (~0.1331 min-1) than the pristine Co3O4/chlorite system. Besides, the refiled OVs can be easily restored by re-exposure to UV light, indicating the sustainability of the oxygen atom trap. The OV-Co3O4 was further fabricated on a polyacrylonitrile membrane for back-end water purification, achieving continuous flow degradation of pollutants with low cobalt leakage. This work presents an enhancement strategy for constructing OV as an oxygen-atom trapping site in heterogeneous advanced oxidation processes and provides insight into modulating the formation of ≡Co(IV)=O via defect engineering.
ABSTRACT
Organic semiconductors (OSCs) are one of the most promising candidates for flexible, wearable and large-area electronics. However, the development of n-type OSCs has been severely held back due to the poor stability of their most candidates, that is, the intrinsically high reactivity of negatively charged polarons to oxygen and water. Here we demonstrate a general strategy based on vitamin C to stabilize n-type OSCs, remarkably improving the performance and stability of their device, for example, organic field-effect transistors. Vitamin C scavenges reactive oxygen species and inhibits their generation by sacrificial oxidation and non-sacrificial triplet quenching in a cascade process, which not only lastingly prevents molecular structure from oxidation damage but also passivates the latent electron traps to stabilize electron transport. This study presents a way to overcome the long-standing stability problem of n-type OSCs and devices.
ABSTRACT
Most of the nanozymes have been obtained based on trial and error, for which the application is usually compromised by enzymatic activity regulation due to a vague catalytic mechanism. Herein, a hollow axial Mo-Pt single-atom nanozyme (H-MoN5@PtN4/C) is constructed by a two-tier template capture strategy. The axial ligand can induce Mo 4d orbital splitting, leading to a rearrangement of spin electrons (↑ ↑ â ↑↓) to regulate enzymatic activity. This creates catalase-like activity and enhances oxidase-like activity to catalyze cascade enzymatic reactions (H2O2 â O2 â O2â¢-), which can overcome tumor hypoxia and accumulate cytotoxic superoxide radicals (O2â¢-). Significantly, H-MoN5@PtN4/C displays destructive d-π conjugation between the metal and substrate to attenuate the restriction of orbitals and electrons. This markedly improves enzymatic performance (catalase-like and oxidase-like activity) of a Mo single atom and peroxidase-like properties of a Pt single atom. Furthermore, the H-MoN5@PtN4/C can deplete overexpressed glutathione (GSH) through a redox reaction, which can avoid consumption of ROS (O2â¢- and â¢OH). As a result, H-MoN5@PtN4/C can overcome limitations of a complex tumor microenvironment (TME) for tumor-specific therapy based on TME-activated catalytic activity.
Subject(s)
Electrons , Ligands , Humans , Platinum/chemistry , Catalase/chemistry , Catalase/metabolism , Catalysis , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/metabolism , Glutathione/chemistry , Glutathione/metabolism , Nanostructures/chemistryABSTRACT
Single-atom enzymes (SAzymes) exhibit great potential for chemodynamic therapy (CDT); while, general application is still challenged by their instability and unavoidable side effects during delivery. Herein, a manganese-based polyoxometalate single-atom enzyme (Mn-POM SAE) is first introduced into tumor-specific CDT, which exhibits tumor microenvironment (TME)-activated transition of nontoxicity-to-toxicity. Different from traditional POM materials, the aggregates of low-toxic Mn-POM SAE nanospheres are obtained at neutral conditions, facilitating efficient delivery and avoiding toxicity problems in normal tissues. Under acid TME conditions, these nanospheres are degraded into smaller units of toxic Mn(II)-PW11; thus, initiating cancer cell-specific therapy. The released active units of Mn(II)-PW11 exhibit excellent multienzyme-like activities (including peroxidase (POD)-like, oxidase (OXD)-like, catalase (CAT)-like, and glutathione peroxidase (Gpx)-like activities) for the synergistic cancer therapy due to the stabilized high valence Mn species (MnIII/MnIV). As demonstrated by both intracellular evaluations and in vivo experiments, ROS is generated to cause damage to lysosome membranes, further facilitating acidification and impaired autophagy to enhance cancer therapy. This study provides a detailed investigation on the acid-triggered releasing of active units and the electron transfer in multienzyme-mimic-like therapy, further enlarging the application of POMs from catalytical engineering into cancer therapy.
Subject(s)
Neoplasms , Tungsten Compounds , Tungsten Compounds/chemistry , Tungsten Compounds/pharmacology , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Animals , Tumor Microenvironment/drug effects , Manganese/chemistry , Cell Line, Tumor , Enzymes/metabolism , Enzymes/chemistry , Nanospheres/chemistry , Mice , Reactive Oxygen Species/metabolism , Hydrogen-Ion Concentration , Polyelectrolytes , AnionsABSTRACT
Human adenovirus (HAdV) is a significant viral pathogen causing severe acute respiratory infections (SARIs) in children. To improve the understanding of type distribution and viral genetic characterization of HAdV in severe cases, this study enrolled 3404 pediatric SARI cases from eight provinces of China spanning 2017-2021, resulting in the acquisition of 112 HAdV strains. HAdV-type identification, based on three target genes (penton base, hexon, and fiber), confirmed the diversity of HAdV types in SARI cases. Twelve types were identified, including species B (HAdV-3, 7, 55), species C (HAdV-1, 2, 6, 89, 108, P89H5F5, Px1/Ps3H1F1, Px1/Ps3H5F5), and E (HAdV-4). Among these, HAdV-3 exhibited the highest detection rate (44.6%), followed by HAdV-7 (19.6%), HAdV-1 (12.5%), and HAdV-108 (9.8%). All HAdV-3, 7, 55, 4 in this study belonged to dominant lineages circulating worldwide, and the sequences of the three genes demonstrated significant conservation and stability. Concerning HAdV-C, excluding the novel type Px1/Ps3H1F1 found in this study, the other seven types were detected both in China and abroad, with HAdV-1 and HAdV-108 considered the two main types of HAdV-C prevalent in China. Two recombinant strains, including P89H5F5 and Px1/Ps3H1F1, could cause SARI as a single pathogen, warranting close monitoring and investigation for potential public health implications. In conclusion, 5 years of SARI surveillance in China provided crucial insights into HAdV-associated respiratory infections among hospitalized pediatric patients.
Subject(s)
Adenovirus Infections, Human , Adenoviruses, Human , Respiratory Tract Infections , Child , Humans , Adenoviruses, Human/genetics , Sequence Analysis, DNA/methods , Phylogeny , Adenoviridae/genetics , China/epidemiology , Respiratory Tract Infections/epidemiologyABSTRACT
Förster resonance energy transfer (FRET) has been widely applied in fluorescence imaging, sensing and so on, while developing useful strategy of boosting FRET efficiency becomes a key issue that limits the application. Except optimizing spectral properties, promoting orientation factor (κ2) has been well discussed but rarely utilized for boosting FRET. Herein, we constructed binary nano-assembling of two thermally activated delayed fluorescence (TADF) emitters (2CzPN and DMAC-DPS) with J-type aggregate of cyanine dye (C8S4) as doping films by taking advantage of their electrostatic interactions. Time-resolved spectroscopic measurements indicated that 2CzPN/Cy-J films exhibit an order of magnitude higher kFRET than DMAC-DPS/Cy-J films. Further quantitative analysing on kFRET and kDET indicated higher orientation factor (κ2) in 2CzPN/Cy-J films play a key role for achieving fast kFRET, which was subsequently confirmed by anisotropic measurements. Corresponding DFT/TDDFT calculation revealed strong "two-point" electrostatic anchoring in 2CzPN/Cy-J films that is responsible for highly orientated transitions. We provide a new strategy for boosting FRET in nano-assemblies, which might be inspired for designing FRET-based devices of sensing, imaging and information encryption.
ABSTRACT
Nanozymes have shown great promise in reactive oxygen species (ROS)-mediated tumor therapy with mitigated side effects but are normally limited by the complex tumor microenvironment (TME). Herein, to overcome the adverse effects of TME, such as tumor hypoxia and high endogenous glutathione (GSH), an aptamer-functionalized Pd@MoO3-x nano-hydrangea (A-Pd@MoO3-x NH) is constructed for high-efficiency cancer therapy. Utilizing the irregular shape characteristics of nano Pd, the A-Pd@MoO3-x NH nanozyme simultaneously exposes catalase-like Pd(111) and oxidase-like Pd(100) surface facets as dual active centers. This can catalyze cascade enzymatic reactions to overcome the negative effects of tumor hypoxia caused by the accumulation of cytotoxic superoxide (O2â¢-) radicals in TME without any external stimuli. In addition, the nanozyme can effectively degrade the overexpressed glutathione (GSH) through the redox reaction to avoid nontherapeutic consumption of O2â¢- radicals. More significantly, as a reversible electron station, MoO3-x can extract electrons from H2O2 decomposing on Pd(111) or GSH degradation and transfer them back to Pd(100) through oxygen bridges or few Mo-Pd bonds. This can synergistically enhance enzyme-like activities of dual active centers and the GSH-degrading ability to enrich O2â¢- radicals. In this way, the A-Pd@MoO3-x NH nanozyme can selectively and remarkably kill tumor cells while keeping the normal cell line unharmed.
Subject(s)
Electrons , Neoplasms , Humans , Hydrogen Peroxide , Catalysis , Cell Line , Glutathione , Neoplasms/drug therapy , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
The genomic landscape of recombination plays an essential role in evolution. Patterns of recombination are highly variable along chromosomes, between sexes, individuals, populations, and species. In many eukaryotes, recombination rates are elevated in sub-telomeric regions and drastically reduced near centromeres, resulting in large low-recombining (LR) regions. The processes of recombination are influenced by genetic factors, such as different alleles of genes involved in meiosis and chromatin structure, as well as external environmental stimuli like temperature and overall stress. In this work, we focused on the genomic landscapes of recombination in a collection of 916 rye (Secale cereale) individuals. By analysing population structure among individuals of different domestication status and geographic origin, we detected high levels of admixture, reflecting the reproductive biology of a self-incompatible, wind-pollinating grass species. We then analysed patterns of recombination in overlapping subpopulations, which revealed substantial variation in the physical size of LR regions, with a tendency for larger LR regions in domesticated subpopulations. Genome-wide association scans (GWAS) for LR region size revealed a major quantitative-trait-locus (QTL) at which, among 18 annotated genes, an ortholog of histone H4 acetyltransferase ESA1 was located. Rye individuals belonging to domesticated subpopulations showed increased synaptonemal complex length, but no difference in crossover frequency, indicating that only the recombination landscape is different. Furthermore, the genomic region harbouring rye ScESA1 showed moderate patterns of selection in domesticated subpopulations, suggesting that larger LR regions were indirectly selected for during domestication to achieve more homogeneous populations for agricultural use.
ABSTRACT
We demonstrate an isotropic device called 540-degree deflecting lens, which has symmetric refractive index and can deflect parallel beam by 540 degrees. The expression of its gradient refractive index is obtained and generalized. We discover it's an optical absolute instrument with self-imaging characteristic. Using conformal mapping, we deduce its general version in one-dimensional space. We also introduce a combined lens called the generalized inside-out 540-degree deflecting lens similar to the inside-out Eaton lens. Ray tracing and wave simulations are used to demonstrate their characteristics. Our study expands the family of absolute instruments and provides new ideas to design optical systems.
ABSTRACT
Reactions in confined spaces exhibit unique reactivity, while how the confinement effect enhances reactions remains unclear. Herein, the reaction in the confined space of a nanopipette reactor was examined by in situ nano-electrospray mass spectrometry (nanoESI-MS). The indole cation-radical cyclization was selected as the model reaction, catalyzed by a common visible-light-harvesting complex Ru(bpz)3(PF6)2 (1% eq.) rather than traditional harsh reaction conditions (high temperature or pressure, etc.). As demonstrated by in situ nanoESI-MS, this reaction was readily promoted in the nanopipette under mild conditions, while it was inefficient in both normal flasks and microdroplets. Both experimental and theoretical evidence demonstrated the formation of concentrated Ru(II)-complexes on the inner surface of the nanopipette, which facilitated the accelerated reactions. As a result, dissociative reactive cation radicals with lower HOMO-LUMO gap were generated from the Ru(II)-complexes by ligand-to-metal charge transfer (LMCT). Furthermore, the crucial cation radical intermediates were captured and dynamically monitored via in situ nanoESI-MS, responsible for the electronically matched [4 + 2] cycloaddition and subsequent intramolecular dehydrogenation. This work inspires a deeper understanding of the unique reactions in confined spaces.
Subject(s)
Ruthenium , Spectrometry, Mass, Electrospray Ionization , Cyclization , Spectrometry, Mass, Electrospray Ionization/methods , Light , Cations/chemistry , Ruthenium/chemistryABSTRACT
Accurately controlling catalytic activity and mechanism as well as identifying structure-activity-selectivity correlations in Fenton-like chemistry is essential for designing high-performance catalysts for sustainable water decontamination. Herein, active center size-dependent catalysts with single cobalt atoms (CoSA), atomic clusters (CoAC), and nanoparticles (CoNP) were fabricated to realize the changeover of catalytic activity and mechanism in peroxymonosulfate (PMS)-based Fenton-like chemistry. Catalytic activity and durability vary with the change in metal active center sizes. Besides, reducing the metal size from nanoparticles to single atoms significantly modulates contributions of radical and nonradical mechanisms, thus achieving selective/nonselective degradation. Density functional theory calculations reveal evolutions in catalytic mechanisms of size-dependent catalytic systems over different Gibbs free energies for reactive oxygen species generation. Single-atom site contact with PMS is preferred to induce nonradical mechanisms, while PMS dissociates and generates radicals on clusters and nanoparticles. Differences originating from reaction mechanisms endow developed systems with size-dependent selectivity and mineralization for treating actual hospital wastewater in column reactors. This work brings an in-depth understanding of metal size effects in Fenton-like chemistry and guides the design of intelligent catalysts to fulfill the demand of specific scenes for water purification.
Subject(s)
Cobalt , Decontamination , Catalysis , WaterABSTRACT
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common respiratory critical syndrome that currently has no effective therapeutic interventions. Pulmonary macrophages play a principal role in the initiation and progression of the overwhelming inflammation in ALI/ARDS. Here, a type of fluorous-tagged bioactive peptide nanoparticle termed CFF13F is developed, which can be efficiently internalized by macrophages and suppress the excessive expression of cytokines and the overproduction of reactive oxygen species (ROS) triggered by lipopolysaccharide (LPS). The cytoprotective effect of CFF13F may be attributed to the lysosomal-stabilization property and regulation of the antioxidative system. Moreover, intratracheal pretreatment with CFF13F can effectively reduce local and systematic inflammation, and ameliorate pulmonary damage in an LPS-induced ALI murine model. The therapeutic efficacy of CFF13F is affected by the administration routes, and the local intratracheal injection is found to be the optimal choice for ALI treatment, with preferred biodistribution profiles. The present study provides solid evidence of the potent immunomodulatory bioactivity of the fluorous-tagged peptide nanoparticles CFF13F in vitro and in vivo, and sheds light on the development of novel efficient nanodrugs for ALI/ARDS.
Subject(s)
Acute Lung Injury , Nanoparticles , Respiratory Distress Syndrome , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Animals , Cytokines/metabolism , Disease Models, Animal , Inflammation/drug therapy , Inflammation/metabolism , Lipopolysaccharides/pharmacology , Lung , Lysosomes/metabolism , Macrophages, Alveolar , Mice , Mice, Inbred C57BL , Reactive Oxygen Species/metabolism , Tissue DistributionABSTRACT
AIMS: To examine the differences in decisional conflict, decision regret, self-stigma and quality of life among breast cancer survivors who chose different surgeries, as well as the effects of decisional conflict, decision regret and self-stigma on quality of life. DESIGN: Observational study. METHODS: Paper and online surveys were used to collect data from March to September 2020. The Chinese version of the Decisional Conflict Scale, Decision Regret Scale, Self-Stigma Form and Functional Assessment of Cancer Treatment-B were used to measure the corresponding health outcomes for breast cancer survivors who chose different surgeries from three university-affiliated hospitals. One-way analysis of variance, Pearson's correlation coefficient and hierarchical multiple regression analysis were used for data analysis. RESULTS: Among the 448 participants, only 21% chose breast conservative surgery, while 79% chose mastectomy with or without reconstruction. Women who chose mastectomy with reconstruction reported higher decisional conflict (p = .028) and more decision regret (p = .013) than women who chose breast conservative surgery; women who chose mastectomy without reconstruction indicated higher decisional conflict (p = .015), more decision regret (p < .001), and higher self-stigma (p = .034) than women who chose breast conservative surgery. Decisional conflict (r = -.430), decision regret (r = -.495), and self-stigma (r = -.561) were negatively correlated with quality of life. After controlling for sociodemographic and clinical variables, decisional conflict and decision regret explained 19.7% and self-stigma explained 12.9% of the variance in quality of life. CONCLUSION: Decisional conflict, decision regret and self-stigma vary according to different breast surgeries and are greatly associated with the quality of life of breast cancer survivors. IMPACT: Future studies are warranted to investigate the decision-making process and the underlying reasons for surgical choices. Decision support strategies pre-surgery are needed to inform women about the risks and benefits of surgery options. Moreover, psychosocial support post-surgery is warranted to relieve women's self-stigma, thus improving their quality of life.
Subject(s)
Breast Neoplasms , Cancer Survivors , Breast Neoplasms/psychology , Breast Neoplasms/surgery , Cross-Sectional Studies , Decision Making , Emotions , Female , Humans , Mastectomy/psychology , Quality of LifeABSTRACT
Applying organic-inorganic hybrid perovskite quantum dots (PQDs) to photocatalytic nitrogen fixation is hindered long-term by the inherent instability in water and tedious preparations. Here, to realize PQD-catalyzed photocatalytic N2 reduction reaction (NRR), water-resistant PQDs are simply prepared through one-step electrospray synthesis in microseconds. During the fast electrospray, PQDs of Zn/PbO-doped methylammonium lead bromide (Zn/PbO/PC-Zn/MAPbBr3 , MA: CH3 NH3 ) are prepared and part-encapsulated by polycarbonate. The synthesis maintains good water resistance, whose restriction on charge transport is overcome skillfully. Simultaneously, substitution of Zn with Pb on water-resistant surface is also achieved, which fabricates new Zn-oxygen vacancies (Zn-OVs) with Zn/PbO-Zn/MAPbBr3 type I heterojunction. This facilitates efficient electron transfer from internal heterojunction interface of Zn/MAPbBr3 PQDs to the surface of Zn/PbO. Demonstrated by theoretical calculations, Zn-OVs promote chemisorption and polarization of N2 . In addition, s-electrons in exposed Zn become active due to changes of electron filling of Zn orbitals under OVs' co-doping. Thus, photocatalytic N2 reduction reaction catalyzed by organic-inorganic hybrid PQDs is first achieved in aqueous phase without sacrificial agents being added. This initiates possibilities for photocatalytic applications of organic-inorganic hybrid PQDs in aqueous phase.
Subject(s)
Quantum Dots , Calcium Compounds , Nitrogen Fixation , Oxides , Oxygen , Titanium , Water , ZincABSTRACT
Combining solution-based and surface-assisted synthesis, we demonstrate the first synthesis of NBN-doped bis-tetracene (NBN-BT) and peri-tetracene (NBN-PT). The chemical structures are clearly elucidated by high-resolution scanning tunneling microscopy (STM) in combination with noncontact atomic force microscopy (nc-AFM). Scanning tunneling spectroscopy (STS) characterizations reveal that NBN-BT and NBN-PT possess higher energy gaps than bis-tetracene and peri-tetracene. Interestingly, NBN-BT can undergo stepwise one-electron oxidation and convert into its corresponding radical cation and then to its dication. The energy gap of the NBN-BT dication is similar to that of bis-tetracene, indicating their isoelectronic relationship. Moreover, a similar energy gap between the NBN-PT dication and peri-tetracene can be predicted by DFT calculations. This work provides a novel synthesis along with characterizations of multi-NBN-doped zigzag-edged peri-acenes with tunable electronic properties.
ABSTRACT
Understanding and controlling isomerization at the single molecular level should provide new insight into the molecular dynamics and design guidelines of functional devices. Scanning tunneling microscopy (STM) has been demonstrated to be a powerful tool to study isomerization of single molecules on a substrate, by either electric field or inelastic electron tunneling mechanisms. A similar molecular isomerization process can in principle be induced by mechanical force; however, relevant study has remained elusive. Here, we demonstrate that isomerization of a N,N-dimethylamino-dianthryl-benzene molecule on Ag(100) can be mechanically driven by the STM tip. The existence of an out-of-plane dimethylamino group in the molecule is found to play a pivotal role in the isomerization process by providing a steric hindrance effect for asymmetric interaction between the STM tip and the molecule. This underlying mechanism is further confirmed by performing molecular dynamics simulations, which show agreement with experimental results. Our work opens the opportunity to manipulate the molecular configuration on the basis of mechanical force.
ABSTRACT
We report the first bottom-up synthesis of NBN-doped zigzag-edged GNRs (NBN-ZGNR1 and NBN-ZGNR2) through surface-assisted polymerization and cyclodehydrogenation based on two U-shaped molecular precursors with an NBN unit preinstalled at the zigzag edge. The resultant zigzag-edge topologies of GNRs are elucidated by high-resolution scanning tunneling microscopy (STM) in combination with noncontact atomic force microscopy (nc-AFM). Scanning tunneling spectroscopy (STS) measurements and density functional theory (DFT) calculations reveal that the electronic structures of NBN-ZGNR1 and NBN-ZGNR2 are significantly different from those of their corresponding pristine fully-carbon-based ZGNRs. Additionally, DFT calculations predict that the electronic structures of NBN-ZGNRs can be further tailored to be gapless and metallic through one-electron oxidation of each NBN unit into the corresponding radical cations. This work reported herein provides a feasible strategy for the synthesis of GNRs with stable zigzag edges yet tunable electronic properties.
ABSTRACT
Recently, the emergence of photoactive metal-organic frameworks (MOFs) has given great prospects for their applications as photocatalytic materials in visible-light-driven hydrogen evolution. Herein, a highly photoactive visible-light-driven material for H2 evolution was prepared by introducing methylthio terephthalate into a MOF lattice via solvent-assisted ligand-exchange method. Accordingly, a first methylthio-functionalized porous MOF decorated with Pt co-catalyst for efficient photocatalytic H2 evolution was achieved, which exhibited a high quantum yield (8.90 %) at 420â nm by use sacrificial triethanolamine. This hybrid material exhibited perfect H2 production rate as high as 3814.0â µmol g-1 h-1 , which even is one order of magnitude higher than that of the state-of-the-art Pt/MOF photocatalyst derived from aminoterephthalate.
ABSTRACT
BACKGROUND: Chronic diseases such as chronic obstructive pulmonary disease (COPD) have been linked to low levels of physical activity (PA) and higher frequency of leisure sedentary behavior (LSB). The main causes of COPD include respiratory and peripheral muscle dysfunction, low levels of PA, and LSB which are associated with a higher risk of developing COPD. The attribution relationship between PA or LSB and COPD risk or COPD respiratory insufficiency is unclear. To explore this further, we conducted a Mendelian randomization (MR) study using a genotype-simulated randomized trial group to systematically evaluate the causal relationships of PA/LSB on COPD risk and respiratory insufficiency. METHODS: The exposure data were obtained from large-scale genome-wide association studies (GWAS), including the PA dataset (N = 729,373) and LSB dataset (N = 1,109,337). The outcome data were derived from the Finn-Gen COPD dataset (N = 381,392). The causal effects were estimated with IVW1, MR-Egger, and WM2. Sensitivity analysis was conducted using Cochran's Q test, MR-Egger intercept test, MR-PRESSO3, leave-one-out analysis, and funnel plot to estimate the robustness of our findings. RESULTS: Genetically predicted leisure television (TV) watching significantly increased the risk of COPD (OR = 2.4895, 95 % CI: 1.85259 to 3.34536; P = 1.44 × 10-9) and COPD respiratory insufficiency (OR = 2.55, 95 % CI: 1.53 to 4.27; P = 3.54 × 10-4). No casual effect of other PA or LSB phenotypes on COPD risk or respiratory insufficiency was observed. CONCLUSION: Our study provides evidence that TV watching may increase the risk of COPD and its related respiratory insufficiency. These findings emphasized the importance of promoting regular physical exercise and reducing leisure sedentary behavior to prevent COPD.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Respiratory Insufficiency , Humans , Sedentary Behavior , Genome-Wide Association Study , Mendelian Randomization Analysis , Exercise , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/genetics , Leisure ActivitiesABSTRACT
BACKGROUND AND MAIN BODY: Although interactions between the nervous and immune systems have been recognized decades ago, it has become increasingly appreciated that neuroimmune crosstalk is among the driving factors of multiple pulmonary inflammatory diseases including acute lung injury (ALI). Here, we review the current understanding of nerve innervations towards the lung and summarize how the neural regulation of immunity and inflammation participates in the onset and progression of several lung diseases, especially ALI. We then present advancements in the development of potential drugs for ALI targeting neuroimmune interactions, including cholinergic anti-inflammatory pathway, sympathetic-immune pathway, purinergic signalling, neuropeptides and renin-angiotensin system at different stages from preclinical investigation to clinical trials, including the traditional Chinese medicine. CONCLUSION: This review highlights the importance of considering the therapeutic strategy of inflammatory diseases within a conceptual framework that integrates classical inflammatory cascade and neuroimmune circuits, so as to deepen the understanding of immune modulation and develop more sophisticated approaches to treat lung diseases represented by ALI. KEY POINTS: The lungs present abundant nerve innervations. Neuroimmune interactions exert a modulatory effect in the onset and progression of lung inflammatory diseases, especially acute lung injury. The advancements of potential drugs for ALI targeting neuroimmune crosstalk at different stages from preclinical investigation to clinical trials are elaborated. Point out the direction for the development of neuroimmune pharmacology in the future.