Beyond oncology: Selinexor's journey into anti-inflammatory treatment and long-term management.

Selinexor, a selective inhibitor of nuclear export (SINE), is gaining recognition beyond oncology for its potential in anti-inflammatory therapy. This review elucidates Selinexor's dual action, highlighting its anti-tumor efficacy in various cancers including hematologic malignancies and solid tumors, and its promising anti-inflammatory effects. In cancer treatment, Selinexor has demonstrated benefits as monotherapy and in combination with other therapeutics, particularly in drug-resistant cases. Its role in enhancing the effectiveness of bone marrow transplants has also been noted. Importantly, the drug's impact on key inflammatory pathways provides a new avenue for the management of conditions like sepsis, viral infections including COVID-19, and chronic inflammatory diseases such as Duchenne Muscular Dystrophy and Parkinson's Disease. The review emphasizes the criticality of managing Selinexor's side effects through diligent dose optimization and patient monitoring. Given the complexities of its broader applications, extensive research is called upon to validate Selinexor's long-term safety and effectiveness, with a keen focus on its integration into clinical practice for a diverse spectrum of disorders.

Potential Gradient-Driven Dual-Functional Electrochromic and Electrochemical Device Based on a Shared Electrode Design.

The integration of electrochromic devices and energy storage systems in wearable electronics is highly desirable yet challenging, because self-powered electrochromic devices often require an open system design for continuous replenishment of the strong oxidants to enable the coloring/bleaching processes. A self-powered electrochromic device has been developed with a close configuration by integrating a Zn/MnO2 ionic battery into the Prussian blue (PB)-based electrochromic system. Zn and MnO2 electrodes, as dual shared electrodes, the former one can reduce the PB electrode to the Prussian white (PW) electrode and serves as the anode in the battery; the latter electrode can oxidize the PW electrode to its initial state and acts as the cathode in the battery. The bleaching/coloring processes are driven by the gradient potential between Zn/PB and PW/MnO2 electrodes. The as-prepared Zn||PB||MnO2 system demonstrates superior electrochromic performance, including excellent optical contrast (80.6%), fast self-bleaching/coloring speed (2.0/3.2 s for bleaching/coloring), and long-term self-powered electrochromic cycles. An air-working Zn||PB||MnO2 device is also developed with a 70.3% optical contrast, fast switching speed (2.2/4.8 s for bleaching/coloring), and over 80 self-bleaching/coloring cycles. Furthermore, the closed nature enables the fabrication of various flexible electrochromic devices, exhibiting great potentials for the next-generation wearable electrochromic devices.

Dietary Methionine Restriction Improves Gut Health and Alters the Plasma Metabolomic Profile in Rats by Modulating the Composition of the Gut Microbiota.

Dietary methionine restriction (MetR) offers an integrated set of beneficial health effects, including delaying aging, extending health span, preventing fat accumulation, and reducing oxidative stress. This study aimed to investigate whether MetR exerts entero-protective effects by modulating intestinal flora, and the effect of MetR on plasma metabolites in rats. Rats were fed diets containing 0.86% methionine (CON group) and 0.17% methionine (MetR group) for 6 weeks. Several indicators of inflammation, gut microbiota, plasma metabolites, and intestinal barrier function were measured. 16S rRNA gene sequencing was used to analyze the cecal microbiota. The MetR diet reduced the plasma and colonic inflammatory factor levels. The MetR diet significantly improved intestinal barrier function by increasing the mRNA expression of tight junction proteins, such as zonula occludens (ZO)-1, claudin-3, and claudin-5. In addition, MetR significantly increased the levels of short-chain fatty acids (SCFAs) by increasing the abundance of SCFAs-producing Erysipclotxichaceae and Clostridium_sensu_stricto_1 and decreasing the abundance of pro-inflammatory bacteria Proteobacteria and Escherichia-Shigella. Furthermore, MetR reduced the plasma levels of taurochenodeoxycholate-7-sulfate, taurocholic acid, and tauro-ursodeoxycholic acid. Correlation analysis identified that colonic acetate, total colonic SCFAs, 8-acetylegelolide, collettiside I, 6-methyladenine, and cholic acid glucuronide showed a significant positive correlation with Clostridium_sensu_stricto_1 abundance but a significant negative correlation with Escherichia-Shigella and Enterococcus abundance. MetR improved gut health and altered the plasma metabolic profile by regulating the gut microbiota in rats.

Ethylenedioxythiophene-Based Small Molecular Donor with Multiple Conformation Locks for Organic Solar Cells with Efficiency of 19.3 .

Ternary organic solar cells (T-OSCs) represent an efficient strategy for enhancing the performance of OSCs. Presently, the majority of high-performance T-OSCs incorporates well-established Y-acceptors or donor polymers as the third component. In this study, a novel class of conjugated small molecules has been introduced as the third component, demonstrating exceptional photovoltaic performance in T-OSCs. This innovative molecule comprises ethylenedioxythiophene (EDOT) bridge and 3-ethylrhodanine as the end group, with the EDOT unit facilitating the creation of multiple conformation locks. Consequently, the EDOT-based molecule exhibits two-dimensional charge transport, distinguishing it from the thiophene-bridged small molecule, which displays fewer conformation locks and provides one-dimensional charge transport. Furthermore, the robust electron-donating nature of EDOT imparts the small molecule with cascade energy levels relative to the electron donor and acceptor. As a result, OSCs incorporating the EDOT-based small molecule as the third component demonstrate enhanced mobilities, yielding a remarkable efficiency of 19.3 %, surpassing the efficiency of 18.7 % observed for OSCs incorporating thiophene-based small molecule as the third component. The investigations in this study underscore the excellence of EDOT as a building block for constructing conjugated materials with multiple conformation locks and high charge carrier mobilities, thereby contributing to elevated photovoltaic performance in OSCs.

Discovery of novel thiophene-3-carboxamide derivatives as potential VEGFR-2 inhibitors with anti-angiogenic properties.

VEGFR-2 is an attractive target for the development of anti-tumor drugs and plays a crucial role in tumor angiogenesis. This study reports a series of novel thiophene-3-carboxamide derivatives based on PAN-90806 as VEGFR-2 inhibitors, among which compound 14d exhibits excellent anti-proliferative activity against HCT116, MCF7, PC3, and A549 cell lines, and has effective VEGFR-2 inhibitory activity with an IC50 value of 191.1 nM. Additionally, CETSA results indicated that VEGFR-2 was a relevant target of compound 14d in the cell lines, and compound 14d could also inhibit VEGFR-2 protein phosphorylation in A549 cell line. Furthermore, compound 14d inhibited colony formation, cell migration, and HUVECs tube formation in a dose-dependent manner. The mechanism by which 14d induced cancer cell death involves blocking the cell cycle, increasing ROS production, inducing apoptosis, and dose-dependently reducing the levels of phosphorylated ERK and MEK. Molecular docking and molecular dynamics simulations had shown that compound 14d could stably bind to the active site of VEGFR-2. These results confirmed that compound 14d might be a promising lead compound for anti-angiogenesis.

Renal Artery Coil Embolization as an Endovascular Approach for Establishing a Rabbit Model of Chronic Kidney Disease.

PURPOSE: To investigate the safety and feasibility of renal artery coil embolization for establishing chronic kidney disease (CKD) in rabbits. MATERIALS AND METHODS: Ten male adult New Zealand rabbits underwent renal artery coil embolization. Initially, the main renal artery on 1 side was completely embolized, followed by embolization of approximately two-thirds of the primary branches of the contralateral renal artery 1 week later. Four rabbits were randomly chosen for sacrifice at 4 weeks after embolization, whereas the remaining 6 were sacrificed at 8 weeks after embolization. The assessment encompassed the animals' general condition, angiography, biochemical parameters, inflammatory markers, and histopathological examination of the kidneys and hearts. RESULTS: Four weeks after embolization, serum creatinine level showed a substantial increase (2.4 mg/dL [SD ± 0.6]; P = .009 vs baseline), with a subsequent 4.12-fold elevation at 8 weeks after embolization (4.9 mg/dL [SD ± 1.4]; P < .001 vs baseline). Additionally, considerable increases in serum blood urea nitrogen, calcium, and potassium ions were observed at 8 weeks after embolization (58.3 mg/dL [SD ± 19.0]; P < .001 vs baseline; 23.1 mg/dL [SD ± 4.4]; P < .001 vs baseline; and 6.3 mEq/L [SD ± 0.7]; P < .001 vs baseline, respectively). The completely embolized kidney exhibited notable atrophy, severe fibrosis, and cortical calcification, whereas the contralateral partially embolized kidney displayed compensatory hypertrophy, along with glomerulosclerosis, tubular dilation, tubular casts, and interstitial fibrosis. CONCLUSIONS: Renal artery coil embolization proved to be effective and safe for establishing a CKD model in rabbits.

Stabilizing Solid Electrolyte Interphase on Liquid Metal Via Dynamic Hydrogel-Derived Carbon Framework Encapsulation.

Eutectic gallium-indium liquid metal (EGaIn-LM), with a considerable capacity and unique self-healing properties derived from its intrinsic liquid nature, gains tremendous attention for lithium-ion batteries (LIBs) anode. However, the fluidity of the LM can trigger continuous consumption of the electrolyte, and its liquid-solid transition during the lithiation/de-lithiation process may result in the rupture of the solid electrolyte interface (SEI). Herein, LM is employed as an initiator to in situ assemble the 3D hydrogel for dynamically encapsulating itself; the LM nanoparticles can be homogeneously confined within the hydrogel-derived carbon framework (HDC) after calcination. Such design effectively alleviates the volume expansion of LM and facilitates electron transportation, resulting in a superior rate capability and long-term cyclability. Further, the "dual-layer" SEI structure and its key components, including the robust LiF outer layer and corrosion-resistant and ionic conductive LiGaOx inner layer are revealed, confirming the involvement of LM in the formation of SEI, as well as the important role of carbon framework in reducing interfacial side reactions and SEI decomposition. This work provides a distinct perspective for the formation, structural evolution, and composition of SEI at the liquid/solid interface, and demonstrates an effective strategy to construct a reliable matrix for stabilizing the SEI.

LncRNA-mediated cartilage homeostasis in osteoarthritis: a narrative review.

Osteoarthritis (OA) is a degenerative disease of cartilage that affects the quality of life and has increased in morbidity and mortality in recent years. Cartilage homeostasis and dysregulation are thought to be important mechanisms involved in the development of OA. Many studies suggest that lncRNAs are involved in cartilage homeostasis in OA and that lncRNAs can be used to diagnose or treat OA. Among the existing therapeutic regimens, lncRNAs are involved in drug-and nondrug-mediated therapeutic mechanisms and are expected to improve the mechanism of adverse effects or drug resistance. Moreover, targeted lncRNA therapy may also prevent or treat OA. The purpose of this review is to summarize the links between lncRNAs and cartilage homeostasis in OA. In addition, we review the potential applications of lncRNAs at multiple levels of adjuvant and targeted therapies. This review highlights that targeting lncRNAs may be a novel therapeutic strategy for improving and modulating cartilage homeostasis in OA patients.

Prognostic value of metabolic syndrome in patients with heart failure and malnutrition.

BACKGROUND: Malnutrition is severely associated with worst prognosis of patients with heart failure (HF). Malnourished patients with the metabolic syndrome (MS) can result in a double burden of malnutrition. We aimed to investigate the impact of the MS on clinical outcomes in malnourished HF patients. METHODS: We examined 529 HF patients at risk of malnutrition with a mean age of (66 ± 10) years and 78% (415) were male. Nutritional status defined primarily by the prognostic nutritional index (PNI), with PNI < 40 being defined as malnutrition. The follow-up endpoint was cardiovascular death or all-cause death. RESULTS: During the 36-month follow-up, survival rates for cardiovascular and all-cause death were significantly lower in the MS group than in the non-MS group (log-rank P < 0.01). Multivariate Cox proportional hazards regression models showed that MS was independently associated with cardiovascular death (HR:1.759, 95%CI:1.351-2.291, p < 0.001) and all-cause death (HR:1.326, 95%CI:1.041-1.689, p = 0.022) in malnourished patients with HF. MS significantly increased the predictive value of cardiovascular death (AUC:0.669, 95%CI:0.623-0.715, p < 0.001) and all-cause death (AUC:0.636, 95%CI:0.585-0.687, p < 0.001) on the basis of established risk factors. The predictive effect of MS on cardiovascular death was independent of sex, age, functional class and left ventricular ejection fraction. CONCLUSIONS: In malnourished patients with HF, MS is an independent risk factor for cardiovascular and all-cause mortality. MS significantly enhance the predictive value for clinical events in patients.

Dynamic evolution and obstacle factor analysis of green development in China's agriculture and rural areas based on entropy-based TOPSIS model.

Green development of agriculture and rural areas (GDARA) is an essential part of rural revitalization and high-quality development. Based on 2011 to 2020 provincial panel data from China, the entropy-based Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) model is constructed to measure the level of GDARA, finding that the overall level during the sample period was positive. Then the regional differences mainly from intra-regional were revealed by the methods of Dagum Gini coefficient and Kernel density estimation and were shrinking overall. Besides, the results of Markov chain transfer matrix show the dynamic characteristics clearly, which the low-level regions shift to the middle and high levels with a greater probability. The results of the spatial autocorrelation test display that GDARA has a spatial clustering effect. Finally, the industrial upgrading and the business income of leisure agriculture are respectively proven to hinder GDARA at most by the Obstacle degree model empirically. Based on a series of empirical tests, a few relevant policy recommendations are proposed to promote the road to strong agriculture and rural areas in China.

Discovery of Melittin as Triple-Action Agent: Broad-Spectrum Antibacterial, Anti-Biofilm, and Potential Anti-Quorum Sensing Activities.

The development of antibiotic-resistant microorganisms is a major global health concern. Recently, there has been an increasing interest in antimicrobial peptides as a therapeutic option. This study aimed to evaluate the triple-action (broad-spectrum antibacterial, anti-biofilm, and anti-quorum sensing activities) of melittin, a membrane-active peptide present in bee venom. The minimum inhibitory concentration and minimum bactericidal concentration of the melittin were determined using the microdilution method and agar plate counting. Growth curve analysis revealed that melittin showed a concentration-dependent antibacterial activity. Scanning electron microscope analysis revealed that melittin treatment altered the morphology. Confocal laser scanning microscope revealed that melittin increased the membrane permeability and intracellular ROS generation in bacteria, all of which contribute to bacterial cell death. In addition, the crystal violet (CV) assay was used to test the anti-biofilm activity. The CV assay demonstrated that melittin inhibited biofilm formation and eradicated mature biofilms. Biofilm formation mediated by quorum sensing (QS) plays a major role in this regard, so molecular docking and molecular dynamics analysis confirmed that melittin interacts with LasR receptors through hydrogen bonds, and further evaluates the anti-QS activity of melittin through the production of virulence factors (pyocyanin, elastase, and rhamnolipid), exopolysaccharides secretion, and bacterial motility, that may be the key to inhibiting the biofilm formation mechanism. The present findings highlight the promising role of melittin as a broad-spectrum antibacterial, anti-biofilm agent, and potential QS inhibitor, providing a new perspective and theoretical basis for the development of alternative antibiotics.

Exposure to bisphenol A affects transcriptome-wide N6-methyladenine methylation in ovarian granulosa cells.

Bisphenol A (BPA) is an endocrine disruptor of potential reproductive toxicities. Increasingly research elucidated that BPA exposure to the environment would change the epigenetic modifications of transcriptome, but the mechanism by which BPA affects m6A methylation in interfering with female reproductive health remains uncertain. Therefore, this study preliminarily proposed and tested the hypothesis that BPA exposure alters the m6A modification level in transcripts in female ovarian granulosa cells. After BPA was exposed to granulosa cells for 24 h, RNA methylation related regulatory genes (such as METTL3, METTL14, ALKBH5, FTO) and the global m6A levels showed significant differences. Next, we applied MERIP-seq analysis to obtain information on the genome-wide m6A modification changes and identified 1595 differentially methylated mRNA transcripts, and 50 differentially methylated lncRNA transcripts. Further joint analysis of gene common expression showed that 33 genes were hypermethylated and up-regulated, 71 were hypermethylated and down-regulated, 49 were hypomethylated and up-regulated, and 20 were hypomethylated and down-regulated. Enriched Gene Ontology (GO) and biological pathway analysis revealed that these unique genes were mainly enriched in lipid metabolism, cell proliferation, and apoptosis related pathways. Six of these genes (mRNAs IMPA1, MCOLN1, DCTN3, BRCA2, and lncRNAs MALAT1, XIST) were validated using RT-qPCR and IGV software. Through comprehensive analysis of epitranscriptome and protein-protein interaction (PPI) data, lncRNAs MALAT1 and XIST are expected to serve as new markers for BPA interfering with the female reproductive system. In brief, these data show a novel and necessary connection between the damage of BPA exposure on female ovarian granulosa cells and RNA methylation modification.

Synthesis of gadolinium-enhanced glioma images on multisequence magnetic resonance images using contrastive learning.

BACKGROUND: Gadolinium-based contrast agents are commonly used in brain magnetic resonance imaging (MRI), however, they cannot be used by patients with allergic reactions or poor renal function. For long-term follow-up patients, gadolinium deposition in the body can cause nephrogenic systemic fibrosis and other potential risks. PURPOSE: Developing a new method of enhanced image synthesis based on the advantages of multisequence MRI has important clinical value for these patients. In this paper, an end-to-end synthesis model structure similarity index measure (SSIM)-based Dual Constrastive Learning with Attention (SDACL) based on contrastive learning is proposed to synthesize contrast-enhanced T1 (T1ce) using three unenhanced MRI images of T1, T2, and Flair in patients with glioma. METHODS: The model uses the attention-dilation generator to enlarge the receptive field by expanding the residual blocks and to strengthen the feature representation and context learning of multisequence MRI. To enhance the detail and texture performance of the imaged tumor area, a comprehensive loss function combining patch-level contrast loss and structural similarity loss is created, which can effectively suppress noise and ensure the consistency of synthesized images and real images. RESULTS: The normalized root-mean-square error (NRMSE), peak signal-to-noise ratio (PSNR), and SSIM of the model on the independent test set are 0.307  ± $\pm$  0.12, 23.337  ± $\pm$  3.21, and 0.881  ± $\pm$  0.05, respectively. CONCLUSIONS: Results show this method can be used for the multisequence synthesis of T1ce images, which can provide valuable information for clinical diagnosis.

Relationship between trimethylamine N-oxide and the risk of hypertension in patients with cardiovascular disease: A meta-analysis and dose-response relationship analysis.

BACKGROUND: The gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) has recently been recognized to be one of the risk factors for cardiovascular disease (CVD). However, there is a scarcity of data on the relationship between circulating TMAO levels and hypertension in patients with CVD. Meta analysis and a dose-response relationship were used in this study to assess the relationship between circulating trimethylamine N-oxide levels and the risk of hypertension in patients with CVD. METHODS: CNKI, Wanfang Database, Pubmed, Embase, Cochrane Library, and Web of Science were searched up to June 01, 2023. Meta-analysis and dose-response analysis of relative risk data from prospective cohort studies reporting on the relationship between circulating TMAO levels and hypertension risk in patients with CVD were conducted. RESULTS: Fifteen studies with a total of 15,498 patients were included in the present meta-analysis. Compared with a lower circulating TMAO level, a higher TMAO level was associated with a higher risk of hypertension in patients with CVD (RR = 1.14,95%CI (1.08, 1.20)). And the higher the TMAO level, the greater the risk of hypertension. The dose-response analysis revealed a linear dose-response relationship between circulating TMAO levels and the risk of hypertension in patients with CVD. The risk of hypertension increased by 1.014% when the circulating TMAO level increased by 1 µ mol/L. CONCLUSION: In patients with CVD, the level of circulating TMAO is significantly related to the risk of hypertension. The risk of hypertension increased by 1.014% for every 1 µ mol/L increase in circulating TMAO levels.

[Retracted] MicroRNA­338­3p functions as tumor suppressor in breast cancer by targeting SOX4.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the GAPDH control western blotting assay data shown in Figs. 5D and 6B, the cell­cycle data in Fig. 4A, the cell apoptotic data in Fig. 4B and the Transwell cell invasion assay in Fig. 3B were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to International Journal of Oncology, or were under consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published previously, the Editor of International Journal of Oncology has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 47: 1594­1602, 2015; DOI: 10.3892/ijo.2015.3114].

Associations of latent patterns of parent‒child communication with communication quality and mental health outcomes among Chinese left-behind children.

BACKGROUND: Parent‒child communication in migrant families is essential to family bonds and the mental health of left-behind children (LBC). Little is known about the different patterns of communication between migrant parents and LBC and associated communication quality and mental health outcomes. METHODS: A sample of 2,183 Chinese children (mean age = 12.95 ± 1.29 years) from Anhui province, including LBC whose parents had both migrated (n = 1,025) and children whose parents had never migrated (never-LBC, n = 1,158), was analyzed. With the LBC sample, latent class analysis was applied to identify the patterns of parent‒child communication. Multinomial logistic regression analysis was conducted to assess the associations between the sociodemographic variables and class membership of LBC. Analysis of covariance and chi-square tests were used to compare communication quality and mental health outcome differences among the classes of LBC and between each of the classes and never-LBC. RESULTS: Five latent classes of communication formed through different media or channels between migrant parents and their LBC were identified. Higher household economic status (OR = 2.81, p < 0.05) was associated with adequate communication. LBC in Class 1, defined by frequent technologically-mediated and face-to-face communication, had a significantly higher quality of communication with their migrant parents (F = 8.92, p < 0.001) and better mental health than those in other latent classes; these children did not have significantly worse mental health outcomes compared to never -LBC. CONCLUSIONS: Facilitating multichannel parent‒child communication is a practical way of reducing mental health inequities between LBC and their peers.

Mechanisms underlying the relationship between the intersectionality of multiple social identities with depression among US adults: A population-based study on the mediating roles of lifestyle behaviors.

BACKGROUND: Despite substantial efforts to investigate the inequalities in mental health among people with marginalized identities, most research has concentrated on single social identities rather than complete persons. The current study aimed to explore the mechanisms underlying the relationship between the intersectionality of multiple social identities with depression among US adults. METHODS: Data for this study came from the National Health and Nutrition Examination Survey waves between 2015 and 2018, including a total of 11,268 US adults. A latent class analysis (LCA) was conducted to identify latent subpopulations based on sex, race/ethnicity, immigrant status, disability, household income, employment status, and education level. Interclass differences in lifestyle factors and depression were examined. Multiple mediation analysis was used to examine the mediating roles of lifestyle behaviors. RESULTS: LCA identified four potential subpopulations: "least marginalized", "immigrant minorities", "disabled, less-educated non-workers", and "low-income minorities" groups. There was enormous heterogeneity in mental health among immigrant minority individuals. The "disabled, less-educated non-workers" group had the highest rates of depression; in contrast, the "immigrant minorities" group had the best mental health, even better than that of the "least marginalized" group. Distributions of lifestyle factors followed a similar pattern. In addition, lifestyle behaviors significantly mediated the relationship between intersectional social identities and depression. LIMITATIONS: The cross-sectional design prevented establishment of the causality of relationships. CONCLUSIONS: This study suggests that applying a person-centered approach is important when examining intersectional inequalities in mental health and highlights the effects of structural social hierarchies on individuals' health behaviors and mental health.