Cervical Cancer Cell-derived Tie1 Expression Via PI3K/AKT Signaling Pathway Promotes Tumour Progression.

BACKGROUND: Tie1 orphan receptor has become a focus of research, Tie1 can form a polymer with Tie2, regulate the Ang/Tie2 pathway and play a vital role in pathological angiogenesis and tumor progression, the function of Tie1 has remained uncertain in the progression of cervical cancer (CC). Here, we investigated the functional influences of Tie1 overexpress on CC in vitro and in vivo. METHODS: We used Immunohistochemistry (IHC) analysis to detect the relative expression of Tie1 in CC, and we analyzed its connection with the overall survival (OS) and progression free survival (PFS)of CC patients. To prove the role of Tie1 in cell proliferation and metastatic, Tie1 expression in CC cell lines was upregulated by lentivirus. RESULTS: The high expression of Tie1 in tumor cells of cervical cancer tissues is significantly correlated with FIGO stage, differentiated tumors, tumors with diameters, deep stromal invasion. We found that cell progression was promoted in Tie1-overexpress CC cell lines in vivo and in vitro. Tie1 potentially exerts a commanding influence on the expression of markers associated with epithelial-mesenchymal transition (EMT) and the PI3K/AKT signaling pathway. CONCLUSIONS: Our research indicates that Tie1 is highly connected to CC progression as it may play a role in the EMT process through the PI3K/AKT signaling pathway.

Disulfidptosis features and prognosis in head and neck squamous cell carcinoma patients: unveiling and validating the prognostic signature across cohorts.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a significant health concern with a variable global incidence and is linked to regional lifestyle factors and HPV infections. Despite treatment advances, patient prognosis remains variable, necessitating an understanding of its molecular mechanisms and the identification of reliable prognostic biomarkers. METHODS: We analyzed 959 HNSCC samples and employed batch correction to obtain consistent transcriptomic data across cohorts. We examined 79 disulfidptosis-related genes to determine consensus clusters and utilized high-throughput sequencing to identify genetic heterogeneity within tumors. We established a disulfidptosis prognostic signature (DSPS) using least absolute shrinkage and selection operator (LASSO) regression and developed a prognostic nomogram integrating the DSPS with clinical factors. Personalized chemotherapy prediction was performed using the "pRRophetic" R package. RESULTS: Batch corrections were used to harmonize gene expression data, revealing two distinct disulfidptosis subtypes, C1 and C2, with differential gene expression and survival outcomes. Subtype C1, characterized by increased expression of the MYH family genes ACTB, ACTN2, and FLNC, had a mortality rate of 48.4%, while subtype C2 had a mortality rate of 38.7% (HR = 0.77, 95% CI: 0.633-0.934, P = 0.008). LASSO regression identified 15 genes that composed the DSPS prognostic model, which independently predicted survival (HR = 2.055, 95% CI: 1.420-2.975, P < 0.001). The prognostic nomogram, which included the DSPS, age, and tumor stage, predicted survival with AUC values of 0.686, 0.704, and 0.789 at 3, 5, and 8 years, respectively, indicating strong predictive capability. In the external validation cohort (cohort B), the DSPS successfully identified patients at greater risk, with worse overall survival outcomes in the high-DSPS subgroup (HR = 1.54, 95% CI: 1.17-2.023, P = 0.002) and AUC values of 0.601, 0.644, 0.636, and 0.748 at 3, 5, 8, and 10 years, respectively, confirming the model's robustness. CONCLUSION: The DSPS provides a robust prognostic tool for HNSCC, underscoring the complexity of this disease and the potential for tailored treatment strategies. This study highlights the importance of molecular signatures in oncology, offering a step toward personalized medicine and improved patient outcomes in HNSCC management.

Chitosan-graft-poly(lactic acid)/CD-MOFs degradable composite microspheres for sustained release of curcumin.

The solubility of cyclodextrin metal-organic frameworks (CD-MOFs) in aqueous media making it not suitable as sustained-release drug carrier. Here, curcumin-loaded CD-MOFs (CD-MOFs-Cur) was embedded in chitosan-graft-poly(lactic acid) (CS-LA) via a solid-in-oil-in-oil (s/o/o) emulsifying solvent evaporation method forming the sustained-release composite microspheres. At CS-LA concentration of 20 mg/mL, the composite microspheres showed good sphericity. The average particle size of CS-LA/CD-MOFs-Cur (2:1), CS-LA/CD-MOFs-Cur (4:1) and CS-LA/CD-MOFs-Cur (6:1) composite microspheres was about 9.3, 12.3 and 13.5 µm, respectively. The above composite microspheres exhibited various degradation rates and curcumin release rates. Treating in HCl solution (pH 1.2) for 120 min, the average particle size of above microspheres reduced 28.19 %, 24.34 % and 6.19 %, and curcumin released 86.23 %, 78.37 % and 52.57 %, respectively. Treating in PBS (pH 7.4) for 12 h, the average particle size of above microspheres reduced 30.56 %, 26.56 % and 10.66 %, and curcumin released 68.54 %, 54.32 % and 31.25 %, respectively. Moreover, the composite microspheres had a favorable cytocompatibility, with cell viability of higher than 90 %. These composite microspheres open novel opportunity for sustained drug release of CD-MOFs.

A novel, effective machine learning-based RNA editing profile for predicting the prognosis of lower-grade gliomas.

Patients with low-grade glioma (LGG) may survive for long time periods, but their tumors often progress to higher-grade lesions. Currently, no cure for LGG is available. A-to-I RNA editing accounts for nearly 90% of all RNA editing events in humans and plays a role in tumorigenesis in various cancers. However, little is known regarding its prognostic role in LGG. On the basis of The Cancer Genome Atlas (TCGA) data, we used LASSO and univariate Cox regression to construct an RNA editing site signature. The results derived from the TCGA dataset were further validated with Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) datasets. Five machine learning algorithms (Decision Trees C5.0, XGboost, GBDT, Lightgbm, and Catboost) were used to confirm the prognosis associated with the RNA editing site signature. Finally, we explored immune function, immunotherapy, and potential therapeutic agents in the high- and low-risk groups by using multiple biological prediction websites. A total of 22,739 RNA editing sites were identified, and a signature model consisting of four RNA editing sites (PRKCSH|chr19:11561032, DSEL|chr18:65174489, UGGT1|chr2:128952084, and SOD2|chr6:160101723) was established. Cox regression analysis indicated that the RNA editing signature was an independent prognostic factor, according to the ROC curve (AUC = 0.823), and the nomogram model had good predictive power (C-index = 0.824). In addition, the predictive ability of the RNA editing signature was confirmed with the machine learning model. The sensitivity of PCI-34051 and Elephantin was significantly higher in the high-risk group than the low-risk group, thus potentially providing a marker to predict the effects of lung cancer drug treatment. RNA editing may serve as a novel survival prediction tool, thus offering hope for developing editing-based therapeutic strategies to combat LGG progression. In addition, this tool may help optimize survival risk assessment and individualized care for patients with low-grade gliomas.

Multiphasic lignocellulose-based suspension for oil-water interfacial stabilization: Synergistic adsorption and phase behavior.

This study described the multiphasic and multi-sized lignocellulose-based suspension (LBS) prepared by green method and its adsorption and phase behavior at O/W interface. The LBS consisting of lignin containing microfibrils (LMFs), lignin containing cellulose nanofibers (LCNFs), and lignin nanoparticles (LNPs), was obtained by mechanical fibrillation and high-shear treatments. They had different functions in emulsion stabilization: (1) synergistic irreversible adsorption of LCNFs and LNPs limited the coalescence of droplets and formed micro-sized droplets; (2) droplets filled in the LMFs network creating a strong fiber-droplet network structure. The fluorescent micrographs confirmed the synergistic irreversible adsorption of LCNFs and LNPs on the surface of the droplets, which was conductive to the high interfacial stability. The droplets were deformed rather than being destroyed under the high flow speed. The increasing viscosity, improving gel-like behavior, decreasing creep compliance and increasing yield stress demonstrated that the internal droplets can support the fiber network to delay the destruction under shear force. And the fiber-droplet network can automatically regenerate in situ after completed destruction.

Comparing the infection biology and gene expression differences of Plasmodiophora brassicae primary and secondary zoospores.

Plasmodiophora brassicae (Wor.) is an obligate plant pathogen affecting Brassicae worldwide. To date, there is very little information available on the biology and molecular basis of P. brassicae primary and secondary zoospore infections. To examine their roles, we used microscope to systematically investigate the infection differences of P. brassicae between samples inoculated separately with resting spores and secondary zoospores. The obvious development of P. brassicae asynchrony that is characterized by secondary plasmodium, resting sporangial plasmodium, and resting spores was observed at 12 days in Brassica rapa inoculated with resting spores but not when inoculated with secondary zoospores at the same time. Inoculation with resting spores resulted in much more development of zoosporangia clusters than inoculation with secondary zoospores in non-host Spinacia oleracea. The results indicated that primary zoospore infection played an important role in the subsequent development. To improve our understanding of the infection mechanisms, RNA-seq analysis was performed. Among 18 effectors identified in P. brassicae, 13 effectors were induced in B. rapa seedlings inoculated with resting spores, which suggested that the pathogen and host first contacted, and more effectors were needed. Corresponding to those in B. rapa, the expression levels of most genes involved in the calcium-mediated signaling pathway and PTI pathway were higher in plants inoculated with resting spores than in those inoculated with secondary zoospores. The ETI pathway was suppressed after inoculation with secondary zoospores. The genes induced after inoculation with resting spores were suppressed in B. rapa seedlings inoculated with secondary zoospores, which might be important to allow a fully compatible interaction and contribute to a susceptible reaction in the host at the subsequent infection stage. The primary zoospores undertook an more important interaction with plants.

Sodium Alginate/Modified Bentonite Composite Bead Adsorptive Removal of Norfloxacin: Static and Dynamic Adsorption.

The low-cost calcium-based bentonite modified with anionic and cationic surfactants was granulated by cross-linking to sodium alginate (SA) to promote the adsorption efficiencies of norfloxacin (NOR). The characterization studies illustrated that the intercalation of cetyltrimethylammonium bromide (CTAB) and sodium dodecyl benzene sulfonate (SDBS) was successful. The modification improved the pore structure and the granular SA/organically modified bentonite composite (GOMBt) exhibited a lamellar structure with some roughness. The adsorption kinetics and isotherms indicated that adsorption of NOR on GOMBt was an endothermic process. The effects of various factors on the adsorption of NOR suggested that the maximum adsorption capacity was obtained under acidic conditions and cations improved the adsorption process. A fixed-bed column was employed to investigate the dynamic adsorption characteristics of NOR by GOMBt. The breakthrough time and bed height had a positive correlation; however, the relation of flow rate, pH, and breakthrough time had a negative correlation. The results showed that the dynamic adsorption data of NOR on GOMBt fitted Thomas and Yoon-Nelson models. The internal and external diffusion in GOMBt dynamic adsorption was not a rate-limiting step.

Let-7e-5p, a promising novel biomarker for benzene toxicity, is involved in benzene-induced hematopoietic toxicity through targeting caspase-3 and p21.

Benzene is a common industrial chemical and environmental pollutant. However, the mechanism of hematotoxicity caused by exposure to low doses of benzene is unknown. Let-7e-5p pathway regulatory networks were constructed by bioinformatics analysis using a benzene-induced aplastic anemia (BIAA) mouse model. The MTT assay, EdU staining, flow cytometric analysis, dual luciferase reporter gene assay, and RIP assay were utilized to evaluate the effects of benzoquinone (1,4-BQ) on let-7e-5p pathway. This study consisted of 159 workers with a history of low-level benzene exposure and 159 workers with no history of benzene exposure. After the confounding factors were identified, the associations between let-7e-5p expression and hematotoxicity were assessed by multiple linear regression. Furthermore, we used four machine learning algorithms (decision trees, neural network, Bayesian network, and support vector machines) to construct a predictive model for detecting benzene-causing hematotoxicity in workers. In this study, compared with respective controls, let-7e-5p expression was decreased in BIAA mice and benzene-exposed workers. After 1,4-BQ exposure, let-7e-5p overexpression negatively regulated caspase-3 and p21 expression, protected cells from apoptosis, and facilitated cell proliferation. RIP assays, and dual luciferase reporter gene assays confirmed that let-7e-5p could target p21 and caspase-3 and regulate the cell cycle and apoptosis. The support vector machines classifier achieved the best prediction of benzene-induced hematotoxicity (prediction accuracy = 88.27, AUC = 0.83) by statistically characterizing the internal dose of benzene exposure and the oxidative stress index, as well as the expression levels of let-7e-5p pathway-related genes in benzene-exposed workers. Let-7e-5p may be a potential therapeutic target of benzene-induced hematotoxicity, provide a basis for evaluating the health hazards of long-term and low-dose benzene exposure in workers, and supply a reference for revising occupational health standards.

An easily processable silver nanowires-dual-cellulose conductive paper for versatile flexible pressure sensors.

To date, flexible pressure sensors built on silver nanowires (AgNWs) have attracted tremendous attention, owing to their versatile applications in wearable, human-interactive, health-monitoring devices. Cellulose and its derivatives, which show great promise in serving flexible pressure sensors as the desired substrate due to their natural abundance, biocompatibility, easy processibility, and low costs. Herein, we reported a rational strategy to design a silver nanowires-dual-cellulose conductive paper. Its morphology, chemical and crystal structures, thermal stability, mechanical performances, and electrical properties were carefully studied. The results suggested that good tensile properties (tensile strength ≤8.10 MPa), high electrical conductivity (≤ 1.74 × 104 S·m-1) with long-term stability, and good adhesion stability (bending cycles over 500) were obtained. Furthermore, the use of such conductive paper as substrate for versatile flexible pressure sensors was demonstrated, which exhibited fast response (~ 0.48 s) and high sensitivity, in response to finger motion, voice recognition, and human pulse, etc.

Research development and trends of benzene-induced leukemia from 1990 to 2019-A bibliometric analysis.

Benzene is an occupational and environmental toxicant, causing hematopoietic damage. Our study is aimed to extract the trend of benzene-induced leukemia (BIL) and qualitatively and quantitatively estimate research on it. Publications on BIL were identified from the Web of Science Core Collection (WoSCC). Microsoft Excel 2019 (Redmond, WA) and The CiteSpace 5.6.R5 software (Drexel University, Philadelphia, PA) were used to analyze the publication outcomes, countries, institutions, authors, keywords, and research frontiers. The overall 1152 publications were collected from 1990 to 2019 until November 6, 2020. Environ Health Persp had the highest number of articles published. The USA were the top country in terms of BIL. The Smith MT, Yin SN, Lan Q, and Hayes RB are both listed in the top 10 of co-cited authors, high contribution authors, and the authors of co-cited references. High IF articles account for a considerable proportion, among all the publications. Chinese institutions engaged in BIL and contributed a large part of articles. Exposure population, exposure dose, and exposure risk are the research hotspots in this field. The risk of benzene exposure on childhood leukemia is at issue, and the studies on attributable risk of benzene-induced leukemia are few. More early, sensitive, and specific epigenetic biomarkers of benzolism may be the leading research fields of benzene-induced leukemia in the next few years.

Encapsulation of curcumin in CD-MOFs: promoting its incorporation into water-based products and consumption.

Curcumin has received considerable interest in functional food areas due to its variety of biological effects. However, its utilization is often limited by its insolubility and instability in aqueous solutions. Herein, curcumin was encapsulated in γ-cyclodextrin metal-organic frameworks (CD-MOFs) to achieve immediate release and rapid dissolution in water just by gentle stirring due to the dissociation of CD-MOFs. The released curcumin exhibited remarkably enhanced stability compared to its free form in aqueous solutions due to the inclusion effects of cyclodextrins. Besides, the impacts of temperature, light and gastrointestinal pH on the chemical stability of curcumin released from basic and neutral CD-MOFs were compared. The molar ratios of curcumin : γ-CD in basic CD-MOFs and neutral CD-MOFs were 1 : 1.7 and 1 : 9.8, respectively. Neutral CD-MOFs were more effective in retarding thermal and gastrointestinal degradation of curcumin because all curcumin molecules can form inclusion complexes with cyclodextrin. Basic CD-MOFs were more conducive to prolonging the half-life time of curcumin during photodegradation since its alkalinity darkened the color of curcumin solution causing lower light transmittance. Moreover, CD-MOFs exhibited higher loading and stability of curcumin due to their unique host-guest structure, than their pure cyclodextrin inclusion complex. Curcumin-loaded CD-MOFs having a fast-dissolving ability accompanied by the improved amorphous form stability of curcumin hold great potential as functional additives in instant food.

Study on the reproductive toxicity and mechanism of tri-n-butyl phosphate (TnBP) in Caenorhabditis elegans.

Tri-n-butyl phosphate (TnBP), a typical alkyl organophosphate ester is widely used as an emerging flame retardant for polybrominated diphenyl ethers alternatives, but the potential toxicity and mechanism are unclear. In this study, the reproductive toxicity of TnBP and its related mechanisms were explored using the Caenorhabditis elegans (C. elegans) model. After TnBP (100-1000 µg/L) exposure, brood size and the number of fertilized eggs in the uterus in C. elegans were significantly reduced, the relative area of gonad arm and the number of total germline cells in C. elegans were significantly reduced, germ cell apoptosis and germ cell DNA damage in C. elegans were significantly increased, the level of ROS in C. elegans was significantly increased. Furthermore, TnBP exposure caused abnormal gene expressions of cell apoptosis (ced-9, ced-4 and ced-3), DNA damage (hus-1, clk-2, cep-1 and egl-1) and oxidative stress (mev-1 and gas-1). TnBP exposure can lead to reproductive ability decreased and gonad development impaired in C. elegans, the mechanism of TnBP reduced reproductive ability may be related to germ cell apoptosis, germ cell DNA damage and oxidative stress. Environmental exposure to TnBP may have potential reproductive toxicity.

Tandem approach to NOBIN analogues from arylhydroxylamines and diaryliodonium salts via [3,3]-sigmatropic rearrangement.

Herein, we present a transition-metal free direct O-arylation of arylhydroxylamines employing diaryliodonium salts as arylation reagents to form transient N,O-diarylhydroxylamines that could subsequently undergo [3,3]-sigmatropic rearrangement and re-aromatization to afford structurally diverse NOBIN analogs in good to excellent yields under mild conditions.

Silica nanomaterials induce organ injuries by Ca2+-ROS-initiated disruption of the endothelial barrier and triggering intravascular coagulation.

BACKGROUND: The growing use of silica nanoparticles (SiNPs) in many fields raises human toxicity concerns. We studied the toxicity of SiNP-20 (particle diameter 20 nm) and SiNP-100 (100 nm) and the underlying mechanisms with a focus on the endothelium both in vitro and in vivo. METHODS: The study was conducted in cultured human umbilical vein endothelial cells (HUVECs) and adult female Balb/c mice using several techniques. RESULTS: In vitro, both SiNP-20 and SiNP-100 decreased the viability and damaged the plasma membrane of cultured HUVECs. The nanoparticles also inhibited HUVECs migration and tube formation in a concentration-dependent manner. Both SiNPs induced significant calcium mobilization and generation of reactive oxygen species (ROS), increased the phosphorylation of vascular endothelial (VE)-cadherin at the site of tyrosine 731 residue (pY731-VEC), decreased the expression of VE-cadherin expression, disrupted the junctional VE-cadherin continuity and induced F-actin re-assembly in HUVECs. The injuries were reversed by blocking Ca2+ release activated Ca2+ (CRAC) channels with YM58483 or by eliminating ROS with N-acetyl cysteine (NAC). In vivo, both SiNP-20 and SiNP-100 (i.v.) induced multiple organ injuries of Balb/c mice in a dose (range 7-35 mg/kg), particle size, and exposure time (4-72 h)-dependent manner. Heart injuries included coronary endothelial damage, erythrocyte adhesion to coronary intima and coronary coagulation. Abdominal aorta injury exhibited intimal neoplasm formation. Lung injuries were smaller pulmonary vein coagulation, bronchiolar epithelial edema and lumen oozing and narrowing. Liver injuries included multifocal necrosis and smaller hepatic vein congestion and coagulation. Kidney injuries involved glomerular congestion and swelling. Macrophage infiltration occurred in all of the observed organ tissues after SiNPs exposure. SiNPs also decreased VE-cadherin expression and altered VE-cadherin spatial distribution in multiple organ tissues in vivo. The largest SiNP (SiNP-100) and longest exposure time exerted the greatest toxicity both in vitro and in vivo. CONCLUSIONS: SiNPs, administrated in vivo, induced multiple organ injuries, including endothelial damage, intravascular coagulation, and secondary inflammation. The injuries are likely caused by upstream Ca2+-ROS signaling and downstream VE-cadherin phosphorylation and destruction and F-actin remodeling. These changes led to endothelial barrier disruption and triggering of the contact coagulation pathway.

Performance and microbial characterization of aerobic granular sludge in a sequencing batch reactor performing simultaneous nitrification, denitrification and phosphorus removal with varying C/N ratios.

The mechanism and effect of C/N ratios on the aerobic granules simultaneous nitrification, denitrification and phosphorus removal (SNDPR) system are still unclear. The reactor performance and microbial community dynamics of the system were investigated under variable C/N ratios (20, 10 and 5). The COD, TP and NH4+-N removal remained unaffected with variable C/N ratios. The decreased C/N ratio of five strongly influenced the nitrogen removal. Further investigations revealed that Candidatus_Accumulibacter, Acinetobacter, Candidatus_Competibacter were the predominant genera. Classification of key groups involved in nitrogen and phosphorus removal indicated the lowest C/N ratio resulting in a large microbial community shift. This study might contribute to the application of SNDPR system for the treatment of wastewater. Different C/N ratios led to shift on the microbial community and the dominant was phosphorus-accumulating bacteria. The nitrogen removal efficiency decreased while the removal of COD, TP and NH4+-N remained remarkable with the decreased C/N ratios.

Proanthocyanidin B2 attenuates high-glucose-induced neurotoxicity of dorsal root ganglion neurons through the PI3K/Akt signaling pathway.

High glucose affects primary afferent neurons in dorsal root ganglia by inhibiting neurite elongation, causing oxidative stress, and inducing neuronal apoptosis and mitochondrial dysfunction, which finally result in neuronal damage. Proanthocyanidin, a potent antioxidant, has been shown to have neuroprotective effects. Proanthocyanidin B2 is a common dimer of oligomeric proanthocyanidins. To date, no studies have reported the neuroprotective effects of proanthocyanidin B2 against high-glucose-related neurotoxicity in dorsal root ganglion neurons. In this study, 10 µg/mL proanthocyanidin B2 was used to investigate its effect on 45 mM high-glucose-cultured dorsal root ganglion neurons. We observed that challenge with high levels of glucose increased neuronal reactive oxygen species and promoted apoptosis, decreased cell viability, inhibited outgrowth of neurites, and decreased growth-associated protein 43 protein and mRNA levels. Proanthocyanidin B2 administration reversed the neurotoxic effects caused by glucose challenge. Blockage of the phosphatidylinositol 3 kinase/Akt signaling pathway with 10 µM LY294002 eliminated the protective effects of proanthocyanidin B2. Therefore, proanthocyanidin B2 might be a potential novel agent for the treatment of peripheral diabetic neuropathy.

Ochrobactrum anthropi used to control ammonium for nitrate removal by starch-stabilized nanoscale zero valent iron.

In this study, the hydrogenotrophic denitrifying bacterium Ochrobactrum anthropi was added in to the process of nitrate removal by starch-stabilized nanoscale zero valent iron (nZVI) to minimize undesirable ammonium. The ammonium control performance and cooperative mechanism of this combined process were investigated, and batch experiments were conducted to discuss the effects of starch-stabilized nZVI dose, biomass, and pH on nitrate reduction and ammonium control of this system. The combined system achieved satisfactory performance because the anaerobic iron corrosion process generates H2, which is used as an electron donor for the autohydrogenotrophic bacterium Ochrobactrum anthropi to achieve the autohydrogenotrophic denitrification process converting nitrate to N2. When starch-stabilized nZVI dose was increased from 0.5 to 2.0 g/L, nitrate reduction rate gradually increased, and ammonium yield also increased from 9.40 to 60.51 mg/L. Nitrate removal rate gradually decreased and ammonium yield decreased from 14.93 to 2.61 mg/L with initial OD600 increasing from 0.015 to 0.080. The abiotic Fe0 reduction process played a key role in nitrate removal in an acidic environment and generated large amounts of ammonium. Meanwhile, the nitrate removal rate decreased and ammonium yield also reduced in an alkaline environment.