Gastrodin(GAS),the principal bioactive composition of Gastrodia elata Blume,has potential for pharmaceutical applications.Several studies in recent years have shown that GAS may enhance neurotrophic benefits,reduce in...Gastrodin(GAS),the principal bioactive composition of Gastrodia elata Blume,has potential for pharmaceutical applications.Several studies in recent years have shown that GAS may enhance neurotrophic benefits,reduce inflammation,and act as an antioxidant.In this study,we sought to identify the molecular mechanisms underlying the protective benefits of GAS against colitis induced by dextran sodium sulfate(DSS)in mice.GAS(200 mg/kg)significantly ameliorated the severity of colitis in mice caused by DSS,as evidenced by an increase in colon length,a reduction in disease activity index,a decrease in tissue damage,and a reduction in body weight loss.Additionally,GAS inhibited DSS-induced hyperactivation of inflammation-related NF-κB signaling pathways to reduce the production of inflammatory mediators,thereby mitigating the inflammatory response in mice.Furthermore,the administration of GAS restored the function of the gastrointestinal barrier by increasing the count of goblet cells,as well as the levels of tight junction associated proteins,including Zonula occludens-1(ZO-1),Occludin,and Claudin-3.GAS also influenced the overall richness of the gut microbiota,as shown by 16S rRNA sequencing analysis,consequently boosting the proliferative rate of probiotic species,such as Lachnospiraceae and Muribaculaceae,while reducing the richness of harmful bacteria including Escherichia_Shigella,Enterobacteriaceae,Bacteroidaceae,and Bacteroides.GAS(200 mg/kg)alleviated ulcerative colitis(UC)by modulating gut dysbiosis,as demonstrated by a fecal microbial transplantation(FMT)test.Furthermore,inflammatory damage induced by lipopolysaccharide(LPS)was averted in RAW264.7 cells by GAS administration,hence preventing the NF-κB signaling pathway from being activated in these experimental conditions conducted in vitro.Overall,the data indicate that GAS treatment effectively reduces colitis caused by DSS by regulating gut microbiota,suppressing inflammation,and preserving the mucosal barrier integrity.展开更多
The secretory activities of meibomian glands are regulated by the autonomic nervous system, The change in density and activity of autonomic nerves in meibomian glands during menopause play an important role in the pat...The secretory activities of meibomian glands are regulated by the autonomic nervous system, The change in density and activity of autonomic nerves in meibomian glands during menopause play an important role in the pathogenesis of dry eye. In view of this, we established a dry eye rat model by removing the bilateral ovaries. We used neuropeptide Y and vasoactive intestinal polypeptide as markers of autonomic neurotransmitters. Our results showed that the concentration of estradiol in serum significantly decreased, the density of neuropeptide Y immunoreactivity in nerve fibers significantly increased, the density of vasoactive intestinal polypeptide immunoreactivity in nerve fibers significantly decreased, and the ratio of vasoactive intestinal polypeptide/neuropeptide Y positive staining significantly decreased. These results suggest that a decrease in ovary activity may lead to autonomic nervous system dysfunction, thereby affecting the secretory activity of the meibomian gland, which participates in sexual hormone imbalance-induced dry eye.展开更多
The experiments of the ferrite warm deformation of ultra-low carbon (ULC) Ti-IF steel were carded out on a hot simulator and the influences of deformation temperature, strain, and strain rate on the flow stress were...The experiments of the ferrite warm deformation of ultra-low carbon (ULC) Ti-IF steel were carded out on a hot simulator and the influences of deformation temperature, strain, and strain rate on the flow stress were analyzed. New flow stress models suitable to ferrite warm forming of Ti-IF steel were given on the basis of analyzing the influence of deformation technology parameters on the flow stress.展开更多
Li-air batteries have received much attention in the past several years because of their large theoretical specific energy density, stable output voltage, cost-effective, energy-efficient and pollution free, and have ...Li-air batteries have received much attention in the past several years because of their large theoretical specific energy density, stable output voltage, cost-effective, energy-efficient and pollution free, and have broad application prospects. If it is successfully developed, the battery could be an excellent energy storage device for renewable energy sources such as wind, solar, and tidal energy, which brings a prospect for human to solve the problem of environment pollution and energy crisis. But the electrolyte is a crucial component of Li-air battery and the electrochemical performance of the battery is determined by electrolyte to a great extent. Due to the react violently between lithium and water, it is not practical for Li-air battery to use directly an aqueous electrolyte unless the anode can be protected from degradation. In this review, we presented the latest research progress on the non-aqueous electrolyte, i.e. organic electrolyte, ionic liquid and solid electrolyte. We elaborated the influence of solvents, and possible additives, and/or their combination Li-air battery’s performance. Finally, we provided insights into the prospect of non-aqueous electrolyte for Li-air battery.展开更多
The early detection of gastric cancer(GC)is critical for reducing its high mortality rates[1,2].Gastric xanthoma(GX),a lipid-associated lesion in the gastric mucosa,has been identified as a potential precursor to vari...The early detection of gastric cancer(GC)is critical for reducing its high mortality rates[1,2].Gastric xanthoma(GX),a lipid-associated lesion in the gastric mucosa,has been identified as a potential precursor to various stomach malignancies[3,4].In this study,we comprehensively profiled the gut microbiota,lipid metabolism,and amino acid metabolism to identify novel biomarkers for the early detection of GX,with potential implications for GC prevention and therapy.By employing 16S rRNA sequencing[5,6],transcriptomics[7],and gene ontology(GO)analysis[8],we revealed significant correlations between gut microbiota composition,dysregulated lipid transport,and aberrant amino acid metabolism in GX.These findings underscore the contribution of lipid metabolic dysfunction[9,10]and gut microbiota alterations[11,12]to the pathogenesis of GX,offering promising strategies for early GC detection and targeted intervention.展开更多
The blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation. However, detailed mo...The blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation. However, detailed molecular players involved in formation of BBB are not completely known. Dentin matrix protein I (DMP1)-proteoglycan (PG), which is known to be involved in mineralization of bones and dentin, is also expressed in soft tissues including brain with unknown functions. In the present study, we reported that DMPI-PG was expressed in brain astrocytes and enriched in BBB units. The only glycosylation site of DMP1 is serine89 (S89) in the N-terminal domain of the protein in mouse. Mutant mice with DMP1 point mutations changing S89 to glycine (S89G), which completely eradicated glycosylation of the protein, demonstrated severe BBB disruption. Another breed of DMP1 mutant mice, which lacked the C-terminal domain of DMP1, manifested normal BBB function. The polarity of S89G-DMP1 astrocytes was disrupted and cell-cell adhesion was loosened. Through a battery of analyses, we found that DMP1 glycosylation was critically required for astrocyte maturation both in vitro and in vivo. S89G-DMP1 mutant astrocytes failed to express aquaporin 4 and had reduced laminin and ZO1 expression, which resulted in disruption of BBB. Interestingly, overexpression of wild-type DMP1-PG in mouse brain driven by the nestin promoter elevated laminin and ZO1 expression beyond wild type levels and could effectively resisted intravenous mannitol-induced BBB reversible opening. Taken together, our study not only revealed a novel element, i.e., DMP1-PG, that reg- ulated BBB formation, but also assigned a new function to DMP1-PG.展开更多
Nasopharyngeal carcinoma(NPC)is a common malignant carcinoma of the head and neck,and the biological mechanisms underlying the pathogenesis of NPC remain not fully understood.In the present study,we systematically ana...Nasopharyngeal carcinoma(NPC)is a common malignant carcinoma of the head and neck,and the biological mechanisms underlying the pathogenesis of NPC remain not fully understood.In the present study,we systematically analyzed four independent NPC transcriptomic datasets and focused on identifying the critical molecular networks and novel key hub genes implicated in NPC.We found totally 170 common overlapping differentially expressed genes(DEGs)in the four NPC datasets.GO and KEGG pathway analysis revealed that cell cycle dysregulation is a critical event in NPC.Protein-protein interaction(PPl)network analysis identified a 15 hub-gene corenetwork with overexpressedkinesin family member2C(KIF2C)as a central regulator.Loss-of-function study demonstrated that knockdown of KiF2C significantly inhibited cell growth and cell motility,and delayed cell cycle progression,accompanied with dramatic mitotic defects in spindle formation in NPC cells.RNA-seq analysis revealed that KIF2c knockdown led to deregulation of various downstream genes.KiF2C could also regulate the AKT/mTOR pathways,and enhance paclitaxel sensitivity in NPC cells.Taken together,our results suggest that cell cycle dysregulation is a critical event during NPC pathogenesis and KIF2C is a novel key mitotic hub gene with therapeutic potential in NPC.展开更多
基金financial support from the Project of Health Research Talents of Jilin Province(2023SCZ21)the Department of Science and Technology of Jilin Province(20220202076NC,20220202088NC).
文摘Gastrodin(GAS),the principal bioactive composition of Gastrodia elata Blume,has potential for pharmaceutical applications.Several studies in recent years have shown that GAS may enhance neurotrophic benefits,reduce inflammation,and act as an antioxidant.In this study,we sought to identify the molecular mechanisms underlying the protective benefits of GAS against colitis induced by dextran sodium sulfate(DSS)in mice.GAS(200 mg/kg)significantly ameliorated the severity of colitis in mice caused by DSS,as evidenced by an increase in colon length,a reduction in disease activity index,a decrease in tissue damage,and a reduction in body weight loss.Additionally,GAS inhibited DSS-induced hyperactivation of inflammation-related NF-κB signaling pathways to reduce the production of inflammatory mediators,thereby mitigating the inflammatory response in mice.Furthermore,the administration of GAS restored the function of the gastrointestinal barrier by increasing the count of goblet cells,as well as the levels of tight junction associated proteins,including Zonula occludens-1(ZO-1),Occludin,and Claudin-3.GAS also influenced the overall richness of the gut microbiota,as shown by 16S rRNA sequencing analysis,consequently boosting the proliferative rate of probiotic species,such as Lachnospiraceae and Muribaculaceae,while reducing the richness of harmful bacteria including Escherichia_Shigella,Enterobacteriaceae,Bacteroidaceae,and Bacteroides.GAS(200 mg/kg)alleviated ulcerative colitis(UC)by modulating gut dysbiosis,as demonstrated by a fecal microbial transplantation(FMT)test.Furthermore,inflammatory damage induced by lipopolysaccharide(LPS)was averted in RAW264.7 cells by GAS administration,hence preventing the NF-κB signaling pathway from being activated in these experimental conditions conducted in vitro.Overall,the data indicate that GAS treatment effectively reduces colitis caused by DSS by regulating gut microbiota,suppressing inflammation,and preserving the mucosal barrier integrity.
基金supported by the Key Technology Research & Development Program of Hebei Province,No.10276105D-3the Key Project of Hebei Province Health Department of Medical Science,No.20120154the Key Technology Research & Development Program of Hebei Province Handan City,No.1023108101-2
文摘The secretory activities of meibomian glands are regulated by the autonomic nervous system, The change in density and activity of autonomic nerves in meibomian glands during menopause play an important role in the pathogenesis of dry eye. In view of this, we established a dry eye rat model by removing the bilateral ovaries. We used neuropeptide Y and vasoactive intestinal polypeptide as markers of autonomic neurotransmitters. Our results showed that the concentration of estradiol in serum significantly decreased, the density of neuropeptide Y immunoreactivity in nerve fibers significantly increased, the density of vasoactive intestinal polypeptide immunoreactivity in nerve fibers significantly decreased, and the ratio of vasoactive intestinal polypeptide/neuropeptide Y positive staining significantly decreased. These results suggest that a decrease in ovary activity may lead to autonomic nervous system dysfunction, thereby affecting the secretory activity of the meibomian gland, which participates in sexual hormone imbalance-induced dry eye.
文摘The experiments of the ferrite warm deformation of ultra-low carbon (ULC) Ti-IF steel were carded out on a hot simulator and the influences of deformation temperature, strain, and strain rate on the flow stress were analyzed. New flow stress models suitable to ferrite warm forming of Ti-IF steel were given on the basis of analyzing the influence of deformation technology parameters on the flow stress.
文摘Li-air batteries have received much attention in the past several years because of their large theoretical specific energy density, stable output voltage, cost-effective, energy-efficient and pollution free, and have broad application prospects. If it is successfully developed, the battery could be an excellent energy storage device for renewable energy sources such as wind, solar, and tidal energy, which brings a prospect for human to solve the problem of environment pollution and energy crisis. But the electrolyte is a crucial component of Li-air battery and the electrochemical performance of the battery is determined by electrolyte to a great extent. Due to the react violently between lithium and water, it is not practical for Li-air battery to use directly an aqueous electrolyte unless the anode can be protected from degradation. In this review, we presented the latest research progress on the non-aqueous electrolyte, i.e. organic electrolyte, ionic liquid and solid electrolyte. We elaborated the influence of solvents, and possible additives, and/or their combination Li-air battery’s performance. Finally, we provided insights into the prospect of non-aqueous electrolyte for Li-air battery.
基金supported by the Department of Science and Technology of Jilin Province,China(20210101220JC)the Centrally Guided Local Projects of Linzhi City,China(ZYYD DF2024-04).
文摘The early detection of gastric cancer(GC)is critical for reducing its high mortality rates[1,2].Gastric xanthoma(GX),a lipid-associated lesion in the gastric mucosa,has been identified as a potential precursor to various stomach malignancies[3,4].In this study,we comprehensively profiled the gut microbiota,lipid metabolism,and amino acid metabolism to identify novel biomarkers for the early detection of GX,with potential implications for GC prevention and therapy.By employing 16S rRNA sequencing[5,6],transcriptomics[7],and gene ontology(GO)analysis[8],we revealed significant correlations between gut microbiota composition,dysregulated lipid transport,and aberrant amino acid metabolism in GX.These findings underscore the contribution of lipid metabolic dysfunction[9,10]and gut microbiota alterations[11,12]to the pathogenesis of GX,offering promising strategies for early GC detection and targeted intervention.
基金We thank Dr. Chunlin Qin (Bayler colleage of dentistry, Texas A&M University) for providing us DMP1 antibody. This study was supported by China National Key Research and Development Program (2016YFA0100801 YS), and the National Natural Science Foundation of China (Grant Nos. 8133030 YS and 31620103904 YS), and grants: 2016YFC102705 YS 2014BAI04B07 WZL+1 种基金 81470715 YS TJ1504219036 WZL: 2017BR009 YS.
文摘The blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation. However, detailed molecular players involved in formation of BBB are not completely known. Dentin matrix protein I (DMP1)-proteoglycan (PG), which is known to be involved in mineralization of bones and dentin, is also expressed in soft tissues including brain with unknown functions. In the present study, we reported that DMPI-PG was expressed in brain astrocytes and enriched in BBB units. The only glycosylation site of DMP1 is serine89 (S89) in the N-terminal domain of the protein in mouse. Mutant mice with DMP1 point mutations changing S89 to glycine (S89G), which completely eradicated glycosylation of the protein, demonstrated severe BBB disruption. Another breed of DMP1 mutant mice, which lacked the C-terminal domain of DMP1, manifested normal BBB function. The polarity of S89G-DMP1 astrocytes was disrupted and cell-cell adhesion was loosened. Through a battery of analyses, we found that DMP1 glycosylation was critically required for astrocyte maturation both in vitro and in vivo. S89G-DMP1 mutant astrocytes failed to express aquaporin 4 and had reduced laminin and ZO1 expression, which resulted in disruption of BBB. Interestingly, overexpression of wild-type DMP1-PG in mouse brain driven by the nestin promoter elevated laminin and ZO1 expression beyond wild type levels and could effectively resisted intravenous mannitol-induced BBB reversible opening. Taken together, our study not only revealed a novel element, i.e., DMP1-PG, that reg- ulated BBB formation, but also assigned a new function to DMP1-PG.
基金funded by the National Natural Science Foundation of China(No.81902824)The First Affiliated Hospital of Chongqing Medical University,Chongqing,China.
文摘Nasopharyngeal carcinoma(NPC)is a common malignant carcinoma of the head and neck,and the biological mechanisms underlying the pathogenesis of NPC remain not fully understood.In the present study,we systematically analyzed four independent NPC transcriptomic datasets and focused on identifying the critical molecular networks and novel key hub genes implicated in NPC.We found totally 170 common overlapping differentially expressed genes(DEGs)in the four NPC datasets.GO and KEGG pathway analysis revealed that cell cycle dysregulation is a critical event in NPC.Protein-protein interaction(PPl)network analysis identified a 15 hub-gene corenetwork with overexpressedkinesin family member2C(KIF2C)as a central regulator.Loss-of-function study demonstrated that knockdown of KiF2C significantly inhibited cell growth and cell motility,and delayed cell cycle progression,accompanied with dramatic mitotic defects in spindle formation in NPC cells.RNA-seq analysis revealed that KIF2c knockdown led to deregulation of various downstream genes.KiF2C could also regulate the AKT/mTOR pathways,and enhance paclitaxel sensitivity in NPC cells.Taken together,our results suggest that cell cycle dysregulation is a critical event during NPC pathogenesis and KIF2C is a novel key mitotic hub gene with therapeutic potential in NPC.