scQTLbase: an integrated human single-cell eQTL database.

Genome-wide association studies (GWAS) have identified numerous genetic variants associated with diseases and traits. However, the functional interpretation of these variants remains challenging. Expression quantitative trait loci (eQTLs) have been widely used to identify mutations linked to disease, yet they explain only 20-50% of disease-related variants. Single-cell eQTLs (sc-eQTLs) studies provide an immense opportunity to identify new disease risk genes with expanded eQTL scales and transcriptional regulation at a much finer resolution. However, there is no comprehensive database dedicated to single-cell eQTLs that users can use to search, analyse and visualize them. Therefore, we developed the scQTLbase (http://bioinfo.szbl.ac.cn/scQTLbase), the first integrated human sc-eQTLs portal, featuring 304 datasets spanning 57 cell types and 95 cell states. It contains ∼16 million SNPs significantly associated with cell-type/state gene expression and ∼0.69 million disease-associated sc-eQTLs from 3 333 traits/diseases. In addition, scQTLbase offers sc-eQTL search, gene expression visualization in UMAP plots, a genome browser, and colocalization visualization based on the GWAS dataset of interest. scQTLbase provides a one-stop portal for sc-eQTLs that will significantly advance the discovery of disease susceptibility genes.

Multimodal neuroimaging network associated with executive function in adolescent major depressive disorder patients via cognition-guided magnetic resonance imaging fusion.

Adolescents are high-risk population for major depressive disorder. Executive dysfunction emerges as a common feature of depression and exerts a significant influence on the social functionality of adolescents. This study aimed to identify the multimodal co-varying brain network related to executive function in adolescent with major depressive disorder. A total of 24 adolescent major depressive disorder patients and 43 healthy controls were included and completed the Intra-Extra Dimensional Set Shift Task. Multimodal neuroimaging data, including the amplitude of low-frequency fluctuations from resting-state functional magnetic resonance imaging and gray matter volume from structural magnetic resonance imaging, were combined with executive function using a supervised fusion method named multimodal canonical correlation analysis with reference plus joint independent component analysis. The major depressive disorder showed more total errors than the healthy controls in the Intra-Extra Dimensional Set Shift task. Their performance on the Intra-Extra Dimensional Set Shift Task was negatively related to the 14-item Hamilton Rating Scale for Anxiety score. We discovered an executive function-related multimodal fronto-occipito-temporal network with lower amplitude of low-frequency fluctuation and gray matter volume loadings in major depressive disorder. The gray matter component of the identified network was negatively related to errors made in Intra-Extra Dimensional Set Shift while positively related to stages completed. These findings may help to deepen our understanding of the pathophysiological mechanisms of cognitive dysfunction in adolescent depression.

Identification of hypoxia-related gene signatures based on multi-omics analysis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and one of the malignancies with the highest incidence rate and mortality worldwide. Hypoxia is a typical feature of tumour microenvironment (TME), which affects the progression of LUAD from multiple molecular levels. However, the underlying molecular mechanisms behind LUAD hypoxia are not fully understood. In this study, we estimated the level of hypoxia by calculating a score based on 15 hypoxia genes. The hypoxia scores were relatively high in LUAD patients with poor prognosis and were bound up with tumour node metastasis (TNM) stage, tumour size, lymph node, age and gender. By comparison of high hypoxia score group and low hypoxia score group, 1820 differentially expressed genes were identified, among which up-regulated genes were mainly about cell division and proliferation while down-regulated genes were primarily involved in cilium-related biological processes. Besides, LUAD patients with high hypoxia scores had higher frequencies of gene mutations, among which TP53, TTN and MUC16 had the highest mutation rates. As for DNA methylation, 1015 differentially methylated probes-related genes were found and may play potential roles in tumour-related neurobiological processes and cell signal transduction. Finally, a prognostic model with 25 multi-omics features was constructed and showed good predictive performance. The area under curve (AUC) values of 1-, 3- and 5-year survival reached 0.863, 0.826 and 0.846, respectively. Above all, our findings are helpful in understanding the impact and molecular mechanisms of hypoxia in LUAD.

Bacillus subtilis partially inhibits African swine fever virus infection in vivo and in vitro based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II.

IMPORTANCE: African swine fever virus (ASFV) is a highly fatal swine disease that severely affects the pig industry. Although ASFV has been prevalent for more than 100 years, effective vaccines or antiviral strategies are still lacking. In this study, we identified four Bacillus subtilis strains that inhibited ASFV proliferation in vitro. Pigs fed with liquid biologics or powders derived from four B. subtilis strains mixed with pellet feed showed reduced morbidity and mortality when challenged with ASFV. Further analysis showed that the antiviral activity of B. subtilis was based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II. Our findings offer a promising new strategy for the prevention and control of ASFV that may significantly alleviate the economic losses in the pig industry.

LncRNA RPARP-AS1 promotes the progression of osteosarcoma cells through regulating lipid metabolism.

Osteosarcoma (OS) is a highly malignant tumor, and its dysregulated lipid metabolism is associated with tumorigenesis and unfavorable prognosis. Interestingly, long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of lipid metabolism, exerting notable impacts on tumor proliferation. Nevertheless, the involvement of RPARP-AS1, a novel lipid metabolism-associated lncRNA, remains unexplored in the context of OS. This study aims to identify functionally relevant lncRNAs impacting OS proliferation and lipid metabolism and seeks to shed light on the upstream regulatory mechanisms governing lipogenic enzyme activity. Based on comprehensive bioinformatic analysis and the establishment of a risk model, we identified seven lncRNAs significantly associated with clinical characteristics and lipid metabolism-related genes in patients with OS. Among these, RPARP-AS1 was selected for in-depth investigation regarding its roles in OS proliferation and lipid metabolism. Experimental techniques including RT-qPCR, Western blot, cell viability assay, assessment, and quantification of free fatty acids (FFAs) and triglycerides (TGs) were utilized to elucidate the functional significance of RPARP-AS1 in OS cells and validate its effects on lipid metabolism. Manipulation of RPARP-AS1 expression via ectopic expression or siRNA-mediated knockdown led to alterations in epithelial-mesenchymal transition (EMT) and expression of apoptosis-associated proteins, thereby influencing OS cell proliferation and apoptosis. Mechanistically, RPARP-AS1 was found to augment the expression of key lipogenic enzymes (FABP4, MAGL, and SCD1) and potentially modulate the Akt/mTOR pathway, thereby contributing to lipid metabolism (involving alterations in FFA and TG levels) in OS cells. Collectively, our findings establish RPARP-AS1 as a novel oncogene in OS cells and suggest its role in fostering tumor growth through the enhancement of lipid metabolism.

First Insight into Fetal Exposure to Legacy and Emerging Plasticizers Revealed by Infant Hair and Meconium: Occurrence, Biotransformation, and Accumulation.

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.

Functional metabolomics characterizes the contribution of farnesoid X receptor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome.

Consumption of herbal products containing pyrrolizidine alkaloids (PAs) is one of the major causes for hepatic sinusoidal obstruction syndrome (HSOS), a deadly liver disease. However, the crucial metabolic variation and biomarkers which can reflect these changes remain amphibious and thus to result in a lack of effective prevention, diagnosis and treatments against this disease. The aim of the study was to determine the impact of HSOS caused by PA exposure, and to translate metabolomics-derived biomarkers to the mechanism. In present study, cholic acid species (namely, cholic acid, taurine conjugated-cholic acid, and glycine conjugated-cholic acid) were identified as the candidate biomarkers (area under the ROC curve 0.968 [95% CI 0.908-0.994], sensitivity 83.87%, specificity 96.55%) for PA-HSOS using two independent cohorts of patients with PA-HSOS. The increased primary bile acid biosynthesis and decreased liver expression of farnesoid X receptor (FXR, which is known to inhibit bile acid biosynthesis in hepatocytes) were highlighted in PA-HSOS patients. Furtherly, a murine PA-HSOS model induced by senecionine (50 mg/kg, p.o.), a hepatotoxic PA, showed increased biosynthesis of cholic acid species via inhibition of hepatic FXR-SHP singling and treatment with the FXR agonist obeticholic acid restored the cholic acid species to the normal levels and protected mice from senecionine-induced HSOS. This work elucidates that increased levels of cholic acid species can serve as diagnostic biomarkers in PA-HSOS and targeting FXR may represent a therapeutic strategy for treating PA-HSOS in clinics.

Adsorption behavior of lead, cadmium, and arsenic on manganese-modified biochar: competition and promotion.

Biochar adsorption of heavy metals has been a research hotspot, yet there has been limited reports on the effect of heavy metal interactions on adsorption efficiency in complex systems. In this study, the adsorbent was prepared by pyrolysis of rice straw loaded with manganese (BC-Mn). The interactions of Pb, Cd and As adsorption on BC-Mn were systematically studied. The results of the adsorption isotherms for the binary metal system revealed a competitive adsorption between Pb and Cd, resulting in decreased Pb (from 214.38 mg/g to 148.20 mg/g) and Cd (from 165.73 mg/g to 92.11 mg/g). A notable promotion occurred between As and Cd, showing an increase from 234.93 mg/g to 305.00 mg/g for As and 165.73 mg/g to 313.94 mg/g for Cd. In the ternary metal system, Pb inhibition did not counteract the promotion of Cd and As. Furthermore, the Langmuir isotherm effectively described BC-Mn's adsorption process in monometallic, binary, and ternary metal systems (R2 > 0.9294). Zeta and FTIR analyses revealed simultaneous competition between Pb and Cd for adsorption on BC-Mn's -OH sites. XPS analysis revealed that As adsorption by BC-Mn facilitated the conversion of MnO2 and MnO to MnOOH, resulting in increased hydroxyl radical production on BC-Mn's surface. Simultaneously, Cd combined with the adsorbed As to form ternary Cd-As-Mn complexes, which expedited the removal of Cd. These results help to provide theoretical support as well as technical support for the treatment of Pb-Cd-As contaminated wastewater.

Ferrihydrite transformation impacted by coprecipitation of lignin: Inhibition or facilitation?

Lignin is a common soil organic matter that is present in soils, but its effect on the transformation of ferrihydrite (Fh) remains unclear. Organic matter is generally assumed to inhibit Fh transformation. However, lignin can reduce Fh to Fe(II), in which Fe(II)-catalyzed Fh transformation occurs. Herein, the effects of lignin on Fh transformation were investigated at 75°C as a function of the lignin/Fh mass ratio (0-0.2), pH (4-8) and aging time (0-96 hr). The results of Fh-lignin samples (mass ratios = 0.1) aged at different pH values showed that for Fh-lignin the time of Fh transformation into secondary crystalline minerals was significantly shortened at pH 6 when compared with pure Fh, and the Fe(II)-accelerated transformation of Fh was strongly dependent on pH. Under pH 6, at low lignin/Fh mass ratios (0.05-0.1), the time of secondary mineral formation decreased with increasing lignin content. For high lignosulfonate-content material (lignin:Fh = 0.2), Fh did not transform into secondary minerals, indicating that lignin content plays a major role in Fh transformation. In addition, lignin affected the pathway of Fh transformation by inhibiting goethite formation and facilitating hematite formation. The effect of coprecipitation of lignin on Fh transformation should be useful in understanding the complex iron and carbon cycles in a soil environment.

A review on the transformation of birnessite in the environment: Implication for the stabilization of heavy metals.

Birnessite is ubiquitous in the natural environment where heavy metals are retained and easily transformed. The surface properties and structure of birnessite change with the changes in external environmental conditions, which also affects the fate of heavy metals. Clarifying the effect and mechanism of the birnessite phase transition process on heavy metals is the key to taking effective measures to prevent and control heavy metal pollution. Therefore, the four transformation pathways of birnessite are summarized first in this review. Second, the relationship between transformation pathways and environmental conditions is proposed. These relevant environmental conditions include abiotic (e.g., co-existing ions, pH, oxygen pressure, temperature, electric field, light, aging, pressure) and biotic factors (e.g., microorganisms, biomolecules). The phase transformation is achieved by the key intermediate of Mn(III) through interlayer-condensation, folding, neutralization-disproportionation, and dissolution-recrystallization mechanisms. The AOS (average oxidation state) of Mn and interlayer spacing are closely correlated with the phase transformation of birnessite. Last but not least, the mechanisms of heavy metals immobilization in the transformation process of birnessite are summed up. They involve isomorphous substitution, redox, complexation, hydration/dehydration, etc. The transformation of birnessite and its implication on heavy metals will be helpful for understanding and predicting the behavior of heavy metals and the crucial phase of manganese oxides/hydroxides in natural and engineered environments.

ncFANs v2.0: an integrative platform for functional annotation of non-coding RNAs.

Increasing evidence proves the essential regulatory roles of non-coding RNAs (ncRNAs) in biological processes. However, characterizing the specific functions of ncRNAs remains a challenging task, owing to the intensive consumption of the experimental approaches. Here, we present an online platform ncFANs v2.0 that is a significantly enhanced version of our previous ncFANs to provide multiple computational methods for ncRNA functional annotation. Specifically, ncFANs v2.0 was updated to embed three functional modules, including ncFANs-NET, ncFANs-eLnc and ncFANs-CHIP. ncFANs-NET is a new module designed for data-free functional annotation based on four kinds of pre-built networks, including the co-expression network, co-methylation network, long non-coding RNA (lncRNA)-centric regulatory network and random forest-based network. ncFANs-eLnc enables the one-stop identification of enhancer-derived lncRNAs from the de novo assembled transcriptome based on the user-defined or our pre-annotated enhancers. Moreover, ncFANs-CHIP inherits the original functions for microarray data-based functional annotation and supports more chip types. We believe that our ncFANs v2.0 carries sufficient convenience and practicability for biological researchers and facilitates unraveling the regulatory mechanisms of ncRNAs. The ncFANs v2.0 server is freely available at http://bioinfo.org/ncfans or http://ncfans.gene.ac.

Tech-economic modeling and analysis of agricultural photovoltaic-water systems for irrigation in arid areas.

Affected by the shortage of water resources and land degradation, the sustainable development of agriculture in more and more arid areas will face serious obstacles. The combinations of agricultural photovoltaic, water transportation and irrigation systems are considered as a potential choice to solve above problem. This study aims to investigate the competitiveness of various system configurations to transport water from water resource to agricultural irrigation systems driven by the output power of agricultural photovoltaic. Including the levelized cost of electricity and net present value, a comprehensive techno-economic assessment model is proposed to analyze the agricultural photovoltaic and irrigation systems in arid areas for six scenarios. The applicability of the proposed model in managing regional water and renewable energy nexus systems was tested through application to a real-world case study in the Gansu province, China. Assuming that the baseline transportation distance is 50 km, the results show that exporting water to farmland through electric water trucks shows the best economic performance with the net present value of 13.71 MU$, and every 10 km increase in the transportation distance can decrease the net present value by 1.32 MU$. An important finding is that when the transportation distance was greater than 100 km, pipeline transportation mode was more economical than electric water truck transportation mode. Finally, a sensitivity analysis was carried out to analyze the electricity and water prices, farmland size, photovoltaic efficiency on the economic performance of these systems. Results show that only when the electricity price was greater than 0.08 $/kWh, pipeline transport mode yielded positive benefits, and every 0.1$/m3 increase in the water price can increase the net present value by 0.2 MU$.

Refractory black carbon aerosols in rainwater in the summer of 2019 in Beijing: Mass concentration, size distribution and wet scavenging ratio.

Black carbon (BC) aerosols in the atmosphere play a significant role in climate systems due to their strong ability to absorb solar radiation. The lifetime of BC depends on atmospheric transport, aging and consequently on wet scavenging processes (in-cloud and below-cloud scavenging). In this study, sequential rainwater samples in eight rainfall events collected in 2 mm interval were measured by a tandem system including a single particle soot photometer (SP2) and a nebulizer. The results showed that the volume-weighted average (VWA) mass concentrations of refractory black carbon (rBC) in each rainfall event varied, ranging from 10.8 to 78.9 µg/L. The highest rBC concentrations in the rainwater samples typically occurred in the first fraction from individual rainfall events. The geometric mean median mass-equivalent diameter (MMD) decreased under precipitation, indicating that rBC with larger sizes was relatively aged and preferentially removed by wet scavenging. A positive correlation (R2 = 0.73) between the VWA mass concentrations of rBC in rainwater and that in ambient air suggested the important contribution of scavenging process. Additionally, the contributions of in-cloud and below-cloud scavenging were distinguished and accounted for 74% and 26% to wet scavenging, respectively. The scavenging ratio of rBC particles was estimated to be 0.06 on average. This study provides helpful information for better understanding the mechanism of rBC wet scavenging and reducing the uncertainty of numerical simulations of the climate effects of rBC.

Stereoselective gem-C,B-Glycosylation via 1,2-Boronate Migration.

A novel protocol is established for the long-standing challenge of stereoselective geminal bisglycosylations of saccharides. The merger of PPh3 as a traceless glycosidic leaving group and 1,2-boronate migration enables the simultaneous introduction of C-C and C-B bonds at the anomeric stereogenic center of furanoses and pyranoses. The power of this method is showcased by a set of site-selective modifications of glycosylation products for the construction of bioactive conjugates and skeletons. A scarce metal-free 1,1-difunctionalization process of alkenes is also concomitantly demonstrated.

Prognostic signatures and potential pathogenesis of eRNAs-related genes in colon adenocarcinoma.

Enhancer RNAs (eRNAs) are a subclass of long noncoding RNAs (lncRNAs) that have a wide effect in human tumors. However, the systematic analysis of potential functions of eRNAs-related genes (eRGs) in colon cancer (CC) remains unexplored. In this study, a total of 8231 eRGs including 6236 protein-coding genes and 1995 lncRNAs were identified in CC based on the multiple resources. These eRGs showed higher expression level and stability compared to other genes. What's more, the functions of these eRGs were closely related to cancer. Then a prognostic prediction model with 12 eRGs signatures were obtained for colon adenocarcinoma (COAD) patients. ROC curves showed the AUCs were 0.81, 0.77, and 0.78 for 1-, 3-, and 5-year survival prediction, respectively. And the prognostic model also manifested good performance in the validation datasets. Besides, the expression levels of two prognostic signatures, TMEM220 and LRRN2, were verified to be significantly lower in CC tissues than in adjacent noncancerous tissues (p < .05). Finally, the distinct molecular features were characterized between the high- and low-risk group through multiomics analysis including DNA mutation and methylation. Our results show eRGs signatures based prognostic model has high accuracy and may provide innovative biomarkers in COAD.

The synergistic anticancer effect of the bromodomain inhibitor OTX015 and histone deacetylase 6 inhibitor WT-161 in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a tumour with a high malignancy level and a poor prognosis. First-line chemotherapy for OS has not been improved for many decades. Bromodomain and extraterminal domain (BET) and histone deacetylases (HDACs) regulate histone acetylation in tandem, and BET and HDACs have emerged as potential cancer therapeutic targets. METHODS: Cell proliferation, migration, invasion, colony formation, and sphere-forming assays were performed with the two inhibitors alone or in combination to evaluate their suppressive effect on the malignant properties of OS cells. Apoptosis and the cell cycle profile were measured by flow cytometry. The synergistic inhibitory effect of OTX015/WT-161 on tumours was also examined in a nude mouse xenograft model. RESULTS: The combined therapy of OTX015/WT-161 synergistically inhibited growth, migration, and invasion and induced apoptosis, resulting in G1/S arrest of OS cells. Additionally, OTX015/WT-161 inhibited the self-renewal ability of OS stem cells (OSCs) in a synergistic manner. Further mechanistic exploration revealed that the synergistic downregulation of ß-catenin by OTX015-mediated suppression of FZD2 and WT-161-mediated upregulation of PTEN may be critical for the synergistic effect. Finally, the results of an in vivo assay showed that tumour xenografts were significantly decreased after treatment with the OTX015/WT-161 combination compared with OTX015 or WT-161 alone. CONCLUSIONS: Our findings in this study demonstrated that OTX015 and WT-161 had synergistic anticancer efficacy against OS, and their combination might be a promising therapeutic strategy for OS.

Neuroprotective effects of voluntary exercise and Yisaipu after traumatic brain injury in mice.

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.

Cross-boundary transport and source apportionment for PM2.5 in a typical industrial city in the Hebei Province, China: A modeling study.

Cross-boundary transport of air pollution is a difficult issue in pollution control for the North China Plain. In this study, an industrial district (Shahe City) with a large glass manufacturing sector was investigated to clarify the relative contribution of fine particulate matter (PM2.5) to the city's high levels of pollution. The Nest Air Quality Prediction Model System (NAQPMS), paired with Weather Research and Forecasting (WRF), was adopted and applied with a spatial resolution of 5 km. During the study period, the mean mass concentrations of PM2.5, SO2, and NO2 were observed to be 132.0, 76.1, and 55.5 µg/m3, respectively. The model reproduced the variations in pollutant concentrations in Shahe at an acceptable level. The simulation of online source-tagging revealed that pollutants emitted within a 50-km radius of downtown Shahe contributed 63.4% of the city's total PM2.5 concentration. This contribution increased to 73.9±21.2% when unfavorable meteorological conditions (high relative humidity, weak wind, and low planetary boundary layer height) were present; such conditions are more frequently associated with severe pollution (PM2.5 ≥ 250 µg/m3). The contribution from Shahe was 52.3±21.6%. The source apportionment results showed that industry (47%), transportation (10%), power (17%), and residential (26%) sectors were the most important sources of PM2.5 in Shahe. The glass factories (where chimney stack heights were normally < 70 m) in Shahe contributed 32.1% of the total PM2.5 concentration in Shahe. With an increase in PM2.5 concentration, the emissions from glass factories accumulated vertically and narrowed horizontally. At times when pollution levels were severe, the horizontally influenced area mainly covered Shahe. Furthermore, sensitivity tests indicated that reducing emissions by 20%, 40%, and 60% could lead to a decrease in the mass concentration of PM2.5 of of 12.0%, 23.8%, and 35.5%, respectively.

[Co-amorphous technology to improve dissolution and physical stability of silybin].

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.

Cytoglobin promotes sensitivity to ferroptosis by regulating p53-YAP1 axis in colon cancer cells.

Ferroptosis is an iron-dependent mode of non-apoptotic cell death characterized by accumulation of lipid reactive oxygen species (ROS). As a regulator of ROS, cytoglobin (CYGB) plays an important role in oxygen homeostasis and acts as a tumour suppressor. However, the mechanism by which CYGB regulates cell death is largely unknown. Here, we show that CYGB overexpression increased ROS accumulation and disrupted mitochondrial function as determined by the oxygen consumption rate and membrane potential. Importantly, ferroptotic features with accumulated lipid ROS and malondialdehyde were observed in CYGB-overexpressing colorectal cancer cells. Moreover, CYGB significantly increased the sensitivity of cancer cells to RSL3- and erastin-induced ferroptotic cell death. Mechanically, both YAP1 and p53 were significantly increased based on the RNA sequencing. The knock-down of YAP1 alleviated production of lipid ROS and sensitivity to ferroptosis in CYGB overexpressed cells. Furthermore, YAP1 was identified to be inhibited by p53 knock-down. Finally, high expression level of CYGB had the close correlation with key genes YAP1 and ACSL4 in ferroptosis pathway in colon cancer based on analysis from TCGA data. Collectively, our results demonstrated a novel tumour suppressor role of CYGB through p53-YAP1 axis in regulating ferroptosis and suggested a potential therapeutic approach for colon cancer.