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A prominent cause of cancer-related fatalities with a poor prognosis is lung adenocarcinoma (LUAD). KIF5A, a crucial member of the kinesin superfamily, is linked to drug resistance in malignancies. This work aims to investigate the mechanism of KIF5A in docetaxel (DTX) resistance in LUAD cells. The results of bioinformatics analysis, qRT-PCR and western blot analysis show that KIF5A, which is involved in the glycolysis pathway, is highly expressed in LUAD and is positively correlated with glycolysis-related genes. We further verify that silencing of KIF5A inhibits DTX resistance, glycolysis, and lactate production in LUAD cells via cell counting kit-8 (CCK-8), flow cytometry, Seahorse XFe 96, lactate, and glucose assays. Mechanistically, KIF5A promotes DTX resistance in LUAD, and this effect is attenuated upon the addition of an LDHA inhibitor. Chromatin immunoprecipitation and dual-luciferase reporter assays reveal that FOXP3 transcriptionally activates KIF5A. Knockdown of FOXP3 reduces lactate production and enhances DTX sensitivity in LUAD, which is restored upon simultaneous overexpression of KIF5A. Our findings reveal that FOXP3 increases DTX resistance in LUAD cells by enhancing lactate production through the upregulation of KIF5A level. In conclusion, our study provides a novel treatment target for improving chemosensitivity in LUAD.

Objective To explore the effect of smoking cessation combined with flutamide on improving the lung function and motor function in stable chronic obstructive pulmonary disease (COPD) patients complicated with respiratory failure. Methods A retrospective study was conducted on 100 stable COPD patients complicated with respiratory failure treated from January 2020 to January 2022 at the Second People's Hospital of Liaocheng through convenience sampling and control principles. The patients who were treated with flutimevir served as the control group (n=50) , and those who were given smoking cessation combined with flutimevir served as the observation group (n=50) . The clinical efficacy, pulmonary function indexes, 6-minute walk test (6WMT) , dyspnea score ［modified Medical Research Council (mMRC) ］and serum inflammation markers were compared between two groups. Results The total effective rate in observation group was significantly higher than that in control group (94.00% vs 72.00%, P＜0.01) . After treatment, forced vital capacity (FVC) , forced expiratory volume in the first second (FEV1) and FEV1/FVC ratio in observation group were statistically higher than those in control group (P＜0.05) . Compared with those in control group, 6WMT increased, and mMRC score and levels of serum tumor necrosis factor-α (TNF-α) , interleukin (IL) -8 and IL-6 decreased significantly in observation group (P＜0.05) . Conclusion For the stable COPD patients complicated with respiratory failure, smoking cessation combined with flutamide can effectively improve the pulmonary function and motor function and significantly reduce the degree of dyspnea and the inflammatory response.

BackgroundHepatic arterial infusion (HAI) of oxaliplatin, leucovorin, and fluorouracil (FOLFOX) plus sorafenib has a more desirable effect versus sorafenib for hepatocellular carcinoma (HCC) patients with portal vein invasion. However, considering the high cost of hepatic arterial infusion of chemotherapy (HAIC), this study evaluated the cost-effectiveness of HAIC plus sorafenib (SoraHAIC) versus standard care for HCC patients from the Chinese health system perspective.MethodsA Markov multi-state model was constructed to simulate the disease course and source consumption of SoraHAIC. Costs of primary therapeutic drugs were calculated based on the national bid price, and hepatic artery catheterization fee was collected from the Fujian Provincial Price Bureau. Clinical data, other costs, and utility values were extracted from references. Primary outcomes included life-years (LYs), quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). The robustness of model was verified by uncertainty sensitivity analyses.ResultsSoraHAIC gained 1.18 QALYs (1.68 LYs) at a cost of $65,254, while the effectiveness and cost of sorafenib were 0.52 QALYs (0.79 LYs) and $14,280, respectively. The ICER of SoraHAIC vs sorafenib was $77,132/QALY ($57,153/LY). Parameter that most influenced the ICER was utility of PFS state. The probabilistic sensitivity analysis (PSA) showed that SoraHAIC was not cost-effective in the WTP threshold of 3*Gross Domestic Product (GDP) per capita of China ($30,492/QALY). But about 38.8% of the simulations were favorable to SoraHAIC at the WTP threshold of 3*GDP per capita of Beijing ($72,000/QALY). When 3*GDP per capita of Fujian ($47,285/QALY) and Gansu Province ($14,595/QALY) were used as WTP threshold, the acceptability of SoraHAIC was 0.3% and 0%, respectively.ConclusionsThe study results indicated that SoraHAIC was not cost-effective in medium-, and low-income regions of China. In developed areas of China (Beijing), there was a 38.8% probability that the SoraHAIC regimen would be cost-effective.

As demand for energy increases, the number of "three-high" (high-pressure, high-yield, high-sulfur) gas Wells has doubled, the severe stress fluctuation of pipe string caused by downhole high-pressure environment leads to the failure of rope fracture is particularly prominent. It is easy to cause pipeline blockage and large amount of high-pressure toxic gas leakage caused by tool string accidental falling. Therefore, based on the theory of Love and elastoplastic contact theory, and considering the influence of Poisson's ratio effect, this article establishes a calculation model for tensile fatigue of interaction between rope strands to study the influence of key structural parameters and breaking wire position on stress distribution and fatigue life of rope. The results show that: the core strand of the rope is the main force position, the overall stress shows the trend of decreasing with the increase of winding radius; when the rope is stretched, the axial deformation near the core of the rope is smaller than the deformation far from the core; under the same number of broken wires, the fatigue life of different ropes is related to the location of broken wires, the farther the location of broken wires from the core of the rope, the higher the fatigue life. The research work in this article provides theoretical guidance for the safe operation of ropes in "three-high" gas wells. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rituximab resistance is one of the great challenges in the treatment of diffuse large B-cell lymphoma (DLBCL), but relevant biomarkers and signalling pathways remain to be identified. Coptis chinensis and its active ingredients have antitumour effects; thus, the potential bioactive compounds and mechanisms through which Coptis chinensis acts against rituximab-resistant DLBCL are worth exploring. OBJECTIVE: To elucidate the core genes involved in rituximab-resistant DLBCL and the potential therapeutic targets of candidate monomers of Coptis chinensis. METHODS: Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Similarity Ensemble Approach and Swiss Target Prediction, the main ingredients and pharmacological targets of Coptis chinensis were identified through database searches. Through the overlap between the pharmacological targets of Coptis chinensis and the core targets of rituximab-resistant DLBCL, we identified the targets of Coptis chinensis against rituximab-resistant DLBCL and constructed an active compound-target interaction network. The targets and their corresponding active ingredients of Coptis chinensis against rituximab-resistant DLBCL were molecularly docked. RESULTS: Berberine, quercetin, epiberberine and palmatine, the active components of Coptis chinensis, have great potential for improving rituximab-resistant DLBCL via PIK3CG. CONCLUSION: This study revealed biomarkers and Coptis chinensis-associated molecular functions for rituximab-resistant DLBCL. [ABSTRACT FROM AUTHOR]

Membranes are important in the pharmaceutical industry for the separation of antibiotics and salts. However, its widespread adoption has been hindered by limited control of the membrane microstructure (pore architecture and free‐volume elements), separation threshold, scalability, and operational stability. In this study, 4,4′,4′′,4′′′‐methanetetrayltetrakis(benzene‐1,2‐diamine) (MTLB) as prepared as a molecular building block for fabricating thin‐film composite membranes (TFCMs) via interfacial polymerization. The relatively large molecular size and rigid molecular structure of MTLB, along with its non‐coplanar and distorted conformation, produced thin and defect‐free selective layers (~27 nm) with ideal microporosities for antibiotic desalination. These structural advantages yielded an unprecedented high performance with a water permeance of 45.2 L m−2 h−1 bar−1 and efficient antibiotic desalination (NaCl/adriamycin selectivity of 422). We demonstrated the feasibility of the industrial scaling of the membrane into a spiral‐wound module (with an effective area of 2.0 m2). This module exhibited long‐term stability and performance that surpassed those of state‐of‐the‐art membranes used for antibiotic desalination. This study provides a scientific reference for the development of high‐performance TFCMs for water purification and desalination in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

The development of carbon dioxide (CO2) separation technology is crucial for mitigating global climate change and promoting sustainable development. In this study, we successfully synthesized an array of cross‐linked poly(vinyl alcohol) (PVA) membranes, xALD‐PEG‐ALD‐c‐PVA, with enhanced CO2/N2 separation performance by employing dialdehyde polyethylene glycol (ALD‐PEG‐ALD) as a cross‐linker. The formation of the cross‐linked network structure not only inhibits the crystallization of PVA but also disrupts hydrogen bonding and thus increases fractional free volume of PVA chains. Under the synergistic effect of these multiple factors, the cross‐linked PVA membranes exhibit a significantly improved CO2 permeability. Moreover, they maintain high CO2/N2 selectivity, attributing to the CO2‐philic characteristic of ethylene oxide groups in the cross‐linked structure. At the ALD‐PEG‐ALD content of 1.6 mmol g−1, the xALD‐PEG‐ALD‐c‐PVA membrane demonstrates a CO2 permeability of 41.4 barrer and a CO2/N2 selectivity of 57.4 at 2 bar and 25°C. Furthermore, compared with the pristine PVA membrane, xALD‐PEG‐ALD‐c‐PVA membranes manifest superior mechanical properties and outstanding separation performance for a CO2/N2 (15/85, vol%) gas mixture. The excellent combination of permeability and selectivity makes xALD‐PEG‐ALD‐c‐PVA membranes highly promising for various CO2 separation applications. [ABSTRACT FROM AUTHOR]

Intelligent well technology is an oil and gas well optimization completion technology integrated with underground real-time monitoring, data analysis decision-making and remote control of downhole tools. It's of great significance to the transformation and innovation of China's oil and gas development projects. The author of this paper expounds the definition, principle, composition and characteristics of intelligent well technology, and introduces the development status quo of intelligent well technology abroad, including mature intelligent well system, key technology research of intelligent well and its application technology. After the introduction to the related technology research of intelligent well in China, the author puts forward some opinions on the development of our own complete intelligent well system.