ß-Sitosterol Inhibits Tumor Growth and Amplifies Rituximab Sensitivity through Acid Sphingomyelinase/Ceramide Signaling in Diffuse Large B-Cell Lymphoma.

Rituximab (RTX) resistance is a notable challenge in treating diffuse large B-cell lymphoma (DLBCL). ß-Sitosterol (ß-ST) is a plant sterol that has been found in a broad variety of fruits, spices, and medicinal plants. The antineoplastic properties of ß-ST are established in various solid malignancies; however, its effect on DLBCL is uncharted. This study investigates the role of ß-ST in DLBCL as well as the underlying mechanisms. Our findings indicated that ß-ST impeded DLBCL cell proliferation in a concentration- and time-dependent manner. ß-ST appeared to alter sphingolipid metabolism, facilitate acid sphingomyelinase (ASM) translocation to the plasma membrane, augment ceramide platforms through increased ceramide synthesis, and consequently induce apoptosis in DLBCL cells. Furthermore, we found that RTX initiated both apoptotic and survival pathways in vitro, with the former contingent on the transient activation of the ASM, and ß-ST could amplify the anti-DLBCL efficacy of RTX by modulating ASM/Ceramide (Cer) signaling. Collectively, our findings elucidate the mechanistic role of ß-ST in DLBCL and underscore its potential in amplifying the antineoplastic efficacy of RTX via ASM activation, proposing a potential avenue to improve the efficacy of RTX therapy.

Co-adsorption and selective-adsorption of heavy metals and dyes from aqueous solution by bio-based humus/chitosan hydrogels.

An eco-friendly adsorbent was prepared by reverse suspension crosslinking method to remove multiple pollutants from aqueous solution. Both raw materials, derived from humus (HS) and chitosan (CS), are biodegradable and low-cost natural biopolymers. After combining HS with CS, the adsorption capacity was significantly improved due to compensation effects between the two components. HS/CS exhibited the features of amphoteric adsorption through pH adjustment, enabling it to adsorb not only anionic pollutants (Methyl Orange (MO) and Cr(VI)), but also cationic ones (Methylene Blue (MB) and Pb(II)). The adsorption capacities were approximately 242 mg/g, 69 mg/g, 188 mg/g and 57 mg/g for MO, Cr(VI), MB and Pb(II), respectively. HS/CS showed a slight preference for MO in MO/Cr(VI) co-adsorption system, whereas strong selectivity for MB over Pb(II) in MB/Pb(II) system under acidic condition (pH<3.0). This selective behavior would allow for potential applications in separating MB/Pb(II) effluents and selectively recycling Pb(II) in acidic environment. The isothermal and kinetic adsorption behaviors followed Langmuir model and pseudo-second-order model, respectively. The density functional theory (DFT) confirmed that the interaction between metal ions and adsorbents was primarily attributed to chelation and electrostatic adsorption, owing to nitric and oxygenic functional groups. Whereas, the adsorption mechanisms for dyes were involved in electrostatic attraction, H-bond and π-π bond, due to available hydrogen, oxygen, nitrogen atoms and aromatic groups on the surface of adsorbent and adsorbates. The adsorbent could be efficiently regenerated and retained over 90% of its adsorption capacity after five cycles, which has a potential for practical applications in water treatment.

The METTL3/miR-196a Axis Predicts Poor Prognosis in Non-small Cell Lung Cancer.

Background: METTL3 accelerates m6A modification to influence cancer progression including non-small cell lung cancer (NSCLC). To illustrate the role and underlying mechanism of METTL3 mediated miR-196a upregulation in NSCLC. Method: The global level of m6A modification was detected by qPCR, western blot and immumohistochemical staining. The TCGA, GEPIA, CPTAC and TIMER databases were used to explore the expression change of METTL3, miR-196a and GAS7 in NSCLC patients. Kaplan-Meier analysis was performed to analyze the prognostic value of miR-196a. NSCLC cells overexpressed or knockdown miR-196a were constructed and used for CCK8, colony formation assay, western blot and immunofluorescence in vitro. The effect of miR-196a on tumor growth was investigated in vivo. Result: We found that METTL3 mediated miR-196a were notably enhancive in NSCLC tissues and in NSCLC cells, which is markedly positively related with the serious TNM stage, the large tumor size, the distant metastasis, and the poor prognosis in patients of NSCLC. Further investigation showed that up-regulated miR-196a promoted cell viability and cell autophagy, while down-regulation of miR-196a revealed opposite results in H1299 and A549 cells. In terms of mechanism, we found that miR-196a interacted with GAS7. In addition, GAS7 expression in NSCLC patients may be positively related with the infiltration of immune cell subsets in tumor microenvironment (TME). Conclusion: The axis of METTL3-miR-196a-GAS7 might be a target for molecular targeted therapy, a potential and novel diagnostic marker for NSCLC patients.

The roles of ERIANIN in tumor and innate immunity and its' perspectives in immunotherapy.

Traditional Chinese medicine has been used in China for thousands of years. In 2022, the 14th Five-Year Plan for the Development of Traditional Chinese Medicine was released, aiming to enhance traditional Chinese medicine health services and improve policies and systems for high-quality traditional Chinese medicinal development by 2025. ERIANIN, the main component of the traditional Chinese medicine Dendrobium, plays an important role in anti-inflammatory, antiviral, antitumor, antiangiogenic, and other pharmacological effects. ERIANIN has broad-spectrum antitumor effects, and its tumor-suppressive effects have been confirmed in the study of various diseases, such as precancerous lesions of the stomach, gastric cancer, liver cancer, lung cancer, prostate cancer, bladder cancer, breast cancer, cervical cancer, osteosarcoma, colorectal cancer, leukaemia, nasopharyngeal cancer and melanoma through the multiple signaling pathways. Thus, the aim of this review was to systematically summarise the research on ERIANIN with the aim of serving as a reference for future research on this compound and briefly discuss some future perspectives development of ERIANIN in combined immunotherapy.

Steam migration and temperature distribution in aquifers during remediation using steam injection.

Steam injection technology is commonly used to rapidly remove volatile and semi-volatile organic pollutants in aquifers, and its remediation effect is highly related to steam migration and temperature distribution. However, systematic studies on steam migration and temperature distribution across different types of aquifers are lacking. In this study, the steam migration and temperature distribution in an aquifer were investigated through a series of two-dimensional sandbox experiments with different groundwater velocities, steam injection flow rates, and stratigraphic structures. The experimental results indicated that the temperature distribution in the aquifer was related to the formation permeability and steam injection flow rate. When the hydraulic conductivity of the aquifer was lower than 10-3 cm·s-1, the heating zone in the aquifer had an H-shaped distribution, and when it was higher than 10-2 cm·s-1, the heating zone had a V-shaped distribution for a high steam injection flow rate (1 kgh-1), and an H-shaped distribution for a low injection flow rate (0.5 kgh-1). Under the same injection steam flow rate, the total area of the heating zone in the aquifers with different media was in the following order of sand particle size: coarse sand > fine sand > medium sand. Owing to the heat pipe and heat dispersion effects, the heating zone area in the fine sand aquifer was larger than that of the medium sand aquifer. Groundwater velocity did not affect the area of the heating zone. With the increase in groundwater velocity, the heating zone expanded downstream. In layered heterogeneous aquifers, the upper fine and lower coarse structures formed a steam-blocking interface, resulting in steam accumulation and temperature increase in the lower layer. These findings are significant for improving our understanding of steam migration and temperature distribution in aquifers, leading to an improved design and prediction of the steam remediation required for mitigating aquifer pollution.

Efficacy of integrated traditional Chinese medicine and Western medicine in the treatment of poststroke insomnia: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Western medicine has played an essential role in treating poststroke insomnia (PSI) in China, and traditional Chinese medicine therapy based on Chinese characteristics is also effective. Combined with China's national conditions, we plan to conduct this systematic review and meta-analysis to compare the efficacy of integrated traditional Chinese medicine and Western medicine (INTEGRATED TCM and WM) therapy and Western medicine alone for PSI. METHODS: We will search the following 5 electronic databases: PubMed, Wanfang, Chinese biomedical literature database, the Chongqing VIP Chinese Science and Technology Periodical, and China national knowledge infrastructure. Randomized controlled trials that compared the efficacy of INTEGRATED TCM and WM with Western medicine alone in the treatment of PSI will be considered. Primary outcomes have Treatment effectiveness rate, and Pittsburgh sleep quality index. Secondary outcomes include traditional Chinese medicine syndrome score, Athens insomnia scale, the incidence of adverse reactions, and outcome follow-up. Based on the eligibility criteria, we will conduct literature screening and data extraction. The quality of the included literature will be evaluated using the Cochrane risk of bias tools. We will use Review Manager software (Version 5.3) for data synthesis and statistical analyses. If sources of heterogeneity exist, we will perform a subgroup analysis or sensitivity analysis. A funnel plot will be used to analyze publication bias. RESULTS: This study will provide evidence-based medicine evidence for treatment of PSI with INTEGRATED TCM and WM in terms of its efficacy. CONCLUSION: This systematic review aims to provide new options for INTEGRATED TCM and WM treatment of PSI in terms of its efficacy.

Mechanism and enhancement of Cr(VI) contaminated groundwater remediation by molasses.

The remediation of Cr(VI)-contaminated groundwater with molasses has many advantages compared with traditional in-situ chemical methods, including high cost-effectiveness and negligible secondary contamination. Hence, the reaction conditions and mechanisms of molasses were investigated in this study. The results showed that Cr(VI) was chemically reduced by molasses at acidic pH (3.0), wherein the dominant active components were the hydroxyl and carbonyl groups of molasses. At neutral pH (7.0), molasses mainly acted as an electron donor for direct or indirect reduction of Cr(VI) by microorganisms. The main functional microorganisms were Bacillus and Clostridium Sensu Stricto. Compared with chemical reduction, bio-reduction could completely reduce higher concentrations of Cr(VI) when molasses was added at a concentration of 3 g/L. Ascorbic acid was added to promote the removal rate of bioremediation. Owing to the antioxidant properties of ascorbic acid, the reaction rate increased by 9.3% and 37.5% when 0.05 g/L of ascorbic acid was added to the 50 and 100 mg/L Cr(VI) bioremediation systems, respectively. Due to the decrease in pH during bioremediation, NaHCO3 was added to buffer the pH changes and promote Cr(III) precipitation. Compared with the addition of NaHCO3 and molasses simultaneously, separate additions were more effective for precipitation. Furthermore, X-ray absorption near-edge structure analysis revealed that after chemical reduction and biological reduction, Cr was attached to the solid medium in the form of Cr(III).

Exploring the mechanism of Yizhi Tongmai decoction in the treatment of vascular dementia through network pharmacology and molecular docking.

BACKGROUND: Vascular dementia (VaD) is a degenerative cerebrovascular disease that leads to progressive decline of patients' cognitive ability and memory. Yizhi Tongmai (YZTM) decoction is an empirical prescription first formulated by Professor Guomin Si. Our previous experiments proved the effectiveness of this prescription in the treatment of VaD. In this study, we aimed to use network pharmacology and molecular docking technology to systematically explain the potential anti-VaD mechanism of YZTM. METHODS: We identified the core compounds of YZTM and their potential targets through the TCMSP, BATMAN, and SwissTargetPrediction databases. Then, we identified the molecular targets of YZTM in VaD using the Online Mendelian Inheritance in Man and GeneCards databases. The common targets of YZTM and VaD were screened out, and then the pathways of these target genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery v6.8. Molecular docking was used to verify the relationship between the core compounds and proteins. RESULTS: Through network pharmacology analysis, we discovered that the 5 core compounds in YZTM exert an anti-VaD effect. The potential mechanism of YZTM anti-VaD may be through inhibiting the NLRP3 inflammasome, TNF signaling pathway, and toll-like receptor signaling pathways. Subsequently, key compounds were docked with related proteins in the NLRP3 inflammasome (NLRP3, ASC, caspase-1, interleukin-18, and interleukin-1 ß) using molecular docking technology. The compounds were found to spontaneously bind to the proteins. CONCLUSIONS: YZTM may exert an anti-VaD effect through inhibition of the NLRP3 inflammasome. In addition, TNF signaling pathway and toll-like receptor signaling pathway may also be its underlying mechanism. The application of network pharmacology and molecular docking technology may provide a novel method for research of Chinese herbal medicine. YZTM may also provide a complementary treatment option for patients with VaD.

Water quality assessment and source identification of the Shuangji River (China) using multivariate statistical methods.

Multivariate statistical techniques, including cluster analysis (CA), discriminant analysis (DA), principal component analysis (PCA) and factor analysis (FA), were used to evaluate temporal and spatial variations in and to interpret large and complex water quality datasets collected from the Shuangji River Basin. The datasets, which contained 19 parameters, were generated during the 2 year (2018-2020) monitoring programme at 14 different sites (3192 observations) along the river. Hierarchical CA was used to divide the twelve months into three periods and the fourteen sampling sites into three groups. Discriminant analysis identified four parameters (CODMn, Cu, As, Se) loading more than 68% correct assignations in temporal analysis, while seven parameters (COD, TP, CODMn, F, LAS, Cu and Cd) to load 93% correct assignations in spatial analysis. The FA/PCA identified six factors that were responsible for explaining the data structure of 68% of the total variance of the dataset, allowing grouping of selected parameters based on common characteristics and assessing the incidence of overall change in each group. This study proposes the necessity and practicality of multivariate statistical techniques for evaluating and interpreting large and complex data sets, with a view to obtaining better information about water quality and the design of monitoring networks to effectively manage water resources.