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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.

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]

Covalent organic framework (COF) membranes featuring uniform topological structures and devisable functions, show huge potential in water purification and molecular separation. Nevertheless, the inability of uniform COF membranes to be produced on an industrial scale and their nonenvironmentally friendly fabrication method are the bottleneck preventing their industrial applications. Herein, we report a new green and industrially adaptable scraping‐assisted interfacial polymerization (SAIP) technique to fabricate scalable and uniform TpPa COF membranes. The process used non‐toxic and low‐volatility ionic liquids (ILs) as organic phase instead of conventional organic solvents for interfacial synthesis of TpPa COF layer on a support membrane, which can simultaneously achieve the purposes of (i) improving the greenness of membrane‐forming process and (ii) fabricating a robust membrane that can function beyond the conventional membranes. This approach yields a large‐area, continuous COF membrane (19×25 cm2) with a thickness of 78 nm within a brief period of 2 minutes. The resulting membrane exhibited an unprecedented combination of high permeance (48.09 L m−2 h−1 bar−1) and antibiotic desalination efficiency (e.g., NaCl/adriamycin separation factor of 41.8), which is superior to the commercial benchmarking membranes. [ABSTRACT FROM AUTHOR]

This study leverages the ancient craft of weaving to prepare membranes that can effectively treat oil/water mixtures, specifically challenging nanoemulsions. Drawing inspiration from the core-shell architecture of spider silk, we have engineered fibers, the fundamental building blocks for weaving membranes, that feature a mechanically robust core for tight weaving, coupled with a CO 2 -responsive shell that allows for on-demand wettability adjustments. Tightly weaving these fibers produces membranes with ideal pores, achieving over 99.6% separation efficiency for nanoemulsions with droplets as small as 20 nm. They offer high flux rates, on-demand self-cleaning, and can switch between sieving oil and water nanodroplets through simple CO 2 /N 2 stimulation. Moreover, weaving can produce sufficiently large membranes (4800 cm 2 ) to assemble a module that exhibits long-term stability and performance, surpassing state-of-the-art technologies for nanoemulsion separations, thus making industrial application a practical reality.

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 m 2 ). 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., (© 2024 Wiley-VCH GmbH.)

Background: Malnutrition adversely affects prognosis in various medical conditions, but its implications in older adults with Chronic Obstructive Pulmonary Disease (COPD) in the ICU are underexplored. The geriatric nutritional risk index (GNRI) is a novel tool for assessing malnutrition risk. This study investigates the association between GNRI and 90-day mortality in this population., Methods: We selected older adults with COPD admitted to the ICU from Medical Information Mart for Intensive Care (MIMIC)-IV 2.2 database. A total of 666 patients were categorized into four groups based on their GNRI score: normal nutrition (>98), mild malnutrition (92-98), moderate malnutrition (82-91), and severe malnutrition (≤81) groups. We employed a restricted cubic spline (RCS) analysis to assess the presence of a curved relationship between them and to investigate any potential threshold saturation effect., Results: In multivariate Cox regression analyses, compared with individuals had normal nutrition (GNRI in Q4 >98), the adjusted HR values for GNRI in Q3 (92-98), Q2 (82-91), and Q1 (≤81) were 1.81 (95% CI: 1.27-2.58, p=0.001), 1.23 (95% CI: 0.84-1.79, p=0.296), 2.27 (95% CI: 1.57-3.29, p<0.001), respectively. The relationship between GNRI and 90-day mortality demonstrates an L-shaped curve (p=0.016), with an approximate inflection point at 101.5., Conclusion: These findings imply that GNRI is a useful prognostic tool in older adults with COPD in the ICU. An L-shaped relationship was observed between GNRI and 90-day mortality in these patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wang et al.)

Stimulus-responsive membranes demonstrate promising applications in switchable oil/water emulsion separations. However, they are unsuitable for the treatment of double emulsions like oil-in-water-in-oil (O/W/O) and water-in-oil-in-water (W/O/W) emulsions. For efficient separation of these complicated emulsions, fine control over the wettability, response time, and aperture structure of the membrane is required. Herein, dual-coated fibers consisting of primary photothermal-responsive and secondary CO 2 -responsive coatings are prepared by two steps. Automated weaving of these fibers produces membranes with photothermal- and CO 2 -responsive characteristics and narrow pore size distributions. These membranes exhibit fast switching wettability between superhydrophilicity (under CO 2 stimulation) and high hydrophobicity (under near-infrared stimulation), achieving on-demand separation of various O/W/O and W/O/W emulsions with separation efficiencies exceeding 99.6%. Two-dimensional low-field nuclear magnetic resonance and correlated spectra technique are used to clarify the underlying mechanism of switchable double emulsion separation. The approach can effectively address the challenges associated with the use of stimulus-responsive membranes for double emulsion separation and facilitate the industrial application of these membranes., (© 2024 Wiley‐VCH GmbH.)

The role of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) has been questioned in the era of magnetic resonance imaging (MRI). The purpose of this study was to re-evaluate the efficacy of PCI in patients with LS-SCLC. Three electronic databases were searched, including PubMed, Embase, and the Cochrane Library from January 2012 to April 2022. All relevant publications were included based on the inclusion criteria, and survival data and brain metastasis (BM) rates were extracted and pooled. Ten studies were selected which involved 532 patients who received PCI and 613 patients who did not receive PCI. In pooled estimates, PCI significantly improved overall survival (OS) and progression-free survival (PFS) [hazard ratio (HR) = 0.71, 95% confidence interval (CI): 0.61-0.82, p <0.001; HR = 0.68, 95% CI: 0.48-0.97, p = 0.03, respectively]. Additionally, the use of PCI was associated with a significant reduction in the risk of brain metastasis (BM, risk ratio = 0.64, 95% CI: 0.46-0.90, p = 0.009). In subgroup analyses. The authors found that the PCI effects on OS were independent of region and the use of brain imaging after initial treatment. These findings demonstrate that PCI improves OS and PFS while decreasing the risk of BM in patients with LS-SCLC, implying that PCI remains necessary even in the MRI era. Key Words: Prophylactic cranial irradiation, Small cell lung cancer, Magnetic resonance imaging, Brain metastasis.

Objective: Transbronchial biopsy is a safe manner with fewer complications than percutaneous transthoracic needle biopsy; however, the current diagnostic yield is still necessitating further improvement. We aimed to evaluate the diagnostic yield of using virtual bronchoscopic navigation (VBN) and cone-beam CT (CBCT) for transbronchial biopsy and to investigate the factors that affected the diagnostic sensitivity., Methods: We retrospectively investigated 255 patients who underwent VBN-CBCT-guided transbronchial biopsy at our two centers from May 2021 to April 2022. A total of 228 patients with final diagnoses were studied. Patient characteristics including lesion size, lesion location, presence of bronchus sign, lesion type and imaging tool used were collected and analyzed. Diagnostic yield was reported overall and in groups using different imaging tools., Results: The median size of lesion was 21 mm (range of 15.5-29 mm) with 46.1% less than 2 cm in diameter. Bronchus sign was present in 87.7% of the patients. The overall diagnostic yield was 82.1%, and sensitivity for malignancy was 66.3%. Patients with lesion > 2 cm or with bronchus sign were shown to have a significantly higher diagnostic yield. Four patients had bleeding and no pneumothorax occurred., Conclusion: Guided bronchoscopy with VBN and CBCT was an effective diagnostic method and was associated with a high diagnostic yield in a safe manner. In addition, the multivariant analysis suggested that lesion size and presence of bronchus sign could be a predictive factor for successful bronchoscopic diagnosis., (© 2024. The Author(s).)

Covalent organic framework (COF) membranes featuring uniform topological structures and devisable functions, show huge potential in water purification and molecular separation. Nevertheless, the inability of uniform COF membranes to be produced on an industrial scale and their nonenvironmentally friendly fabrication method are the bottleneck preventing their industrial applications. Herein, we report a new green and industrially adaptable scraping-assisted interfacial polymerization (SAIP) technique to fabricate scalable and uniform TpPa COF membranes. The process used non-toxic and low-volatility ionic liquids (ILs) as organic phase instead of conventional organic solvents for interfacial synthesis of TpPa COF layer on a support membrane, which can simultaneously achieve the purposes of (i) improving the greenness of membrane-forming process and (ii) fabricating a robust membrane that can function beyond the conventional membranes. This approach yields a large-area, continuous COF membrane (19×25 cm 2 ) with a thickness of 78 nm within a brief period of 2 minutes. The resulting membrane exhibited an unprecedented combination of high permeance (48.09 L m -2 h -1 bar -1 ) and antibiotic desalination efficiency (e.g., NaCl/adriamycin separation factor of 41.8), which is superior to the commercial benchmarking membranes., (© 2023 Wiley-VCH GmbH.)