Quantifying and Decoupling Molecular Interactions of Ionic Liquids with Gold Electrodes.

This work combined gold colloid probe atomic force microscopy (AFM) with a quartz crystal microbalance (QCM) to accurately quantify the molecular interactions of fluorine-free phosphonium-based ionic liquids (ILs) with gold electrode surfaces. First, the interactions of ILs with the gold electrode per unit area (FA', N/m2) were obtained via the force-distance curves measured by gold probe AFM. Second, a QCM was employed to detect the IL amount to acquire the equilibrium number of IL molecules adsorbed onto the gold electrode per unit area (NIL, Num/m2). Finally, the quantified molecular interactions of ILs with the gold electrode (F0, nN/Num) were estimated. F0 is closely related to the IL composition, in which the IL with the same anion but a longer phosphonium cation exhibits a stronger molecular interaction. The changes in the quantified interactions of gold with different ILs are consistent with the interactions predicted by the extended Derjaguin-Landau-Verwey-Overbeek theory, and the van der Waals interaction was identified as the major contribution of the overall interaction. The quantified molecular interaction is expected to enable the direct experimental-derived interaction parameters for molecular simulations and provide the virtual design of novel ILs for energy storage applications.

Targeting MicroRNA in myopia: Current insights.

Myopia, the most prevalent eye condition, has sparked notable interest regarding its origin and prevention. MicroRNAs (miRNAs) are short, non-coding RNA strands typically consisting of 18-24 nucleotides. They play a central role in post-transcriptional gene regulation and are closely associated with both normal and pathological processes in organisms. Recent advances in next-generation sequencing and bioinformatics have provided novel insights into miRNA expression and its regulatory role in myopia. This review discusses the distinct expression patterns, regulatory functions, and potential pathways of miRNAs involved in the onset and progression of myopia. The primary objective of this review was to provide valuable insights into molecular mechanisms underlying myopia and the contribution of miRNAs. These insights are expected to pave the way for further exploration of the molecular mechanisms, diagnosis, treatment, and clinical applications of myopia.

RTCB deficiency triggers colitis in mice by influencing the NF-κB and Wnt/ß-catenin signaling pathways.

RNA terminal phosphorylase B (RTCB) has been shown to play a significant role in multiple physiological processes. However, the specific role of RTCB in the mouse colon remains unclear. In this study, we employ a conditional knockout mouse model to investigate the effects of RTCB depletion on the colon and the potential molecular mechanisms. We assess the efficiency and phenotype of Rtcb knockout using PCR, western blot analysis, histological staining, and immunohistochemistry. Compared with the control mice, the Rtcb-knockout mice exhibit compromised colonic barrier integrity and prominent inflammatory cell infiltration. In the colonic tissues of Rtcb-knockout mice, the protein levels of TNF-α, IL-8, and p-p65 are increased, whereas the levels of IKKß and IκBα are decreased. Moreover, the level of GSK3ß is increased, whereas the levels of Wnt3a, ß-catenin, and LGR5 are decreased. Collectively, our findings unveil a close association between RTCB and colonic tissue homeostasis and demonstrate that RTCB deficiency can lead to dysregulation of both the NF-κB and Wnt/ß-catenin signaling pathways in colonic cells.

Prognostic Model Associated with Necroptosis in Colorectal Cancer based on Transcriptomic Analysis and Experimental Validation.

PURPOSE: Numerous studies have emphasised the importance of necroptosis in the malignant progression of colorectal cancer (CRC). However, whether necroptosis-related genes (NRGs) can be used to predict the prognosis of CRC remains to be revealed. METHODS: Patients with CRC were divided into two clusters based on the expression of NRGs, and prognosis was compared between the two clusters. A prognostic model was established based on NRGs, and its predictive efficiency was validated using Kaplan-Meier (K-M) curves, receiver operating characteristic (ROC) curves and a nomogram. Immune infiltration, single-cell and drug sensitivity analyses were used to examine the effects of NRGs on the prognosis of CRC. RESULTS: The prognostic model served as a valid and independent predictor of CRC prognosis. Immune infiltration and single-cell analyses revealed that the unique immune microenvironment of CRC was regulated by NRGs. Drug sensitivity analysis showed that patients in the high- and low-risk groups were sensitive to different drugs. In addition, H2BC18 was found to play an important role in regulating the malignant progression of CRC. CONCLUSION: This study provides novel insights into precision immunotherapy based on NRGs in CRC. The NRG-based prognostic model may help to identify targeted drugs and develop more effective and individualised treatment strategies for patients with CRC.

Dopamine Receptor 1 Treatment Promotes Epithelial Repair of Corneal Injury by Inhibiting NOD-Like Receptor Protein 3-Associated Inflammation.

Purpose: To elucidate the influence of dopamine receptor 1 (DRD1) on the proliferation of mouse corneal epithelial cells (MCECs) under inflammatory conditions. Methods: In vitro, immortalized MCECs (iMCECs) were treated with IL-1ß, with and without pcDNA3.1_DRD1. Primary MCECs (pMCECs) were exposed to IL-1ß, with and without DRD1 agonist (A68930). Cell proliferation was quantified using the Cell Counting Kit-8 (CCK-8) assay and immunofluorescence staining for Ki-67 and p63. Expression levels of NOD-like receptor protein 3 (NLRP3), IL-1ß, and IL-6 were assessed. To establish a corneal injury model in mice, a 2-mm superficial keratectomy was performed. Either 0.1% A68930 or PBS was topically administered three times daily to the injured eyes for up to 5 days post-injury. Immunofluorescence analysis was employed to evaluate the expression of Ki-67, p63, and CD45 in mouse corneas. Western blotting and real-time quantitative PCR were utilized for quantitative analysis of DRD1, NLRP3, IL-1ß, and IL-6 in mouse corneas. Corneal epithelial regeneration was monitored through fluorescein sodium staining for a duration of up to 5 days following the injury. Results: Overexpression of DRD1 and A68930 promoted MCEC proliferation and suppressed the expression of NLRP3, IL-1ß, and IL-6 in vitro. Topical application of the 0.1% A68930 following mechanical corneal injury in mice led to increased Ki-67 and p63 expression compared to PBS treatment. Furthermore, topical administration of the 0.1% A68930 reduced the expression of CD45, NLRP3, IL-1ß, and IL-6. Analysis with fluorescein sodium indicated accelerated corneal epithelial regeneration in the 0.1% A68930 treatment group. Conclusions: DRD1 treatment counteracts NLRP3-associated inflammation and facilitates epithelial repair of corneal injury.

Circadian rhythm, ipRGCs, and dopamine signalling in myopia.

Myopia, a common ophthalmic disorder, places a high economic burden on individuals and society. Genetic and environmental factors influence myopia progression; however, the underlying mechanisms remain unelucidated. This paper reviews recent advances in circadian rhythm, intrinsically photosensitive retinal ganglion cells (ipRGCs), and dopamine (DA) signalling in myopia and proposes the hypothesis of a circadian rhythm brain retinal circuit in myopia progression. The search of relevant English articles was conducted in the PubMed databases until June 2023. Based on the search, emerging evidence indicated that circadian rhythm was associated with myopia, including circadian genes Bmal1, Cycle, and Per. In both humans and animals, the ocular morphology and physiology show rhythmic oscillations. Theoretically, such ocular rhythms are regulated locally and indirectly via the suprachiasmatic nucleus, which receives signal from the ipRGCs. Compared with the conventional retinal ganglion cells, ipRGCs can sense the presence of light because of specific expression of melanopsin. Light, together with ipRGCs and DA signalling, plays a crucial role in both circadian rhythm and myopia. In summary, regarding myopia progression, a circadian rhythm brain retinal circuit involving ipRGCs and DA signalling has not been well established. However, based on the relationship between circadian rhythm, ipRGCs, and DA signalling in myopia, we hypothesised a circadian rhythm brain retinal circuit.

Impact of human mobility on the epidemic spread during holidays.

COVID-19 has posed formidable challenges as a significant global health crisis. Its complexity stems from factors like viral contagiousness, population density, social behaviors, governmental regulations, and environmental conditions, with interpersonal interactions and large-scale activities being particularly pivotal. To unravel these complexities, we used a modified SEIR epidemiological model to simulate various outbreak scenarios during the holiday season, incorporating both inter-regional and intra-regional human mobility effects into the parameterization scheme. In addition, evaluation metrics were used to evaluate the accuracy of the model simulation by comparing the congruence between simulated results and recorded confirmed cases. The findings suggested that intra-city mobility led to an average surge of 57.35% in confirmed cases of China, while inter-city mobility contributed to an average increase of 15.18%. In the simulation for Tianjin, China, a one-week delay in human mobility attenuated the peak number of cases by 34.47% and postponed the peak time by 6 days. The simulation for the United States revealed that human mobility played a more pronounced part in the outbreak, with a notable disparity in peak cases when mobility was considered. This study highlights that while inter-regional mobility acted as a trigger for the epidemic spread, the diffusion effect of intra-regional mobility was primarily responsible for the outbreak. We have a better understanding on how human mobility and infectious disease epidemics interact, and provide empirical evidence that could contribute to disease prevention and control measures.

MKRN1 promotes colorectal cancer metastasis by activating the TGF-ß signalling pathway through SNIP1 protein degradation.

BACKGROUND: The Makorin ring finger protein 1 (MKRN1) gene, also called RNF61, is located on the long arm of chromosome 7 and is a member of the RING finger protein family. The E3 ubiquitin ligase MKRN1 is closely linked to tumour development, but the exact mechanism needs to be elucidated. In this study, we aimed to investigate the specific mechanism and role of MKRN1 in colorectal cancer (CRC) development. METHODS: MKRN1 expression in CRC was analysed using the Cancer Cell Line Encyclopaedia and the Cancer Genome Atlas (TCGA) databases. Rectal tumour tissues were frozen to explore the MKRN1 expression in CRC and its clinical significance. The impact of MKRN1 on CRC cell proliferation and migration was observed using CCK8, colony formation, wound healing, and transwell assays. A combination of MKRN1 quantitative proteomics, ubiquitination modification omics analysis, and a string of in vitro and in vivo experiments revealed the potential mechanisms by which MKRN1 regulates CRC metastasis. RESULTS: MKRN1 expression was significantly elevated in CRC tissues compared to paracancerous tissues and was positively linked with prognosis (P < 0.01). MKRN1 downregulation inhibits CRC cell proliferation, migration, and invasion. Conversely, MKRN1 overexpression promotes the proliferation, migration, and invasion of CRC cells. Mechanistically, MKRN1 induces epithelial-mesenchymal transition (EMT) in CRC cells via ubiquitination and degradation of Smad nuclear-interacting protein 1 (SNIP1). Furthermore, SNIP1 inhibits transforming growth factor-ß (TGF-ß) signalling, and MKRN1 promotes TGF-ß signalling by degrading SNIP1 to induce EMT in CRC cells. Finally, using conditional knockout mice, intestinal lesions and metastatic liver microlesions were greatly reduced in the intestinal knockout MKRN1 group compared to that in the control group. CONCLUSIONS: High MKRN1 levels promote TGF-ß signalling through ubiquitination and degradation of SNIP1, thereby facilitating CRC metastasis, and supporting MKRN1 as a CRC pro-cancer factor. The MKRN1/SNIP1/TGF-ß axis may be a potential therapeutic target in CRC.

Platinum-loaded dendritic mesoporous silica as novel ethylene scavenger to extend shelf life of banana (Musa nana).

Ethylene, released from fruits and vegetables (F&V) after harvest and during storage, often accelerates the ripening or over-ripening and may be caused decay, leading to substantial economic loss. Dendritic mesoporous silica supported (DMS) platinum (Pt/DMS) catalyst as ethylene scavenger was prepared and various characterization results indicated that the as-prepared Pt/DMS with ultra-low Pt loading exhibited excellent ethylene scavenging performance, which could maintain the complete ethylene conversion (100%) over 50 h at 25 °C and even 0 °C for 100 min with superior consecutive cycles by repeating the use of Pt/DMS. The presence of Pt/DMS delayed banana softening, and browning, reduced weight loss and kept the freshness for 14 days. In conclusion, the active packaging incorporated with Pt/DMS catalysts with high ethylene scavenging efficiency is expected to be extremely beneficial to the post-harvest storage life of other fruits and vegetables that needs further related investigation.

Programmable Interactions of Cellulose Acetate with Octadecyltrichlorosilane-Functionalized SiO2 Nanoparticles.

It is significant to understand the interfacial interactions involved between the cellulose acetate (CA) and dispersed nanomaterials, in which the enhanced interaction improves the mechanical behavior of CA. In this work, the amendments of CA with SiO2 nanoparticles have been found to be endowed by grafting varying concentrations (0, 3, 5, and 6%) of octadecyltrichlorosilane (OTS). Aided by SiO2 colloid probe atomic force microscopy (AFM with a probe diameter of 20 µm), the adhesion force between CA and SiO2 is found to be programmable by tuning OTS concentrations functionalized onto SiO2 surfaces. The adhesion forces of 5% OTS-functionalized SiO2 with CA are the strongest, followed by the ones of 0, 3, and 6% OTS, resulting in a smoother and denser morphology on the film with 5% OTS. The AFM-measured approaching force-distance curves have been further compared to predictions by the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory, in which the XDLVO force is summed as the Liftshitz-van der Waals force (FLW), the electrostatic double-layer force (FEL), and the acid-base interaction force (FAB). FLW and FEL do not change significantly with OTS concentrations functionalized onto SiO2. However, FAB is sensitive to the functionalized OTS concentration onto SiO2 and significantly contributes to the interaction force of the composite films with 5% OTS, promoting the formation of a smooth and dense surface feature with a considerable mechanical performance demonstrated by load-displacement curves from a nanoindenter. This is highly encouraging and suggests that nanomaterials can be incorporated into CA to effectively improve their mechanical compatibility by programming the interaction between the CA matrix and nanomaterials.

The role of dietary salt in metabolism and energy balance: Insights beyond cardiovascular disease.

Dietary salt (NaCl) is essential to an organism's survival. However, today's diets are dominated by excessive salt intake, which significantly impacts individual and population health. High salt intake is closely linked to cardiovascular disease (CVD), especially hypertension, through a number of well-studied mechanisms. Emerging evidence indicates that salt overconsumption may also be associated with metabolic disorders. In this review, we first summarize recent updates on the mechanisms of salt-induced CVD, the effects of salt reduction and the use of salt substitution as a therapy. Next, we focus on how high salt intake can impact metabolism and energy balance, describing the mechanisms through which this occurs, including leptin resistance, the overproduction of fructose and ghrelin, insulin resistance and altered hormonal factors. A further influence on metabolism worth noting is the reported role of salt in inducing thermogenesis and increasing body temperature, leading to an increase in energy expenditure. While this result could be viewed as a positive metabolic effect because it promotes a negative energy balance to combat obesity, caution must be taken with this frame of thinking given the deleterious consequences of chronic high salt intake on cardiovascular health. Nevertheless, this review highlights the importance of salt as a noncaloric nutrient in regulating whole-body energy homeostasis. Through this review, we hope to provide a scientific framework for future studies to systematically address the metabolic impacts of dietary salt and salt replacement treatments. In addition, we hope to form a foundation for future clinical trials to explore how these salt-induced metabolic changes impact obesity development and progression, and to elucidate the regulatory mechanisms that drive these changes, with the aim of developing novel therapeutics for obesity and CVD.

Immobilizing Ionic Liquids onto Functionalized Surfaces for Sensing Volatile Organic Compounds.

Herein, a highly sensitive volatile organic compound (VOC) gas sensor is demonstrated using immobilized ionic liquid (IL), 1-butyl-3-methylimidazolium hexafluorophosphate, onto surfaces functionalized by the quaternary ammonium group -N+R, -COOH, and -NH2, i.e., N+-IL, COOH-IL, and NH2-IL, respectively. These functional groups ensure highly tunable interactions between the IL and surfaces, efficiently modulating the electrical resistance of the immobilized IL upon exposure to acetone and toluene. The immobilized IL to both acetone and toluene displays significant electronic resistance changes at a concentration of 150 ppm, falling in the order NH2-IL > N+-IL > COOH-IL for acetone while COOH-IL > NH2-IL > N+-IL for toluene. A better gaseous sensing ability is achieved in COOH-IL for toluene than acetone, while this does not hold in the case of NH2-IL and N+-IL surfaces because of the completely different ion structuring of the IL at these functionalized surfaces. The accelerated ion mobility in the IL that is immobilized onto functionalized surfaces is also responsible for the strong gaseous sensing response, which is demonstrated further by the atomic force microscopy-measured smaller friction coefficient. This is highly encouraging and suggests that ILs can be immobilized by a network formed by surface functionalization to easily and cheaply detect VOCs at ppm concentrations.

Discovery of New Glucose Uptake Inhibitors as Potential Anticancer Agents by Non-Radioactive Cell-Based Assays.

Tumor cells rely on aerobic glycolysis to support growth and survival, thus require more glucose supply. Glucose transporters GLUTs, primarily GLUT1, are overexpressed in various cancers. Targeting GLUTs has been regarded as a promising anticancer strategy. In this study, we first evaluated 75 potential GLUT1 inhibitors obtained from virtual screening of the NCI chemical library by a high-throughput cell-based method using a fluorescent glucose analogue 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy-d-glucose (2-NBDG) in COS-7 and SKOV3 cells that express high levels of GLUT1. Four compounds, #12, #16, #43 and #69, that significantly inhibited glucose uptake were further evaluated using flow cytometry directly measuring 2-NBDG uptake at the single-cell level and a Glucose Uptake-GloTM assay indirectly measuring 2-deoxy-d-glucose uptake in SKOV3, COS-7 or MCF-7 cells. The inhibitory effect on cancer cell growth was also determined in SKOV3 and MCF-7 cells, and #12 exhibited the best growth inhibitory effect equivalent to a known GLUT1 inhibitor WZB117. Although the anticancer effect of the identified potential GLUT1 inhibitors was moderate, they may enhance the activity of other anticancer drugs. Indeed, we found that #12 synergistically enhanced the anticancer activity of metformin in SKOV3 ovarian cancer cells.

Microstructural probing of phosphonium-based ionic liquids on a gold electrode using colloid probe AFM.

Atomic force microscopy (AFM) with a gold colloid probe modeled as the electrode surface is employed to directly capture the contact resonance frequency of two phosphonium-based ionic liquids (ILs) containing a common anion [BScB]- and differently lengthened cations ([P6,6,6,14]+ and [P4,4,4,8]+). The comparative interfacial studies are performed by creating IL films on the surface of gold, followed by measuring the wettability, thickness of the films, adhesion forces, surface morphology and AFM-probed contact resonance frequency. In addition, the cyclic voltammetry and impedance spectroscopy measurements of the neat ILs are measured on the surface of the gold electrode. The IL with longer cation alkyl chains exhibits a well-defined thin film on the electrode surface and enhanced the capacitance than the shorter chain IL. The AFM contact resonance frequency and force curves reveal that the longer IL prefers to form stiffer ion layers at the gold electrode surface, suggesting the "…anion-anion-cation-cation…" bilayer structure, in contrast, the shorter-chain IL forms the softer cation-anion alternating structure, i.e., "…anion-cation-anion-cation…".

CO2/CH4 Separation via Carbon-Based Membrane: The Dynamic Role of Gas-Membrane Interface.

Membrane separation is considered one of the most promising CO2/CH4 separation technologies currently available because it is a safe, environment-friendly, and economical method. However, the inability of membrane materials to reconcile the trade-off between permeability and permeation selectivity limits their further applications; moreover, the mechanism underlying this process is unclear, which is mainly determined by the performance of gas adsorption and diffusion. Therefore, this paper describes the effect of gas adsorption and diffusion on membrane separation by assessing the fundamental gas-membrane and gas-gas interactions. Combining molecular simulation methods (Monte Carlo and molecular dynamics simulation) and a thermodynamic model called "linearized nonequilibrium thermodynamic transfer model", we investigate the permeability and permeation selectivity for CO2/CH4 in five carbon-based membranes and propose a general method for screening membrane materials. The interaction-dominated mechanism derived in this work provides new insights into membrane separation and facilitates the screening of high-performance membrane materials.

Integrated analysis of the M2 macrophage-related signature associated with prognosis in ovarian cancer.

Background: M2 macrophages play an important role in cancer development. However, the underlying biological fator affecting M2 macrophages infiltration in ovarian cancer (OV) has not been elucidated. Methods: R software v 4.0.0 was used for all the analysis. The expression profile and clinical information of OV patients enrolled in this study were all downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Results: The CIBERSORT algorithm was used to quantify the M2 macrophage infiltration in OV tissue, which was found a risk factor for patients survival. Based on the limma package, a total of 196 DEGs were identified between OV patients with high and low M2 macrophage infiltration, which were defined as M2 macrophages related genes. Finally, the genes PTGFR, LILRA2 and KCNA1 were identified for prognosis model construction, which showed a great prediction efficiency in both training and validation cohorts (Training cohort, 1-year AUC = 0.661, 3-year AUC = 0.682, 8-year AUC = 0.846; Validation cohort, 1-year AUC = 0.642, 3-year AUC = 0.716, 5-year AUC = 0.741). Clinical correlation showed that the riskscore was associated with the worse clinical features. Pathway enrichment analysis showed that in high risk patients, the pathway of epithelial-mesenchymal transition (EMT), TNF-α signaling via NFKB, IL2/STAT5 signaling, apical junction, inflammatory response, KRAS signaling, myogenesis were activated. Moreover, we found that the PTGFR, LILRA2 and KCNA1 were all positively correlated with M2 macrophage infiltration and PTGFR was significantly associated with the pathway of autophagy regulation. Moreover, we found that the low risk patients might be more sensitive to cisplatin, while high risk patient might be more sensitive to axitinib, bexarotene, bortezomib, nilotinib, pazopanib. Conclusions: In this study, we identified the genes associated with M2 macrophage infiltration and developed a model that could effectively predict the prognosis of OV patients.

Enhanced Formaldehyde Oxidation Performance of the Mesoporous TiO2(B)-Supported Pt Catalyst: The Role of Hydroxyls.

As one of the crystal phases of titania, TiO2(B) was first utilized as a catalyst carrier for the oxidation of formaldehyde (HCHO). The mesoporous TiO2(B) loaded with Pt nanoparticles enhanced the HCHO oxidation reaction whose reaction rate was 4.5-8.4 times those of other crystalline TiO2-supported Pt catalysts. Simultaneously, Pt/TiO2(B) exhibited long-term stable HCHO oxidation performance. The structural characterization results showed that in comparison with Pt/anatase, Pt/TiO2(B) had more abundant hydroxyls, facilitating increasing the content of oxygen species. Studies on the role of hydroxyls in HCHO oxidation of Pt/TiO2(B) illustrated that synergistic involvement of terminally bound hydroxyls and bridging hydroxyls in HCHO oxidation accelerated the transformation from HCHO to formate via dioxymethylene. Moreover, hydroxyls could avoid the accumulation of excessive formate on Pt/TiO2(B) and promote the rapid oxidation of CO. Accordingly, the hydroxyl groups could accelerate each substep of formaldehyde oxidation, which enabled Pt/TiO2(B) to exhibit excellent formaldehyde oxidation performance.

[Melatonin Induced Apoptosis of RPMI 8226 Cells through Endoplasmic Reticulum Stress].

OBJECTIVE: To investigate the effect of melatonin (MLT) on the proliferation and apoptosis of human multiple myeloma cell line RPMI 8226 and its possible mechanism. METHODS: RPMI 8226 cells were cultured in vitro, and different concentrations of MLT were treated on RPMI 8226 cells. The effects of MLT on RPMI 8226 cell proliferation were detected by CCK-8 assay and methylcellulose cloning assay, and the effects of MLT on cell apoptosis were detected by AnnexinV-FITC /PI, flow cytometry. Western blot was used to determine the expression of apoptosis and endoplasmic reticulum stress-related proteins in each group, and CCK-8 assay was used to determine the effect of MLT combined with bortezemib on the viability of RPMI 8226 cells. RESULTS: MLT inhibited the proliferation of RPMI 8226 cells in a dose- and time-dependent manner (r=-0.9777，r=-0.9951). With the increase of MLT concentration, the number of clones decreased, the apoptosis of RPMI 8226 cells increased (P<0.05), the expression of anti-apoptotic protein XIAP decreased, the expression of apoptotic proteins Bax and Caspase3 increased, and the expression of endoplasmic reticulum stress-related proteins increased. Compared with the control group, the survival of RPMI 8226 cells in the MLT and BTZ combined group significantly decreased (P<0.01). CONCLUSION: MLT can inhibit the proliferation of RPMI 8226 cells, promote the apoptosis of RPMI 8226 cells, and enhance the anti-tumor effect of BTZ on RPMI 8226 cells. The mechanism may be related to endoplasmic reticulum stress.

Identification of an Autophagy-Related Signature Based on Whole Bone Marrow Sequencing for the Prognosis and Immune Microenvironment Characterization of Multiple Myeloma.

Myeloma (MM) is a malignant plasma cell disorder, which is incurable owing to its drug resistance. Autophagy performs an integral function in homeostasis, survival, and drug resistance in multiple myeloma (MM). Therefore, the purpose of the present research was to identify potential autophagy-related genes (ARGs) in patients with MM. We downloaded the transcriptomic data (GSE136400) of patients with MM, as well as the corresponding clinical data from the Gene Expression Omnibus (GEO); the patients were classified at random into two groups in a ratio of 6: 4, with 212 samples in the training dataset and 142 samples in the test dataset. Both multivariate and univariate Cox regression analyses were performed to identify autophagy-related genes. The univariate Cox regression analysis demonstrated that 26 ARGs had a significant correlation with overall survival (OS). We constructed an autophagy-related risk prognostic model based on six ARGs: EIF2AK2 (ENSG00000055332), KIF5B (ENSG00000170759), MYC (ENSG00000136997), NRG2 (ENSG00000158458), PINK1 (ENSG00000158828), and VEGFA (ENSG00000112715) using LASSO-Cox regression analysis to predict risk outcomes, which revealed substantially shortened OS duration in the high-risk cohort in contrast with that in the low-risk cohort. Therefore, the ARG-based model significantly predicted the MM patients' prognoses and was verified in an internal test set. Differentially expressed genes were found to be predominantly enriched in pathways associated with inflammation and immune regulation. Immune infiltration of tumor cells resulted in the formation of a strong immunosuppressive microenvironment in high-risk patients. The potential therapeutic targets of ARGs were subsequently analyzed via protein-drug network analysis. Therefore, a prognostic model for MM was established via a comprehensive analysis of ARGs, through using the clinical models; we have further revealed the molecular landscape features of multiple myeloma.