Recent evidences showed that long noncoding RNAs (lncRNAs) are frequently dysregulated and play important roles in various cancers. Clear cell renal cell carcinoma (ccRCC) is one of the leading cause ...of cancer-related death, largely due to the metastasis of ccRCC. However, the clinical significances and roles of lncRNAs in metastatic ccRCC are still unknown.
lncRNA expression microarray analysis was performed to search the dysregulated lncRNA in metastatic ccRCC. quantitative real-time PCR was performed to measure the expression of lncRNAs in human ccRCC samples. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of lncRNAs on ccRCC cell proliferation, migration, invasion and in vivo metastasis. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and western blot were performed to explore the molecular mechanisms underlying the functions of lncRNAs.
The microarray analysis identified a novel lncRNA termed metastatic renal cell carcinoma-associated transcript 1 (MRCCAT1), which is highly expressed in metastatic ccRCC tissues and associated with the metastatic properties of ccRCC. Multivariate Cox regression analysis revealed that MRCCAT1 is an independent prognostic factor for ccRCC patients. Overexpression of MRCCAT1 promotes ccRCC cells proliferation, migration, and invasion. Depletion of MRCCAT1 inhibites ccRCC cells proliferation, migration, and invasion in vitro, and ccRCC metastasis in vivo. Mechanistically, MRCCAT1 represses NPR3 transcription by recruiting PRC2 to NPR3 promoter, and subsequently activates p38-MAPK signaling pathway.
MRCCAT1 is a critical lncRNA that promotes ccRCC metastasis via inhibiting NPR3 and activating p38-MAPK signaling. Our results imply that MRCCAT1 could serve as a prognostic biomarker and therapeutic target for ccRCC.
Herein, we observed near-infrared electrochemiluminescence (NIR ECL) emission from tetraphenylethylene nanocrystals (TPE NCs), which exhibit high ECL efficiency and excellent biocompatibility ...compared with the current NIR ECL emitters (such as semiconductor quantum dots and metal nanoclusters). The strong ECL signal of TPE NCs originates from the aggregation-induced enhanced ECL emission
improvement of the efficiency of electron hole recombination and suppression of the nonradiative transition. Impressively, the TPE NCs exhibit an enormous red-shifted ECL emission (678 nm) relative to the blue-light photoluminescence (PL) emission (440 nm). Compared to fluorescence imaging which is limited by photobleaching and autofluorescence, the NIR ECL emission of TPE NCs is highly favorable to diminish background interference over visible light and realize deeper tissue penetration, which expands the ECL emission of organic nanomaterials to the NIR region for broader biological applications.
Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, ...industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 μg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1β, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role.
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•Perinatal exposure to EHDPHP led to neuroinflammation and oxidative stress in dams and pups.•EHDPHP upregulated the expressions of inflammation and oxidative stress related biomarkers.•Inulin attenuated EHDPHP-associated oxidative stress and neuroinflammation in both dams and pups.
Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut ...microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.
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•Methamphetamine (METH) exposure induced reproductive toxicity in male mice.•METH exposure caused changes in the gut microbiome and compromised the integrity of the intestinal barrier.•METH exposure altered the testicular transcriptome and metabolic expression profiles.•Fecal microbiota transplantation conveyed similar reproductive damage from METH-treated mice to healthy recipient mice.
Layered oxides have become the research focus of cathode materials for sodium‐ion batteries (SIBs) due to the low cost, simple synthesis process, and high specific capacity. However, the poor air ...stability, unstable phase structure under high voltage, and slow anionic redox kinetics hinder their commercial application. In recent years, the concept of manipulating orbital hybridization has been proposed to simultaneously regulate the microelectronic structure and modify the surface chemistry environment intrinsically. In this review, the hybridization modes between atoms in 3d/4d transition metal (TM) orbitals and O 2p orbitals near the region of the Fermi energy level (EF) are summarized based on orbital hybridization theory and first‐principles calculations as well as various sophisticated characterizations. Furthermore, the underlying mechanisms are explored from macro‐scale to micro‐scale, including enhancing air stability, modulating high working voltage, and stabilizing anionic redox chemistry. Meanwhile, the origin, formation conditions, and different types of orbital hybridization, as well as its application in layered oxide cathodes are presented, which provide insights into the design and preparation of cathode materials. Ultimately, the main challenges in the development of orbital hybridization and its potential for the production application are also discussed, pointing out the route for high‐performance practical sodium layered oxide cathodes.
Based on orbital hybridization theory, the challenges of layered oxide cathodes in terms of air stability, high voltage, anion redox chemistry, and improving the intrinsic characteristics through interactions between the 3d/4d transition metal and the O 2p atomic orbitals are summarized. This strategy of modulating orbitals hybridization will promote the development of sodium layered oxide cathodes and its commercialization process.
Accumulating evidence suggests long noncoding RNAs (lncRNAs) play an important role in cancer progression. However, the function of lncRNA SNHG7 in colorectal cancer (CRC) remains unclear. In this ...study, SNHG7 expression was significantly upregulated in CRC tissues, especially in aggressive cases. In accordance, high level of SNHG7 was observed in CRC cell lines compared to normal colon cells. Furthermore, SNHG7 overexpression promoted the proliferation, migration, and invasion of CRC cell lines, while SNHG7 depletion inhibited invasion and cell viability in vitro. Mechanistically, knockdown of SNHG7 inhibited GALNT1 and EMT markers (E-cadherin and Vimentin). Importantly, SNHG7 directly interacted with miR-216b and downregulation of miR-216b reversed efficiently the suppression of GALNT1 induced by SNHG7 siRNA. Moreover, overexpression of SNHG7 significantly enhanced the tumorigenesis and liver metastasis of SW480 cells in vivo. SNHG7 positively regulated GALNT1 level through sponging miR-216b, and played an oncogenic role in CRC progression. Together, our study elucidated the role of SNHG7 as an miRNA sponge in CRC, and shed new light on lncRNA-directed diagnostics and therapeutics in CRC.
Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, ...a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy.
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•METH induced hepatotoxicity and enterotoxicity.•Propionate, rather than acetate or butyrate, ameliorates METH-induced hepatotoxicity and enterotoxicity.•Propionate supplementation ...ameliorates intestinal permeability and suppressed the LPS-TLR4-NF-κB pathway, ultimately improving the dysfunction of METH-induced liver and colon.
The abuse of methamphetamine (METH) has emerged as a major public health concern, causing liver and intestinal damage upon exposure. Short chain fatty acids (SCFAs) produced by dietary fiber, including acetate, propionate, and butyrate, have been reported to alleviate various liver toxicities and exhibit distinct physiological effects. However, the role of SCFAs in mitigating METH-induced liver and intestinal damage remains unexplored. This study is designed to elucidate this potential therapeutic effect, by administering either METH or saline via injection to BALB/c mice, supplemented with acetate, propionate, or butyrate in their drinking water. We discovered that propionate demonstrated the most significant effect in mitigating pathological changes, glycogen storage, inflammation, and hepatic function impairments in the liver induced by METH. Propionate supplementation attenuated damage to the intestinal epithelial barrier, restored mucus-secreting cells, inhibited intestinal inflammation, suppressed intestinal hyperpermeability, and reduced lipopolysaccharide (LPS) leakage caused by METH. With the alleviation of LPS endotoxemia, the TLR4/MyD88/NF-κB pathway associated with inflammation in the liver and colon was inhibited. In conclusion, propionate supplementation ameliorated hepatic and colon dysfunction and inflammation resulting from METH exposure through suppression of the TLR4/MyD88/NF-κB pathway.
The appearance of generative adversarial networks (GAN) provides a new approach and framework for computer vision. Compared with traditional machine learning algorithms, GAN works via adversarial ...training concept and is more powerful in both feature learning and representation. GAN also exhibits some problems, such as non-convergence, model collapse, and uncontrollability due to high degree of freedom. How to improve the theory of GAN and apply it to computer-vision-related tasks have now attracted much research efforts. In this paper, recently proposed GAN models and their applications in computer vision are systematically reviewed. In particular, we firstly survey the history and development of generative algorithms, the mechanism of GAN, its fundamental network structures, and theoretical analysis of the original GAN. Classical GAN algorithms are then compared comprehensively in terms of the mechanism, visual results of generated samples, and Frechet Inception Distance. These networks are further evaluated from network construction, performance, and applicability aspects by extensive experiments conducted over public datasets. After that, several typical applications of GAN in computer vision, including high-quality samples generation, style transfer, and image translation, are examined. Finally, some existing problems of GAN are summarized and discussed and potential future research topics are forecasted.
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