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1.
Small ; : e2400978, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38593307

RESUMEN

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.

2.
Small ; 19(17): e2207266, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36693790

RESUMEN

Exploiting clean energy is essential for sustainable development and sunlight-driven photocatalytic water splitting represents one of the most promising approaches toward this goal. Metal-organic frameworks (MOFs) are competent photocatalysts owing to their tailorable functionality, well-defined structure, and high porosity. Yet, the introduction of the unambiguous metal-centered active site into MOFs is still challenging since framework motifs capable of anchoring metal ions firmly are lacking. Herein, the assembly using 1,4-dicarboxylbenzene-2,3-dithiol (H2 dcbdt) and Zr-Oxo clusters to give a thiol-functionalized UiO-66 type framework, UiO-66-dcbdt, is reported. The thiocatechols on the struts are allowed to capture transition metal (TM) ions to generate UiO-66-dcbdt-M (M  = Fe, Ni, Cu) with unambiguous metal-thiocatecholate moieties for photocatalytic hydrogen evolution reaction (HER). UiO-66-dcbdt-Cu is found the best catalyst exhibiting an HER rate of 4.18 mmol g-1  h-1  upon irradiation with photosensitizing Ru-polypyridyl complex. To skip the use of the external sensitizer, UiO-66-dcbdt-Cu is heterojunctioned with titanium dioxide (TiO2 ) and achieves an HER rate of 12.63 mmol g-1  h-1  (32.3 times that of primitive TiO2 ). This work represents the first example of MOF assembly employing H2 dcbdt as the mere linker followed by chelation with TM ions and undoubtedly fuels the rational design of MOF photocatalysts bearing well-defined active sites.

3.
Inorg Chem ; 62(13): 5229-5236, 2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-36960995

RESUMEN

A robust and porous Ni-based metal-organic framework (MOF), NiL1, was assembled from Ni(II) ions and a dipyrazolate linker (L12-). A Ni(II)-anchored MOF catalyst Ni@NiL1-Sal has been successfully prepared by post-synthetic modification (PSM) condensation between NiL1 with salicylaldehyde, followed by chelation of Ni(II) ions by salicylaldimine as a secondary active site. Ni@NiL1-Sal with carbon black was found to exhibit enhanced electrocatalytic hydrogen evolution reaction (HER) performance (the smallest overpotential, 384 mV, and Tafel slope, 87 mV dec-1) when compared with primitive NiL1 and NiL1-Sal. Such improvement in HER highlights the creation of unambiguous secondary active sites as an avenue to the rational design of a functional MOF-based electrocatalyst.

4.
Inorg Chem ; 61(36): 14352-14360, 2022 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-36026539

RESUMEN

The useful yet underutilized backfolded design is invoked here for functionalizing porous solids with the versatile carbazole function. Specifically, we attach carbazole groups as backfolded side arms onto the backbone of a linear dicarboxyl linker molecule. The bulky carbazole side arms point away from the carboxyl links and do not disrupt the Zr-carboxyl framework formation; namely, the resultant MOF solid ZrL1 features the same net as that of the unfunctionalized dicarboxyl linker, also known as the PCN-111 net or UiO-66 net. The ZrL1 structure features only half linker occupancy (about 6 out of the 12 linkers around the Zr6O8 cluster being missing) and partially collapses upon activation (acetone exchange and evacuation). Notably, the stability improves after heating in diphenyl oxide at 260 °C (POP-260 treatment; to form ZrL1-260), as indicated by the higher crystallinity and surface area of the activated ZrL1-260 sample. The ZrL1-260 samples achieve 72% yield in photocatalyzing reductive dehalogenation of phenacyl bromide; ZrL1 can detect nitro-aromatic compounds via fluorescence quenching, with selectivity and sensitivity toward 4-nitroaniline, featuring a limit of detection of 96 ppb.


Asunto(s)
Estructuras Metalorgánicas , Compuestos Organometálicos , Carbazoles , Fluorescencia , Estructuras Metalorgánicas/química , Nitrocompuestos , Compuestos Organometálicos/química , Ácidos Ftálicos
5.
Inorg Chem ; 61(48): 19475-19482, 2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-36414025

RESUMEN

Bearing triazine-centered linkers, three primitive metal-organic frameworks (MOFs) with a Zr6O4 cluster have been prepared as ZrL1 (without any branch), ZrL2 (with -F), and ZrL3 (with -SCH3). The electrocatalytic hydrogen evolution reaction (HER) by their pristine and transition metal-loaded (TM-loaded) forms was studied. It was found that the loading of TM ions could enhance the electrocatalytic power of these TM-loaded MOFs in HER, as reflected by their lower overpotentials and smaller Tafel slopes when compared with primitive MOFs. More importantly, the best electrocatalytic HER performance of ZrL3-TM among all TM-loaded MOFs studied in this work highlights the effective housing of TM ions for unambiguous active sites through cooperative coordination by triazinic N and thioether pendants. This work proposes microenvironment regulation of MOFs as an effective strategy to enhance the electrocatalytic activity of MOF materials.


Asunto(s)
Estructuras Metalorgánicas , Elementos de Transición , Hidrógeno , Iones , Triazinas
6.
Respir Res ; 22(1): 149, 2021 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-33985501

RESUMEN

BACKGROUND: To investigate whether the administration of hydrogen/oxygen mixture was superior to oxygen in improving symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: This prospective, randomized, double-blind, controlled clinical trial in 10 centres enrolled patient with AECOPD and a Breathlessness, Cough, and Sputum Scale (BCSS) score of at least 6 points. Eligible patients were randomly assigned (in a 1:1 ratio) to receive either hydrogen/oxygen mixture or oxygen therapy. Primary endpoint was the change from baseline in BCSS score at day 7. Adverse events (AEs) were recorded to evaluate safety. RESULTS: Change of BCSS score in Hydrogen/oxygen group was larger than that in Oxygen group (- 5.3 vs. - 2.4 point; difference: - 2.75 [95% CI - 3.27 to - 2.22], meeting criteria for superiority). Similar results were observed in other time points from day 2 through day 6. There was a significant reduction of Cough Assessment Test score in Hydrogen/oxygen group compared to control (- 11.00 vs. - 6.00, p < 0.001). Changes in pulmonary function, arterial blood gas and noninvasive oxygen saturation did not differ significantly between groups as well as other endpoints. AEs were reported in 34 (63.0%) patients in Hydrogen/oxygen group and 42 (77.8%) in Oxygen group. No death and equipment defects were reported during study period. CONCLUSIONS: The trial demonstrated that hydrogen/oxygen therapy is superior to oxygen therapy in patient with AECOPD with acceptable safety and tolerability profile. TRIAL REGISTRATION: Name of the registry: U.S National Library of Medicine Clinical Trials; Trial registration number: NCT04000451; Date of registration: June 27, 2019-Retrospectively registered; URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/study/NCT04000451?term=04000451&draw=2&rank=1 .


Asunto(s)
Hidrógeno/administración & dosificación , Pulmón/fisiopatología , Terapia por Inhalación de Oxígeno , Enfermedad Pulmonar Obstructiva Crónica/terapia , Administración por Inhalación , Anciano , China , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Hidrógeno/efectos adversos , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno/efectos adversos , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Factores de Tiempo , Resultado del Tratamiento
7.
Inorg Chem ; 60(8): 5757-5763, 2021 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-33787239

RESUMEN

The infusion of metal guests into (i.e., metalating) the porous medium of metal-organic frameworks (MOFs) is a topical approach to wide-ranging functionalization purposes. We report the notable interactions of AgSbF6 guests with the designer MOF host ZrL1 [Zr6O4(OH)7(L1)4.5(H2O)4]. (1) The heavy-atom guests of AgSbF6 induce order in the MOF host to allow the movable alkyne side arm to be fully located by X-ray diffraction, but they themselves curiously remain highly disordered and absent in the strucutral model. The enhanced order of the framework can be generally ascribed to interaction of the silver guests with the host alkyne and thioether functions, while the invisible heavy-atom guest represents a new phenomenon in the metalation of open framework materials. (2) The AgSbF6 guests also participate in the thermocyclization of the vicinal alkyne units of the L1 linker (at 450 °C) and form the rare nanoparticle of Ag3Sb supported on the concomitantly formed nanographene network. The resulted composite exhibits high electrical conductivity (1.0 S/cm) as well as useful, mitigated catalytic activity for selectively converting nitroarenes into the industrially important azo compounds, i.e., without overshooting to form the amine side products. The heterogeneous/cyclable catalysis entails only the cheap reducing reagents of NaBH4, ethanol, and water, with yields being generally close to 90%.

8.
Inorg Chem ; 60(22): 17315-17324, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34735125

RESUMEN

Using a carbon-rich designer metal-organic framework (MOF), we open a high-yield synthetic strategy for iron-nitrogen-doped carbon (Fe-N-C) nanotube materials that emulate the electrocatalysis performance of commercial Pt/C. The Zr(IV)-based MOF solid boasts multiple key functions: (1) a dense array of alkyne units over the backbone and the side arms, which are primed for extensive graphitization; (2) the open, branched structure helps maintain porosity for absorbing nitrogen dopants; and (3) ferrocene units on the side arms as atomically dispersed precursor catalyst for targeting micropores and for effective iron encapsulation in the carbonized product. As a result, upon pyrolysis, over 89% of the carbon component in the MOF scaffold is successfully converted into carbonized products, thereby contrasting the easily volatilized carbon of most MOFs. Moreover, over 97% of the iron ends up being encased as acid-resistant Fe/Fe3C nanoparticles in carbon nanotubes/carbon matrices.

9.
Inorg Chem ; 60(1): 161-166, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-33306390

RESUMEN

The cruciform linker molecule here features two designer functions: the pyrazole donors for framework construction, and the vicinal alkynyl units for benzannulation to form nanographene units into the Ni8-pyrazolate scaffold. Unlike the full 12 connections of the Ni8(OH)4(H2O)2 clusters in other Ni8-pyrazolate networks, significant linker deficiency was observed here, leaving about half of the Ni(II) sites capped by acetate ligands, which can be potentially removed to open the metal sites for reactivity. The crystalline Ni8-pyrazolate scaffold also retains the crystalline order even after thermal treatments (up to 300 °C) that served to partially graphitize the neighboring alkyne units. The resultant nanographene components enhance the electroactive properties of the porous hosts, achieving hydrogen evolution reaction (HER) activity that rivals that of topical nickel/palladium-enabled materials.

10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(10): 955-960, 2021 Oct 10.
Artículo en Zh | MEDLINE | ID: mdl-34625931

RESUMEN

OBJECTIVE: To explore the clinical characteristics and prognostic values of TP53 gene variant in patients with acute leukemia(AL). METHODS: The clinical data of 44 newly diagnosed AL patients with TP53 variant detected by next generation sequencing (NGS) were analyzed retrospectively. Targeted sequencing technique containing 108 leukemia-related genes was used for variant analysis, and conventional R-banding technique was used for karyotype analysis. The clinical features, cytogenetics, gene variant, curative effect and survival of AL patients with TP53 gene variant were analyzed. RESULTS: The median age of AML patients with TP53 gene variant (46 years) was higher than that of ALL patients (17.5 years), and the median number of bone marrow blasts (40.5%) was lower than the latter (89.2%), the differences were statistically significant (P< 0.01). A total of 28 cases of abnormal karyotype were detected, of which 25 cases were complex karyotype, 16 cases were monomeric karyotype, 14 cases had -17/17p-. The detection rates of TP53 in complex karyotype, monomeric karyotype and -17/17p- were 59.5%, 38.1% and 33.3%, respectively. Subgroup analysis showed that the detection rate of TP53 gene abnormalities in AML and ALL complex karyotypes was 73.1% and 40% respectively, the difference was statistically significant. A total of 41 TP53 gene variant types were found, and the median variant frequency was 43.58%. 75.6% variant was located in the DNA binding domain. The concomitant variant genes were mainly TET2 and IKZF1. Among 18 AML and 17 ALL patients who could be evaluated the curative effect, the CR rate of one course of treatment was 22.2% and 94.12% respectively, and the difference was statistically significant. The median RFS of 4 cases of AML with CR and 16 cases of ALL with CR were 174 and 246 days respectively, the difference was statistically insignificant. The median OS of AML and ALL was 20 and 375 days respectively, the difference was statistically significant. CONCLUSION: The TP53 gene variant is associated with the complex karyotype of AML, but has no significant effect on ALL. The variant site of TP53 gene was mainly distributed in the DNA binding domain. The remission rate of AML with TP53 gene variant was lower than that of ALL. The prognosis of AL patients with TP53 gene variant is poor, so allogeneic hematopoietic stem cell transplantation should be performed as soon as possible to prolong the survival of the patients.


Asunto(s)
Leucemia Mieloide Aguda , Proteína p53 Supresora de Tumor , Enfermedad Aguda , Humanos , Leucemia Mieloide Aguda/genética , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/genética
11.
Angew Chem Int Ed Engl ; 60(21): 12116-12123, 2021 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-33723915

RESUMEN

Solid-state lithium metal batteries built with composite polymer electrolytes using cubic garnets as active fillers are particularly attractive owing to their high energy density, easy manufacturing and inherent safety. However, the uncontrollable formation of intractable contaminant on garnet surface usually aggravates poor interfacial contact with polymer matrix and deteriorates Li+ pathways. Here we report a rational designed intermolecular interaction in composite electrolytes that utilizing contaminants as reaction initiator to generate Li+ conducting ether oligomers, which further emerge as molecular cross-linkers between inorganic fillers and polymer matrix, creating dense and homogeneous interfacial Li+ immigration channels in the composite electrolytes. The delicate design results in a remarkable ionic conductivity of 1.43×10-3  S cm-1 and an unprecedented 1000 cycles with 90 % capacity retention at room temperature is achieved for the assembled solid-state batteries.

12.
Inorg Chem ; 59(8): 5626-5631, 2020 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-32233407

RESUMEN

Finely dispersed Co(0) and CoO species were efficiently loaded into a stable metal-organic framework to impart catalytic activities to the porous solid. The metalation of the MOF host is facilitated by the dense arrays of accessible alkyne units that boost the alkyne-Co2(CO)8 interaction. The tetrakis(4-carboxylphenylethynyl)pyrene linker, with eight symmetrically backfolded alkyne side arms, features strong fluorescence and a dendritic Sierpinski shape. The resultant Zr(IV)-MOF features NU-901 topology (scu net, with rhombus channels) and breathing properties (e.g., the contracted (porous) phase reverts to the as-made phase upon contact with DMF (dimethylformamide)). The inserted Co2(CO)8 guests quickly react with air to form atomically dispersed CoO species (nondiffracting), and subsequent thermal treatment at 600 °C of the CoO-loaded solid generates an electrocatalyst for the oxygen evolution reaction (OER).

13.
Epidemiol Infect ; 148: e132, 2020 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-32611465

RESUMEN

Hubei province in China has had the most confirmed coronavirus disease 2019 (COVID-19) cases and has reported sustained transmission of the disease. Although Lu'an city is adjacent to Hubei province, its community transmission was blocked at the early stage, and the impact of the epidemic was limited. Therefore, we summarised the overall characteristics of the entire epidemic course in Lu'an to help cities with a few imported cases better contain the epidemic. A total of 69 confirmed COVID-19 cases and 11 asymptomatic carriers were identified in Lu'an during the epidemic from 12 January to 21 February 2020. Fifty-two (65.0%) cases were male, and the median age was 40 years. On admission, 56.5% of cases had a fever as the initial symptom, and pneumonia was present in 89.9% of cases. The mean serial interval and the mean duration of hospitalisation were 6.5 days (95% CI: 4.8-8.2) and 18.2 days (95% CI: 16.8-19.5), respectively. A total of 16 clusters involving 60 cases (17 first-generation cases and 43 secondary cases) were reported during the epidemic. We observed that only 18.9% (7/37) index cases resulted in community transmission during the epidemic in Lu'an, indicating that the scale of the epidemic was limited to a low level in Lu'an city. An asymptomatic carrier caused the largest cluster, involving 13 cases. Spread of COVID-19 by asymptomatic carriers represents an enormous challenge for countries responding to the pandemic.


Asunto(s)
Portador Sano/virología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Adolescente , Adulto , Anciano , COVID-19 , Portador Sano/epidemiología , Portador Sano/transmisión , Niño , Preescolar , China/epidemiología , Ciudades/epidemiología , Análisis por Conglomerados , Infecciones por Coronavirus/transmisión , Femenino , Fiebre , Humanos , Lactante , Tiempo de Internación , Masculino , Persona de Mediana Edad , Neumonía Viral/transmisión , Vigilancia de la Población/métodos , Factores de Tiempo , Adulto Joven
14.
Org Biomol Chem ; 17(24): 6032-6037, 2019 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-31165853

RESUMEN

We synthesized self-similar molecules (G3 and G2; based on phenylalkynyl backbones) with symmetrically backfolded shapes inspired by the famous fractal of a Sierpinski triangle. Unlike the more traditional, starburst dendrimers, the centripetal-shaped Sierpinski molecules feature side branches symmetrically bent away from the growth direction of the main branch, thus contrasting the natural-tree shape. Molecule G3 exhibits three distinct levels of the structural hierarchy comprising the primary, secondary and tertiary branches, while the smaller G2 contains only features of the 1st and 2nd orders. In spite of the much larger conjugated backbone of G3, its solution UV-vis absorption and fluorescence exhibit no red shift relative to G2. In a test of nitrobenzene sensing, a thin film of G3 deposited from THF was more sensitively quenched in fluorescence than the smaller G2.

15.
Chem Commun (Camb) ; 60(59): 7578-7581, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38953148

RESUMEN

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.

16.
Front Cell Infect Microbiol ; 14: 1294971, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38633749

RESUMEN

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.


Asunto(s)
Aspergilosis Pulmonar Invasiva , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estudios Retrospectivos , Proteína C-Reactiva/análisis , Biomarcadores , Polipéptido alfa Relacionado con Calcitonina
17.
Front Pharmacol ; 15: 1270661, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38659586

RESUMEN

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.

18.
Front Cell Infect Microbiol ; 14: 1386506, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660492

RESUMEN

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.


Asunto(s)
Reposicionamiento de Medicamentos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Enfermedad Pulmonar Obstructiva Crónica , Sitios de Carácter Cuantitativo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Humanos , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple
19.
ACS Appl Mater Interfaces ; 15(29): 35107-35116, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37440272

RESUMEN

Inspired by the practical need to remove persistent perfluoro pollutants from the environment, we leverage cutting-edge crystal engineering approaches. For this, we set our eyes on a recent porous coordination framework system based on the Ni8-oxo cluster and pyrazolate linkers as it is known for its stability to bases and other harsh environmental conditions. Our designer linker molecule here features (1) pyrazole donors masked by t-butyloxycarbonyl and (2) ethynyl side units protected by triisopropylsilyl groups. The former solvothermally demasks to assemble the Ni8-pyrazolate framework, in which the triisopropylsilyl groups can be post-synthetically cleaved by guest fluoride ions to unveil the terminal alkyne group (-CCH). The ethynyl groups of the framework solid offer versatile reactions for functionalization, as with perfluorophenyl azide (via a click reaction) to afford the two prongs of the 1,2,3-triazole base unit and the perfluoro unit. Together, these two functions make for an effective adsorbent for the topical acid pollutants of perfluorooctanoic acid and perfluorooctanesulfonic acid, with a high apparent rate constant (kobs) of 0.99 g mg-1 h-1 and large maximum uptake capacity (qmax) of 268.5 mg g-1 for perfluorooctanoic acid and kobs of 0.77 g mg-1 h-1 and qmax of 142.1 mg g-1 for perfluorooctanesulfonic acid.

20.
Clin Respir J ; 17(9): 951-961, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37586707

RESUMEN

BACKGROUND: To help elderly patients with severe or very severe chronic obstructive pulmonary disease (COPD) with pulmonary rehabilitation, we have developed Zheng's supine rehabilitation exercise (ZSRE). Currently, none of the terminal or critically ill patients with severe exercise limitation can complete the 6-min walking distance (6MWD) and cardiopulmonary exercise testing (CPET). METHODS: In this study, we discuss the definition of the standardized 3-min simulated pedal motion (3MSPM) test and its operational specifications. Also, we evaluate the minimal clinically important difference (MCID) value of the 3MSPM. RESULTS: The results showed that the mMRC score of COPD patients with acute exacerbation of dyspnea was progressively reduced from the second day of respiratory rehabilitation, and the difference between the first and seventh days was statistically significant (p < 0.000, χ2 = 176.664). 6MWD increased progressively, and the difference between 6MWD on day 1-7 was statistically significant (p = 0.024, F = 2.443). The difference between 3MSPM on day 1-7 was also statistically significant (p < 0.000, F = 4.481). Further analysis showed that 6MWD was negatively correlated with mMRC (p < 0.000, OR = -0.524). 3MSPM was positively correlated with 6MWD (p < 0.000, OR = 0.640) but negatively correlated with mMRC (p < 0.000, OR = -0.413). There is a linear regression relationship between 6MWD and 3MSPM, that is, 6MWD = 14.151 + 0.301 * 3MSPM, adjusted R2 = 0.401. CONCLUSION: Based on the regression equation, 3MSPM can predict 6MWD, and it can be used as a simple exercise endurance method to evaluate patients with safety hazards in underground activities or who cannot complete the 6MWD test. The minimum clinically important difference value is increased by 23.


Asunto(s)
Diferencia Mínima Clínicamente Importante , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Anciano , Estudios Prospectivos , Prueba de Esfuerzo , Ejercicio Físico , Tolerancia al Ejercicio
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