Impact of Hydrostatic Pressure on Molecular Structure and Dynamics of the Sodium and Chloride Ions in Portlandite Nanopores.

In order to address the issues of energy depletion, more resources are being searched for in the deep sea. Therefore, research into how the deep-sea environment affects cement-based materials for underwater infrastructure is required. This paper examines the impact of ocean depth (0, 500, 1000, and 1500 m) on the ion interaction processes in concrete nanopores using molecular dynamics simulations. At the portlandite interface, the local structural and kinetic characteristics of ions and water molecules are examined. The findings show that the portlandite surface hydrophilicity is unaffected by increasing depth. The density profile and coordination number of ions alter as depth increases, and the diffusion speed noticeably decreases. The main cause of the ions' reduced diffusion velocity is expected to be the low temperature. This work offers a thorough understanding of the cement hydration products' microstructure in deep sea, which may help explain why cement-based underwater infrastructure deteriorates over time.

Mobilizing endogenous neuroprotection: the mechanism of the protective effect of acupuncture on the brain after stroke.

Given its high morbidity, disability, and mortality rates, ischemic stroke (IS) is a severe disease posing a substantial public health threat. Although early thrombolytic therapy is effective in IS treatment, the limited time frame for its administration presents a formidable challenge. Upon occurrence, IS triggers an ischemic cascade response, inducing the brain to generate endogenous protective mechanisms against excitotoxicity and inflammation, among other pathological processes. Stroke patients often experience limited recovery stages. As a result, activating their innate self-protective capacity [endogenous brain protection (EBP)] is essential for neurological function recovery. Acupuncture has exhibited clinical efficacy in cerebral ischemic stroke (CIS) treatment by promoting the human body's self-preservation and "Zheng Qi" (a term in traditional Chinese medicine (TCM) describing positive capabilities such as self-immunity, self-recovery, and disease prevention). According to research, acupuncture can modulate astrocyte activity, decrease oxidative stress (OS), and protect neurons by inhibiting excitotoxicity, inflammation, and apoptosis via activating endogenous protective mechanisms within the brain. Furthermore, acupuncture was found to modulate microglia transformation, thereby reducing inflammation and autoimmune responses, as well as promoting blood flow restoration by regulating the vasculature or the blood-brain barrier (BBB). However, the precise mechanism underlying these processes remains unclear. Consequently, this review aims to shed light on the potential acupuncture-induced endogenous neuroprotective mechanisms by critically examining experimental evidence on the preventive and therapeutic effects exerted by acupuncture on CIS. This review offers a theoretical foundation for acupuncture-based stroke treatment.

Efficacy of Chinese Medicine Treatment Based on Syndrome Differentiation for Primary Insomnia: A Randomized Placebo Controlled Triple-Blinded Trial.

OBJECTIVE: To assess efficacy of Chinese medicine (CM) on insomnia considering characteristics of treatment based on syndrome differentiation. METHODS: A total of 116 participants aged 18 to 65 years with moderate and severe primary insomnia were randomized to the placebo (n=20) or the CM group (n=96) for a 4-week treatment and a 4-week follow-up. Three CM clinicians independently prescribed treatments for each patient based on syndromes differentiation. The primary outcome was change in total sleep time (TST) from baseline. Secondary endpoints included sleep onset latency (SOL), wake time after sleep onset (WASO), sleep efficiency, Pittsburgh Sleep Quality Index (PSQI) and CM symptoms. RESULTS: The CM group had an average 0.6 h more (95% confidence interval (CI): 0.3-0.9, P<0.001) TST and 34.1% (10.3%-58.0%, P=0.005) more patients beyond 0.5 h TST increment than that of the placebo group. PSQI was changed -3.3 (-3.8 to -2.7) in the CM group, a -2.0 (-3.2 to -0.8, P<0.001) difference from the placebo group. The CM symptom score in the CM group decreased -2.0 (-3.3 to -0.7, P=0.003) more than the placebo group. SOL and WASO changes were not significantly different between groups. The analysis of prescriptions by these clinicians revealed blood deficiency and Liver stagnation as the most common syndromes. Prescriptions for these clinicians displayed relative stability, while the herbs varied. All adverse events were mild and were not related to study treatment. CONCLUSION: CM treatment based on syndrome differentiation can increase TST and improve sleep quality of primary insomnia. It is effective and safe for primary insomnia. In future studies, the long-term efficacy validation and the exploratory of eutherapeutic clinicians' fixed herb formulas should be addressed (Registration No. NCT01613183).

Profuse color-evolution based aptasensor for mucin 1 detection utilizing urease-mediated color mixing of the mixed pH indicator.

Mucin 1 is a significant tumor marker, and developing portable and cost-effective methods for its detection is crucial, especially in resource-limited areas. Herein, we developed an innovative approach for mucin 1 detection using a visible multicolor aptasensor. Urease-encapsulated DNA microspheres were used to mediate multicolor change facilitated by the color mixing of the mixed pH indicator, a mixed methyl red and bromocresol green solution. Distinct color changes were exhibited in response to varying mucin 1 concentrations. Notably, the color mixing of the mixed pH indicator was used to display various hues of colors, broadening the range of color variation. And color tonality is much easier to differentiate than color intensity, improving the resolution with naked-eyes. Besides, the variation of color from red to green (a pair of complementary colors) enhanced the color contrast, heightening sensitivity for visual detection. Importantly, the proposed method was successfully applied to detect mucin 1 in real samples, demonstrating a clear differentiation of colors between the samples of healthy individuals and breast cancer patients. The use of a mixed pH indicator as a multichromatic substrate offers the merits of low cost, fast response to pH variation, and plentiful color-evolution. And the incorporation of calcium carbonate microspheres to encapsulate urease ensures stable urease activity and avoids the need for extra urease decoration. The color-mixing dependent strategy opens a new way for multicolor detection of MUC1, characterized by vivid color changes.

Can environmental policies improve marine ecological efficiency? Examining China's Ecological Civilization Pilot Zones.

Terrestrial ecosystems can benefit from environmental protection policies; however, their impact on marine ecological efficiency deserves further exploration. This study uses China's Ecological Civilization Pilot Zone (ECZ) policy as an example of a quasi-natural experimental study, with data from 11 coastal provinces in China from 2006 to 2019 as the initial sample. First, a Super-SBM model considers undesired outputs to measure marine eco-efficiency, while a synthetic control method (SCM) investigates the effect of environmental regulations on marine eco-efficiency. The results show that ECZ policies can promote marine eco-efficiency and the effect mechanisms of these policies are discussed from national and regional perspectives. This study contributes to the current literature by theoretically evaluating the impact of ECZ policies on the marine environment in coastal areas, enriching the mechanism of integrated environmental policies on marine ecological protection, and providing references for formulating and implementing environmental policies.

Mechanisms of angiogenesis in tumour.

Angiogenesis is essential for tumour growth and metastasis. Antiangiogenic factor-targeting drugs have been approved as first line agents in a variety of oncology treatments. Clinical drugs frequently target the VEGF signalling pathway during sprouting angiogenesis. Accumulating evidence suggests that tumours can evade antiangiogenic therapy through other angiogenesis mechanisms in addition to the vascular sprouting mechanism involving endothelial cells. These mechanisms include (1) sprouting angiogenesis, (2) vasculogenic mimicry, (3) vessel intussusception, (4) vascular co-option, (5) cancer stem cell-derived angiogenesis, and (6) bone marrow-derived angiogenesis. Other non-sprouting angiogenic mechanisms are not entirely dependent on the VEGF signalling pathway. In clinical practice, the conversion of vascular mechanisms is closely related to the enhancement of tumour drug resistance, which often leads to clinical treatment failure. This article summarizes recent studies on six processes of tumour angiogenesis and provides suggestions for developing more effective techniques to improve the efficacy of antiangiogenic treatment.

Shape-memory microfluidic chips for fluid and droplet manipulation.

Fluid manipulation is an important foundation of microfluidic technology. Various methods and devices have been developed for fluid control, such as electrowetting-on-dielectric-based digital microfluidic platforms, microfluidic pumps, and pneumatic valves. These devices enable precise manipulation of small volumes of fluids. However, their complexity and high cost limit the commercialization and widespread adoption of microfluidic technology. Shape memory polymers as smart materials can adjust their shape in response to external stimuli. By integrating shape memory polymers into microfluidic chips, new possibilities for expanding the application areas of microfluidic technology emerge. These shape memory polymers can serve as actuators or regulators to drive or control fluid flow in microfluidic systems, offering innovative approaches for fluid manipulation. Due to their unique properties, shape memory polymers provide a new solution for the construction of intelligent and automated microfluidic systems. Shape memory microfluidic chips are expected to be one of the future directions in the development of microfluidic technology. This article offers a summary of recent research achievements in the field of shape memory microfluidic chips for fluid and droplet manipulation and provides insights into the future development direction of shape memory microfluidic devices.

A ratiometric fluorescence probe for bisulfite detection in live cells and meat samples.

The development of reliable probe technology for the detection of bisulfite (HSO3-) in situ in food and biological samples is contributing significantly to food quality and safety assurance as well as community health. In this work, a responsive probe, EHDI, is developed for ratiometric fluorescence detection of HSO3- in aqueous solution, meat samples, and living cells. The probe is designed based on the HSO3- triggered 1,4-addition of electron deficit C = C bond of EHDI. As a result of this specific 1,4-addition, the π-conjugation system was destructed, resulting in blue shifts of the emission from 687 to 440 nm and absorption from 577 to 355 nm. The probe has good water solubility, high sensitivity and selectivity, allowing it to be used for imaging of HSO3- internalization and production endogenously. The capability of probe EHDI for HSO3- was then validated by traditional HPLC technology, enabling accurately detect HSO3- in beef samples. The successful development of this probe thus offers a new tool for investigating HSO3- in situ in food and biological conditions.

Pressure and multicolor dual-mode detection of mucin 1 based on the pH-regulated dual-enzyme mimic activities of manganese dioxide nanosheets.

Mucin 1 is an essential tumor biomarker, and developing cost-effective and portable methods for mucin 1 detection is crucial in resource-limited settings. Herein, the pH-regulated dual-enzyme mimic activities of manganese dioxide nanosheets were demonstrated, which were integrated into an aptasensor for dual-mode detection of mucin 1. Under acidic conditions, manganese dioxide nanosheets with oxidase mimic activities catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine sulfate, producing visible multicolor signals; while under basic conditions, manganese dioxide nanosheets with catalase mimic activities were used as catalyst for the decomposition of hydrogen peroxide, generating gas pressure signals. The proposed method allows the naked eye detection of mucin 1 through multicolor signal readout and the quantitative detection of mucin 1 with a handheld pressure meter or a UV-vis spectrophotometer. The study demonstrates that manganese dioxide nanosheets with pH-regulated dual-enzyme mimic activities can facilitate multidimensional transducing signals. The use of manganese dioxide nanosheets for the transduction of different signals avoids extra labels and simplifies the operation procedures. Besides, the signal readout mode can be selected according to the available detection instruments. Therefore, the use of manganese dioxide nanosheets with pH-regulated dual-enzyme mimic activities for dual-signal readout provides a new way for mucin 1 detection.

Low serum total cholesterol levels predict inferior prognosis of patients with POEMS syndrome.

Low serum cholesterol levels are associated with increased tumor morbidity and mortality. However, the relationship between serum lipid profile and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is still unclear. The aim of our study was to clarify the importance of the serum lipid profile in predicting the severity and prognosis of patients with POEMS syndrome. Forty-three patients with newly diagnosed POEMS syndrome admitted to the Department of Hematology of Jiangsu Provincial People's Hospital between August 2013 and February 2023 were selected. They had explicit serum lipid profiles. There were 27 males and 16 females with a median age of 54 years (range, 28-77 years). Survival curves were plotted using the Kaplan-Meier method, and comparisons between the two groups were performed using the log-rank test. The Cox proportional-hazards model examined risk factors associated with the prognosis of POEMS syndrome. Receiver-operator characteristic (ROC) curves assessed the predictive accuracy. 23 (53.5%) patients had low total cholesterol (TC) levels. Low levels of TC were concerned with unfavorable progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.004), and at the same time, the low circulating TC concentration was an independent risk factor for PFS (p = 0.020) and OS (p = 0.011). Low TC values could improve the risk stratification, especially in high-risk patients. In conclusion, low serum TC levels may predict inferior prognosis in patients with POEMS syndrome; in future clinical application, low TC may be a reliable indicator of prognosis.

Circ-Bptf Ameliorates Learning and Memory Impairments via the miR-138-5p/p62 Axis in APP/PS1 Mice.

Alzheimer's disease (AD) is a common age-associated progressive neurodegenerative disorder that is implicated in the aberrant regulation of numerous circular RNAs (circRNAs). Here, we reported that circ-Bptf, a conserved circRNA derived from the Bptf gene, showed an age-dependent decrease in the hippocampus of APP/PS1 mice. Overexpression of circ-Bptf significantly reversed dendritic spine loss and learning and memory impairment in APP/PS1 mice. Moreover, we found that circ-Bptf was predominantly localized to the cytoplasm and upregulated p62 expression by binding to miR-138-5p. Furthermore, the miR-138-5p mimics reversed the decreased expression of p62 induced by the silencing of circ-Bptf. Together, our findings suggested that circ-Bptf ameliorated learning and memory impairments via the miR-138-5p/p62 axis in APP/PS1 mice. It may act as a potential player in AD pathogenesis and therapy.

Qualitative and Quantitative Analytical Techniques of Nucleic Acid Modification Based on Mass Spectrometry for Biomarker Discovery.

Nucleic acid modifications play important roles in biological activities and disease occurrences, and have been considered as cancer biomarkers. Due to the relatively low amount of nucleic acid modifications in biological samples, it is necessary to develop sensitive and reliable qualitative and quantitative methods to reveal the content of any modifications. In this review, the key processes affecting the qualitative and quantitative analyses are discussed, such as sample digestion, nucleoside extraction, chemical labeling, chromatographic separation, mass spectrometry detection, and data processing. The improvement of the detection sensitivity and specificity of analytical methods based on mass spectrometry makes it possible to study low-abundance modifications and their biological functions. Some typical nucleic acid modifications and their potential as biomarkers are displayed, and efforts to improve diagnostic accuracy are discussed. Future perspectives are raised for this research field.

Recent Advances in Detection of Hydroxyl Radical by Responsive Fluorescence Nanoprobes.

Hydroxyl radical (•OH), a highly reactive oxygen species (ROS), is assumed as one of the most aggressive free radicals. This radical has a detrimental impact on cells as it can react with different biological substrates leading to pathophysiological disorders, including inflammation, mitochondrion dysfunction, and cancer. Quantification of this free radical in-situ plays critical roles in early diagnosis and treatment monitoring of various disorders, like macrophage polarization and tumor cell development. Luminescence analysis using responsive probes has been an emerging and reliable technique for in-situ detection of various cellular ROS, and some recently developed •OH responsive nanoprobes have confirmed the association with cancer development. This paper aims to summarize the recent advances in the characterization of •OH in living organisms using responsive nanoprobes, covering the production, the sources of •OH, and biological function, especially in the development of related diseases followed by the discussion of luminescence nanoprobes for •OH detection.

Crystal Thermal Transport in Altermagnetic RuO_{2}.

We demonstrate the emergence of a pronounced thermal transport in the recently discovered class of magnetic materials-altermagnets. From symmetry arguments and first-principles calculations performed for the showcase altermagnet, RuO_{2}, we uncover that crystal Nernst and crystal thermal Hall effects in this material are very large and strongly anisotropic with respect to the Néel vector. We find the large crystal thermal transport to originate from three sources of Berry's curvature in momentum space: the Weyl fermions due to crossings between well-separated bands, the strong spin-flip pseudonodal surfaces, and the weak spin-flip ladder transitions, defined by transitions among very weakly spin-split states of similar dispersion crossing the Fermi surface. Moreover, we reveal that the anomalous thermal and electrical transport coefficients in RuO_{2} are linked by an extended Wiedemann-Franz law in a temperature range much wider than expected for conventional magnets. Our results suggest that altermagnets may assume a leading role in realizing concepts in spin caloritronics not achievable with ferromagnets or antiferromagnets.

Isomorphic Insertion of Ce(III)/Ce(IV) Centers into Layered Double Hydroxide as a Heterogeneous Multifunctional Catalyst for Efficient Meerwein-Ponndorf-Verley Reduction.

The development of highly active acid-base catalysts for transfer hydrogenations of biomass derived carbonyl compounds is a pressing challenge. Solid frustrated Lewis pairs (FLP) catalysis is possibly a solution, but the development of this concept is still at a very early stage. Herein, stable, phase-pure, crystalline hydrotalcite-like compounds were synthesized by incorporating cerium cations into layered double hydroxide (MgAlCe-LDH). Besides the insertion of well-isolated cerium centers surrounded by hydroxyl groups, the formation of hydroxyl vacancies near the aluminum centers, which were formed by the insertion of cerium centers into the layered double hydroxides (LDH) lattice, was also identified. Depending on the initial cerium concentration, LDHs with different Ce(III)/Ce(IV) ratios were produced, which had Lewis acidic and basic characters, respectively. However, the acid-base character of these LDHs was related to the actual Ce(III)/Ce(IV) molar ratios, resulting in significant differences in their catalytic performance. The as-prepared structures enabled varying degrees of transfer hydrogenation (Meerwein-Ponndorf-Verley MPV reduction) of biomass-derived carbonyl compounds to the corresponding alcohols without the collapse of the original lamellar structure of the LDH. The catalytic markers through the test reactions were changed as a function of the amount of Ce(III) centers, indicating the active role of Ce(III)-OH units. However, the cooperative interplay between the active sites of Ce(III)-containing specimens and the hydroxyl vacancies was necessary to maximize catalytic efficiency, pointing out that Ce-containing LDH is a potentially commercial solid FLP catalysts. Furthermore, the crucial role of the surface hydroxyl groups in the MPV reactions and the negative impact of the interlamellar water molecules on the catalytic activity of MgAlCe-LDH were demonstrated. These solid FLP-like catalysts exhibited excellent catalytic performance (cyclohexanol yield of 45%; furfuryl alcohol yield of 51%), which is competitive to the benchmark Sn- and Zr-containing zeolite catalysts, under mild reaction conditions, especially at low temperature (T = 65 °C).

Advances and Perspectives of Responsive Probes for Measuring γ-Glutamyl Transpeptidase.

Gamma-glutamyltransferase (GGT) is a plasma-membrane-bound enzyme that is involved in the γ-glutamyl cycle, like metabolism of glutathione (GSH). This enzyme plays an important role in protecting cells from oxidative stress, thus being tested as a key biomarker for several medical conditions, such as liver injury, carcinogenesis, and tumor progression. For measuring GGT activity, a number of bioanalytical methods have emerged, such as chromatography, colorimetric, electrochemical, and luminescence analyses. Among these approaches, probes that can specifically respond to GGT are contributing significantly to measuring its activity in vitro and in vivo. This review thus aims to highlight the recent advances in the development of responsive probes for GGT measurement and their practical applications. Responsive probes for fluorescence analysis, including "off-on", near-infrared (NIR), two-photon, and ratiometric fluorescence response probes, are initially summarized, followed by discussing the advances in the development of other probes, such as bioluminescence, chemiluminescence, photoacoustic, Raman, magnetic resonance imaging (MRI), and positron emission tomography (PET). The practical applications of the responsive probes in cancer diagnosis and treatment monitoring and GGT inhibitor screening are then highlighted. Based on this information, the advantages, challenges, and prospects of responsive probe technology for GGT measurement are analyzed.

Real-world prognostic significance of attaining minimal residual disease negativity in newly diagnosed multiple myeloma.

The aim of the study was to evaluate the prognostic impact of minimal residual disease (MRD) in the real-world setting and the interaction between MRD and molecular risk, clinical response and autologous stem-cell transplant (ASCT). A retrospective analysis of 275 newly diagnosed multiple myeloma (NDMM) patients who achieved very good partial remission (VGPR) or better before maintenance were involved. We examined MRD status by multiparameter flow cytometry (MFC). At a median follow-up of 37 months (4-88 months), In patients who achieved ≥ VGPR, those with MRD negativity had significantly longer PFS (51 vs. 26 months; P < 0.001) and OS (Not reached: NR vs. 62 months, P < 0.001) than those with MRD positivity. MRD positivity was the independent prognostic factor for PFS with hazard ratios of 2.650 (95% CI 1.755-4.033, P < 0.001) and OS with hazard ratios of 2.122 (95% CI 1.155-3.899, P = 0.015). Achieving MRD negativity was able to ameliorate a poor prognosis associated with genetic high risk. MRD negativity was associated with better PFS regardless of ASCT treatment. MRD status was more predictable for clinical outcome than conventional clinical responses. Moreover, Sustained MRD negativity ≥ 12 or ≥ 24 months improved both PFS and OS. Patients with NDMM who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes regardless of high-risk cytogenetics, ASCT and clinical responses in a real-world setting.

Enhancing plant biotechnology by nanoparticle delivery of nucleic acids.

Plant biotechnology plays a crucial role in developing modern agriculture and plant science research. However, the delivery of exogenous genetic material into plants has been a long-standing obstacle. Nanoparticle-based delivery systems are being established to address this limitation and are proving to be a feasible, versatile, and efficient approach to facilitate the internalization of functional RNA and DNA by plants. The nanoparticle-based delivery systems can also be designed for subcellular delivery and controlled release of the biomolecular cargo. In this review, we provide a concise overview of the recent advances in nanocarriers for the delivery of biomolecules into plants, with a specific focus on applications to enhance RNA interference, foreign gene transfer, and genome editing in plants.

Modified Chinese quince oligomeric proanthocyanidin protects deep-frying oil quality by inhibiting oxidation.

Chinese quince (Chaenomeles sinensis) fruit is an underutilized resource, rich in proanthocyanidins with antioxidant ability but poor lipid solubility. In this study, a novel modified oligomeric proanthocyanidin (MOPA) was prepared, which exhibited favorable lipid solubility (354.52 mg/100 g). It showed higher radical scavenging abilities than commercial antioxidant-BHA (butylated hydroxyanisole), both at 0.4-0.5 mg/mL. The addition of MOPA (0.04 %wt.) significantly increased the oxidative stability index of the soybean oil from 5.52 to 8.03 h, which was slightly lower than that of BHA (8.35 h). Analysis of the physicochemical properties and composition of oil during deep-frying showed that MOPA demonstrated significant antioxidant effects and effectively restricted the oil oxidation. This inhibition also delays the formation of heterocyclic amines (HAs) in fried food, thereby reducing the migration of HAs from food to deep-frying oil. Therefore, MOPA is a promising novel liposoluble antioxidant for protecting the quality of deep-frying oil.

Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer.

OBJECTIVES: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. METHODS: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. RESULTS: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. CONCLUSIONS: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. Video Abstract.