Oncolytic Newcastle disease virus carrying the IL24 gene exerts antitumor effects by inhibiting tumor growth and vascular sprouting.

The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional approaches. Newcastle disease virus (NDV), a nonpathogenic oncolytic virus, exhibits multifunctional anticancer properties by selectively infecting, replicating, and eliminating tumor cells. To enhance NDV's antitumor activity, four oncolytic NDV viruses were developed, incorporating IL24 and/or GM-CSF genes at different gene loci using reverse genetics. In vitro experiments revealed that oncolytic NDV virus augmented the antitumor efficacy of the parental virus rClone30, inhibiting tumor cell proliferation, inducing tumor cell fusion, and promoting apoptosis. Moreover, NDV carrying the IL24 gene inhibited microvessel formation in CAM experiments. Evaluation in a mouse model of liver cancer confirmed the therapeutic efficacy of oncolytic NDV viral therapy. Tumors in mice treated with oncolytic NDV virus significantly decreased in size, accompanied by tumor cell detachment and apoptosis evident in pathological sections. Furthermore, oncolytic NDV virus enhanced T cell and dendritic cell production and substantially improved the survival rate of mice with hepatocellular carcinoma, with rClone30-IL24(P/M) demonstrating significant therapeutic effects. This study establishes a basis for utilizing oncolytic NDV virus as an antitumor agent in clinical practice.

Lopinavir enhances anoikis by remodeling autophagy in a circRNA-dependent manner.

Macroautophagy/autophagy-mediated anoikis resistance is crucial for tumor metastasis. As a key autophagy-related protein, ATG4B has been demonstrated to be a prospective anti-tumor target. However, the existing ATG4B inhibitors are still far from clinical application, especially for tumor metastasis. In this study, we identified a novel circRNA, circSPECC1, that interacted with ATG4B. CircSPECC1 facilitated liquid-liquid phase separation of ATG4B, which boosted the ubiquitination and degradation of ATG4B in gastric cancer (GC) cells. Thus, pharmacological addition of circSPECC1 may serve as an innovative approach to suppress autophagy by targeting ATG4B. Specifically, the circSPECC1 underwent significant m6A modification in GC cells and was subsequently recognized and suppressed by the m6A reader protein ELAVL1/HuR. The activation of the ELAVL1-circSPECC1-ATG4B pathway was demonstrated to mediate anoikis resistance in GC cells. Moreover, we also verified that the above pathway was closely related to metastasis in tissues from GC patients. Furthermore, we determined that the FDA-approved compound lopinavir efficiently enhanced anoikis and prevented metastasis by eliminating repression of ELAVL1 on circSPECC1. In summary, this study provides novel insights into ATG4B-mediated autophagy and introduces a viable clinical inhibitor of autophagy, which may be beneficial for the treatment of GC with metastasis.

KIAA1429 facilitates metastasis via m6A-YTHDC1-dependent RND3 down-regulation in hepatocellular carcinoma cells.

N6-methyladenosine (m6A), a dynamically reversible modification in eukaryotic RNAs, modulates gene expression and pathological processes in various tumors. KIAA1429, the largest component of the m6A methyltransferase complex, plays an important role in m6A modification. However, the underlying mechanism of KIAA1429 in hepatocellular carcinoma (HCC) remains largely unknown. Immunohistochemical assay was performed to examine the expression of KIAA1429 in HCC tissues. Transwell, wound healing and animal experiments were used to investigate the influence of KIAA1429 on cell migration and invasion. The mRNA high-throughput sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (MeRIP-seq) were performed to screen the downstream target of KIAA1429. RNA stability assays, RNA immunoprecipitation assay (RIP), MeRIP-qPCR and luciferase assay were used to evaluate the relationship between KIAA1429 and the m6A-modified genes. Results showed that the expression level of KIAA1429 was significantly higher in HCC tissues than in adjacent tissues, and the upregulation of KIAA1429 could promote HCC metastasis in vitro and in vivo. Mechanistically, we confirmed that KIAA1429 negatively regulated the tumor suppressor, Rho family GTPase 3 (RND3), by decreasing its mRNA stability in coordination with the m6A reader YTHDC1. Moreover, we demonstrated that KIAA1429 could regulate the m6A modification of RND3 mRNA via its RNA binding domain. Our data indicated that KIAA1429 exerted its oncogenic role by inhibiting RND3 expression in an m6A-dependent manner, suggesting that KIAA1429 might be a potential prognostic biomarker and therapeutic target in HCC.

Circular RNA vaccine in disease prevention and treatment.

CircRNAs are a class of single-stranded RNAs with covalently linked head-to-tail topology. In the decades since its initial discovery, their biogenesis, regulation, and function have rapidly disclosed, permitting a better understanding and adoption of them as new tools for medical applications. With the development of biotechnology and molecular medicine, artificial circRNAs have been engineered as a novel class of vaccines for disease treatment and prevention. Unlike the linear mRNA vaccine which applications were limited by its instability, inefficiency, and innate immunogenicity, circRNA vaccine which incorporate internal ribosome entry sites (IRESs) and open reading frame (ORF) provides an improved approach to RNA-based vaccination with safety, stability, simplicity of manufacture, and scalability. However, circRNA vaccines are at an early stage, and their optimization, delivery and applications require further development and evaluation. In this review, we comprehensively describe circRNA vaccine, including their history and superiority. We also summarize and discuss the current methodological research for circRNA vaccine preparation, including their design, synthesis, and purification. Finally, we highlight the delivery options of circRNA vaccine and its potential applications in diseases treatment and prevention. Considering their unique high stability, low immunogenicity, protein/peptide-coding capacity and special closed-loop construction, circRNA vaccine, and circRNA-based therapeutic platforms may have superior application prospects in a broad range of diseases.

Occupancy-aided ventilation for airborne infection risk control: Continuously or intermittently reduced occupancies?

Ventilation is an important engineering measure to control the airborne infection risk of acute respiratory diseases, e.g., Corona Virus Disease 2019 (COVID-19). Occupancy-aided ventilation methods can effectively improve the airborne infection risk control performance with a sacrifice of decreasing working productivity because of the reduced occupancy. This study evaluates the effectiveness of two occupancy-aided ventilation methods, i.e., the continuously reduced occupancy method and the intermittently reduced occupancy method. The continuously reduced occupancy method is determined by the steady equation of the mass conservation law of the indoor contaminant, and the intermittently reduced occupancy method is determined by a genetic algorithm-based optimization. A two-scenarios-based evaluation framework is developed, i.e., one with targeted airborne infection risk control performance (indicated by the mean rebreathed fraction) and the other with targeted working productivity (indicated by the accumulated occupancy). The results show that the improvement in the airborne infection risk control performance linearly and quadratically increases with the reduction in the working productivity for the continuously reduced occupancy method and the intermittently reduced occupancy method respectively. At a given targeted airborne infection risk control performance, the intermittently reduced occupancy method outperforms the continuously reduced occupancy method by improving the working productivity by up to 92%. At a given targeted working productivity, the intermittently reduced occupancy method outperforms the continuously reduced occupancy method by improving the airborne infection risk control performance by up to 38%.

High capacity adsorption of antimony in biomass-based composite and its consequential utilization as battery anode.

Antimony is more than an emerging pollutant in water but a scare resource. In this study, we report an adsorbent with the record capacity so far from the balanced view of Sb(III) and Sb(V). The composite adsorbent was fabricated by encapsulating hollow Fe3O4 nanosphere with the EDTA grafted chitosan, and it has superhigh adsorption capacity of for 657.1 mg/g for Sb(III) and 467.3 mg/g for Sb(V), respectively. The mechanism study reveals that the adsorption of Sb initializes from the Fe3O4, propagates along the chitosan with hydrogen bond, and terminates at the inner sphere complex with the EDTA moiety in the adsorbent. In view of the ultra-high adsorption capacity of the adsorbent, the recovered adsorbent that contains abundant (>36.4%) highly dispersed antimony nanoparticles (600-FCSE-Sb) is applied to Li-ion battery anode after reduction. This article provides a new idea for connecting water treatment and electric energy storage.

Ventilation indices for evaluation of airborne infection risk control performance of air distribution.

Air distribution is an effective engineering measure to fight against respiratory infectious diseases like COVID-19. Ventilation indices are widely used to indicate the airborne infection risk of respiratory infectious diseases due to the practical convenience. This study investigates the relationships between the ventilation indices and airborne infection risk to suggest the proper ventilation indices for the evaluation of airborne infection risk control performance of air distribution. Besides the commonly used ventilation indices of the age of air (AoA), air change effectiveness (ACE), and contaminant removal effectiveness (CRE), this study introduces two ventilation indices, i.e., the air utilization effectiveness (AUE) and contaminant dispersion index (CDI). CFD simulations of a hospital ward and a classroom served by different air distributions, including mixing ventilation, displacement ventilation, stratum ventilation and downward ventilation, are validated to calculate the ventilation indices and airborne infection risk. A three-step correlation analysis based on Spearman's rank correlation coefficient, Pearson correlation coefficient, and goodness of fit and a min-max normalization-based error analysis are developed to qualitatively and quantitatively test the validity of ventilation indices respectively. The results recommend the integrated index of AUE and CDI to indicate the overall airborne infection risk, and CDI to indicate the local airborne infection risk respectively regardless of the effects of air distribution, supply airflow rate, infectivity intensity, room configuration and occupant distribution. This study contributes to airborne transmission control of infectious respiratory diseases with air distribution.

Biochar microtube interconnected hydrotalcite nanosheets for the adsorption of aqueous Sb(III).

Actuated by the non-ionic heavy metal of antimony (Sb) contaminants with undesired toxicity to the environment and human health, capturing Sb is urgent to remedy contaminated water. Herein, the lamellar MnCo hydrotalcite was grown on catkin-derived biochar through the in situ etching of ZIF-L to construct a hierarchical microtube@nanosheet hybrid (CLMH) for Sb immobilization. The adsorption behaviour and mechanism of trivalent antimony (Sb (III)) on the CLMH were investigated. The CLMH shows good pH applicability for capturing Sb(III) at pH from 2 to 9. The excellent adsorption capacity of CLMH for Sb(III) is 247.62 mg g-1at 303 K, and the endothermic process is proved by the positive value of ΔH0(10.54 kJ mol-1). The adsorption process is fitted with the intra-particle diffusion model, which can be described with external mass transfer, intraparticle diffusion in pores, and equilibrium stage. The adsorption mechanism is proved, which includes the bind of Metal-O-Sb bonds by inner-sphere complex, the embedding of Sb in the intercalation of hydrotalcite, redox between Mn and Sb, and functional groups dependent anchoring effect. The work benefits the understanding of the antimony removal behaviour over the hierarchical microtube@nanosheet hybrids.

Impact of MiRNAs and LncRNAs on Multidrug Resistance of Gastric Cancer.

Multi-drug resistance (MDR) is characterized by the resistance of tumor cells to some antitumor drugs with different structures and mechanisms after the use of a single chemotherapy drug or even the first use of the drug. Notably, MDR has become the largest obstacle to the success of gastric cancer chemotherapies. Non-coding RNAs are defined as a class of RNAs that do not have the ability to code proteins. They are widely involved in important biological functions in life activities. Multiple lines of evidence demonstrated that ncRNAs are closely related to human cancers, including gastric cancer. However, the relationship between ncRNAs and MDR in gastric cancer has been reported, yet the mechanisms are not fully clarified. Therefore, in this review, we systematically summarized the detailed molecular mechanisms of lncRNAs (long noncoding RNAs) and miRNAs (microRNAs) associated with MDR in gastric cancer. Additionally, we speculate that the abnormal expression of ncRNAs is likely to be a novel potential therapeutic target reversing MDR for gastric cancer. Future therapeutics for gastric cancer will most likely be based on noncoding RNAs (ncRNAs) that regulate MDR-related genes.

Contaminant removal and contaminant dispersion of air distribution for overall and local airborne infection risk controls.

Proper air distribution is crucial for airborne infection risk control of infectious respiratory diseases like COVID-19. Existing studies evaluate and compare the performances of different air distributions for airborne infection risk control, but the mechanisms of air distribution for airborne infection risk control remain unclear. This study investigates the mechanisms of air distribution for both overall and local airborne infection risk controls. The experimentally validated CFD models simulate the contaminant concentration fields in a hospital ward based on which the airborne infection risks of COVID-19 are evaluated with the dilution-based expansion of the Wells-Riley model. Different air distributions, i.e., stratum ventilation, displacement ventilation, and mixing ventilation, with various supply airflow rates are tested. The results show that the variations of the overall and local airborne infection risks under different air distributions and different supply airflow rates are complicated and non-linear. The contaminant removal and the contaminant dispersion are proposed as the mechanisms for the overall and local airborne infection risk controls, respectively, regardless of airflow distributions and supply airflow rates. A large contaminant removal ability benefits the overall airborne infection risk control, with the coefficient of determination of 0.96 between the contaminant removal index and the reciprocal of the overall airborne infection risk. A large contaminant dispersion ability benefits the local airborne infection risk control, with the coefficient of determination of 0.99 between the contaminant dispersion index and the local airborne infection risk.

Lactic acid, a driver of tumor-stroma interactions.

Warburg effect is one of the hallmarks of tumor favoring the suppression of normal oxidative phosphorylation (OxPhos) and the adaptation to hypoxia. In addition to providing continuous energy to meet the demands of tumors, acceleratedWarburg effect also producesa large amount of lactic acid. Lactic acid shuttles between different cell populations within the tumor microenvironment (TME) and confers tumor cells to interact with surrounding cells, which has emerged as a new phenomenon in the field of tumor biology and tumorigenesis. Lactic acid not only fulfills the energetic demands of stromal cells, but becomes a major regulator of their activity by serving as a signaling molecule. Activated stromal cells in turn support tumor development. In this review, we discuss the role of lactic acid in transformation and oncogenic function of stromal cells including fibroblasts, macrophages, adipocytes and vascular endothelial cells, and suggest the relevance of lactic acid in therapy response and essential questions in this field.

Tumor-derived or non-tumor-derived exosomal noncodingRNAs and signaling pathways in tumor microenvironment.

The tumor microenvironment (TME) involved in multiple pathological processes of tumors is highly complex. Exosomes, as organelles, can be produced by some cells in the TME and have been verified as a special carriers and a key factor for communication between tumor and TME-associated cells. Noncoding RNAs (ncRNAs) involved in tumorigenesis and development have been demonstrated to be released into the TME by exosomes. However, the detailed regulatory functions of exosomal ncRNAs through signaling pathways in the TME are still unclear. In this review, we systematically summarized the detailed molecular mechanisms by which exosomal ncRNAs mediate the modulation of both tumor cells and nontumor cells. Exosomal ncRNAs in the TME exhibited the potential ability to influence cancer development through signaling pathways, including PTEN signaling, NF-κB signaling, Wnt/ß-catenin signaling, PI3K/AKT signaling, etc. Expressly, considering that research on circRNAs has gained much momentum in recent years, we more thoroughly described the implication of exosomal circRNAs in the regulation of signaling. Our review might hopefully inspire a deeper understanding of exosomal ncRNA function in terms of signaling pathways. We speculated that exosomal ncRNAs, as useful biomarkers and therapeutic targets, play an important role in the diagnosis and prognosis of cancer.

Investigation of antimony adsorption on a zirconium-porphyrin-based metal-organic framework.

A zirconium-porphyrin based organic framework PCN-222 was employed for investigating the adsorption performance of Sb(III) in aqueous solution. It is proved that the adsorbent has the advantages of rapid adsorption and high capacity. Interestingly, we discover that PCN-222 shows pH-dependent adsorption performance, with higher capacity at pH = 2 and 8 than at pH = 5. According to XPS and FT-IR analyses, an adsorption model of PCN-222 with pH = 2, 5, and 8 is proposed, that is, zirconium clusters combine with antimony at different pH values with bidentate complexes, monodentate complexes, and alkaline monodentate complexes, thus producing an excellent adsorption effect. Moreover, the porphyrin ring is also beneficial for the adsorption of antimony. In addition, PCN-222 shows good regeneration and recycling performance, and it is a promising adsorbent as well as a platform for investigating the removal of Sb(III) in water treatment.

Lactic acid in tumor invasion.

Invasion involves tumor cells altering their cell-matrix interactions and acquiring motility for metastatic spread. Invasive tumor cells exhibit dysregulated metabolism and enhanced aerobic glycolysis, leading to nutrient depletion, hypoxia, and lactic acid production. Lactic acid is a byproduct of glycolysis capable of promoting oncogenic progression, but its role in tumor invasion is unclear. A growing number of studies have demonstrated that lactic acid regulates the degradation of collagen Ⅳ, collagen Ⅶ, and glycoprotein; the synthesis of collagen Ⅰ; and multiple signaling pathways, including TGF-ß/Smad, Wnt/ß-catenin, IL-6/STAT3, and HGF/MET, which are associated with basement membrane (BM) remodeling and epithelial-mesenchymal transition (EMT), two hallmarks of the tumor invasive process. In the present review, we summarize BM remodeling and EMT in tumor invasion, discuss the emerging roles and molecular mechanisms of lactic acid in these processes, and provide insights for further research.

Insights into adsorptive removal of antimony contaminants: Functional materials, evaluation and prospective.

The application of antimony containing compounds in the industry has generated considerable antimony contaminants, which requires to develop methods that are as efficient as possible to remove antimony from water in the view of human health. The adsorption is among the most high-efficiency and reliable purification methods for hazardous materials due to the simple operation, convenient recycling and low cost. Herein, this review systematically summarizes the functional materials that are used to adsorb antimony from water, including metal (oxides) based materials, carbon-based materials, MOFs and molecular sieves, layered double hydroxides, natural materials, and organic-inorganic hybrids. The iron-based adsorbents stand out among these adsorbents because of their excellent performance. Moreover, the interaction between antimony and different functional materials is discussed in detail, while the inner-sphere complexation, hydrogen bond as well as ligand exchange are the main impetus during antimony adsorption. In addition, the desorption methods in adsorbents recycling are also comprehensively summarized. Furthermore, we propose an adsorption capacity balanced evaluation function (ABEF) based on the reported results to evaluate the performance of the antimony adsorption materials for both Sb(III) and Sb(V), as antimony usually has two valence forms of Sb(III) and Sb(V) in wastewater. Another original insight in this review is that we put forward a potential application prospect for the antimony-containing waste adsorbents. The feasible future development includes the utilization of the recycled antimony-containing waste adsorbents in catalysis and energy storage, and this will provide a green and sustainable pathway for both antimony removal and resourization.

ClC-3: A Novel Promising Therapeutic Target for Atherosclerosis.

Chloride channel 3 (ClC-3), a Cl-/H+ antiporter, has been well established as a member of volume-regulated chloride channels (VRCCs). ClC-3 may be a crucial mediator for activating inflammation-associated signaling pathways by regulating protein phosphorylation. A growing number of studies have indicated that ClC-3 overexpression plays a crucial role in mediating increased plasma low-density lipoprotein levels, vascular endothelium dysfunction, pro-inflammatory activation of macrophages, hyper-proliferation and hyper-migration of vascular smooth muscle cells (VSMCs), as well as oxidative stress and foam cell formation, which are the main factors responsible for atherosclerotic plaque formation in the arterial wall. In the present review, we summarize the molecular structures and classical functions of ClC-3. We further discuss its emerging role in the atherosclerotic process. In conclusion, we explore the potential role of ClC-3 as a therapeutic target for atherosclerosis.

Sex differences in hemispheric lateralization of attentional networks.

Males and females differ in various abilities. However, sex differences in hemispheric lateralization of attentional processing are still not well-understood. Using a lateralized version of the attentional network test that combines the Posner cueing paradigm and visual field methodology, we aimed to examine sex differences in the lateralization of several attentional processes including alerting, executive control, orienting benefit, reorienting, and orienting cost. Fifty-six females and 59 males participated in this study. We found a left visual field (right hemisphere) advantage for alerting defined by the differences between no-cue and center-cue conditions in the male group, but it was mainly attributed to the left visual field advantage in the no-cue condition. In contrast, the female group exhibited a left visual field advantage in the center-cue condition. Both groups showed preferences to the left visual field for reorienting and orienting cost, but females exhibited larger effects. This indicates that the two sexes exhibit similarities in terms of the lateralization of these two attentional processes. Furthermore, the interactions between executive control and reorienting/orienting cost were more efficient in males than in females. The current study highlights sex differences in the hemispheric lateralization of attentional networks and possible underlying neural substrates.

Selective Synthesis of Symmetrical Secondary Amines from Nitriles with a Pt-CuFe/Fe3 O4 Catalyst and Ammonia Borane as Hydrogen Donor.

Hydrogenation of nitriles is an efficient and environmentally friendly route to synthesize symmetrical secondary amines, but it usually produces a mixture of amines, imines, and hydrogenolysis by-products. Herein we report a magnetic quaternary-component Pt-CuFe/Fe3 O4 nanocatalyst system for the selective synthesis of symmetrical secondary amines with ammonia borane as hydrogen donor. The catalyst with a low Pt loading (0.456 wt%) is the source of the activity, and the d-band electron transfer from Cu to Fe enhances the selectivity. This synergistic effect results in the transformation of benzonitrile to dibenzylamine with excellent conversion (up to 99 %) and nearly quantitative selectivity (up to 96 %) under mild reaction conditions, nevertheless, the reaction TOF is as high as up to 1409.9 h-1 . A variety of nitriles are suitable for the synthesis of symmetrical secondary amines. More importantly, unwanted hydrogenolysis byproducts, especially toluene, is not detected at all. In addition, the catalyst is magnetically recoverable, and it can be reused up to five times.

Association between childhood psychological resilience and school violence awareness in rural areas of Southern Henan / 中国学校卫生

Objective@#To understand the relationship between childhood psychological resilience and of school violence awareness in rural areas in southern Henan, and to provide support and reference for the prevention and control of school violence.@*Methods@#A total of 6 484 primary school children in grades 4-6 in the rural areas of Dengzhou, Xincai and Gushi counties in southern Henan were surveyed for psychological resilience and awareness on school violence.@*Results@#The average score of psychological resilience of grade 4-6 pupils in rural areas of southern Henan was (39.92±8.18), and the average score of school violence awareness was (60.78±6.19). In terms of age, gender, grade, school type, personality, class performance, academic performance, smoking, intimate friends, playing games, truancy, loitering outside the school, relationship with siblings, father s education, mother s education, parental conflict, parenting style, the proportion of primary school students in different level of school violence awareness varied statistically different (P<0.01). Multivariate Logistic regression showed, after controlling for confounding factors, psychological resilience was an independent influencing factor affecting awareness on school violence (OR=1.06, 95%CI=1.05-1.08), with better psychological resilience, being associated with higher school violence awareness (P<0.01).@*Conclusion@#The level of school violence awareness and psychological resilience of pupils in southern Henan is relatively low. The higher level of psychological resilience, the higher level of school violence awareness; psychological resilience might be improved through education and household parenting modification to prevent and reduce the incidence of violence on campus.

Reduced Lateralization of Attention in Action Video Game Players.

There is increasing evidence that action video game players (AVGPs) possess superior performance in various tasks, especially those measuring attentional abilities. The current study aimed to examine the lateralization of attentional components in AVGPs. Twenty-nine AVGPs and twenty-six non-AVG players (NAVGPs) were recruited based on their frequency and intensity of playing action video games in the last 6 months. A lateralized attentional network test was used to measure the lateralization of attentional components in the two groups. The results showed that AVGPs exhibited comparable performance in the left and right hemispheres for reorienting and executive components. However, NAVGPs exhibited a significant difference between the two hemispheres for the two components. The findings indicate that AVG playing is closely associated with reduced lateralization of attentional networks.