Construction of Covalent-Organic Frameworks (COFs) from Amorphous Covalent Organic Polymers via Linkage Replacement.

Covalent-organic frameworks (COFs) as porous crystalline materials show promising potential applications. However, developing facile strategies for the construction of COFs directly from amorphous covalent organic polymers (COPs) is still a great challenge. To this end, we report a novel approach for easy preparation of COFs from amorphous COPs through the linkage replacement under different types of reactions. Four COFs with high crystallinity and porosity were constructed via the linkage substitution of polyimide-linked COPs to imine-linked COFs as well as imine-linked COPs to polyimide-linked COFs. The realization of the linkage substitution would significantly expand the research scope of COFs.

A Novel Strategy for the Construction of Covalent Organic Frameworks from Nonporous Covalent Organic Polymers.

The field of covalent organic frameworks (COFs) has been developed significantly in the past decade on account of their important characteristics and vast application potential. On the other hand, the discovery of novel synthetic methodology is still a challenging task to further promote the preparation of COFs. Herein, an interesting protocol for the conversion of amorphous nonporous covalent organic polymers (COPs) to COFs was established, affording four COFs with high crystallinity and porosity. Specifically, imine-linked amorphous COP-1 was successfully converted to COF-1-4 by replacing one type of linker with other organic building blocks. The realization of this conversion provides a facile method for constructing COFs from COPs.

Bone morphogenetic protein 4 inhibits liposaccharide-induced inflammation in the airway.

Bone morphogenetic protein 4 (BMP4) is a multifunctional growth factor that belongs to the TGF-ß superfamily. The role of BMP4 in lung diseases is not fully understood. Here, we demonstrate that BMP4 was upregulated in lungs undergoing lipopolysaccharide (LPS)-induced inflammation, and in airway epithelial cells treated with LPS or TNF-α. BMP4 mutant (BMP4(+/-) ) mice presented with more severe lung inflammation in response to LPS or Pseudomonas aeruginosa, and lower bacterial load compared with that in BMP4(+/+) mice. Knockdown of BMP4 by siRNA increased LPS and TNF-α-induced IL-8 expression in 16HBE human airway epithelial cells and in primary human bronchial epithelial cells. Similarly, peritoneal macrophages from BMP4(+/-) mice produced greater levels of TNF-α and keratinocyte chemoattractant (KC) upon LPS treatment compared with cells from BMP4(+/+) mice. Administration of exogenous BMP4 attenuated the upregulation of TNF-α, IL-8, or KC induced by LPS and/or TNF-α in airway epithelial cells, and peritoneal macrophages. Finally, partial deficiency of BMP4 in BMP4(+/-) mice protected the animals from restrictive lung function reduction upon chronic LPS exposure. These results indicate that BMP4 plays an important anti-inflammatory role, controlling the strength and facilitating the resolution of acute lung inflammation; yet, BMP4 also contributes to lung function impairment during chronic lung inflammation.

Tanshinone IIA inhibits lipopolysaccharide-induced MUC1 overexpression in alveolar epithelial cells.

The anti-inflammatory function of tanshinone IIA (TIIA), an active natural compound from Chinese herbal medicine Danshen, has been well recognized, and therefore TIIA has been widely used to treat various inflammatory conditions associated with cardiac and lung diseases. Mucin 1 (Muc1) plays important anti-inflammatory roles in resolution of acute lung inflammation. In this study, we investigated the effects of TIIA on LPS-induced acute lung inflammation, as well as its relationship to Muc1 expression in mouse lung and MUC1 in human alveolar epithelial cells. TIIA pretreatment significantly inhibited LPS-induced pulmonary inflammation in both Muc1 wild-type (Muc1(+/+)) and knockout (Muc1(-/-)) mice, as manifested by reduced neutrophil infiltration and reduced TNF-α and keratinocyte chemoattractant levels in bronchoalveolar lavage fluid. The inhibitory effects of TIIA on airway inflammation were associated with reduced expression of Muc1 in Muc1(+/+) mouse lung. Moreover, pretreatment with TIIA significantly inhibited LPS-induced MUC1 expression and TNF-α release in A549 alveolar epithelial cells. TNF-α upregulated MUC1 mRNA and protein expression in A549 cells, which was inhibited by pretreatment with TIIA. The LPS-induced MUC1 expression was blocked when A549 cells were transfected with siRNA targeting for TNF-α receptor 1. Furthermore, TIIA inhibited LPS-induced nuclear translocation of NF-κB and upregulation of Toll-like receptor 4 in A549 cells. Taken together, these results demonstrate that TIIA suppressed LPS-induced acute lung inflammation regardless of the presence of Muc1, and TIIA inhibited LPS- and TNF-α-induced MUC1/Muc1 expression in airway epithelial cells, suggesting that MUC1/Muc1 does not account for the mechanisms of the anti-inflammatory effects of TIIA in the airway.

Age affects vascular morphology and predictiveness of anatomical landmarks for aortic zones in trauma patients: implications for resuscitative endovascular balloon occlusion of the aorta.

PURPOSE: Understanding the vascular morphology is fundamental for resuscitative endovascular balloon occlusion of the aorta. This study aimed to evaluate the effect of aging on length and diameter of aorta and iliac arteries in trauma patients, and to investigate the predictiveness of anatomical landmarks for aortic zones. METHODS: A total of 235 patients in a regional trauma center registry from September 1, 2018, to January 3, 2024, participated in the study. Reconstruction of computed tomography was applied to the torso area. The marginal diameter and length of aorta and iliac arteries were measured. Anatomical landmark distances and aortic marginal lengths were compared. RESULTS: The length and diameter of aorta and iliac arteries increased with age, and a tortuous and enlarged morphology was observed in older patients. There was a good regression between age and diameter of the aorta. Neither the jugular notch, the xiphisternal joint, nor the umbilicus could reliably represent specific margins of aortic zones. The distance between the mid-sternum and femoral artery (427 ± 25 to 442 ± 25 mm for right, and 425 ± 28 to 440 ± 26 mm for left) was predictive for zone 1 in all groups. The distance between the lower one-third junction of the xiphisternum to the umbilicus and femoral artery (232 ± 19 to 240 ± 17 mm for right, and 229 ± 20 to 237 ± 19 mm for left) was predictive for zone 3 aorta. CONCLUSION: Aging increases the length and diameter of aorta and iliac arteries, with a tortuous and enlarged morphology in geriatric populations. The mid-sternum and the lower one-third junction of the xiphisternum to the umbilicus were predictive landmarks for zone 1 and zone 3, respectively.

Tanshinone IIA sulfonate protects against cigarette smoke-induced COPD and down-regulation of CFTR in mice.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by abnormal inflammation, persistent and progressive lung function decline. The anti-inflammatory actions of tanshinone IIA, which is the most important active component from Chinese herbal medicine Danshen, have been well studied. However, it remains unknown whether sodium tanshinone IIA sulfonate (STS) protects against the development of COPD. Here we found that STS inhalation (5 mg/kg, 30 min per session, twice a day) significantly attenuated lung function decline, airspace enlargement, mucus production, bronchial collagen deposition, inflammatory responses and oxidative stress caused by cigarette smoke (CS) and lipopolysaccharide (LPS) exposures in mice. Moreover, treatment with STS (10 µg/ml) reduced CS extract (CSE)-induced IL-6 and IL-8 secretion in human bronchial epithelial (16HBE) cells. The anti-inflammatory actions of STS were associated with inhibition of ERK1/2 and NF-κB activations. Interestingly, STS inhibited CS-induced reduction of cystic fibrosis transmembrane conductance regulator (CFTR) in mouse lungs and in 16HBE cells. Treatment with a specific CFTR inhibitor CFTR-Inh172 augmented CSE-induced ERK1/2 and NF-κB-dependent inflammatory responses, but abolished the inhibitory action of STS on IL-6 and IL-8 secretion in 16HBE cells. These results demonstrate that CS-induced COPD and down-regulation of CFTR are prevented by STS.

Reduced nuclear translocation of serum response factor is associated with skeletal muscle atrophy in a cigarette smoke-induced mouse model of COPD.

Skeletal muscle atrophy and dysfunction are common complications in the chronic obstructive pulmonary disease (COPD). However, the underlying molecular mechanism remains elusive. Serum response factor (SRF) is a transcription factor which is critical in myocyte differentiation and growth. In this study, we established a mouse COPD model induced by cigarette smoking (CS) exposure for 24 weeks, with apparent pathophysiological changes, including increased airway resistance, enlarged alveoli, and skeletal muscle atrophy. Levels of upstream regulators of SRF, striated muscle activator of Rho signaling (STARS), and ras homolog gene family, member A (RhoA) were decreased in quadriceps muscle of COPD mice. Meanwhile, the nucleic location of SRF was diminished along with its cytoplasmic accumulation. There was a downregulation of the target muscle-specific gene, Igf1. These results suggest that the CS is one of the major causes for COPD pathogenesis, which induces the COPD-associated skeletal muscle atrophy which is closely related to decreasing SRF nucleic translocation, consequently downregulating the SRF target genes involved in muscle growth and nutrition. The STARS/RhoA signaling pathway might contribute to this course by impacting SRF subcellular distribution.