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An assembly between 1,4-dicarboxylbenzene-2,3-dithiol (H2dcbdt) and different transition metal ions successfully produced 2D metal-organic frameworks (M-dcbdt, M = Ni, Co or Fe) composed of unprecedented butterfly-shaped metal-bis(dithiolene) (MS4) linkers in one-pot fashion. Such strategy provides easier access to the [MS4]-rich network and lowers the prerequisite to explore their applications.
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Background: Bufei Huoxue capsule (BFHX) is widely used for the clinical treatment of chronic obstructive pulmonary disease (COPD) in China. Objectives: The aim of this study is to explore the effects on COPD and the underlying mechanism of BFHX. The process and methods: In this study, we established a COPD mouse model through cigarette smoke (CS) exposure in combination with lipopolysaccharide (LPS) intratracheal instillation. Subsequently, BFHX was orally administrated to COPD mice, and their pulmonary function, lung pathology, and lung inflammation, including bronchoalveolar lavage fluid (BALF) cell count and classification and cytokines, were analyzed. In addition, the anti-oxidative stress ability of BFHX was detected by Western blotting, and the bacterial diversity, abundance, and fecal microbiome were examined using 16S rRNA sequencing technology. Outcome: BFHX was shown to improve pulmonary function, suppress lung inflammation, decrease emphysema, and increase anti-oxidative stress, whereas 16S rRNA sequencing indicated that BFHX can dynamically regulate the diversity, composition, and distribution of the intestinal flora microbiome and regulate the lysine degradation and phenylalanine metabolism of COPD mice. These results highlight another treatment option for COPD and provide insights into the mechanism of BFHX.
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Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition that significantly impacts public health. Unfortunately, there are few effective treatment options available. Mendelian randomization (MR) has been utilized to repurpose existing drugs and identify new therapeutic targets. The objective of this study is to identify novel therapeutic targets for COPD. Methods: Cis-expression quantitative trait loci (cis-eQTL) were extracted for 4,317 identified druggable genes from genomics and proteomics data of whole blood (eQTLGen) and lung tissue (GTEx Consortium). Genome-wide association studies (GWAS) data for doctor-diagnosed COPD, spirometry-defined COPD (Forced Expiratory Volume in one second [FEV1]/Forced Vital Capacity [FVC] <0.7), and FEV1 were obtained from the cohort of FinnGen, UK Biobank and SpiroMeta consortium. We employed Summary-data-based Mendelian Randomization (SMR), HEIDI test, and colocalization analysis to assess the causal effects of druggable gene expression on COPD and lung function. The reliability of these druggable genes was confirmed by eQTL two-sample MR and protein quantitative trait loci (pQTL) SMR, respectively. The potential effects of druggable genes were assessed through the phenome-wide association study (PheWAS). Information on drug repurposing for COPD was collected from multiple databases. Results: A total of 31 potential druggable genes associated with doctor-diagnosed COPD, spirometry-defined COPD, and FEV1 were identified through SMR, HEIDI test, and colocalization analysis. Among them, 22 genes (e.g., MMP15, PSMA4, ERBB3, and LMCD1) were further confirmed by eQTL two-sample MR and protein SMR analyses. Gene-level PheWAS revealed that ERBB3 expression might reduce inflammation, while GP9 and MRC2 were associated with other traits. The drugs Montelukast (targeting the MMP15 gene) and MARIZOMIB (targeting the PSMA4 gene) may reduce the risk of spirometry-defined COPD. Additionally, an existing small molecule inhibitor of the APH1A gene has the potential to increase FEV1. Conclusions: Our findings identified 22 potential drug targets for COPD and lung function. Prioritizing clinical trials that target these identified druggable genes with existing drugs or novel medications will be beneficial for the development of COPD treatments.
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Reposicionamento de Medicamentos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doença Pulmonar Obstrutiva Crônica , Locos de Características Quantitativas , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Humanos , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Background: The prevalence of invasive pulmonary aspergillosis (IPA) among patients with chronic obstructive pulmonary disease (COPD) is steadily increasing, leading to high mortality. Although early diagnosis can significantly reduce mortality, the efficacy of current diagnostic methods is limited. Consequently, there is a need for novel approaches for early IPA detection. Methods: This retrospective study involved 383 hospitalized COPD patients with GOLD stages III and IV. The IPA group (67 patients) and non-IPA group (316 patients) were identified at the First Affiliated Hospital of Guangzhou Medical University between January 2016 and February 2022. We analyzed common serological indicators in our hospital to identify predictive indicators for the early diagnosis of IPA in COPD patients. Results: The sensitivity and specificity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), lactate dehydrogenase (LDH), and ceruloplasmin (CER) for diagnosing IPA in COPD patients were as follows: CRP (91.2%, 57.7%), ESR (77.5%, 73.0%), PCT (60.5%, 71.4%), LDH (50.0%, 88.8%), and CER (60.7%, 74.3%). Combinations of biomarkers, such as CRP-ESR, CRP-LDH, ESR-LDH, ESR-CER, and LDH-CER, showed promising diagnostic potential, with larger area under the curve (AUC) values for IPA diagnosis in COPD patients. However, no statistically significant difference was observed between the diagnostic efficacy of single biomarkers and combined biomarkers. Notably, compared to those in the unassisted ventilation group, the patients in the assisted ventilation group (including noninvasive ventilation and tracheal intubation/incision-assisted ventilation group) exhibited significantly greater PCT and LDH levels, while the CER significantly decreased (p=0.021). There were no significant differences in biomarker levels between the ICU group and the non-ICU group. CRP (p<0.01), ESR (p=0.028), PCT (p<0.01), and CER (p<0.01) were positively correlated with hospitalization duration, whereas LDH was not correlated with hospitalization duration. Conclusion: Our study highlights the diagnostic potential of CRP, ESR, PCT, LDH, and CER for IPA in COPD patients. CRP and LDH can also initially predict the need for assisted ventilation, while CRP can initially estimate the length of hospitalization. This study represents the first report of the potential of CER for diagnosing IPA, suggesting its significance for further research.
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Aspergilose Pulmonar Invasiva , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos Retrospectivos , Proteína C-Reativa/análise , Biomarcadores , Pró-CalcitoninaRESUMO
Lead (Pb) poisoning and CO2-induced global warming represent two exemplary environmental and energy issues threatening humanity. Various biomass-derived materials are reported to take up Pb and convert CO2 electrochemically into low-valent carbon species, but these works address the problems separately rather than settle the issues simultaneously. In this work, cheap, natural ellagic acid (EA) extracted from common plants is adopted to assemble a stable metal-organic framework (MOF), EA-Pb, by effective capture of Pb2+ ions in an aqueous medium (removal rate close to 99%). EA-Pb represents the first structurally well-defined Pb-based MOF showing selective electrocatalytic CO2-to-HCOO- conversion with Faradaic efficiency (FE) of 95.37% at -1.08 V versus RHE. The catalytic mechanism is studied by 13CO2 labeling, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and theoretical calculation. The use of EA-Pb as an electrocatalyst for CO2 reduction represents a 2-in-1 solution of converting detrimental wastes (Pb2+) as well as natural resources (EA) into wealth (electrocatalytic EA-Pb) for addressing the global warming issue.
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Background: Zheng's supine rehabilitation exercise (ZSRE) can be performed by elderly patients with the acute exacerbation of severe or extremely severe chronic obstructive pulmonary disease (COPD) with high safety and compliance and was helpful for their recovery. Investigation is warranted of the compliance and rehabilitation effects of ZSRE performed at home in patients with COPD. Methods: We performed telephone interviews with 157 patients with COPD who were hospitalized on the 26th floor of the National Clinical Research Center for Respiratory Disease and who received COPD education and ZSRE training from 1 September 2015 to 31 August 2016. We retrospectively analyzed the patients' compliance with performing ZSRE at home after discharge and the frequency of hospitalization for treatment of acute exacerbation in both the previous and subsequent years. Results: Among the 157 patients, 66 failed to complete home ZSRE after discharge (non-rehabilitation group), 41 performed home ZSRE once a day after discharge (one-session rehabilitation group), and 50 performed home ZSRE at least twice a day after discharge (multiple-session rehabilitation group). The home ZSRE compliance rate was 57.96% (91/157). There were no significant differences in the mean number of hospitalizations in the year prior to receiving COPD education and ZSRE training among the non-rehabilitation group (1.06±0.75), one-session rehabilitation group (1.27±0.78), and multiple-session rehabilitation group (1.16±0.91). However, there was a significant difference in the mean number of hospitalizations among the groups in the year following discharge (1.44±1.17, 0.78±0.82, and 0.66±0.75, respectively). The number of hospitalizations significantly increased in the non-rehabilitation group and significantly decreased in the one- and multiple-session rehabilitation groups. Conclusions: Home ZSRE can be performed with high compliance by elderly patients with severe or extremely severe COPD and can reduce the number of readmissions.