Search

Curcumin is widely recognized for its diverse antitumor properties, ranging from breast cancer to many other types of cancers. However, its role in the tumor microenvironment remains to be elucidated. In this study, we established a 3D tumor spheroids model that can simulate the growth environment of tumor cells and visualized the antitumor metabolic alteration caused by curcumin using mass spectrometry imaging technology. Our results showed that curcumin not only exerts a profound impact on the growth and proliferation of breast cancer cells but in situ multivariate statistical analysis also reveals the significant effect on the overall metabolic profile of tumor spheroids. Meanwhile, our visualization map characterized curcumin metabolic processes of reduction and glucuronidation in tumor spheroids. More importantly, abnormal metabolic pathways related to lipid metabolism and polyamine metabolism were also remodeled at the metabolite and gene levels after curcumin intervention. These insights deepen our comprehension of the regulatory mechanism of curcumin on the tumor metabolic network, furnishing powerful references for antitumor treatment.

Eclipta prostrata L. has been used in traditional medicine and known for its liver-protective properties for centuries. Wedelolactone (WEL) and demethylwedelolactone (DWEL) are the major coumarins found in E. prostrata L. However, the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease (NAFLD) still remains to be explored. Utilizing a well-established zebrafish model of thioacetamide (TAA)-induced liver injury, the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis. Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver. The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped, and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized. Based on spatial metabolomics and transcriptomics, we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL. Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD, and presents a “multi-omics” platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Abstract Adverse skin reactions caused by ionizing radiation are collectively called radiation dermatitis (RD), and the use of nanomedicine is an attractive approach to this condition. Therefore, we designed and large-scale synthesized fullerenols that showed free radical scavenging ability in vitro. Next, we pretreated X-ray-exposed cells with fullerenols. The results showed that pretreatment with fullerenols significantly scavenged intracellular reactive oxygen species (ROS) produced and enhanced the antioxidant capacity, protecting skin cells from X-ray-induced DNA damage and apoptosis. Moreover, we induced RD in mice by applying 30 Gy of X-ray irradiation, followed by treatment with fullerenols. We found that after treatment, the RD scores dropped, and the histological results systematically demonstrated that topically applied fullerenols could reduce radiation-induced skin epidermal thickening, collagen deposition and skin appendage damage and promote hair regeneration after 35 days. Compared with Trolamine cream, a typical RD drug, fullerenols showed superior radiation protection. Overall, the in vitro and in vivo experiments proved that fullerenols agents against RD.

During influenza A virus infection, the viral RNA polymerase transcribes the viral negative-sense segmented RNA genome and replicates it in a two-step process via complementary RNA within viral ribonucleoprotein (vRNP) complexes. While numerous viral and host factors involved in vRNP functions have been identified, dissecting the roles of individual factors remains challenging due to the complex cellular environment in which vRNP activity has been studied. To overcome this challenge, we reconstituted viral transcription and a full cycle of replication in a test tube using vRNPs isolated from virions and recombinant factors essential for these processes. This novel system uncovers the minimal components required for influenza virus replication and also reveals new roles of regulatory factors in viral replication. Moreover, it sheds light on the molecular interplay underlying the temporal regulation of viral transcription and replication. Our highly robust in vitro system enables systematic functional analysis of factors modulating influenza virus vRNP activity and paves the way for imaging key steps of viral transcription and replication.

Growing evidence suggests that bone health is programmed in early life. Maternal diet may influence the skeletal development of offspring. We aimed to determine the possible effects of high-fructose intake during pregnancy on different aspects of long bone morphology in the offspring of rats and to initially explore the possible mechanisms. Pregnant Sprague-Dawley rats were randomly divided into four groups and intragastrically administered the same dose of distilled water (CON, n = 12), 20 g/kg/day glucose (GLU, n = 12), 10 g/kg/day fructose (LFRU, n = 12), or 20 g/kg/day fructose (HFRU, n = 12) for 21 days during gestation. Computed tomography was used to analyze the cortical and cancellous bones of the distal femur of the offspring rats, and circulating bone metabolic biomarkers were measured using enzyme immunoassay. The results showed that high-fructose intake during pregnancy could decrease body weight, impair glucose metabolism, and increase serum leptin and uric acid in offspring. The offspring in the HFRU group had higher levels of the N-terminal propeptide of type I procollagen (PINP) and the C-telopeptide of type I collagen (CTX). The bone mean density (BMD), the total cross-sectional area inside the periosteal envelope (Tt.Ar), cortical bone area (Ct.Ar), medullary (or marrow) area (Ma.Ar), and trabecular mean density of the offspring in the HFRU group were lower than those in the CON group. Tartrate-resistant acid phosphatase (Trap) staining showed that high-fructose intake during pregnancy could increase the number of osteoclasts and increase the absorption area. Our results suggested that excessive fructose intake during pregnancy could inhibit skeletal development in offspring. Thus, attention to fructose intake during pregnancy is important for bone development in offspring.

Influenza viruses carry their own RNAdependent RNA-polymerase that is highly conserved and a promising anti-viral target. Combining functional and structural data, Keown et al. characterise the inhibitory effect of nanobodies on 1918 pandemic H1N1 influenza strain polymerase complex and identify sensitive sites interfering with polymerase activity in vitro.

Innovation ecosystem management is now a new paradigm in innovation management research. Innovation ecosystems are dynamic innovation alliances based on noncontractual governance. In this paper, a traditional cooperative innovation game model and a cooperative innovation game model with noncontractual mechanism are developed and compared. The results show that the cooperation formed only by contractual mechanisms’ model is unstable and the system is likely to collapse. The noncontractual mechanism can be used as a supplement to the contractual mechanism to make the game develop towards a stable “cooperation-cooperation” state. The research conclusion of this paper will make the core companies in the innovation ecosystem realize the important role of noncontractual mechanism and help them make decisions.

Background. The exosome is of vital importance throughout the entire progression of cancer. Because of the lack of effective biomarkers in ovarian cancer (OV), we intend to investigate the connection between exosomes and tumor immune microenvironment to verify that exosome-related genes (ERGs) can precisely forecast the prognosis of OV patients. Methods. First, 117 ERGs in The Cancer Genome Atlas (TCGA) dataset were recognized. Afterwards, the risk signature consisting of four ERGs with prognostic significance was built by univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis. We also validated the risk signature by Kaplan-Meier analysis, receiver operating characteristic curve analysis and principal component analysis. Furthermore, gene set enrichment analysis was performed to compare the enrichment patterns between the two risk subgroups. The connections between the exosome-related gene risk score (ERGRS) and clinical features, immune infiltration, immune checkpoint-related genes, copy number variation, and drug sensitivity were explored. We also assessed the function of the ERGRS to forecast immunotherapeutic efficacy by immunophenoscore (IPS). Results. The high-risk group had a worse prognosis than the group with low risk. We verified that the established model possessed a relatively good prognostic value. Pathway enrichment analysis indicated that the genome-wide group with low risk was enriched in immune-related pathways. We discovered that resting dendritic cells and stromal scores were upregulated in patients with high risk in the TCGA and Gene Expression Omnibus (GEO) cohorts. Moreover, the expression of six common immune checkpoint inhibitor targets was assessed, which revealed that the expression levels of CD274 (PD-L1), PDCD1 (PD-1), and IDO1 in patients with high risk were lower than those in patients with low risk. Afterwards, the low-risk group had higher IPS across the four immunotherapies, implying that it had better effects of immunotherapies. Conclusion. Our study demonstrates that the exosome-related gene risk model is closely associated with immune infiltration. It can well forecast the prognosis of OV patients and guide the selection of immunotherapeutic strategies.

The incidence of porcine pasteurellosis in China is so widespread that it is difficult to clearly understand the prevalence and maintain continuous monitoring. In order to reduce immense negative economic impact on the livestock industry; monitoring, early warning, and visual management systems are highly desirable. In this study, a monitoring and early warning system for porcine pasteurellosis was established based on Web Geographical Information System (WebGIS) technology. By establishing a path analysis function, buffer analysis function, and hot spot analysis function, it can provide a method of support and control of infectious diseases. For early warning of disease, four common interpolation methods were tested, all of which showed that the affected area of porcine pasteurellosis in China was mainly concentrated in the south of the mainland. A cross-validation method was used to compare the four interpolation methods. The cross-validation showed that the inverse distance weighting (IDW) method was suitable for forecasting the occurrence of porcine pasteurellosis in China. Finally, using C sharp (C#) as the development language and WebGIS technology, a monitoring and early warning system based on Browser/Server structure was developed. This is the first monitoring and early warning system of porcine pasteurellosis based on WebGIS. The performance of the WebGIS technology indicated a great potential for animal infectious disease applications and provided a foundation for future work.

Rapeseed (Brassica napus L.) is a nutritious vegetable, while cadmium (Cd) pollution threatens the growth, productivity, and food security of rapeseed. By studying the effects of iminodisuccinic acid (IDS), an easily biodegradable and environmental friendly chelating agent, on Cd distribution at the organ and cellular level, we found IDS promoted dry matter accumulation of rapeseed and increased the contents of photosynthetic pigment in leaves. Inhibited root-shoot Cd transport resulted in higher activity of antioxidant enzymes and decreased hydrogen peroxide (H2O2) and malondialdehyde (MDA) accumulation in leaves, which indicated that IDS contributed to alleviating Cd-caused oxidative damage in leaf cells. Additionally, IDS increased Cd subcellular distribution in cell wall (CW), especially in covalently bound pectin (CSP), and relieved Cd toxicity in organelle of leaves. IDS also enhanced demethylation of CSP. The Cd content in CSP, demethylation degree, and pectin methylesterase activity of CSP increased by 37.95%, 13.34%, and 13.16%, respectively, while IDS did not change the contents of different CW components. The improved Cd fixation in leaf CW was mainly attributed to enhance demethylation of covalently bound pectin (CSP) and Cd chelation with CSP.

In the context of COVID-19, the research on various aspects of the venipuncture robot field has become increasingly hot, but there has been little research on robotic needle insertion angles, primarily performed at a rough angle. This will increase the rate of puncture failure. Furthermore, there is sometimes significant pain due to the patients’ differences. This paper investigates the optimal needle entry angle decision for a dorsal hand intravenous injection robot. The dorsal plane of the hand was obtained by a linear structured light scan, which was used as a basis for calculating the needle entry angle. Simulation experiments were also designed to determine the optimal needle entry angle. Firstly, the linear structured optical system was calibrated and optimized, and the error function was constructed and solved iteratively by the optimization method to eliminate measurement error. Besides, the dorsal hand was scanned to obtain the spatial point clouds of the needle entry area, and the least squares method was used to fit it to obtain the dorsal hand plane. Then, the needle entry angle was calculated based on the needle entry area plane. Finally, the changes in the penetration force under different needle entry angles were analyzed to determine the optimal needle insertion angle. According to the experimental results, the average error of the optimized structured light plane position was about 0.1 mm, which meets the needs of the project, and a large angle should be properly selected for needle insertion during the intravenous injection.

Nitrogen oxide (NOx) is a major gaseous pollutant in flue gases from power plants, industrial processes, and waste incineration that can have adverse impacts on the environment and human health. Many denitrification (de-NOx) technologies have been developed to reduce NOx emissions in the past several decades. This paper provides a review of the recent literature on NOx post-combustion purification methods with different reagents. From the perspective of changes in the valence of nitrogen (N), purification technologies against NOx in flue gas are classified into three approaches: oxidation, reduction, and adsorption/absorption. The removal processes, mechanisms, and influencing factors of each method are systematically reviewed. In addition, the main challenges and potential breakthroughs of each method are discussed in detail and possible directions for future research activities are proposed. This review provides a fundamental and systematic understanding of the mechanisms of denitrification from flue gas and can help researchers select high-performance and cost-effective methods.

Abstract Background Agrochemicals, such as pesticides and fertilizers used in the current conventional agriculture (CA), have contaminating effects on environments as well as food, which pose significant risks to non-target organisms and even human health. Under these environmental pressures, ecological agriculture (EA), using organic fertilizer for crop growth, was developed without pesticides to substitute CA gradually worldwide. However, EA has still not become popular in the Chinese mountain area. To identify the major factors that influence the application of EA, rice cultivation between EA and CA was compared by analyzing soil physical–chemical properties, and soil bacterial and plant diversity in Chongqing. Besides, in considering the economic benefits of small-scale paddy ecosystem, net present value (NPV) method was applied for quantification and evaluation between EA and CA. Results The rice yield of EA (3700 kg/ha) was significantly lower than that of CA (7500 kg/ha). Soil total nitrogen (TN, 2.24 ± 0.16 g/kg) and available potassium (AK, 70.67 ± 9.88 mg/kg) in CA were higher than those in EA, with amounts of 1.45 ± 0.18 g/kg (TN) and 54.00 ± 5.89 mg/kg (AK). Soil organic matter (SOM) of CA (55.6 ± 5.8 g/kg) was distinctly higher than that of EA (24.4 ± 1.43 g/kg), whereas pore water DOC concentration in EA (71.11 ± 7.28 mg/L) was higher than that in CA (61.07 ± 6.61 mg/L). Plant richness, bacterial diversity of ACE and Chao1 in EA were significantly higher than in CA (P

Viral macrodomains possess the ability to counteract host ADP-ribosylation, a post-translational modification implicated in the creation of an antiviral environment via immune response regulation. This brought them into focus as promising therapeutic targets, albeit the close homology to some of the human macrodomains raised concerns regarding potential cross-reactivity and adverse effects for the host. Here, we evaluate the structure and function of the macrodomain of SARS-CoV-2, the causative agent of COVID-19. We show that it can antagonize ADP-ribosylation by PARP14, a cellular (ADP-ribosyl)transferase necessary for the restriction of coronaviral infections. Furthermore, our structural studies together with ligand modelling revealed the structural basis for poly(ADP-ribose) binding and hydrolysis, an emerging new aspect of viral macrodomain biology. These new insights were used in an extensive evolutionary analysis aimed at evaluating the druggability of viral macrodomains not only from the Coronaviridae but also Togaviridae and Iridoviridae genera (causing diseases such as Chikungunya and infectious spleen and kidney necrosis virus disease, respectively). We found that they contain conserved features, distinct from their human counterparts, which may be exploited during drug design.

λ-Carrageenan (Carr), a seaweed polysaccharide, is used as a proinflammatory agent in research. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, exerts immunomodulatory, antioxidant, anti-inflammatory, antitumor, anti-malarial and anti-HIV effects. The aim of this study was to investigate whether BA exerts anti-inflammatory effect against Carr-induced paw edema in mice, and how BA could mediate the expression of inflammation-associated MAPK-COX-2-PGE2 signal pathway. BA pretreatment significantly reduced the inflammatory response to Carr-induced paw edema, especially at 4 h after injection. BA reduced the serum levels of pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-5, IL-6, GM-CSF, KC, MCP-1 and PGE2 in Carr-treated mice, and increased those of anti-inflammatory cytokines, such as IL-12. It also increased SOD, CAT and GSH-Px activities, and GSH content, and reduced MDA content in the liver of Carr-treated mice. Besides, BA reduced neutrophil infiltration in the basal and subcutaneous layers of the paw of Carr-treated mice, decreased the expression of COX-2 protein, and reduced the phosphorylation of JNK, p38 and ERK1/2. These results indicated that the protective effect of BA on Carr-induced paw edema might be due to its alleviation of inflammatory response and inhibition of oxidative stress, possibly by inhibiting MAPK-COX-2-PGE2 signaling pathway activation.

Asphalt rubber (AR) is a sustainable paving material with merits including waste tire consumption, low traffic noise, and enhanced mechanical performance. However, the poor workability and storage stability limited its further application. This study attempted to alleviate these two concerns of AR simultaneously by incorporating heavy bio oil (HBO). To achieve this goal, bio-AR binders with three different mixing sequences were prepared. A series of rheological and chemical tests were conducted. Test results prove that the bio-AR binders exhibited superior rutting and fatigue resistance compared to AR binder. The viscosity values of bio-ARs were closed to AR modified with commercial warm mix additive, which indicates enhancement in workability. Due to the relatively high density of HBO, the density difference between the asphalt liquid phase and crumb rubber in the bio-AR system narrowed, which brought improved storage stability. Among bio-ARs prepared with different mixing sequences, the direct mixing one (ARB) had the most satisfied overall performance. The early incorporation of HBO had limited negative influence on binder performance, but allowed for more energy saving during the bio-AR binder production. Future study will be conducted on performance of bio-AR mixtures and quantitative estimation of its energy saving during the blending and compacting process.

Gradation segregation strongly affects the service performance of asphalt pavement. However, rare studies focus on the influences of segregation on asphalt mixture as it is difficult to simulate segregation in a laboratory. This paper presents a research aiming to evaluate the effects of gradation segregation using the two dimensional (2D) discrete element method (DEM). To achieve this objective, the gradation segregation levels are defined according to the differences between control and segregated gradations. Based on this, asphalt mixtures with three gradations at three segregation levels were selected. The corresponding 2D DEM models were then built using Particle Flow Code 2D (PFC 2D). The aggregate skeletons in the asphalt mixture were determined separately by means of the contact point and contact force. Based on this, the variations on the aggregate skeleton, aggregate distribution, and mechanical properties of the asphalt mixture under vertical load were studied at three different segregation levels. This study indicates that the aggregate skeleton in asphalt mixture can be affected by the gradation segregation. The correlation between gradation segregation and mechanical property is also determined in this study.

Engineering performance of asphalt pavement highly depends on the properties of bitumen, the bonding material to glue aggregates and fillers together. During the service period, bitumen is exposed to sunlight, oxygen and vehicle loading which in turn leads to aging and degradation. A comprehensive understanding of the aging mechanism of bitumen is of critical importance to enhance the durability of asphalt pavement. This study aims to determine the relations between micro-mechanics, chemical composition, and macro-mechanical behavior of aged bitumen. To this end, the effect of aging on micro-mechanics, chemical functional groups, and rheological properties of bitumen were evaluated by atomic force microscope, Fourier transform infrared spectroscopy and dynamic shear rheometer tests, respectively. Results indicated that aging obviously increased the micro-surface roughness of bitumen. A more discrete distribution of micromechanics on bitumen micro-surface was noticed and its elastic behavior became more significant. Aging also resulted in raised content of carbonyl, sulfoxide, and aromatic ring functional groups. In terms of rheological behavior, the storage modulus of bitumen apparently increased after aging due to the transformation of viscous fractions to elastic fractions, making it stiffer and less viscous. By correlation analysis, it is noted that the bitumen rheological behavior was closely related to its micro-mechanics.

Using CO2 as the primary feedstock offers the potential for high-value utilization of CO2 while forging sustainable pathways for producing valuable natural products, such as l-tyrosine. Cascade catalysis is a promising approach but limited by stringent purity demands of nexus molecules. We developed an abiotic/biotic cascade catalysis using blended nexus molecules for l-tyrosine synthesis. Specifically, we begin by constructing a solid-state reactor to reduce CO2 electrochemically, yielding a mixture of acetic acid and ethanol, which serves as the blended nexus molecules. Subsequently, we use genetic engineering to introduce an ethanol utilization pathway and a tyrosine producing pathway to Escherichia coli to facilitate l-tyrosine production. The ethanol pathway synergistically cooperated with the acetic acid pathway, boosting l-tyrosine production rate (nearly five times higher compared to the strain without ethanol utilization pathway) and enhancing carbon efficiency. Our findings demonstrate that using blended nexus molecules could potentially offer a more favorable strategy for the cascade catalysis aimed at producing valuable natural products. [ABSTRACT FROM AUTHOR]

Microtubule nucleation is mediated by γ-tubulin ring complexes (γ-TuRCs). In most eukaryotes, a GCP4/5/4/6 “core” complex promotes γ-tubulin small complex (γ-TuSC) association to generate cytosolic γ-TuRCs. Unlike γ-TuSCs, however, this core complex is non-essential in various species and absent from budding yeasts. In Drosophila, Spindle defective-2 (Spd-2) and Centrosomin (Cnn) redundantly recruit γ-tubulin complexes to mitotic centrosomes. Here, we show that Spd-2 recruits γ-TuRCs formed via the GCP4/5/4/6 core, but Cnn can recruit γ-TuSCs directly via its well-conserved CM1 domain, similar to its homologs in budding yeast. When centrosomes fail to recruit γ-tubulin complexes, they still nucleate microtubules via the TOG domain protein Mini-spindles (Msps), but these microtubules have different dynamic properties. Our data, therefore, help explain the dispensability of the GCP4/5/4/6 core and highlight the robustness of centrosomes as microtubule organizing centers. They also suggest that the dynamic properties of microtubules are influenced by how they are nucleated. [ABSTRACT FROM AUTHOR]