RESUMEN

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease, and developing an effective treatment remains a challenge. The limited therapeutic options are primarily delivered by the oral route, among which pirfenidone (PFD) improves pulmonary dysfunction and patient quality of life. However, its high dose and severe side effects (dyspepsia and systemic photosensitivity) limit its clinical value. Intratracheal aerosolization is an excellent alternative method for treating lung diseases because it increases the concentration of the drug needed to reach the focal site. Tetrahedral framework nucleic acid (tFNA) is a drug delivery system with exceptional delivery capabilities. Therefore, we synthesized a PFD-tFNA (Pt) complex using tFNA as the delivery vehicle and achieved quantitative nebulized drug delivery to the lungs via micronebulizer for lung fibrosis treatment. In vivo, Pt exhibited excellent immunomodulatory capacity and antioxidant effects. Furthermore, Pt reduced mortality, gradually restored body weight and improved lung tissue structure. Similarly, Pt also exhibited superior fibrosis inhibition in an in vitro fibrosis model, as shown by the suppression of excessive fibroblast activation and epithelial-mesenchymal transition (EMT) in epithelial cells exposed to TGF-ß1. Conclusively, Pt, a complex with tFNA as a transport system, could enrich the therapeutic regimen for IPF via intratracheal aerosolization inhalation.

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Fibrosis is an excessive wound-healing response induced by repeated or chronic external stimuli to tissues, significantly impacting quality of life and primarily contributing to organ failure. Organ fibrosis is reported to cause 45% of all-cause mortality worldwide. Despite extensive efforts to develop new antifibrotic drugs, drug discovery has not kept pace with the clinical demand. Currently, only pirfenidone and nintedanib are approved by the FDA to treat pulmonary fibrotic illness, whereas there are currently no available antifibrotic drugs for hepatic, cardiac or renal fibrosis. The development of fibrosis is closely related to epigenetic alterations. The field of epigenetics primarily studies biological processes, including chromatin modifications, epigenetic readers, DNA transcription and RNA translation. The bromodomain and extra-terminal structural domain (BET) family, a class of epigenetic readers, specifically recognizes acetylated histone lysine residues and promotes the formation of transcriptional complexes. Bromodomain-containing protein 4 (BRD4) is one of the most well-researched proteins in the BET family. BRD4 is implicated in the expression of genes related to inflammation and pro-fibrosis during fibrosis. Inhibition of BRD4 has shown promising anti-fibrotic effects in preclinical studies; however, no BRD4 inhibitor has been approved for clinical use. This review introduces the structure and function of BET proteins, the research progress on BRD4 in organ fibrosis, and the inhibitors of BRD4 utilized in fibrosis. We emphasize the feasibility of targeting BRD4 as an anti-fibrotic strategy and discuss the therapeutic potential and challenges associated with BRD4 inhibitors in treating fibrotic diseases.

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This data article quantifies the extent of shared bicycle riding risks for shared-bicycle riders in urban China. The data were collected through a WeChat-based online survey, with a valid sample of 1960 respondents. It reports the basic descriptive statistics through eight tables concerning various unsafe shared bicycle riding behaviors, and complete frequency data from riders concerning eight unsafe riding behaviors. The data can be used for comparisons with other studies using the same outcome measures, which are valuable to generate specialized and targeted solutions to reduce unsafe riding behaviors. For further information, please refer to the full article entitled "Unsafe riding behaviors of shared-bicycle riders in urban China: A retrospective survey".(Wu et al., 2019).

RESUMEN

Shared-bicycle use has skyrocketed in urban China, but little is known about the safety of bicycle users. The Chinese popular media reports multiple risky riding behaviors among shared bicycle riders, but scientific research on the topic is lacking. Therefore, we conducted a retrospective WeChat-based online survey to examine how often shared bicycle riders report engaging in risky cycling behaviors in urban China. Eight unsafe shared bicycle riding behaviors were assessed: not wearing helmets, running red lights, cycling against the traffic flow, riding in lanes designed for motor vehicles, riding in lanes designed for pedestrians, carrying passengers on bicycles, using cell phones while riding, and eating while riding. In total, 1960 valid questionnaires were collected. The proportion of participants who reported always or often having unsafe riding behavior in the past month, ranged from 1.1% for carrying passengers on the bicycles to 97.6% for failing to wear a helmet. Demographic characteristics were associated with unsafe behaviors through multivariate logistic regression, with male riders and riders aged 25 years or younger more likely to ride while using cell phones than females (AOR = 2.94) and those 36 years or older (AOR = 3.57). Cyclists with undergraduate education were more likely to wear helmets than those with postgraduate education or higher (AOR = 0.21). Compared to riders from central municipalities governed directly by the central government, riders from provincial capitals, deputy provincial cities, and smaller cities were at higher risks of riding in lanes for pedestrians, respectively (AOR = 1.59, 2.82 and 1.61). Riders who rode over 5 h a week and who rode on weekends were more likely to carry passengers than those who rode less than 1 h a week (AOR = 4.72) and those who rode only on weekdays (AOR = 3.93). We conclude that shared-bicycle riders frequently engage in some unsafe riding behaviors in urban China. Younger age, lower level of education, and longer hours of riding each week are associated with greater risks of some unsafe riding behaviors. Shared bicycles offer substantial benefit to societal health and transportation, but evidence-based interventions should be considered to reduce risks from unsafe shared bicycle riding behaviors. A well-designed road infrastructure with dedicated on-road bicycle lanes and readily-accessible comfortable, low-cost, and safe helmets may also reduce unsafe riding behaviors and unwanted crashes and injuries for shared bicycle riders.

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Anodization is a promising method to change the topography and wettability of titanium (Ti) implant. The formed TiO2 nanotubes (TiNTs) arrays could enhance the biological properties of Ti implants. In this study, to investigate the possibility of TiNTs arrays on a Ti implant surface as nano-reservoirs for small molecular drugs when using in orthopedic and dental prosthesis, TiNTs on a Ti implant surface were prepared. Then, aspirin and/or vitamin C were loaded into TiNTs as model drugs. Meanwhile, low molecular weight polylactic acid (PLA, Mw=3000) was synthesized and loaded alternately along with aspirin or vitamin C. The release rates of aspirin and vitamin C with/or without PLA loading were investigated by using a UV-Vis spectrometer. The results showed that when loading without PLA, drugs released quickly with presence of burst release. However, when loading with PLA, the cumulative release duration of aspirin and vitamin C was prolonged to over 240h. Molecular dynamics (MD) simulation and dissipative particle dynamics (DPD) simulation results proved that when loading with PLA, PLA molecules aggregated gradually and formed clusters or micelles in these nanotubes. Meanwhile, drug molecules were captured and distributed inside the PLA matrix, which retarding the release of drugs. Only when PLA micelles degrade gradually in body fluid, drugs could be released slowly from nanotubes. These knowledge laid ground basis for the following biological experiments.

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