Adipocyte Progenitor Pools Composition and Cellular Niches Affect Adipogenesis Divergence in Porcine Subcutaneous and Intramuscular Fat.

Intramuscular fat (IMF) contributed positively to pork quality, whereas subcutaneous fat (SCF) was often considered to be a detrimental factor impacting growth and carcass traits. Reducing SCF while maintaining optimal IMF levels requires a thorough understanding of the adipogenic differences between these two adipose depots. Our study explored the differences in adipogenesis between porcine IMF and SCF, and the results showed that subcutaneous adipocytes (SCAs) demonstrate a greater potential for adipogenic differentiation, both in vivo and in vitro. Lipidomic and transcriptomic analyses suggested that intramuscular adipocytes (IMAs) are more inclined to biosynthesize unsaturated fatty acids. Furthermore, single-cell RNA sequencing (scRNA-seq) was employed to dissect the intrinsic and microenvironmental discrepancies in adipogenesis between porcine IMF and SCF. Comparative analysis indicated that SCF was enriched with preadipocytes, exhibiting an enhanced adipogenic potential, while IMF was characterized by a higher abundance of stem cells. Furthermore, coculture analyses of porcine intramuscular adipogenic cells and myogenetic cells indicated that the niche of IMAs inhibited its adipogenic differentiation. Cell communication analysis identified 160 ligand-receptor pairs and channels between adipogenic and myogenetic cells in IMF. Collectively, our study elucidated two intrinsic and microenvironmental novel mechanisms underpinning the divergence in adipogenesis between porcine SCF and IMF.

Inonotus obliquus aqueous extract inhibits intestinal inflammation and insulin metabolism defects in Drosophila.

In biomedical research, the fruit fly (Drosophila melanogaster) is among the most effective and flexible model organisms. Through the use of the Drosophila model, molecular mechanisms of human diseases can be investigated and candidate pharmaceuticals can be screened. White rot fungus Inonotus obliquus is a member of the family Hymenochaetaceae. Due to its multifaceted pharmacological effects, this fungus has been the subject of scientific investigation. Nevertheless, the precise mechanisms by which Inonotus obliquus treats diseases remain unclear. In this study, we prepared an aqueous extract derived from Inonotus obliquus and demonstrated that it effectively prevented the negative impacts of inflammatory agents on flies, including overproliferation and overdifferentiation of intestinal progenitor cells and decreased survival rate. Furthermore, elevated reactive oxygen species levels and cell death were alleviated by Inonotus obliquus aqueous extract, suggesting that this extract inhibited intestinal inflammation. Additionally, Inonotus obliquus aqueous extract had an impact on the insulin pathway, as it alleviated growth defects in flies that were fed a high-sugar diet and in chico mutants. In addition, we determined the composition of Inonotus obliquus aqueous extract and conducted a network pharmacology analysis in order to identify prospective key compounds and targets. In brief, Inonotus obliquus aqueous extract exhibited considerable potential as a therapeutic intervention for human diseases. Our research has established a foundational framework that supports the potential clinical implementation of Inonotus obliquus.

Separation of Mono-/Divalent Ions via Controlled Dynamic Adsorption/Desorption at Polythiophene Coated Carbon Surface with Flow-Electrode Capacitive Deionization.

Capacitive deionization for selective separation of ions is rarely reported since it relies on the electrostatic attraction of oppositely charged ions with no capability to distinguish ions of different valent states. Using molecular dynamic simulation, a screening process identified a hybrid material known as AC/PTh, which consists of activated carbon with a thin layer of polythiophene (PTh) coating. By utilizing AC/PTh as electrode material implementing the short-circuit cycle (SCC) mode in flow-electrode capacitive deionization (FCDI), selective separation of mono-/divalent ions can be realized via precise control of dynamic adsorption and desorption of mono-/divalent ions at a particular surface. Specifically, AC/PTh shows strong interaction with divalent ions but weak interaction with monovalent ions, the distribution of divalent ions can be enriched in the electric double layer after a couple of adsorption-desorption cycles. At Cu2+/Na+ molar ratio of 1:40, selectivity toward divalent ions can reach up to 110.3 in FCDI SCC mode at 1.0 V. This work presents a promising strategy for separating ions of different valence states in a continuously operated FCDI device.

Isolation, Identification, and Carbonate Mineralization Characteristics of a Newly Carbonic Anhydrase-Producing Strain.

Carbonic anhydrase-producing microorganisms can rely on their metabolism for carbon sequestration and carbonate precipitation, which is a relatively effective mode among the known microbially induced carbonate precipitation (MICP) methods. A newly carbonic anhydrase-producing strain was isolated from soil samples. 16S rDNA gene sequencing showed this strain had 99.18% sequence identity to Chryseobacterium gambrini. Various culture parameters (temperature, pH, rotational speed, inoculum size, and metal ions) were optimized for optimal microbial growth and CA activities. Optimal culture conditions were as follows: temperature of 30 °C, pH 6-7, rotational speed 150 rpm, and inoculum size 1%. It was observed that Co2+ and Mn2+ can improve CA activity with optimal concentrations of 0.02 mM and 0.01 mM, respectively. Furthermore, the introduction of CO2 for 15 min daily leads to a 36% increase in the final production of biotic CaCO3, reaching 2.884 g/L. Characterization of the mineralization precipitates was conducted to reveal the mechanism of the carbonic anhydrase-producing bacterium. Lastly, an analysis of the crystalline species and content of the biogenic CaCO3 was performed to lay the groundwork for future crystalline adjustments and to offer technical support for the application of the calcium method.

Orostachys malacophylla (pall.) fisch extracts alleviate intestinal inflammation in Drosophila.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys malacophylla (Pall.) Fisch (O. malacophylla) is a succulent herbaceous plant that is the Orostachys genus of Crassulaceae family. O. malacophylla has been widely used as a traditional Chinese medicine with antioxidant, anti-inflammatory, anti-febrile, antidote, anti-Toxoplasma gondii properties. However, the biological function of alleviating intestinal inflammation and key bioactive compounds were still unknown. AIM OF THE STUDY: We used a Drosophila model to study the protective effects and bioactive compounds of O. malacophylla water extract (OMWE) and butanol extract (OMBE) on intestinal inflammation. MATERIALS AND METHODS: Drosophila intestinal inflammation was induced by oral invasion of dextran sodium sulfate (DSS) or Erwinia carotovora carotovora 15 (Ecc15). We revealed the protective effects of two extracts by determining intestinal reactive oxygen species (ROS) and antimicrobial peptide (AMP) levels and intestinal integrity, and using network pharmacology analysis to identify bioactive compounds. RESULTS: We demonstrated that both OMWE and OMBE could ameliorate the detrimental effects of DSS, including a decreased survival rate, elevated ROS levels, increased cell death, excessive proliferation of ISCs, acid-base imbalance, and disruption of intestinal integrity. Moreover, the overabundance of lipid droplets (LDs) and AMPs by Ecc15 infection is mitigated by these extracts, thereby enhancing the flies' resistance to adverse stimuli. In addition, we used widely targeted metabolomics and network pharmacology analysis to identify bioactive compounds associated with IBD healing that are present in OMWE and OMBE. CONCLUSIONS: In summary, our research indicates that OMWE and OMBE significantly mitigate intestinal inflammation and have the potential to be effective therapeutic agents for IBD in humans.

Quantitative proteomic and metabolomic profiling reveals different osmoregulation mechanisms of tilapia cells coping with different hyperosmotic stress.

This study aimed to investigate the different regulatory mechanisms of euryhaline fish under regular hyperosmotic and extreme hyperosmotic stress. The OmB (Oreochromis mossambicus brain) cells were exposed to three treatments: control, regular hyperosmotic stress and extreme hyperosmotic stress. After 12 h exposure, proteomics, metabolomics analyses and integrative analyses were explored. Both kinds of stress lead to lowering cell growth and morphology changes, while under regular hyperosmotic stress, the up-regulated processes related with compatible organic osmolytes synthesis are crucial strategy for the euryhaline fish cell line to survive; On the other hand, under extreme hyperosmotic stress, the processes related with cell apoptosis and cell cycle arrest are dominant. Furthermore, down-regulated pyrimidine metabolism and several ribosomal proteins partially participated in the lowered cell metabolism and increased cell death under both kinds of hyperosmotic stress. The PI3K-Akt and p53 signaling pathways were involved in the stagnant stage of cell cycles and induction of cell apoptosis under both kinds of hyperosmotic stress. However, HIF-1, FoxO, JAK-STAT and Hippo signaling pathways mainly contribute to disrupting the cell cycle, metabolism and induction of cell apoptosis under extreme hyperosmotic stress. SIGNIFICANCE: In the past, the research on fish osmoregulation mainly focused on the transcription factors and ion transporters of osmoregulation, the processes between osmotic sensing and signal transduction, and the associations between signaling pathways and regulation processes have been poorly understood. Investigating fish cell osmoregulation and potential signal transduction pathways is necessary. With the advancements in omics research, it is now feasible to investigate the relationship between environmental stress and molecular responses. In this study, we aimed to explore the signaling pathways and substance metabolism mode during hyper-osmoregulation in OmB cell line, to reveal the key factors that are critical to cell osmoregulation.

A Biodegradable, Adhesive, and Stretchable Hydrogel and Potential Applications for Allergic Rhinitis and Epistaxis.

Bioadhesive hydrogels have attracted considerable attention as innovative materials in medical interventions and human-machine interface engineering. Despite significant advances in their application, it remains critical to develop adhesive hydrogels that meet the requirements for biocompatibility, biodegradability, long-term strong adhesion, and efficient drug delivery vehicles in moist conditions. A biocompatible, biodegradable, soft, and stretchable hydrogel made from a combination of a biopolymer (unmodified natural gelatin) and stretchable biodegradable poly(ethylene glycol) diacrylate is proposed to achieve durable and tough adhesion and explore its use for convenient and effective intranasal hemostasis and drug administration. Desirable hemostasis efficacy and enhanced therapeutic outcomes for allergic rhinitis are accomplished. Biodegradation enables the spontaneous removal of materials without causing secondary damage and minimizes medical waste. Preliminary trials on human subjects provide an essential foundation for practical applications. This work elucidates material strategies for biodegradable adhesive hydrogels, which are critical to achieving robust material interfaces and advanced drug delivery platforms for novel clinical treatments.

Competitive Coordination-Oriented Monodispersed Cobalt Sites on a N-Rich Porous Carbon Microsphere Catalyst for High-Performance Zn-Air Batteries.

Metal/nitrogen-doped carbon single-atom catalysts (M-N-C SACs) show excellent catalytic performance with a maximum atom utilization and customizable tunable electronic structure. However, precisely modulating the M-Nx coordination in M-N-C SACs remains a grand challenge. Here, we used a N-rich nucleobase coordination self-assembly strategy to precisely regulate the dispersion of metal atoms by controlling the metal ratio. Meanwhile, the elimination of Zn during pyrolysis produced porous carbon microspheres with a specific surface area of up to 1151 m2 g-1, allowing maximum exposure of Co-N4 sites and facilitating charge transport in the oxygen reduction reaction (ORR) process. Thereby, the monodispersed cobalt sites (Co-N4) in N-rich (18.49 at%) porous carbon microspheres (CoSA/N-PCMS) displayed excellent ORR activity under alkaline conditions. Simultaneously, the Zn-air battery (ZAB) assembled with CoSA/N-PCMS outperformed Pt/C+RuO2-based ZABs in terms of power density and capacity, proving that they have good prospects for practical application.

Transcriptome, intestinal microbiome and histomorphology profiling of differences in the response of Chinese sea bass (Lateolabrax maculatus) to Aeromonas hydrophila infection.

The Chinese sea bass (Lateolabrax maculatus) is an important aquaculture fish, but diseases caused by Aeromonas hydrophila have led to severe economic losses to the aquaculture industry in recent years. To date, only a few studies have focused on the relationship between the intestinal immune response and changes in intestinal microbes by A. hydrophila infection. Here, we report the transcriptome and intestinal changes in infected sea bass. Histopathological results showed that severe steatosis and vacuolation occurred in the liver and that the intestinal villi and mesentery were seriously affected after infection. By extracting total RNA from intestinal tissue and studying the transcriptome profile, 1,678 genes (1,013 upregulated and 665 downregulated) were identified as significantly differentially expressed genes (DEGs). These genes are involved in many immune-related signalling pathways, such as the NOD-like receptor, C-type lectin receptor, and Toll-like receptor signalling pathways. Moreover, the intestinal microbes of sea bass changed significantly after infection. Interestingly, at the genus level, there was an increase in Serratia, Candida arthromitus and Faecalibacterium as well as a decrease in Akkermansia and Parabacteroides after infection. The results also indicated that some of the DEGs involved in the immune response were related to the genus level of intestinal microbiota. Finally, there was a relationship between gene expression patterns and the bacterial structure in the host intestine. Our study provides a reference for the study of the immune response and particular functions of intestinal microbes of sea bass after pathogen infection.

Surface deformation tracking in monocular laparoscopic video.

Image-guided surgery has been proven to enhance the accuracy and safety of minimally invasive surgery (MIS). Nonrigid deformation tracking of soft tissue is one of the main challenges in image-guided MIS owing to the existence of tissue deformation, homogeneous texture, smoke and instrument occlusion, etc. In this paper, we proposed a piecewise affine deformation model-based nonrigid deformation tracking method. A Markov random field based mask generation method is developed to eliminate tracking anomalies. The deformation information vanishes when the regular constraint is invalid, which further deteriorates the tracking accuracy. Atime-series deformation solidification mechanism is introduced to reduce the degradation of the deformation field of the model. For the quantitative evaluation of the proposed method, we synthesized nine laparoscopic videos mimicking instrument occlusion and tissue deformation. Quantitative tracking robustness was evaluated on the synthetic videos. Three real videos of MIS containing challenges of large-scale deformation, large-range smoke, instrument occlusion, and permanent changes in soft tissue texture were also used to evaluate the performance of the proposed method. Experimental results indicate the proposed method outperforms state-of-the-art methods in terms of accuracy and robustness, which shows good performance in image-guided MIS.

Cellulose nanofibers carbon aerogel based single-cobalt-atom catalyst for high-efficiency oxygen reduction and zinc-air battery.

Single-atom catalysts (SACs) have opened up unprecedented possibilities for expediting oxygen reduction reaction (ORR) kinetics owing to their ultrahigh intrinsic activities. However, precisely controlling over the atomically dispersed metal-Nx sites on carbon support while fulfilling the utmost utilization of metal atoms remain the key obstacles. Here, atomically distributed Co-N4 sites anchored on N-doped carbon nanofibers aerogel (Co SAs/NCNA) is controllably attained through a direct pyrolysis of metal-chelated cellulose nanofibers (TOCNFs-Cd2+/Co2+) hydrogel precursor. The usage of Cd salt assists the assembly of cross-linked aerogel, creates a large number of interior micropores and defects, and favors the physical isolation of Co atoms. The hierarchically porous biomass carbon aerogel (2265.1 m2/g) offers an advantageous platform to facilitate accessibility of the catalytic centers, also renders rapid mass diffusion and electron-transfer paths throughout its 3D architecture. Notably, Co SAs/NCNA affords a paramount ORR activity and respectable durability when integrated into zinc-air battery devices.

Regulating Surface Wettability and Charge Density of Porous Carbon Particles by In Situ Growth of Polyaniline for Constructing an Efficient Electrical Percolation Network in Flow-Electrode Capacitive Deionization.

Both electrical conductivity and surface wettability are required for the selection of active carbon materials in flow-electrode capacitive deionization, while a trade-off exists between these two properties. In this work, a hybrid material with a thin layer of polyaniline (PANI) coating on activated carbon (AC/PANI) was successfully developed to retain excellent electrical conductivity and acquire good surface wettability. By adjusting the dosage of initiator, AC/PANI composites with different loading fractions of PANI were obtained. The electrochemical testing demonstrated that the AC/PANI composites have higher specific capacitance and lower ion diffusion resistance compared to pure AC, resulting in better desalinization performance. Specifically, with a feed concentration of 1600 mg/L, excellent adsorption capacity and high charge efficiency can be simultaneously achieved at 13.51 mg/g and 92.21%, respectively. Benefiting from the formation of a continuous electrical percolation network and reduced solid/liquid interfacial transport resistance, a 39% enhancement of average salt adsorption rate (from 0.54 to 0.75 µmol/min/cm2) was obtained.

Solar Driven Gas Phase Advanced Oxidation Processes for Methane Removal - Challenges and Perspectives.

Methane (CH4 ) is a potent greenhouse gas and the second highest contributor to global warming. CH4 emissions are still growing at an alarmingly high pace. To limit global warming to 1.5 °C, one of the most effective strategies is to reduce rapidly the CH4 emissions by developing large-scale methane removal methods. The purpose of this perspective paper is threefold. (1) To highlight the technology gap dealing with low concentration CH4 (at many emission sources and in the atmosphere). (2) To analyze the challenges and prospects of solar-driven gas phase advanced oxidation processes for CH4 removal. And (3) to propose some ideas, which may help to develop solar-driven gas phase advanced oxidation processes and make them deployable at a climate significant scale.

Dexmedetomidine Inhibits NF-κB-Transcriptional Activity in Neurons Undergoing Ischemia-Reperfusion by Regulating O-GlcNAcylation of SNW1.

Dexmedetomidine (Dex) is neuroprotective in ischemia-reperfusion (I/R) by suppressing inflammation but the underlying molecular mechanisms are not known. SNW domain-containing protein 1 (SNW1) is a coactivator of the pro-inflammatory transcription factor NF-κB p65. Because SNW1 is regulated by O-GlcNAcylation, we aimed to determine whether this modification influences NF-κB transcriptional activity in neurons undergoing I/R and how Dex may affect the O-GlcNAcylation of SNW1. SH-SY5Y and PC12 cells under hypoxia/reoxygenation (H/R) conditions were treated with Dex and with inhibitors of O-GlcNAc transferase (OGT). O-GlcNAc levels in SNW1 and effects of SNW1 on NF-κB p65 were determined by immunoprecipitation. H/R increased SNW1 protein levels but inhibited O-GlcNAcylation of SNW1. A Luciferase reporter assay demonstrated that increased SNW1 levels led to increased NF-κB p65 activity and increased secretion of neuron-derived inflammatory factors demonstrated by ELISA. Dex reversed the H/R-induced increase of SNW1 protein by upregulating OGT and enhancing O-GlcNAcylation of SNW1. Dex suppression of the SNW1/NF-κB complex resulted in neuroprotection in vitro and in a middle cerebral artery occlusion model in vivo. PKA and ERK1/2 inhibitors abolished the effect of Dex on OGT protein. Taken together, these data indicate that Dex inhibits NF-κB-transcriptional activity in neurons undergoing I/R by regulating O-GlcNAcylation of SNW1.

High-fat diet blunts T-cell responsiveness in Nile tilapia.

The reduced stress resistance and increased disease risk associated with high-fat diet (HFD) in animals have attracted increasing attention. However, the effects of HFD on adaptive immunity in early vertebrates, especially non-tetrapods, remain unknown. In this study, using Nile tilapia (Oreochromis niloticus) as a model, we investigated the effects of HFD on the primordial T-cell response in fish. Tilapia fed with an HFD for 8 weeks showed impaired lymphocyte homeostasis in the spleen, as indicated by the decreased number of both T and B lymphocytes and increased transcription of proinflammatory cytokines interferon-γ and interleukin-6. Moreover, lymphocytes isolated from HFD-fed fish or cultured in lipid-supplemented medium exhibited diminished T-cell activation in response to CD3ε monoclonal antibody stimulation. Moreover, HFD-fed tilapia infected by Aeromonas hydrophila showed decreased T-cell expansion, increased T-cell apoptosis, reduced granzyme B expression, and impaired infection elimination. Additionally, HFD attenuated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activity in tilapia lymphocytes, which in turn upregulated fatty acid synthesis but downregulated fatty acid ß-oxidation. Altogether, our results suggest that HFD impairs lymphocyte homeostasis and T cell-mediated adaptive immune response in tilapia, which may be associated with the abnormal lipid metabolism in lymphocytes. These findings thus provide a novel perspective for understanding the impact of HFD on the adaptive immune response of early vertebrates.

New insights into the influence of myo-inositol on carbohydrate metabolism during osmoregulation in Nile tilapia (Oreochromis niloticus).

A two-factor (2 × 3) orthogonal test was conducted to investigate the effects of dietary myo-inositol (MI) on the osmoregulation and carbohydrate metabolism of euryhaline fish tilapia (Oreochromis niloticus) under sustained hypertonic stress (20 practical salinity units [psu]). 6 diets containing either normal carbohydrate (NC, 30%) or high carbohydrate (HC, 45%) levels, with 3 levels (0, 400 and 1,200 mg/kg diet) of MI, respectively, were fed to 540 fish under 20 psu for 8 weeks. Dietary MI supplementation significantly improved growth performance and crude protein content of whole fish, and decreased the content of crude lipid of whole fish (P < 0.05). Curled, disordered gill lamella and cracked gill filament cartilage were observed in the gill of fish fed diets without MI supplementation. The ion transport capacity in gill was significantly improved in the 1,200 mg/kg MI supplementation groups compared with the 0 mg/kg MI groups (P < 0.05). Moreover, the contents of Na+, K+, Cl- in serum were markedly reduced with the dietary MI supplementation (P < 0.05). The fish fed 1,200 mg/kg MI supplementation had the highest MI content in the gills and the lowest MI content in the serum (P < 0.05). Additionally, the fish fed with 1,200 mg/kg MI supplementation had the highest MI synthesis capacity in gills and brain (P < 0.05). Dietary MI markedly promoted the ability of carbohydrate metabolism in liver (P < 0.05). Moreover, fish in the 1,200 mg/kg MI groups had the highest antioxidant capacity (P < 0.05). This study indicated that high dietary carbohydrate would intensify stress, and impair the ability of osmoregulation in tilapia under a long-term hypersaline exposure. The supplementation of MI at 1,200 mg/kg in the high carbohydrate diet could promote carbohydrate utilization and improve the osmoregulation capacity of tilapia under long-term hypertonic stress.

Real-time biomechanical modelling of the liver using LightGBM model.

BACKGROUND: Accurate and real-time biomechanical modelling of the liver is a major challenge in computer-assisted surgery. Finite element method is often used to predict the deformation of organs for its high modelling accuracy. However, its high computation cost hinders its application in real time, such as virtual surgery simulations. METHOD: A liver model with biomechanical properties similar to real one is created using finite element method and a data set of the liver deformation with different forces (whose magnitude ranges from 0.1 to 0.5 N in omni-direction) acting on different surface points is generated. The mechanical behaviour of liver is simulated in real time by a tree-based LightGBM regression model trained with the generated data set. RESULTS: In comparison with the Random Forest and XGBoost, the LightGBM model achieves the best accuracy with 0.0774 mm, 0.0786 mm, 0.0801 mm in the mean absolute error (MAE) and 0.0591 mm, 0.0609 and 0.0622 mm in the root mean square error (RMSE) along x, y and z axis, respectively. In addition, it only takes 33 ms for the LightGBM model to estimate the deformation of the liver, which is much faster than finite element model (29.91 s). CONCLUSION: These results lay a foundation for the future development of real-time virtual surgery systems of simulating liver deformation during minimally invasive surgeries using our method.

Integration of Untargeted Metabolomics with Transcriptomics Provides Insights into Beauvericin Biosynthesis in Cordyceps chanhua under H2O2-Induced Oxidative Stress.

Cordyceps chanhua is an important cordycipitoid mushroom widely used in Asia and beyond. Beauvericin (BEA), one of the bioactive compounds of C. chanhua, has attracted much attention because of its medicinal value and food safety risk. In order to clear up the relationship between oxidative stress and BEA synthesis, we investigated the impact of H2O2-induced oxidative stress on the secondary metabolism of C. chanhua using untargeted metabolomics and a transcript profiling approach. Metabolic profiling of C. chanhua mycelia found that in total, 73 differential metabolites were identified, including organic acids, phospholipids, and non-ribosomal peptides (NRPs), especially the content of BEA, increasing 13-fold under oxidative stress treatment. Combining transcriptomic and metabolomic analyses, we found that the genes and metabolites associated with the NRP metabolism, especially the BEA biosynthesis, were highly significantly enriched under H2O2-induced stress, which indicated that the BEA metabolism might be positive in the resistance of C. chanhua to oxidative stress. These results not only aid in better understanding of the resistance mechanisms of C. chanhua against oxidative stress but also might be helpful for molecular breeding of C. chanhua with low BEA content.

The role of PICT1 in RPL11/Mdm2/p53 pathway-regulated inhibition of cell growth induced by topoisomerase IIα inhibitor against cervical cancer cell line.

Our previous work showed that a podophyllum derivative (D-3F), named 4-N-(2-Amino-3-fluoropyridine) -4-deoxidation-4'-demethylepipofophyllotoxin, inhibits the activity of topoisomerase II (TOPO II) and then results in DNA damage. Also, D-3F increases the expression of p53 to induce cervical cancer HeLa cell apoptosis by enhancing its stability, due to the translocation of RPL11 to interact with Mdm2 and then consequently causing the blockage of the Mdm2-p53 feedback loop. In present study, we further explored the detailed mechanism of the antitumor activity of D-3F against cervical cancer cell line. Firstly, the decreased level of protein interacting with carboxyl terminus 1 (PICT1) in cervical cancer cell lines (HeLa and SiHa) treated with D-3F, exerted its potent inhibitory effect on cellular proliferation, which was dependent on the inhibition of TOPO IIα activity induced by D-3F in vitro. In addition, the downregulation of PICT1 was required to enhancement of p53 stability, resulted from its promoting the nucleoplasmic translocation of RPL11 to bind to Mdm2 following D-3F treatment. Altogether, it demonstrated that the reduction of PICT1 level in HeLa cell line, as well as SiHa exposed to D-3F, a TOPO IIα inhibitor, may play an essential role in the regulation of RPL11/Mdm2/p53 pathway to induce cell apoptosis. Besides, it suggested the potential of this podophyllum derivative (D-3F) as an alternative agent for therapy in cervical cancer.

Pb2+ Responsive Cu-In-Zn-S Quantum Dots With Low Cytotoxicity.

Water-soluble Cu-In-Zn-S quantum dots (CIZS QDs) with orange fluorescence have been synthesized with a glutathione (GSH) as stabilizer via facile a one-step hydrothermal method. The optimal reaction conditions of CIZS QDs including temperature, time, pH, and the molar ratios of precursors were studied. TEM results indicate that the aqueous-dispersible CIZS QDs are quasi-spherical, and the average diameters are 3.76 nm with excellent fluorescent stability. Furthermore, the cytotoxicity of CIZS QDs was investigated by the microcalorimetry combining with TEM and the IC 50 was 10.2 µM . CIZS QDs showed a promising perspective in applications such as a fluorescent probe for bioimaging and biolabeling due to the low cytotoxicity and good biocompatibility. Moreover, the CIZS QDs can distinguish Pb2+ ion from other ions, offering great potentials in lead ion determination in drinking water. According to the results of UV, XRD, FL, PL, and ITC methods, the mechanism of CIZS QDs-Pb2+ assay is due to hydrogen bonding or van der Waals forces in the formation of Pb2+ and CIZS QDs.