Oleandrin enhances radiotherapy sensitivity in lung cancer by inhibiting the ATM/ATR-mediated DNA damage response.

Despite active clinical trials on the use of Oleandrin alone or in combination with other drugs for the treatment of solid tumors, the potential synergistic effect of Oleandrin with radiotherapy remains unknown. This study reveals a new mechanism by which Oleandrin targets ATM and ATR kinase-mediated radiosensitization in lung cancer. Various assays, including clonogenic, Comet, immunofluorescence staining, apoptosis and Cell cycle assays, were conducted to evaluate the impact of oleandrin on radiation-induced double-strand break repair and cell cycle distribution. Western blot analysis was utilized to investigate alterations in signal transduction pathways related to double-strand break repair. The efficacy and toxicity of the combined therapy were assessed in a preclinical xenotransplantation model. Functionally, Oleandrin weakens the DNA damage repair ability and enhances the radiation sensitivity of lung cells. Mechanistically, Oleandrin inhibits ATM and ATR kinase activities, blocking the transmission of ATM-CHK2 and ATR-CHK1 cell cycle checkpoint signaling axes. This accelerates the passage of tumor cells through the G2 phase after radiotherapy, substantially facilitating the rapid entry of large numbers of inadequately repaired cells into mitosis and ultimately triggering mitotic catastrophe. The combined treatment of Oleandrin and radiotherapy demonstrated superior inhibition of tumor proliferation compared to either treatment alone. Our findings highlight Oleandrin as a novel and effective inhibitor of ATM and ATR kinase, offering new possibilities for the development of clinical radiosensitizing adjuvants.

[The involvement and underlying mechanism of the aryl hydrocarbon receptor (AhR) in the impairment of male mammalian fertility induced by environmental pollutants].

In recent decades, there has been a consistent decline in semen quality across the globe, with environmental pollution emerging as the predominant factor. Persistent organic pollutants (POPs) have garnered considerable attention due to their potent biological toxicity and resistance to natural degradation. Within this class of pollutants, polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) have been identified as detrimental agents that can disrupt cellular physiological functions by activating aryl hydrocarbon receptor (AhR). However, the precise role of AhR in the adverse effects of environmental pollutants on male mammalian fertility remains incompletely understood. This article provides a comprehensive review of the impact of various environmental pollutants, specifically PAHs such as benzo[a]pyrene, 3-methylcholanthrene, and 7,12-dimethylbenzo[a]anthracene, HAHs including 2,3,7,8-tetrachlorodibenzo-p-dioxins, polychlorinated biphenyls, polybrominated diphenyl ethers, and the pollutant complex PM2.5, as well as cigarette smoke condensates, on male mammalian reproductive function. Additionally, this review focuses on the role of the AhR in mediating these effects. The objective of this review is to elucidate the involvement of AhR in the regulation of male mammalian fertility, thereby offering insights for prospective investigations into the interplay between AhR and male reproductive function, as well as the etiology of idiopathic male infertility in clinic.

Nattokinase's Neuroprotective Mechanisms in Ischemic Stroke: Targeting Inflammation, Oxidative Stress, and Coagulation.

Aims: Nattokinase (NK), a potent serine endopeptidase, has exhibited a variety of pharmacological effects, including thrombolysis, anti-inflammation, and antioxidative stress. Building on previous research highlighting NK's promise in nerve regeneration, our study investigated whether NK exerted protective effects in transient middle cerebral artery occlusion (tMCAO)-induced cerebral ischemia-reperfusion injury and the underlying mechanisms. Results: The rats were administered NK (5000, 10000, 20000 FU/kg, i.g., 7 days before surgery, once daily). We showed that NK treatment dose dependently reduced the infarction volume and improved neurological symptoms, decreased the proinflammatory and coagulation cytokines levels, and attenuated reactive oxygen species (ROS) in the infarcted area of tMCAO rats. We also found that NK could exert neuroprotective effects in a variety of vitro models, including the microglia inflammation model and neuronal oxygen-glucose deprivation/reperfusion (OGD/R) model. Notably, NK effectively countered OGD/R-induced neuron death, modulating diverse pathways, including autophagy, apoptosis, PARP-dependent death, and endoplasmic reticulum stress. Furthermore, the neuroprotection of NK was blocked by phenylmethylsulfonyl fluoride (PMSF), a serine endopeptidase inhibitor. We revealed that heat-inactive NK was unable to protect against tMCAO injury and other vitro models, suggesting NK attenuated ischemic injury by its enzymatic activity. We conducted a proteomic analysis and found inflammation and coagulation were involved in the occurrence of tMCAO model and in the therapeutic effect of NK. Innovation and Conclusion: In conclusion, these data demonstrated that NK had multifaceted neuroprotection in ischemic brain injury, and the therapeutic effect of NK was related with serine endopeptidase activity.

Tadpole-Like Polar Molecule Encapsulated in a Two-in-One Supramolecular Cage: Molecular Motion, Phase Transition and Ferroelectricity.

Molecule-inclusive closed cage compounds present a unique platform for molecular motion in an isolated environment. This study showcases the incorporation of a tadpole-like polar molecule (1-propyl-1H-imidazole, PIm) into a supramolecular cage formed by duad semicage p-tert-butylcalix[4]arene. The ferroelectric phase transition as well as the cage-confined motion of encapsulated PIm was studied in detail. The unusual quadrastable state of the PIm in the paraelectric phase allows for the modulation of dipolar polarization over a broad temperature/frequency range. This compound represents the first example of a clathrate molecular ferroelectric featuring a molecule-inclusive supramolecular cage, and it also contributes to the understanding of cage-confined molecular dynamics.

Silk-based intelligent fibers and textiles: structures, properties, and applications.

Multifunctional fibers represent a cornerstone of human civilization, playing a pivotal role in numerous aspects of societal development. Natural biomaterials, in contrast to synthetic alternatives, offer environmental sustainability, biocompatibility, and biodegradability. Among these biomaterials, natural silk is favored in biomedical applications and smart fiber technology due to its accessibility, superior mechanical properties, diverse functional groups, controllable structure, and exceptional biocompatibility. This review delves into the intricate structure and properties of natural silk fibers and their extensive applications in biomedicine and smart fiber technology. It highlights the critical significance of silk fibers in the development of multifunctional materials, emphasizing their mechanical strength, biocompatibility, and biodegradability. A detailed analysis of the hierarchical structure of silk fibers elucidates how these structural features contribute to their unique properties. The review also encompasses the biomedical applications of silk fibers, including surgical sutures, tissue engineering, and drug delivery systems, along with recent advancements in smart fiber applications such as sensing, optical technologies, and energy storage. The enhancement of functional properties of silk fibers through chemical or physical modifications is discussed, suggesting broader high-end applications. Additionally, the review addresses current challenges and future directions in the application of silk fibers in biomedicine and smart fiber technologies, underscoring silk's potential in driving contemporary technological innovations. The versatility and sustainability of silk fibers position them as pivotal elements in contemporary materials science and technology, fostering the development of next-generation smart materials.

Identification of stable reference genes for relative quantification of long RNA expression in urinary extracellular vesicles.

Urinary extracellular vesicles (uEVs) are rich in valuable biomolecule information which are increasingly recognized as potential biomarkers for various diseases. uEV long RNAs are among the critical cargos capable of providing unique transcriptome information of the source cells. However, consensus regarding ideal reference genes for relative long RNAs quantification in uEVs is not available as of date. Here we explored stable reference genes through profiling the long RNA expression by RNA-seq following unsupervised analysis and validation studies. Candidate reference genes were identified using four algorithms: NormFinder, GeNorm, BestKeeper and the Delta Ct method, followed by validation. RNA profile showed uEVs contained abundant long RNAs information and the core transcriptome was related to cellular structures, especially ribosome which functions mainly as translation, protein and RNA binding molecules. Analysis of RNA-seq data identified RPL18A, RPL11, RPL27, RACK1, RPSA, RPL41, H1-2, RPL4, GAPDH, RPS27A as candidate reference genes. RT-qPCR validation revealed that RPL41, RPSA and RPL18A were reliable reference genes for long RNA quantification in uEVs from patients with diabetes mellitus (DM), diabetic nephropathy (DN), IgA nephropathy (IgAN) and prostate cancer (PCA). Interestingly, RPL41 also outperformed traditional reference genes in renal tissues of DN and IgAN, as well as in plasma EVs of several types of cancers. The stable reference genes identified in this study may facilitate development of uEVs as novel biomarkers and increase the accuracy and comparability of biomarker studies.

Exploring the therapeutic mechanisms of Coptidis Rhizoma in gastric precancerous lesions: a network pharmacology approach.

BACKGROUND: Gastric precancerous lesions are a critical stage in the development of gastric cancer or gastric adenocarcinoma, and their outcome plays an important role in the malignant progression of gastric cancer. Coptidis Rhizoma has a good effect on Gastric precancerous lesions. However, the specific mechanisms of its action remain incompletely elucidated. METHODS: Network pharmacology and molecular docking techniques were used to explore the active ingredients and molecular mechanism of Coptidis Rhizoma in treating gastric precancerous lesions. The active compounds of Coptidis Rhizoma and their potential gastric precancerous lesions related targets were obtained from TCMSP, GeneCards, and OMIM databases. An interaction network based on protein-protein interactions (PPIs) was constructed to visualize the interactions between hub genes. Analysis of GO enrichment and KEGG pathway were conducted using the DAVID database. An investigation of interactions between active compounds and potential targets was carried out by molecular docking. Finally, animal experiments were conducted to verify the effect and mechanism of Coptidis Rhizoma in treating precancerous lesions of gastric cancer. RESULTS: A total of 11 active compounds and 95 anti-gastric precancerous lesions targets of Coptidis Rhizoma were screened for analysis. GO enrichment analysis showed that the mechanism of Coptidis Rhizoma acting on gastric precancerous lesions involves gene expression regulation and apoptosis regulation. KEGG pathway enrichment analysis showed that Coptidis Rhizoma against gastric precancerous lesions involving the AKT /HIF-1α/VEGF signalling pathway. Molecular docking simulations indicated potential interactions between these compounds and core targets involved in anti-gastric precancerous lesions activity. In addition, it was confirmed in vivo that Berberine and Coptidis Rhizoma may reverse atrophy and potential intestinal metaplasia by inhibiting the expression of p-AKT, HIFA, and VEGF. CONCLUSION: Bioactive compounds in Coptidis Rhizoma have the potential to prevent atrophy and intestinal metaplasia. These compounds function by regulating the proteins implicated in AKT /HIF-1α/VEGF signalling pathways that are crucial in gastric epithelial cell differentiation, proliferation and maturation.

Controlling the nutritional status score: a new tool for predicting postoperative mortality in patients with infrarenal abdominal aortic aneurysm treated with endovascular aneurysm repair.

Background: AAA is a fatal condition that commonly occurs during vascular surgery. Nutritional status exerts a significant influence on the prognosis of various pathological conditions Scores from the CONUT screening tool have been shown to predict outcomes of certain malignancies and chronic diseases. However, the ramifications of nutritional status on AAA patients undergoing EVAR have not been elucidated in prior studies. In this study, we aimed to elucidate the correlation between CONUT scores and postoperative prognostic outcomes in patients with AAA undergoing EVAR. Methods: This was a retrospective review of 177 AAA patients treated with EVAR from June 2018 to November 2019 in a single center. Patient characteristics, CONUT scores, and postoperative status were collected. These patients were stratified into groups A and B according to CONUT scores. Subsequently, a comparative analysis of the baseline characteristics between the two cohorts was conducted. Cox proportional hazards and logistic regression analyses were employed to identify the autonomous predictors of mid-term mortality and complications, respectively. Results: Compared with group A, patients in group B had higher midterm mortality (p < 0.001). Univariate analysis showed that CONUT scores; respiratory diseases; stent types; preoperative Hb, CRP, PT, and Fb levels were risk factors for death. Multivariate analysis confirmed that CONUT score [HR, 1.276; 95% CI, 1.029-1.584; p = 0.027] was an independent risk factor for mortality. Logistic regression analysis showed that prior arterial disease, smoking, and D-dimer levels were risk factors, although multivariate analysis showed smoking (OR, 3.492; 95% CI, 1.426-8.553; p = 0.006) was an independent risk factor. Kaplan-Meier curves showed that patients in group B had shorter mid-term survival than those in group A (log-rank p < 0.001). Conclusion: Malnutrition was strongly associated with mid-term mortality in patients with infrarenal AAA treated with EVAR.

Extracellular Vesicles Containing circMYBL1 Induce CD44 in Adenoid Cystic Carcinoma Cells and Pulmonary Endothelial Cells to Promote Lung Metastasis.

Adenoid cystic carcinoma (ACC) is a rare malignant epithelial neoplasm that arises in secretory glands and commonly metastasizes to the lungs. MYBL1 is frequently overexpressed in ACC and has been suggested to be a driver of the disease. In this study, we identified a circular RNA (circRNA) derived from MYBL1 pre-mRNA that was accompanied by the overexpression of MYBL1 in ACC. Overexpression of circMYBL1 was correlated with increased lung metastasis and poor overall survival in patients with ACC. Ectopic circMYBL1 overexpression promoted malignant phenotypes and lung metastasis of ACC cells. Mechanistically, circMYBL1 formed a circRNA-protein complex with CCAAT enhancer-binding protein ß (CEBPB), which inhibited ubiquitin-mediated degradation and promoted nuclear translocation of CEBPB. In the nucleus, circMYBL1 increased the binding of CEBPB to the CD44 promoter region and enhanced its transcription. In addition, circMYBL1 was enriched in small extracellular vesicles (sEV) isolated from the plasma of patients with ACC. Treatment with sEVs containing circMYBL1 in sEVs enhanced prometastatic phenotypes of ACC cells, elevated the expression of CD44 in human pulmonary microvascular endothelial cells (HPMEC), and enhanced the adhesion between HPMECs and ACC cells. Moreover, circMYBL1 encapsulated in sEVs increased the arrest of circulating ACC cells in the lung and enhanced lung metastatic burden. These data suggest that circMYBL1 is a tumor-promoting circRNA that could serve as a potential biomarker and therapeutic target for ACC. Significance: circMYBL1 stabilizes CEBPB and upregulates CD44 to promote adhesion between cancer cells and endothelial cells and enables lung metastasis of adenoid cystic carcinoma, suggesting that inhibition of this axis could improve patient outcomes.

Applicability of the generalized wind profile model over mountainous forests.

The analytical equation based on Monin-Obukhov (M-O) similarity theory (i.e., wind profile equation) has been adopted since 1970s for using in the prediction of wind vertical profile over flat terrains, which is mature and accurate. However, its applicability over complex terrains remains unknown. This applicability signifies the accuracy of the estimations of aerodynamic parameters for the boundary layer of non-flat terrain, such as zero-displacement height (d) and aerodynamic roughness length (z0), which will determine the accuracy of frequency correction and source area analysis in calculating carbon, water, and trace gas fluxes based on vorticity covariance method. Therefore, the validation of wind profile model in non-flat terrain is the first step to test whether the flux model needs improvement. We measured three-dimensional wind speed data by using the Ker Towers (three towers in a watershed) at Qingyuan Forest CERN in the Mountainous Region of east Liaoning Province, and compared them with data from Panjin Agricultural Station in the Liaohe Plain, to evaluate the applicability of a generalized wind profile model based on the Monin-Obukhov similarity theory on non-flat terrain. The results showed that the generalized wind profile model could not predict wind speeds accurately of three flux towers separately located in different sites, indicating that wind profile model was not suitable for predicting wind speeds in complex terrains. In the leaf-off and leaf-on periods, the coefficient of determination (R2) between observed and predicted wind speeds ranged from 0.12 to 0.30. Compared to measured values, the standard error of the predicted wind speeds was high up to 2 m·s-1. The predicted wind speeds were high as twice as field-measured wind speed, indicating substantial overestimation. Nevertheless, this model correctly predicted wind speeds in flat agricultural landscape in Panjin Agricultural Station. The R2 between observed wind speeds and predicted wind speed ranged from 0.90 to 0.93. The standard error between observed and predicted values was only 0.5 m·s-1. Results of the F-test showed that the root-mean-square error of the observed and predicted wind speeds in each secondary forest complex terrain was much greater than that in flat agricultural landscape. Terrain was the primary factor affecting the applicability of wind profile model, followed by seasonality (leaf or leafless canopy). The wind profile model was not applicable to the boundary-layer flows over forest canopies in complex terrains, because the d was underestimated or both the d and z0 were underestimated, resulting in inaccurate estimation of aerodynamic height.

Advances and Challenges in Electrolyte Development for Magnesium-Sulfur Batteries: A Comprehensive Review.

Magnesium-sulfur batteries are an emerging technology. With their elevated theoretical energy density, enhanced safety, and cost-efficiency, they have the ability to transform the energy storage market. This review investigates the obstacles and progress made in the field of electrolytes which are especially designed for magnesium-sulfur batteries. The primary focus of the review lies in identifying electrolytes that can facilitate the reversible electroplating and stripping of Mg2+ ions whilst maintaining compatibility with sulfur cathodes and other battery components. The review also addresses the critical issue of managing the shuttle effect on soluble magnesium polysulfide by looking at the innovative engineering methods used at the sulfur cathode's interface and in the microstructure design, both of which can enhance the reaction kinetics and overall battery efficiency. This review emphasizes the significance of reaction mechanism analysis from the recent studies on magnesium-sulfur batteries. Through analysis of the insights proposed in the latest literature, this review identifies the gaps in the current research and suggests future directions which can enhance the electrochemical performance of Mg-S batteries. Our analysis highlights the importance of innovative electrolyte solutions and provides a deeper understanding of the reaction mechanisms in order to overcome the existing barriers and pave the way for the practical application of Mg-S battery technology.

ALMS1-IT1: A Key Player in the Novel Disulfidptosis-Related LncRNA Prognostic Signature for Head and Neck Squamous Cell Carcinoma.

Disulfidptosis is a newly discovered form of programmed cell death that is induced by disulfide stress. It is closely associated with various cancers, including head and neck squamous cell carcinoma (HNSCC). However, the factors involved in the modulation of disulfidptosis-related genes (DRGs) still remain unknown. In this study, we established and validated a novel risk score model composed of 11 disulfidptosis-related lncRNAs (DRLs) based on 24 DRGs in HNSCC. The results revealed strong correlations between the 11-DRL prognostic signature and clinicopathological features, immune cell infiltration, immune-related functions, and disulfidptosis-associated pathways, including NADPH and disulfide oxidoreductase activities. Furthermore, we studied and verified the involvement of ALMS1-IT1, one of the 11 model DRLs, in the disulfidptosis of HNSCC cell lines. A series of assays demonstrated that ALMS1-IT1 modulated cell death under starvation conditions in a pentose phosphate pathway (PPP)-dependent manner. Knockdown of ALMS1-IT1 inhibited the PPP, contributing to a decline in NADPH levels, which resulted in the formation of multiple intermolecular disulfide bonds between actin cytoskeleton proteins and the collapse of F-actin in the cytoplasm. Therefore, ALMS1-IT1, which is highly expressed in SLC7A11high cells, can be considered a promising therapeutic target for disulfidptosis-focused treatment strategies for cancer and other diseases.

Advances of Layered Double Hydroxide-Based Materials for Tumor Imaging and Therapy.

Layered double hydroxides (LDH) are a class of functional anionic clays that typically consist of orthorhombic arrays of metal hydroxides with anions sandwiched between the layers. Due to their unique properties, including high chemical stability, good biocompatibility, controlled drug loading, and enhanced drug bioavailability, LDHs have many potential applications in the medical field. Especially in the fields of bioimaging and tumor therapy. This paper reviews the research progress of LDHs and their nanocomposites in the field of tumor imaging and therapy. First, the structure and advantages of LDH are discussed. Then, several commonly used methods for the preparation of LDH are presented, including co-precipitation, hydrothermal and ion exchange methods. Subsequently, recent advances in layered hydroxides and their nanocomposites for cancer imaging and therapy are highlighted. Finally, based on current research, we summaries the prospects and challenges of layered hydroxides and nanocomposites for cancer diagnosis and therapy.

Inflammation-related molecular signatures involved in the anticancer activities of brigatinib as well as the prognosis of EML4-ALK lung adenocarcinoma patient.

Although ALK tyrosine kinase inhibitors (ALK-TKIs) have shown remarkable benefits in EML4-ALK positive NSCLC patients compared to conventional chemotherapy, the optimal sequence of ALK-TKIs treatment remains unclear due to the emergence of primary and acquired resistance and the lack of potential prognostic biomarkers. In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed responsiveness to brigatinib and ceritinib. Transcriptomic analysis revealed that brigatinib suppressed the activation of multiple inflammatory signaling pathways, potentially contributing to its anti-tumor activity. Moreover, we constructed a prognostic model based on the expression of IL6, CXCL1, and CXCL5, providing novel perspectives for predicting prognosis in EML4-ALK positive NSCLC patients. In summary, our results delineate clinical responses of sequential ALK-TKIs treatments and provide insights into the mechanisms underlying the superior effects of brigatinib in patients harboring ALKG1269A mutation and resistant towards alectinib, lorlatinib and crizotinib. The molecular signatures model based on the combination of IL6, CXCL1 and CXCL5 has the potential to predict prognosis of EML4-ALK positive NSCLC patients.

[Comparison on biological activities of Lycium barbarum polysaccharides extracted with five methods].

Studying the physicochemical properties and biological activities of Lycium barbarum polysaccharides(LBPs) is of great significance. The previous study had extracted LBPs(LBP-1, LBP-2, LBP-3, LBP-4, and LBP-5) by five different methods(cold water extraction, boiling water reflux extraction of the residue after cold water extraction, ultrasonic extraction with 50% ethanol, ultrasonic extraction with 25% ethanol of the residue after 50% ethanol extraction, and hot water extraction). In this study, the structures of the obtained five LBPs were characterized by UV spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Furthermore, the antioxidant, blood lipid-lowering, nitrosation-inhibting, acetylcholinesterase-inhibiting, and tyrosinase-inhibiting activities of the five LBPs were measured in vitro. The results showed that high-temperature extraction destroyed the polysaccharide structure, while ultrasound-assisted extraction ensured the structural integrity. The thermal stability and degradation behaviors differed among the five LBPs. However, the UV spectroscopic results of the five LBPs did not show significant differences, and all of the five LBPs showed the characteristic absorption peaks of proteins. LBP-3 and LBP-4 exhibited strong antioxidant activity, while LBP-3 had the strongest blood lipid-lowering activity. In addition, LBP-3 outperformed other LBPs in inhibiting nitrosation and acetylcholineste-rase, and LBP-2 showed the strongest inhibitory effect on tyrosinase. This study explored the effects of different extraction methods on the physicochemical properties and biological activities of LBPs, with a view to providing a basis for the selection of suitable extraction methods to obtain LBPs with ideal biological activities.

Investigating the Integration and the Long-Term Use of Smart Speakers in Older Adults' Daily Practices: Qualitative Study.

BACKGROUND: As smart speakers become more popular, there have been an increasing number of studies on how they may benefit older adults or how older adults perceive them. Despite the increasing ownership rates of smart speakers among older adults, studies that examine their integration and the long-term use in older adults' daily practices are scarce. OBJECTIVE: This study aims to uncover the integration of smart speakers into the daily practices of older adults over the long term, contributing to an in-depth understanding of maintained technology use among this demographic. METHODS: To achieve these objectives, the study interviewed 20 older adults who had been using smart speakers for over 6 months. These semistructured interviews enabled participants to share their insights and experiences regarding the maintained use of smart speakers in the long term. RESULTS: We identified 4 dimensions of the long-term use of smart speakers among older adults, including functional integration, spatial integration, cognitive integration, and semantic integration. For the functional integration of smart speakers, the study reported different types of use, including entertainment, information collection, medication reminders, companionship, environment modification, and emergency calls. For the spatial integration of smart speakers, the study showed older adults' agency in defining, changing, and reshaping daily practices through the spatial organization of smart speakers. For the cognitive integration of smart speakers, the findings showed the cognitive processes involved in adapting to and incorporating smart speakers into daily habits and routines. For the semantic integration of smart speakers, the findings revealed that older adults' enjoyable user experience and strong bonds with the device contributed to their acceptance of occasional functional errors. Finally, the study proposed several suggestions for designers and developers to better design smart speakers that promote maintainable use behaviors among older adults. CONCLUSIONS: On the basis of the findings, this study highlighted the importance of understanding how older adults use smart speakers and the practices through which they integrate them into their daily routines. The findings suggest that smart speakers can provide significant benefits for older adults, including increased convenience and improved quality of life. However, to promote maintainable use behaviors, designers and developers should consider more about the technology use contexts and the specific needs and preferences of older adults when designing these devices.

Efficient conversion of propane in a microchannel reactor at ambient conditions.

The oxidative dehydrogenation of propane, primarily sourced from shale gas, holds promise in meeting the surging global demand for propylene. However, this process necessitates high operating temperatures, which amplifies safety concerns in its application due to the use of mixed propane and oxygen. Moreover, these elevated temperatures may heighten the risk of overoxidation, leading to carbon dioxide formation. Here we introduce a microchannel reaction system designed for the oxidative dehydrogenation of propane within an aqueous environment, enabling highly selective and active propylene production at room temperature and ambient pressure with mitigated safety risks. A propylene selectivity of over 92% and production rate of 19.57 mmol mCu-2 h-1 are simultaneously achieved. This exceptional performance stems from the in situ creation of a highly active, oxygen-containing Cu catalytic surface for propane activation, and the enhanced propane transfer via an enlarged gas-liquid interfacial area and a reduced diffusion path by establishing a gas-liquid Taylor flow using a custom-made T-junction microdevice. This microchannel reaction system offers an appealing approach to accelerate gas-liquid-solid reactions limited by the solubility of gaseous reactant.

NAT10/CEBPB/vimentin signalling axis promotes adenoid cystic carcinoma malignant phenotypes in vitro.

OBJECTIVE: To explore the biological function and mechanisms of CEBPB and NAT10-mediated N4-acetylcytidine (ac4c) modification in salivary adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: CEBPB and NAT10 were knocked down in SACC-LM cells by siRNA transfection and overexpressed in SACC-83 cells by plasmid transfection. Malignant phenotypes were evaluated using CCK-8, Transwell migration and colony formation assays. Real-time PCR, western blotting, ChIP and acRIP were used to investigate the molecular mechanisms involved. RESULTS: We found that CEBPB was highly expressed in SACC tissues and correlated with lung metastasis and unfavourable prognosis. Gain- and loss-of-function experiments revealed that CEBPB promoted SACC malignant phenotypes. Mechanistically, CEBPB exerted its oncogenic effect by binding to the vimentin gene promoter region to enhance its expression. Moreover, NAT10-mediated ac4c modification led to stabilization and overexpression of CEBPB in SACC cells. We also found that NAT10, the only known human enzyme responsible for ac4C modification, promoted SACC cell migration, proliferation and colony formation. Moreover, CEBPB overexpression restored the inhibitory effect of NAT10 knockdown on malignant phenotypes. CONCLUSIONS: Our study reveals the critical role of the newly identified NAT10/CEBPB/vimentin axis in SACC malignant progression, and the findings may be applied to improve treatment for SACC.

Multiphoton imaging of the monosachharide induced formation of fluorescent advanced glycation end products in tissues.

We studied the in vitro rate of fluorescent advanced glycation end products (fAGEs) formation with multiphoton microscopy in different porcine tissues (aorta, cornea, kidney, dermis, and tendon). These tissues were treated with d-glucose, d-galactose, and d-fructose, three primary monosaccharides found in human diets. We found that the use of d-fructose resulted in the highest glycation rate, followed by d-galactose and then d-glucose. Moreover, compared to non-collagen tissue constituents such as elastic fibers and cells, the rate of tissue glycation was consistently higher in collagen, suggesting that collagen is a more sensitive target for fAGE formation. However, we also found that collagen in different tissues exhibits different rates of fAGE formation, with slower rates observed in tightly packed tissues such as cornea and tendon. Our study suggests that for fAGE to be developed into a long-term glycemic biomarker, loosely organized collagen tissues located in the proximity of vasculature may be the best targets.