Identification of Lipotoxicity-Related Biomarkers in Diabetic Nephropathy Based on Bioinformatic Analysis.

Objective: This study is aimed at investigating diagnostic biomarkers associated with lipotoxicity and the molecular mechanisms underlying diabetic nephropathy (DN). Methods: The GSE96804 dataset from the Gene Expression Omnibus (GEO) database was utilized to identify differentially expressed genes (DEGs) in DN patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the DEGs. A protein-protein interaction (PPI) network was established to identify key genes linked to lipotoxicity in DN. Immune infiltration analysis was employed to identify immune cells with differential expression in DN and to assess the correlation between these immune cells and lipotoxicity-related hub genes. The findings were validated using the external dataset GSE104954. ROC analysis was performed to assess the diagnostic performance of the hub genes. The Gene set enrichment analysis (GSEA) enrichment method was utilized to analyze the key genes associated with lipotoxicity as mentioned above. Result: In this study, a total of 544 DEGs were identified. Among them, extracellular matrix (ECM), fatty acid metabolism, AGE-RAGE, and PI3K-Akt signaling pathways were significantly enriched. Combining the PPI network and lipotoxicity-related genes (LRGS), LUM and ALB were identified as lipotoxicity-related diagnostic biomarkers for DN. ROC analysis showed that the AUC values for LUM and ALB were 0.882 and 0.885, respectively. The AUC values for LUM and ALB validated in external datasets were 0.98 and 0.82, respectively. Immune infiltration analysis revealed significant changes in various immune cells during disease progression. Macrophages M2, mast cells activated, and neutrophils were significantly associated with all lipotoxicity-related hub genes. These key genes were enriched in fatty acid metabolism and extracellular matrix-related pathways. Conclusion: The identified lipotoxicity-related hub genes provide a deeper understanding of the development mechanisms of DN, potentially offering new theoretical foundations for the development of diagnostic biomarkers and therapeutic targets related to lipotoxicity in DN.

Dual-Strategy Tailoring Molecular Structures of Dopant-Free Hole Transport Materials for Efficient and Stable Perovskite Solar Cells.

Dopant-free hole transport materials (HTMs) are ideal materials for highly efficient and stable n-i-p perovskite solar cells (PSCs), but most current design strategies for tailoring the molecular structures of HTMs are limited to single strategy. Herein, four HTMs based on dithienothiophenepyrrole (DTTP) core are devised through dual-strategy methods combining conjugate engineering and side chain engineering. DTTP-ThSO with ester alkyl chain that can form six-membered ring by the S⋅⋅⋅O noncovalent conformation lock with thiophene in the backbone shows good planarity, high-quality film, matching energy level and high hole mobility, as well as strong defect passivation ability. Consequently, a remarkable power conversion efficiency (PCE) of 23.3 % with a nice long-term stability is achieved by dopant-free DTTP-ThSO-based PSCs, representing one of the highest values for un-doped organic HTMs based PSCs. Especially, the fill factor (FF) of 82.3 % is the highest value for dopant-free small molecular HTMs-based n-i-p PSCs to date. Moreover, DTTP-ThSO-based devices have achieved an excellent PCE of 20.9 % in large-area (1.01 cm2) devices. This work clearly elucidates the structure-performance relationships of HTMs and offers a practical dual-strategy approach to designing dopant-free HTMs for high-performance PSCs.

New keratose sponges after the end-Permian extinction provide insights into biotic recoveries.

We challenge the prevailing view that the end-Permian extinction impeded the Triassic evolution of sponges. Here, we report a deep-water community dominated by abundant keratose sponges in the lowest Triassic strata from Southwest China. The sponge fossils occur as dark elliptical imprints in mudstone with distinct oscula on their tops. The structure of preserved fibers suggests closest affinity with the extant Dictyoceratida, an aspiculate demosponge. The exceptional preservation plays a crucial role in retaining their exquisite structures. Sedimentary, taphonomic, pyrite framboid, and trace elemental analyses indicate that the sponges proliferated in an oxygen-poor habitat, demonstrating the high tolerance of sponges to severe conditions. Sponge proliferation is a signal of environmental upheaval but they also stabilized the ecosystem, driving the first phase of biotic recovery after the end-Permian extinction.

Effect of moxibustion for "nourishing the kidney and benefiting the marrow" on knee osteoarthritis. / "补肾益髓"æ³•è‰¾ç¸æ²»ç–—è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žçš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To compare the clinical effect between two acupoint regimens of moxibustion on knee osteoarthritis (KOA), and observe the influences on the serum content of interleukin 1α (IL-1α), interleukin-17A (IL-17A), tumor necrosis factor α (TNF-α), bone gla protein (BGP) and osteoprotegerin (OPG). METHODS: KOA patients were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 3 cases dropped off). In the observation group, moxibustion was applied to Xiyan (EX-LE5), Dubi (ST35), Zusanli (ST36), Dazhu (BL11), Xuanzhong (GB39) and Yongquan (KI1) on the affected side. In the control group, EX-LE5, ST35 and ST36 were selected on the affected side. One session of treatment took 30 min in each group, delivered 3 times a week and the duration of treatment was 4 weeks. The scores of Western Ontario and McMaster University (WOMAC) and visual analogue scale (VAS) were observed and the serum content of IL-1α, IL-17A, TNF-α, BGP and OPG of the two groups were measured before and after treatment. RESULTS: Compared with those before treatment, the WOMAC score, VAS score and the serum content of IL-1α, IL-17A and TNF-α were decreased (P<0.05), and the content of BGP and OPG were increased (P<0.05) after treatment. Compared with the control group, the WOMAC score, VAS score and the serum content of IL-1α and TNF-α in the observation group were lower (P<0.05), and the content of BGP and OPG were higher (P<0.05). The total effective rate of the observation group was 89.5% (34/38), and that of the control group was 83.8% (31/37), with no statistically significant difference. CONCLUSIONS: Moxibustion therapy of "nourishing the kidney and benefiting the marrow" can relieve joint pain, improve joint function, reduce the level of inflammatory factors and ameliorate bone metabolic indicators. The effect of the acupoint regimen in this moxibustion therapy is better than that of the local acupoint selection.

Invasion by Cenchrus spinifex changes the soil microbial community structure in a sandy grassland ecosystem.

Continuous nitrogen deposition increases the nitrogen content of terrestrial ecosystems and alters the soil nitrogen cycling process. Invasive plants have strong environmental adaptability, which can not only affect the composition and diversity of soil microbial community but also significantly affect the transformation process of soil nitrogen, leading to successful invasion. Currently, research on invasive plant soil ecosystems mainly focused on changes in soil nutrients and soil microorganisms. As an invasive annual grass weed with strong ecological adaptability, the impact of Cenchrus spinifex at different growth periods on soil environment and soil microbial structure composition and diversity in sandy grassland ecosystems is still unclear. In this study, soil samples were collected from four habitats with different degrees of invasion in situ during the vegetation and reproductive growth periods of Cenchrus spinifex. High-throughput sequencing and qPCR technology were used to analyze the changes in the composition, structure and diversity characteristics of the soil microbial communities during Cenchrus spinifex invasion. The results indicated that Cenchrus spinifex invasion had different effects on the soil environment at different growth periods, and Cenchrus spinifex had a preference for the utilization of ammonium nitrogen during vegetation growth period. Moreover, Cenchrus spinifex invasion significantly changed the composition and structure of soil bacterial communities, and the response of soil bacterial and fungal communities to the invasion was inconsistent. Additionally, the bacterial network was more stable than the fungal network. At different growth periods, Cenchrus spinifex had a significant impact on the key microbial communities of soil nitrogen cycling. The invasion increased the abundance of nifH and AOA-amoA, while decreased the abundance of AOA-amoB. Alkaline hydrolyzed nitrogen, total nitrogen and total phosphorus content were key factors that affect vegetation growth period and change the key microbial communities of nitrogen cycling. Alkaline hydrolyzed nitrogen, total phosphorus and organic carbon were key factors in reproductive growth period that alter the nitrogen cycling of key microbial communities.

Inhibition of Autophagy in Renal Cells With Human, Urine-derived, Stem-cell Exosomes to Improve Diabetic Nephropathy.

Context: Clinicians can use stem cells to repair kidney injury. The kidneys' exosome secretions hold the secret to this therapeutic impact. Exosomes from urine-derived stem cells can prevent and treat glomerular damage that diabetes can cause, but the underlying process has remained a mystery. Objective: The study aimed to investigate the protective impact of exosomes from urine-derived stem cells (USCs) against diabetic nephropathy (DN) and to determine the mechanisms involved. Design: The research team performed an animal study. Setting: The study took place at the Affiliated Hospital of Jiujiang University in Jiujiang, Jiangxi, China. Animals: The animals were rats, SD male rats, weighing 200-220g, 40 animals, purchased from Weitong Lihua Experimental Animal Technology Co., Ltd. (certificate number: SCXK (Beijing) 2021-0006). Intervention: Except for a control group, the rats in the groups had induced DN. The five groups, with 10 rats each, were: (1) the negative control group, which received 0.2 ml of PBS solution; (2) the DN group, a second negative control group, which received 0.2 ml of PBS solution, (3) the inhibitor group, an intervention group that received 20 mg/kg of autophagy inhibitor; (4) the exosomes group, an intervention group that received 100 ug/kg of exosomes; and (5) the exosomes + inhibitor group, an intervention group that received 100 ug/kg of exosomes + 20 mg/kg of autophagy inhibitor. From week 8, for four weeks the team injected the inhibitor, exosomes, and exosomes + inhibitor groups with the appropriate treatments using the rats' tail veins. Outcome Measures: The research team: (1) examined the USCs in the exosomes of stem cells; (2) assessed the rats' weights and fasting blood glucose (FBG), using a blood glucose meter; (3) used Coomassie brilliant blue (CBB) staining to determine the amount of protein in the rats' urine and assessed their biochemical indexes; and (4) used Western blot (WB) and a quantitative polymerase chain reaction (Q-PCR) to detect autophagy and the signal transduction pathway. Results: Human exosomes from USCs alleviated injury in the rats that DN caused by reducing urinary-protein levels, serum creatinine (SCR), blood urea nitrogen (BUN), glomerular cell accumulation, and kidney weights. In rats with induced DN, the exosomes + inhibitor significantly reduced the activation of the mTOR signaling pathway, reduced the autophagy of their kidney cells, increased the protein expression of Bcl-2 in the kidney tissues, and lessened the damage to glomerular cells. Conclusions: Human urine-derived stem cell exosomes can significantly reduce the activation of the mTOR signaling pathway, reduce the autophagy of rats' kidney cells, increase the protein expression of LC3B in kidney tissues, and reduce the damage to glomerular cells. By blocking the mTOR signaling pathway, human urogenic exosomes can alleviate the signs and symptoms of DN.

Design, synthesis, and pharmacological evaluation of quinazoline derivatives as novel and potent pan-JAK inhibitors.

Janus kinases (JAKs) play a critical role in modulating the function and expression of inflammatory cytokines related to rheumatoid arthritis (RA). Herein, we report the design, synthesis, and structure-activity relationships (SARs) of a series of novel quinazoline derivatives as JAK inhibitors. Among these inhibitors, compound 11n showed high potency against JAKs (JAK1/JAK2/JAK3/TYK2, IC50 = 0.40, 0.83, 2.10, 1.95 nM), desirable metabolic characters, and excellent pharmacokinetic properties. In collagen-induced arthritis (CIA) models, compound 11n exhibited significant reduction in joint swelling with good safety, which could be served as a potential therapeutic candidate for the treatment of inflammatory diseases.

Changes in grassland soil types lead to different characteristics of bacterial and fungal communities in Northwest Liaoning, China.

Introduction: Soil microbial communities are critical in regulating grassland biogeochemical cycles and ecosystem functions, but the mechanisms of how environmental factors affect changes in the structural composition and diversity of soil microbial communities in different grassland soil types is not fully understood in northwest Liaoning, China. Methods: We investigated the characteristics and drivers of bacterial and fungal communities in 4 grassland soil types with 11 sites across this region using high-throughput Illumina sequencing. Results and Discussion: Actinobacteria and Ascomycota were the dominant phyla of bacterial and fungal communities, respectively, but their relative abundances were not significantly different among different grassland soil types. The abundance, number of OTUs, number of species and diversity of both bacterial and fungal communities in warm and temperate ecotone soil were the highest, while the warm-temperate shrub soil had the lowest microbial diversity. Besides, environmental factors were not significantly correlated with soil bacterial Alpha diversity index. However, there was a highly significant negative correlation between soil pH and Shannon index of fungal communities, and a highly significant positive correlation between plant cover and Chao1 index as well as Observed species of fungal communities. Analysis of similarities showed that the structural composition of microbial communities differed significantly among different grassland soil types. Meanwhile, the microbial community structure of temperate steppe-sandy soil was significantly different from that of other grassland soil types. Redundancy analysis revealed that soil total nitrogen content, pH and conductivity were important influencing factors causing changes in soil bacterial communities, while soil organic carbon, total nitrogen content and conductivity mainly drove the differentiation of soil fungal communities. In addition, the degree of connection in the soil bacterial network of grassland was much higher than that in the fungal network and soil bacterial and fungal communities were inconsistently limited by environmental factors. Our results showed that the microbial community structure, composition and diversity of different grassland soil types in northwest Liaoning differed significantly and were significantly influenced by environmental factors. Microbial community structure and the observation of soil total nitrogen and organic carbon content can predict the health changes of grassland ecosystems to a certain extent.

Release Behavior of Liquid Crystal Monomers from Waste Smartphone Screens: Occurrence, Distribution, and Mechanistic Modeling.

Liquid crystal display (LCD) screens can release many organic pollutants into the indoor environment, including liquid crystal monomers (LCMs), which have been proposed as a novel class of emerging pollutants. Knowing the release pathways and mechanisms of LCMs from various components of LCD screens is important to accurately assess the LCM release and reveal their environmental transport behavior and fate in the ambient environment. A total of 47, 43, and 33 out of 64 target LCMs were detected in three disassembled parts of waste smartphone screens, including the LCM layer (LL), light guide plate (LGP), and screen protector (SP), respectively. Correlation analysis confirmed LL was the source of LCMs detected in LGP and SP. The emission factors of LCMs from waste screen, SP, and LGP parts were estimated as 2.38 × 10-3, 1.36 × 10-3, and 1.02 × 10-3, respectively. A mechanism model was developed to describe the release behaviors of LCMs from waste screens, where three characteristics parameters of released LCMs, including average mass proportion (AP), predicted subcooled vapor pressures (PL), and octanol-air partitioning coefficients (Koa), involving coexistence of absorption and adsorption mechanisms, could control the diffusion-partitioning. The released LCMs in LGP could reach diffusion-partition equilibrium more quickly than those in SP, indicating that LCM release could be mainly governed through SP diffusions.

HPLC-based metabolomics of Dendrobium officinale revealing its antioxidant ability.

Dendrobium officinale is an orchid with medicinal and nutritional properties that has received increasing attention because of its health benefits; however, there is limited information about the metabolic basis of these properties. In this report, secondary metabolites and the antioxidant activity of D. officinale stem samples from three provenances were analyzed, using a UHPLC-QqQ-MS/MS-based metabolomics approach. In total, 411 metabolites were identified including 8 categories such as flavonoids and phenolic acids, 136 of which were differential metabolites. These differentially accumulated metabolites (DAMs) were mainly enriched in secondary metabolic pathways such as flavone, flavonol, tropane, piperidine, pyridine, isoquinoline alkaloid biosynthesis and tyrosine metabolism. The metabolomic profiling suggested that the quantity and content of flavonoid compounds accounted for the highest proportion of total metabolites. Hierarchical cluster analysis (HCA) showed that the marker metabolites of D. officinale from the three provenances were mainly flavonoids, alkaloids and phenolic acids. Correlation analysis identified that 48 differential metabolites showed a significant positive correlation with antioxidant capacity (r ³ 0.8 and p < 0.0092), and flavonoids were the main factors affecting the different antioxidant activities. It is worth noting that quercetin-3-O-sophoroside-7-O-rhamnoside and dihydropinosylvin methyl ether might be the main compounds causing the differences in antioxidant capacity of Yunnan provenance (YN), Zhejiang provenance (ZJ), and Guizhou provenance (GZ). These finding provides valuable information for screening varieties, quality control and product development of D. officinale.

Mercury evidence from southern Pangea terrestrial sections for end-Permian global volcanic effects.

The latest Permian mass extinction (LPME) was triggered by magmatism of the Siberian Traps Large Igneous Province (STLIP), which left an extensive record of sedimentary Hg anomalies at Northern Hemisphere and tropical sites. Here, we present Hg records from terrestrial sites in southern Pangea, nearly antipodal to contemporaneous STLIP activity, providing insights into the global distribution of volcanogenic Hg during this event and its environmental processing. These profiles (two from Karoo Basin, South Africa; two from Sydney Basin, Australia) exhibit significant Hg enrichments within the uppermost Permian extinction interval as well as positive Δ199Hg excursions (to ~0.3‰), providing evidence of long-distance atmospheric transfer of volcanogenic Hg. These results demonstrate the far-reaching effects of the Siberian Traps as well as refine stratigraphic placement of the LPME interval in the Karoo Basin at a temporal resolution of ~105 years based on global isochronism of volcanogenic Hg anomalies.

Facile Synthesis of Carbon Dots from Amido Black 10b for Sensing in Real Samples.

Herein, a one-step hydrothermal synthesis method was adopted to fabricate carbon dots (CDs) from amido black 10b in a sodium hydroxide solution. The morphology and composition of the CDs were investigated by XRD, FTIR TEM, XPS, UV-vis, and fluorescence spectroscopy. The obtained CDs (AB-CDs) with an average diameter of 19.4 nm displayed a well-dispersed characteristic in aqueous solutions. The as-prepared CDs showed bright blue fluorescence and good photostability, with a high quantum yield of 24.1%. AB-CDs displayed a selective and noticeable turn-off response to Fe3+. Accordingly, the quantitative detection of Fe3+ was achieved in the range of 5-200 µmol L-1 with a detection limit of 1.84 µmol L-1. The fluorescence response mechanism of Fe3+ to AB-CDs was ascribed to static quenching due to the emergence of the ground-state complex. Moreover, ascorbic acid could restore the fluorescence of AB-CDs quenched by Fe3+ by reducing Fe3+ to Fe2+. The developed nanoprobe was used to detect ascorbic acid with a limit of detection of 7.26 µmol L-1 in the range of 20-300 µmol L-1. Furthermore, the developed sensing system was successfully applied for an Fe3+ assay in a lake water sample and ascorbic acid detection in a human urine sample. The AB-CD-based analytical system showed its latent practical value in the chemical analysis and bioanalytical fields.

Early Cretaceous Keteleerioxylon Wood in the Songliao Basin, Northeast China, and Its Geographic and Environmental Implications.

The extant Keteleeria is endemic to east and southeast Asia, while Keteleeria-like trees were widely distributed in the northern hemisphere in Earth's history. In this paper, we reported a novel wood fossil of Keteleerioxylon changchunense Shi, Sun, Meng et Yu sp. nov., collected from the middle part of the Yingcheng Formation, Yingcheng Coal Mine, Changchun City, Jilin Province, northeast China. The quantitative growth-ring analyses of K. changchunense indicate that it was evergreen with a leaf longevity of 1-3 years, which is consistent with the foliar retention of extant Keteleeria. Its high ring-markedness index (RMI) indicates that the climate seasonality was pronounced during the Early Albian period in the Songliao Basin, northeast China. The fossil records of Keteleeria and closely related taxa indicate that this group might have originated from high latitudes in the northern hemisphere, then spread and migrated southward during the Late Jurassic and Cretaceous periods, gradually decreased in the Cenozoic period, and so far only survives in east and southeast Asia.

Intensified continental chemical weathering and carbon-cycle perturbations linked to volcanism during the Triassic-Jurassic transition.

Direct evidence of intense chemical weathering induced by volcanism is rare in sedimentary successions. Here, we undertake a multiproxy analysis (including organic carbon isotopes, mercury (Hg) concentrations and isotopes, chemical index of alteration (CIA), and clay minerals) of two well-dated Triassic-Jurassic (T-J) boundary sections representing high- and low/middle-paleolatitude sites. Both sections show increasing CIA in association with Hg peaks near the T-J boundary. We interpret these results as reflecting volcanism-induced intensification of continental chemical weathering, which is also supported by negative mass-independent fractionation (MIF) of odd Hg isotopes. The interval of enhanced chemical weathering persisted for ~2 million years, which is consistent with carbon-cycle model results of the time needed to drawdown excess atmospheric CO2 following a carbon release event. Lastly, these data also demonstrate that high-latitude continental settings are more sensitive than low/middle-latitude sites to shifts in weathering intensity during climatic warming events.

Effect of aging and rejuvenation on adhesion properties of modified asphalt binder based on AFM.

The adhesion between asphalt binder and aggregate is very important to the performance and durability of asphalt pavement. In order to explore the characterisation of modified asphalt binder in microstructure during aging and rejuvenation, the virgin asphalt binder and three kinds of modified asphalt binder (styrene-butadiene-styrene block copolymer (SBS), rubber powder and high viscosity and high elasticity [HVHE] modifier) in different aging and rejuvenation condition were prepared. The micromorphology and surface adhesion were measured by atomic force microscopy. The average roughness value was used as the index to evaluate the micromorphology of asphalt binder. The surface adhesion was used as the index to evaluate the adhesion properties of asphalt binder. Results show that the "bee" structure of SBS-modified asphalt binder increased slightly after long-term aging, and the recovery effect of aromatics oil was the closest to that of the unaged one. The rubber powder-modified asphalt binder and HVHE-modified asphalt binder showed the spot structure. And no matter for short-term aging or long-term aging, aromatics oil had the best recovery effect on micro morphology. The adhesion of the three modified asphalts would decrease gradually after aging. The effects of three kinds of rejuvenator on the adhesion of SBS-modified asphalt binder and rubber powder-modified asphalt binder were different. Rejuvenator, aromatic oil and warm mix asphalt mixture (WMA) additive could rejuvenate the loss of adhesion of HVHE-modified asphalt binder to a certain extent.

In Situ Generated Novel 1H MRI Reporter for ß-Galactosidase Activity Detection and Visualization in Living Tumor Cells.

For wide applications of the lacZ gene in cellular/molecular biology, small animal investigations, and clinical assessments, the improvement of noninvasive imaging approaches to precisely assay gene expression has garnered much attention. In this study, we investigate a novel molecular platform in which alizarin 2-O-ß-d-galactopyranoside AZ-1 acts as a lacZ gene/ß-gal responsive 1H-MRI probe to induce significant 1H-MRI contrast changes in relaxation times T 1 and T 2 in situ as a concerted effect for the discovery of ß-gal activity with the exposure of Fe3+. We also demonstrate the capability of this strategy for detecting ß-gal activity with lacZ-transfected human MCF7 breast and PC3 prostate cancer cells by reaction-enhanced 1H-MRI T 1 and T 2 relaxation mapping.

ZnI2-Catalyzed Aminotrifluoromethylation Cyclization of Alkenes Using PhICF3Cl.

We report here an alternatively catalytic aminotrifluoromethylation of alkenes using PhICF3Cl as a bifunctional reagent along with ZnI2 as a dual catalyst. A combined catalytic strategy was established for the intramolecular aminotrifluoromethylation of 4-pentenamines. As a result, a set of 2-trifluoroethyl-pyrrolidines was obtained in a high selectivity. Mechanism studies revealed that the reaction included an iodine anion-catalyzed radical chlorotrifluoromethylation of alkenes and a sequential Lewis acid-promoted aminocyclization of the resulting chlorotrifluoromethylated intermediates.

Discovery of a novel series of imidazo[1',2':1,6]pyrido[2,3-d]pyrimidin derivatives as potent cyclin-dependent kinase 4/6 inhibitors.

CDK4/6 has been identified as an attractive therapeutic target for treatment of cancer. For unmet clinical needs, a novel class of imidazo [1',2':1,6]pyrido [2,3-d]pyrimidin derivatives, which had distinctive triheteroaryl structure, had been discovered as CDK4/6 inhibitors. The compounds 10b and 10c, displayed the low nanomolar range activities on CDK4/6, desirable antiproliferative activities, excellent metabolic properties, and acceptable pharmacokinetic characters. In Colo-205 and U87MG xenograft models, compounds 10b and 10c also showed significant tumor growth inhibitions with controllable toxicities. All data confirmed that imidazo [1',2':1,6]pyrido [2,3-d]pyrimidin derivatives 10b and 10c could be promising drug candidates for cancer therapy.

Study of POSS on the Properties of Novel Inorganic Dental Composite Resin.

: Various amounts of methacryl polyhedral oligomeric silsesquioxane (POSS) were explored to be incorporated into novel nano SiO2 dental resin composites using light curing method. The scanning electron microscopy (SEM), optical microscopy, fourier transform infrared spectroscopy (FTIR), nanoindentation, nanoscratch and three-point flexure tests were performed. The volumetric shrinkage and mechanical properties such as hardness, elastic modulus, resistance, flexural strength and fracture energy were analyzed. With the additions of POSS, the volume shrinkage decreased and the mechanical properties initially increased. The effects of POSS on these properties were studied to provide a reference for clinically selecting a composite resin with excellent properties.

Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial-mesenchymal transition.

Cervical cancer (CC) is the second most common malignant cancer among women. Gefitinib was one of the first-generation epidermal growth factor receptor-tyrosine kinase inhibitors in clinical trials. However, the underlying mechanism of gefitinib in regulating CC progression remains unknown. In the current study, two CC cell lines, HeLa and Siha, were used to investigate the effects of gefitinib. Cell counting kit-8 assays demonstrated that treatment with gefitinib exerted strong cytotoxicity in HeLa and Siha cells. Flow cytometry was used to examine cell cycle progression and apoptosis. Treatment with gefitinib enhanced the number of cells in the G0/G1 phase and increased apoptosis in HeLa and Siha cells. Furthermore, treatment with gefitinib decreased the protein expression level of Bcl-2 and increased the protein expression level of Bax. Taken together, these results suggest that gefitinib may suppress CC cell proliferation and induce cell cycle arrest and apoptosis. The current study also demonstrated that treatment with gefitinib suppressed epithelial-mesenchymal transition (EMT) as the expression level of the epithelial marker, E-cadherin was increased, while the expression level of the mesenchymal marker, vimentin was decreased. The current study demonstrated that treatment with gefitinib decreased the protein expression levels of phosphorylated-GSK3ß and ß-catenin, which suggests that gefitinib may be a potential novel therapeutic strategy in CC by suppressing the Wnt/ß-catenin signaling pathway and EMT to inhibit tumor metastasis in CC cells. In conclusion, gefitinib may suppress the EMT process during cell invasion and induce cell apoptosis and cell cycle arrest via inhibition of the Wnt/ß-catenin signaling pathway.