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Abstract The hypercoagulable state is a hallmark for patients with multiple myeloma (MM) and is associated with disease progression. Activated platelets secrete exosomes and promote solid tumor growth. However, the role of platelet-derived exosomes in MM is not fully clear. We aim to study the underlying mechanism of how platelet-derived exosomes promote MM cell growth. Flow cytometry, Western blot, proteome analysis, co-immunoprecipitation, immunofluorescence staining, and NOD/SCID mouse subcutaneous transplantation model were performed to investigate the role of exosomal LRG1 on multiple myeloma cell growth. Peripheral blood platelets in MM patients were in a highly activated state, and platelet-rich plasma from MM patients significantly promoted cell proliferation and decreased apoptotic cells in U266 and RPMI8226 cells. Leucine-rich-alpha-2-glycoprotein 1 (LRG1) was significantly enriched in MM platelet-derived exosomes. Blocking LRG1 in recipient cells using LRG1 antibody could significantly eliminate the proliferation-promoting effect of platelet-derived exosomes on MM cells. And high exosomal LRG1 was associated with poor prognosis of patients with MM. Mechanistic studies revealed that LRG1 interacted with Olfactomedin 4 (OLFM4) to accelerate MM progression by activating the epithelial-to-mesenchymal transition (EMT) signaling pathway and promoting angiogenesis. Our results revealed that blocking LRG1 is a promising therapeutic strategy for the treatment of MM.

Abstract Carbon quantum dots (CQDs) have emerged as prominent contenders in the realm of luminescent nanomaterials over the past decade owing to their tunable optical properties, robust photostability, versatile surface functionalization and doping potential, low toxicity, and straightforward synthesis utilizing environmentally friendly precursors. In this review, we commence with a concise introduction, presenting both top‐down and bottom‐up strategies for the eco‐friendly synthesis of CQDs. Subsequently, we delve into a comprehensive examination of CQDs' structure and optical characteristics, encompassing their ultraviolet–visible absorption properties, surface confinement effects, and surface state emissions contributing to room‐temperature photoluminescence (PL). This review proceeds to elucidate recent advancements in modification strategies for CQDs, specifically focusing on surface oxidation, passivation, and the incorporation of heteroatoms. These strategies serve to afford control over the physicochemical properties, facilitating the enhancement of PL through the decoration of highly visible‐responsive CQDs. This enhancement is achieved by suppressing the nonradiative recombination of electron‐hole pairs, enabling red/blue shifts in CQDs for the generation of a full‐color emission spectrum, and regulating the band‐gap and surface states to broaden the photoabsorption range. Finally, we offer an overview of the most recent developments in the applications of fluorescent CQDs, emphasizing their utility in biomedicine, fluorescent sensors, lighting, and displays, as well as photocatalysis.

Abstract Background/Aim Lenvatinib, a multikinase inhibitor, has become a second-line treatment option for unresectable liver cancer, while its monotherapy response rate is limited. Hence, we aim to investigate whether one of the epigenetic inhibitors will be synthetic lethal with Lenvatinib in liver cancer cells. Materials and Methods We performed high-throughput drug screening in combination with Lenvatinib. And we employed CCK-8-based Bliss Synergy Score analysis, colony formation and western blotting to confirm our screening results in both HepG2 and HCCC9810 cells. Results We identified that LSD1 inhibitor Pulrodemstat in combination with Lenvatinib dramatically suppressed the PI3K-AKT signaling and induced a more significant activation of Caspase3 compared to Lenvatinib monotherapy. Conclusion Pulrodemstat synergized with Lenvatinib based on suppression of PI3K-AKT signaling and activation of apoptotic signaling.

BackgroundClinical studies have indicated a comorbidity between sepsis and kidney diseases. Individuals with specific mutations that predispose them to kidney conditions are also at an elevated risk for developing sepsis, and vice versa. This suggests a potential shared genetic etiology that has not been fully elucidated.MethodsSummary statistics data on exposure and outcomes were obtained from genome-wide association meta-analysis studies. We utilized these data to assess genetic correlations, employing a pleiotropy analysis method under the composite null hypothesis to identify pleiotropic loci. After mapping the loci to their corresponding genes, we conducted pathway analysis using Generalized Gene-Set Analysis of GWAS Data (MAGMA). Additionally, we utilized MAGMA gene-test and eQTL information (whole blood tissue) for further determination of gene involvement. Further investigation involved stratified LD score regression, using diverse immune cell data, to study the enrichment of SNP heritability in kidney-related diseases and sepsis. Furthermore, we employed Mendelian Randomization (MR) analysis to investigate the causality between kidney diseases and sepsis.ResultsIn our genetic correlation analysis, we identified significant correlations among BUN, creatinine, UACR, serum urate, kidney stones, and sepsis. The PLACO analysis method identified 24 pleiotropic loci, pinpointing a total of 28 nearby genes. MAGMA gene-set enrichment analysis revealed a total of 50 pathways, and tissue-specific analysis indicated significant enrichment of five pairs of pleiotropic results in kidney tissue. MAGMA gene test and eQTL information (whole blood tissue) identified 33 and 76 pleiotropic genes, respectively. Notably, genes PPP2R3A for BUN, VAMP8 for UACR, DOCK7 for creatinine, and HIBADH for kidney stones were identified as shared risk genes by all three methods. In a series of immune cell-type-specific enrichment analyses of pleiotropy, we identified a total of 37 immune cells. However, MR analysis did not reveal any causal relationships among them.ConclusionsThis study lays the groundwork for shared etiological factors between kidney and sepsis. The confirmed pleiotropic loci, shared pathogenic genes, and enriched pathways and immune cells have enhanced our understanding of the multifaceted relationships among these diseases. This provides insights for early disease intervention and effective treatment, paving the way for further research in this field.

Numerous studies have demonstrated that second language (L2) comprehension is often accompanied by activations in the first language (L1). Using both behavioral measurement and event-related potential (ERP), this study conducted two experiments to investigate whether a direct activation pathway exists from L2 lexical representation to L1 lexical representation (the lexical pathway) in intermediate proficient bilinguals. In Experiment 1, we designed a vowel letter search task on English word pairs, which enables bilinguals to prevent semantic priming in the first 300 ms processing stage after the words’ onset. In Experiment 2, Mandarin–English bilinguals were recruited to complete this task on English word pairs with occasional first character repetition between the Chinese counterparts of a word pair. Results showed a significant main effect within both the P200 and N400 time windows, indicating the activation of bilinguals’ L1 lexical representation during these intervals. However, the main effect of semantic relatedness was only significant in the N400 time window. These results suggest that bilinguals can activate their L1 lexical representation directly before engaging in conceptual representation. This finding supported a lexical pathway of activation from L2 lexical representation to L1 lexical representation during visual-word recognition in intermediate proficient bilinguals.

Based on the performance and acoustic data files of reduced-size open-rotor engines in low-speed wind tunnels, the static sound pressure level was derived by converting the 1-foot lossless spectral density into sound-pressure-level data, the background noise was removed, and the results were corrected according to the environmental parameters of the low-speed wind tunnels. In accordance with the requirements of Annex 16 of the Convention on International Civil Aviation Organization and Part 36 of the Civil Aviation Regulations of China on noise measurement procedures, the takeoff trajectory was physically modeled; the static noise source was mapped onto the takeoff trajectory to simulate the propagation process of the noise during takeoff; and the 24 one-third-octave center frequencies that corresponded to the SPL data were corrected for geometrical dispersion, atmospheric absorption, and Doppler effects, so that the takeoff noise could be corrected to represent a real environment. In addition, the audible processing of noise data with a 110° source pointing angle was achieved, which can be useful for enabling practical observers to analyze the noise characteristics.

Studies have shown that bortezomib resistance in multiple myeloma (MM) is mediated by the abnormalities of various molecules and microenvironments. Exploring these resistance mechanisms will improve the therapeutic efficacy of bortezomib. In this study, bone marrow tissues from three patients with MM, both sensitive and resistant to bortezomib, were collected for circRNA high-throughput sequencing analysis. The relationship between circ_0000337, miR-98-5p, and target gene DNA2 was analyzed by luciferase detection and verified by RT-qPCR. We first found that circ_0000337 was significantly upregulated in bortezomib-resistant MM tissues and cells, and overexpression of circ_0000337 could promote bortezomib resistance in MM cells. circ_0000337 may act as a miR-98-5p sponge to upregulate DNA2 expression, regulate DNA damage repair, and induce bortezomib resistance. Furthermore, it was determined that the increased circ_0000337 level in bortezomib-resistant cells was due to an increased N6-methyladenosine (m6A) level, resulting in enhanced RNA stability. In conclusion, the m6A level of circ_0000337 and its regulation may be a new and potential therapeutic target for overcoming bortezomib resistance in MM.

With the continuous advancement of technology, automated vehicle technology is progressively maturing. It is crucial to comprehend the factors influencing individuals' intention to utilize automated vehicles. This study examined user willingness to adopt automated vehicles. By incorporating age and educational background as random parameters, an ordered Probit model with random parameters was constructed to analyze the influential factors affecting respondents' adoption of automated vehicles. We devised and conducted an online questionnaire survey, yielding 2105 valid questionnaires. The findings reveal significant positive correlations between positive social trust, perceived ease of use, perceived usefulness, low levels of perceived risk, and the acceptance of automated vehicles. Additionally, our study identifies extraversion and openness as strong mediators in shaping individuals' intentions to use automated vehicles. Furthermore, prior experience with assisted driving negatively impacts people's inclination toward embracing automated vehicles. Our research also provides insights for promoting the adoption of automated vehicles: favorable media coverage and a reasonable division of responsibilities can enhance individuals' intentions to adopt this technology.

BackgroundRecent research linked changes in the gut microbiota and serum metabolite concentrations to intracerebral hemorrhage (ICH). However, the potential causal relationship remained unclear. Therefore, the current study aims to estimate the effects of genetically predicted causality between gut microbiota, serum metabolites, and ICH.MethodsSummary data from genome-wide association studies (GWAS) of gut microbiota, serum metabolites, and ICH were obtained separately. Gut microbiota GWAS (N = 18,340) were acquired from the MiBioGen study, serum metabolites GWAS (N = 7,824) from the TwinsUK and KORA studies, and GWAS summary-level data for ICH from the FinnGen R9 (ICH, 3,749 cases; 339,914 controls). A two-sample Mendelian randomization (MR) study was conducted to explore the causal effects between gut microbiota, serum metabolites, and ICH. The random-effects inverse variance-weighted (IVW) MR analyses were performed as the primary results, together with a series of sensitivity analyses to assess the robustness of the results. Besides, a reverse MR was conducted to evaluate the possibility of reverse causation. To validate the relevant findings, we further selected data from the UK Biobank for analysis.ResultsMR analysis results revealed a nominal association (p

The extracellular polymeric substance (EPS) plays a key factor in biofilm formation. However, the research on the importance of each EPS fraction is mainly concentrated in the activated sludge field. In this study, biofilms were cultivated under different hydrodynamic conditions in indoor flumes, and the important regulatory effects of dissolved EPS (SB-EPS), loosely bound EPS (LB-EPS), and tightly bound EPS (TB-EPS) on biofilm formation were investigated. The results indicated that the ratios of soluble EPS (S-EPS), loosely bound EPS (LB-EPS), and tightly bound EPS (TB-EPS) were 27:74:108 in the turbulent flow, 38:48:71 in the transitional flow, and 89:51:51 in the laminar flow. Regarding proportion, TB-EPS and LB-EPS were secreted more in the turbulent flow, while S-EPS was secreted slightly more in the laminar flow. S-EPS lacks the structural strength provided by bound EPS. Under the special bonding effects of LB-EPS and TB-EPS, many microcolonies join to form biofilms. The polysaccharide content in the EPS of biofilms remained dominant under all conditions. Polysaccharides are the core of biofilm formation, which enhance bacterial aggregation and make biofilm dense. Through the mutual verification of the results in the microscopic and macroscopic fields, the mechanism of biofilm formation was further elucidated, especially, in Stage IV, due to the special bonding effects of LB-EPS and TB-EPS, many colonies adhere to the mature biofilm. Further studies are required to investigate the extracellular polysaccharides and proteins in EPS along with their properties in biofilms.

To provide service of all-weather, full automation and high precision deformation monitoring and to furthest reduce the effects of space environment factors on the high precision real-time positioning, on the digital CDRadio edge of RTK GNSS core analytic computing technology fusion algorithm is used, and “the Beidou high-precision geological disaster monitoring system with edge calculation based on broadcasting RTK”is developed, which is characterized by the independent intellectual property rights and structure open. The system can run stably for a long time, and can satisfy the functional requirements and non-functional requirements of all users. Taking the unstable slope of block 8 in the Gemstone Garden in Changzhou District of Wuzhou as an example, the monitoring results from May to November 2020 are analyzed. The monitoring data show that the whole slope body is in the stage of slow development, and the front edge of the slope top has a tendency of peristatically moving and sinking. The whole slope body tends to develop towards the southeast direction. Through the establishment of a good system information interaction platform, the statistical analysis information formed by the system is transmitted to users in a high speed and convenient way, which effectively improves the users' system management, decision-making and application ability. It can fully mine the data resources of the system, provide real-time forecasting services, effectively improve the accuracy and reliability of information collection, transmission, processing, analysis and forecast, comprehensively improve the ability of geological disaster monitoring, early warning and forecast management, and better provide scientific basis for the decision-making and command of management departments at all levels in emergency rescue and disaster relief.

The chemical transformation of carbon dioxide (CO2) not only reduces the amount of carbon dioxide emitted into the Earth’s atmosphere by humans, but also produces carbon compounds that can be used as precursors for chemical and fuel production. Herein, a selective catalytic conversion of carbon dioxide to methanol is achieved by a bifunctional molybdenum disulfide catalyst (MoS2) with magnesium oxide and nickel and potassium promoters. Molybdenum disulfide prepared by the supercritical ethanol method has a large specific surface area and presents good catalytic performance with high methanol selectivity when loaded with potassium (K) and nickel (Ni) promoters. In addition, the catalysts were evaluated and it was founded that the addition of the K-promoter improved methanol selectivity. This research provides a new strategy for improved product selectivity and space–time yield (STY) of methanol in CO2 hydrogenation.

Background: Randomized controlled trials (RCTs) evaluating the influence of personal protective equipment (PPE) on quality of chest compressions during cardiopulmonary resuscitation (CPR) showed inconsistent results. Accordingly, a meta-analysis was performed to provide an overview.Methods: Relevant studies were obtained by search of Medline, Embase, and Cochrane's Library databases. A random-effect model incorporating the potential heterogeneity was used to pool the results.Results: Six simulation-based RCTs were included. Overall, pooled results showed that there was no statistically significant difference between the rate [mean difference (MD): −1.70 time/min, 95% confidence interval (CI): −5.77 to 2.36, P = 0.41, I2 = 80%] or the depth [MD: −1.84 mm, 95% CI: −3.93 to 0.24, P = 0.11, I2 = 73%] of chest compressions performed by medical personnel with and without PPE. Subgroup analyses showed that use of PPE was associated with reduced rate of chest compressions in studies before COVID-19 (MD: −7.02 time/min, 95% CI: −10.46 to −3.57, P < 0.001), but not in studies after COVID-19 (MD: 0.14 time/min, 95% CI: −5.77 to 2.36, P = 0.95). In addition, PPE was not associated with significantly reduced depth of chest compressions in studies before (MD: −3.34 mm, 95% CI: −10.29 to −3.62, P = 0.35) or after (MD: −0.97 mm, 95% CI: −2.62 to 0.68, P = 0.25) COVID-19. No significant difference was found between parallel-group and crossover RCTs (P for subgroup difference both > 0.05).Conclusions: Evidence from simulation-based RCTs showed that use of PPE was not associated with reduced rate or depth of chest compressions in CPR.

Purpose: Circular RNA (circRNA) is a key regulatory factor in the development and progression of human tumors. However, the working mechanism and clinical significance of most circRNAs remain unknown in human cancers, including multiple myeloma (MM).Patients and Methods: This study employs high-throughput circRNA microarray with bioinformatics to identify differentially expressed circRNAs in patients with MM. The hsa_circ_0007841 expressions were observed in the MM tissues of 86 patients. Drug-resistant cell lines and pathological features were also detected. In addition, the relationship between hsa_circ_0007841 expressions in the MM tissues and the pathological features of patients with MM were evaluated and role of hsa_circ_0007841 as a potential biomarker and therapeutic target was assessed.Results: The results show that in the MM cell lines and drug-resistant cell lines, hsa_circ_0007841 expression was significantly upregulated, which was closely associated with disease prognosis. Specifically, hsa_circ_0007841 upregulation was correlated with chromosomal aberrations such as gain 1q21, t (4:14) and mutations in ATR and IRF4 genes. This finding was corroborated in large samples. Finally, bioinformatics analysis showed that eight differentially expressed miRNAs and 10 candidate mRNAs interacted with hsa_circ_0007841, shedding some new light on the basic functional research.Conclusion: This study may be the first to report that hsa_circ_0007841 is significantly upregulated in MM. It also suggests that hsa_circ_0007841 may be a novel biomarker for MM and its involvement in the progression of MM.

Aim: To investigate the prognostic value of lncRNA NR_046683 in multiple myeloma (MM).Methods: High-throughput lncRNA array was combined with bioinformatics techniques to screen differentially expressed lncRNA in MM. qRT-PCR was adopted to determine the expression of target lncRNAs in MM patients and controls.Results: It was found for the first time that lncRNA NR_046683 is closely related to the prognosis of MM. It was also detected in tumor cell lines KM3, U266, especially in drug-resistant cell lines KM3/BTZ and MM1R. The NR_046683 expression differed significantly in patients of different MM subtypes and staging. Moreover, the overexpression of NR-046683 is closely related to β2-microglobulin. We also found that the overexpression of NR-046683 correlates to chromosomal aberrations, such as del(13q14), gain 1q21, and t(4;14).Conclusion: lncRNA NR_046683 can serve as a novel biomarker for potential drug target and prognostic prediction in MM.

BACKGROUND: Cigarette smoking/nicotine exposure in pregnancy shows an increased risk of hypertension in offspring, but the mechanisms are unclear. This study tested the hypothesis that m6A RNA hypomethylation epigenetically regulates vascular NOX (NADPH oxidase) and reactive oxygen species production, contributing to the fetal programming of a hypertensive phenotype in nicotine-exposed offspring. METHODS: Pregnant rats were exposed to episodic chronic intermittent nicotine aerosol (CINA) or saline aerosol control from gestational day 4 to day 21, and experiments were performed in 6-month--old adult offspring. RESULTS: Antenatal CINA exposure augmented Ang II (angiotensin II)--stimulated blood pressure response in male, but not female offspring. Moreover, CINA increased vascular NOX2 expression and superoxide production exclusively in male offspring. Inhibition of NOX2 with gp91ds-tat, both ex vivo and in vivo, mitigated the CINA-induced elevation in superoxide production and blood pressure response. Notably, CINA enhanced the expression of vascular m6A demethylase FTO (fat mass and obesity-associated protein), while reducing the total vascular m6A abundance and specific m6A methylation of the NOX2 gene. Additionally, ex vivo inhibition of FTO with FB23-2 attenuated CINA-induced increases in vascular NOX2 expression. In vitro experiments using human umbilical vein endothelial cells demonstrated that nicotine dose-dependently upregulated FTO and NOX2 protein abundance, which were reversed by treatment with the FTO inhibitor FB23-2 or FTO knockdown using siRNAs. CONCLUSIONS: This study uncovers a new mechanism: m6A demethylase FTO-mediated epigenetic upregulation of vascular NOX2 signaling in CINA-induced hypertensive phenotype. This insight could lead to a therapeutic target for preventing and treating developmental hypertension programming. [ABSTRACT FROM AUTHOR]