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Chronic cough (CC) is a common respiratory disorders, "with prevalence rates as high as 10% ~ 20%. The burden of CC can be severe, as patients with CC experience substantial physical effects (e.g., stress urinary incontinence, sleep disturbance, and chest pain), psychological consequences (e.g., frustration, anxiety, and depression), and social impairments (e.g., social distress/isolation and reduced quality of life). As a result, CC is a frustrating conundrum for patients and clinicians. In this paper, combined with the new concepts of domestic and foreign literature, we expound the concept of CC, epidemiology, pathogenesis, etiological structure, clinical manifestations and auxiliary examination, diagnosis and differential diagnosis, treatment, and future prospects, etc., for peer reference and learn from, so as to promote more in-depth related clinical research. [ABSTRACT FROM AUTHOR]

PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient‐derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can synergistically inhibit GBM. Intriguingly, it is observed that DNA damage lingers after discontinuation of PARPi monotherapy, implying that sequential administration of PARPi followed by BETi can maintain antitumor efficacy while reducing toxicity. In GBM cells with elevated baseline replication stress, the sequential regimen exhibits comparable efficacy to concurrent treatment, protecting normal glial cells with lower baseline replication stress from DNA toxicity and subsequent death. This study provides compelling preclinical evidence supporting the development of innovative drug administration strategies focusing on PARPi for GBM therapy. [ABSTRACT FROM AUTHOR]

Objective: The contribution of hypoxia to the pathophysiology of vascular smooth muscle cells (VSMCs) has not yet been fully elucidated. This study evaluated the effect of hypoxia on the phenotype and function of SMCs derived from the human normal great saphenous veins (NGSVs). Methods: Fifteen NGSV tissue samples were collected. SMCs were isolated and cultured. Proliferation, migration, adhesion, senescence, and the structure of cytoskeletal filaments in SMCs were observed. mRNA and protein expression of Bax, Bcl-2, caspase-3, matrix metalloproteinases (MMP)-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 was detected by fluorescent quantitative polymerase chain reaction and immunoblotting in the cobalt chloride (CoCl2) and the control groups. Results: A decrease in the number of cytoskeletal filaments was observed. mRNA and protein expression of Bas and caspase-3 was significantly decreased, while the quantity of proliferation, migration, adhesion, senescence, and mRNA and protein expression of Bcl-2, MMP-2, MMP-9, TIMP-1, and TIMP-2 in SMCs in the CoCl2 group were significantly increased compared with the control group. Conclusion: Under hypoxic conditions, the phenotype and function of SMCs derived from the human NGSVs were dysregulated, suggesting that VSMCs switch from the contractile phenotype to the secretory or synthetic phenotype, and more dedifferentiate, resulting in extracellular matrix deposition and apoptotic decrease through the intrinsic pathway. [ABSTRACT FROM AUTHOR]

Organophosphorous pesticides pose a significant threat to public health, making its detection critical. Herein, a new fluorescent metal–organic framework, Eu-NDC, was synthesized, which possessed a 3D supramolecular structure assembled through π⋯π interactions between the naphthalene rings in its adjacent coordination-bonded layers. Then, four different products of the Eu-NDC MOF (Eu-NDC-1/2/3/4) with different morphologies were further obtained by altering the ratio of the raw materials. Among them, the fluorescence properties and BET surface area of the micro-nanoscale Eu-NDC-3 were significantly enhanced, making it the most favorable for detection. Eu-NDC-3 as a turn-off fluorescence probe for methyl paraoxon (DMNP) exhibited excellent sensitivity and selectivity, anti-interference and durability. Thus, considering these features, an intelligent logic gate was designed, showing great promise for application in smart sensing. Furthermore, an Eu-NDC-3-loaded electrospun fibrous strip was fabricated as a portable and in situ platform for visual DMNP assay. [ABSTRACT FROM AUTHOR]

Objective: Sulfur mustard (SM) is an important chemical warfare agent. The mechanisms underlying SM toxicity have not been completely elucidated. However, oxidative stress and the subsequent damage to macromolecules have been considered ascrucial steps in SM toxicity. In this study, a rat model of SM-induced acute pulmonary injury was established using an equal toxicity dose (1LD50). This study employed two methods to directly compare oxidative stress indices in serum enzymes and the epithelial cells of the alveolar septa. Methods: Male Sprague-Dawley rats were randomly divided into intraperitoneal SM, intraperitoneal propylene glycol control, tracheal SM, tracheal propylene glycol control, and control groups. SM-induced serum enzyme levels and protein expression in the epithelial cells of the alveolar septa were measured using enzyme-linked immunosorbent assay and immunohistochemistry. Results: Serum levels of superoxide dismutase, catalase, and glutathione peroxidase were upregulated in the intraperitoneal SM group compared with those in the tracheal SM group. Positive expression ratios of CuZn-superoxide dismutase, Mn-superoxide dismutase, paraoxonase-1, and apolipoprotein-1 proteins in the epithelial cells of the alveolar septa in the intraperitoneal SM group were elevated compared with those in the tracheal SM group. Conclusion: Under SM (1LD50) exposure, there were significantly higher serum enzyme levels and protein expressions in the epithelial cells of the alveolar septa of rats injected with SM intraperitoneally compared with SM administered by intratracheal instillation. The results demonstrated that the differences in oxidative stress indices at the molecular level in SM-induced pulmonary injury were dependent on the route of exposure. [ABSTRACT FROM AUTHOR]

Objectives: Superficial venous thrombosis (SVT) is the complications of varicose great saphenous veins (VGSVs), but its pathogenesis remains unclear. This study was designed to measure the changes in expression of matrix metalloproteinases (MMPs) and the tissue inhibitor of metalloproteinases (TIMPs) from SVT, VGSVs, and great saphenous veins (GSVs). Methods: In the venous walls of the three groups, the expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 proteins, protein-positive expression ratios, mRNA expression, and protein expression were determined by immunohistochemistry, polymerase chain reaction, and western blot. Results: The MMP-2, MMP-9, TIMP-1, and TIMP-2 protein-positive expression ratios, mRNA and protein expression in the SVT group were significantly higher than those in the VGSV and the GSV groups. The corresponding expression in the VGSV group were significantly higher than those in the GSV group. Conclusion: Disequilibrium of MMPs and TIMPs in SVT wall occurs due to underlying high hydrostatic pressure and inflammation. These results suggested that MMPs and TIMPs participate in the process of venous wall remodeling. [ABSTRACT FROM AUTHOR]