The published article titled“MicroRNA-98-5p Inhibits Cell Proliferation and Induces Cell Apoptosis in Hepatocellular Carcinoma via Targeting IGF2BP1”has been retracted from Oncology Research,Vol.25,No.7,2017,pp.1117...The published article titled“MicroRNA-98-5p Inhibits Cell Proliferation and Induces Cell Apoptosis in Hepatocellular Carcinoma via Targeting IGF2BP1”has been retracted from Oncology Research,Vol.25,No.7,2017,pp.1117–1127.展开更多
It is well known that transition metal sulfides(TMS)(i.e.,NiS_(2))undergo electrochemical reconstructions to generate highly active Ni_(3)S_(2) during the process of hydrogen evolution reaction(HER)under overpotential...It is well known that transition metal sulfides(TMS)(i.e.,NiS_(2))undergo electrochemical reconstructions to generate highly active Ni_(3)S_(2) during the process of hydrogen evolution reaction(HER)under overpotentials of<500 mV.However,at higher overpotentials,Ni_(3)S_(2) can theoretically be further restructured into Ni and thus form Ni/Ni_(3)S_(2) heterogeneous interface structures,which may provide opportunities to further enhance HER activity of NiS_(2).Here,we selected NiS_(2) as a model electrocatalyst and investigated the influence of the reconstruction results induced from regular to ultrahigh overpotentials on its electrocatalytic hydrogen precipitation performance.The experimental results showed that the most significant enhancement of hydrogen precipitation performance was obtained for the NiS_(2)@CC-900(900 means 900 mV overpotential)sample after the ultra-high overpotential induced reconstruction.Compared with the initial overpotential of 161 mV(10 mA cm^(-2)),the overpotential of the reconstructed sample reduced by 67 mV(42%).The characterization results showed that an ultra-high overpotential of 900 mV induced deep reconstruction of NiS_(2),formed highly reactive Ni/Ni_(3)S_(2) heterogeneous interfaces,which is more conducive to improved HER performance and match well with theoretical calculations results.We demonstrated ultrahigh overpotential was an effective strategy to induce NiS_(2) deeply reconstruction and significantly improve its HER performance,and this strategy was also applicable to CoS_(2) and FeS_(2).This study provides an extremely simple and universal pathway for the reasonable construction of efficient electrocatalysts by induced TMS deeply reconstruction.展开更多
BACKGROUND The progression of non-alcoholic fatty liver disease(NAFLD)to non-alcoholic steatohepatitis(NASH)and liver fibrosis remains poorly understood,though liver sinusoidal endothelial cells(LSECs)are thought to p...BACKGROUND The progression of non-alcoholic fatty liver disease(NAFLD)to non-alcoholic steatohepatitis(NASH)and liver fibrosis remains poorly understood,though liver sinusoidal endothelial cells(LSECs)are thought to play a central role in disease pathogenesis.AIM To investigate the role of TSC22D1 in NAFLD fibrosis through its regulation of LSEC dysfunction and macrophage polarization.METHODS We analysed single-cell transcriptomic data(GSE129516)from NASH and normal INTRODUCTION Non-alcoholic fatty liver disease(NAFLD)is a global health issue associated with increasing rates of obesity and metabolic syndrome.NAFLD encompasses a spectrum of conditions,ranging from simple steatosis to more severe manifestations such as non-alcoholic steatohepatitis(NASH),fibrosis,cirrhosis,and hepatocellular carcinoma.Liver fibrosis represents a critical stage in NAFLD progression because of its strong association with impaired liver function,progression to end-stage liver disease,and increased disease-related mortality[1].The pathogenesis of NAFLD is multifactorial and involves complex interactions between genetic predispositions,insulin resistance,dietary factors,and chronic inflammation[2].Liver sinusoidal endothelial cells(LSECs),which are highly specialized endothelial cells lining the hepatic sinusoids,critically contribute to both the pathogenesis and progression of NAFLD[3,4].In NAFLD,LSECs undergo structural alterations such as reduced fenestrations,which impair hepatic microcirculation and hinder the exchange of lipids and other substances,thereby promoting lipid accumulation in hepatocytes[5].Furthermore,dysfunctional LSECs exacerbate hepatic inflammation and fibrogenesis by releasing pro-inflammatory cytokines and fibrogenic mediators,such as transforming growth factor-β(TGF-β).These factors activate hepatic stellate cells(HSCs),resulting in the pathological accumulation of extracellular matrix components[6].LSECs are also highly susceptible to oxidative stress,further aggravating hepatic injury[7,8].Importantly,LSECs influence macrophage polarization by producing chemotactic and immunomodulatory factors,thereby promoting the recruitment and activation of M1-type pro-inflammatory CONCLUSION In conclusion,this study provides a comprehensive understanding of the role of TSC22D1 in the pathogenesis of NAFLD fibrosis.We elucidated the mechanisms through which TSC22D1 drives LSEC microvascularization and EndMT,as well as its role in promoting the secretion of TWEAK,which induces macrophage polarization towards the M1 phenotype.These findings offer novel insights into the pathophysiology of NAFLD,particularly the interplay between endothelial dysfunction,inflammation,and fibrosis.Importantly,our results highlight the potential of TSC22D1 as a therapeutic target for NAFLD.Future research should focus on validating these mechanisms in human clinical cohorts and deve-loping targeted interventions,such as TSC22D1 inhibitors or modulators of the TWEAK/FN14 signalling pathway,to translate these findings into effective treatments for NAFLD progression to fibrosis.展开更多
We theoretically investigate the magnomechanically induced transparency phenomenon,Fano resonance and the slow-fast light effect in the situation where an atomic ensemble is placed inside the hybrid cavity of an optom...We theoretically investigate the magnomechanically induced transparency phenomenon,Fano resonance and the slow-fast light effect in the situation where an atomic ensemble is placed inside the hybrid cavity of an optomagnomechanical system.The system is driven by dual optical and phononic drives.We show double magnomechanically induced transparency in the probe output spectrum by exploiting the phonon-photon coupling strength.Then,we study the effects of the decay rate of the cavity and the atomic ensemble on magnomechanically induced transparency.In addition,we demonstrate that effective detuning of the cavity field frequency changes the transparency window from a symmetrical to an asymmetrical profile,resembling Fano resonances.Further,the fast and slow light effects in the system are explored.We show that the slow light profile is enhanced by adjusting the phonon-photon coupling strength.This result may have potential applications in quantum information processing and communication.展开更多
Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihyd...Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihydroxy-vitamin D [1,25（OH）2D] are mediated through binding to the vitamin D receptor （VDR）. Here, we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation in vitro. Implantation of these VDR knockdown cells into the mammary fat pad （MDA-MB-231）, subcutaneously （PC3） or intra-tibially （both cell lines） in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls. These growth-retarding effects of VDR knockdown occur in the presence and absence of vitamin D and are independent of whether cells were grown in bone or soft tissues. Transcriptome analysis of VDR knockdown and non-target control cell lines demonstrated that loss of the VDR was associated with significant attenuation in the Wnt/0-catenin signaling pathway. In particular, cytoplasmic and nuclear β-catenin protein levels were reduced with a corresponding downregulation of downstream genes such as Axin2, Cyclin D1, interleukin-6 （IL-6）, and IL-8. Stabilization of 0-catenin using the GSK-3β inhibitor BIO partly reversed the growth-retarding effects of VDR knockdown. Our results indicate that the unliganded VDR possesses hitherto unknown functions to promote breast and prostate cancer growth, which appear to be operational not only within but also outside the bone environment. These novel functions contrast with the known anti-proliferative nuclear actions of the liganded VDR and may represent targets for new diagnostic and therapeutic approaches in breast and prostate cancer.展开更多
The mortality of cancer patients has considerably improved due to progress in surgery, chemotherapy and radiotherapy. However, some types of cancers, such as melanoma, remain refractory to conventional strategies. Alt...The mortality of cancer patients has considerably improved due to progress in surgery, chemotherapy and radiotherapy. However, some types of cancers, such as melanoma, remain refractory to conventional strategies. Although melanoma accounts for only 4% of all dermatological malignancies, it is responsible for 80% of mortalities from skin tumors[11. The reported survival rate of melanoma over 5 years is not yet encouraging due to its chemo-resistance and rapid metastasis. Therefore, it is necessary to develop new drugs with potent activity and weak side-effect against melanoma.展开更多
Dear Editor,Cognitive impairment is a hallmark of neurodegenerative disorders such as Alzheimer’s disease（AD）and Parkinson’s disease.Growing evidence has demonstrated that cognitive impairment is closely associate...Dear Editor,Cognitive impairment is a hallmark of neurodegenerative disorders such as Alzheimer’s disease（AD）and Parkinson’s disease.Growing evidence has demonstrated that cognitive impairment is closely associated with insulin resistance.展开更多
Toll-like receptor （TLR）-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR si...Toll-like receptor （TLR）-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR signaling. Human primary osteoblasts were cultured in collagen gels. Pam3CSK4 （P3C） and Escherichia coli lipopolysaccharide （EcLPS） were used as TLR2 and TLR4 ligand respectively. Porphyromonas gingivalis LPS having TLR2 activity with either TLR4 agonism （Pg1690） or TLR4 antagonism （Pg1449） and mutant E. coli LPS （LPxE/LPxF/WSK） were used. IL-lp, SH2-containing inositol phosphatase-1 （SHIP1） that has regulatory roles in osteogenesis, alkaline phosphatase and mineralization were analyzed. 3α-Aminocholestane （3AC） was used to inhibit SHIP1. Our results suggest that osteoblasts stimulated by P3C, poorly induced IL-1β but strongly upregulated SHIP1 and enhanced osteogenic mediators. On the contrary, EcLPS significantly induced IL-1β and osteogenic mediators were not induced. While Pg1690 downmodulated osteogenic mediators, Pg1449 enhanced osteogenic responses, suggesting that TLR4 signaling annuls osteogenesis even with TLR2 activity. Interestingly, mutant E. coli LPS that induces weak inflammation upregulated osteogenesis, but SHIP1 was not induced. Moreover, inhibiting SHIP1 significantly upregulated TLR2-mediated inflammatory response and downmodulated osteogenesis. In conclusion, these results suggest that induction of weak inflammatory response through TLR2 （with SHIP1 activity） and mutant TLR4 ligands could enhance osteogenesis.展开更多
Present study deals with the straight impact of hypobaric hypoxia on the quantity and composition of some predominant fecal microflora and its functional aspects. For that, isolated fecal contents of rat were exposed ...Present study deals with the straight impact of hypobaric hypoxia on the quantity and composition of some predominant fecal microflora and its functional aspects. For that, isolated fecal contents of rat were exposed to two different simulated air pressures （70 kPa and 40 kPa） for different time durations （1, 3, and 5 h） and the bacterial community composition was compared with normobaric groups （101.3 kPa）. It was found that the total anaerobes, Escherichio coli, Enterbocters spp., Bi^idobocterium spp., CIostridium spp. were increased whereas total aerobes were decreased at both hypobaric treatments. The increased number of amplicon was detected in the pressure-treated groups than the control that clearly mentioned the disruption of microbiota structure at different simulated hypobaric-hypoxia. The amylase, protease, tannase, 13-glucuronidase, and alkaline phosphatase activities were increased at these atmospheric pressures. Thus, the present investigation demonstrates that the hypobaric hypoxia is an important environmental factor which can strongly modulate the composition of intestinal flora as well as microfiora-derived functional aspects.展开更多
Microtubules are involved in a variety of cellular functions such as cell division, intracellular transport, maintenance of cell polarity and flagella and ciliary motility. The heterogeneity of tubulin and microtubule...Microtubules are involved in a variety of cellular functions such as cell division, intracellular transport, maintenance of cell polarity and flagella and ciliary motility. The heterogeneity of tubulin and microtubule-associated proteins is responsible for these different microtubule functions. Many studies have confirmed that the structure and function of the different α-tubulin and β-tubulin subunits can affect the microtubule. The sperm axoneme microtubule has linear fiber filaments which are polymerized by heterodimeric a and β-tubulin, each with a molecular mass of approximately 50 kD[1].展开更多
Trichloroethylene （TCE） is a major pollutant that affects both occupational and general environments. The liver is an important target organ of TCEE. Substantial efforts and remarkable progress into understanding TC...Trichloroethylene （TCE） is a major pollutant that affects both occupational and general environments. The liver is an important target organ of TCEE. Substantial efforts and remarkable progress into understanding TCE cytotoxicity have been made in cultured liver cells. However, the molecular mechanisms by which TCE induces hepatotoxicity are not well understood. SET （also known as protein phosphatase 2A inhibitor, 12PP2A, or template-activating factor-I, TAF-D is a nuclear protein that regulates histone modification, gene transcription, DNA replication, nucleosome assembly,展开更多
Perfluorooctane sulfonate （PFOS） is a class of stable organic compounds with wide industrial,commercial, and consumer applications, such as in textiles, paper, pesticides, and shampoos;. It is readily absorbed, but ...Perfluorooctane sulfonate （PFOS） is a class of stable organic compounds with wide industrial,commercial, and consumer applications, such as in textiles, paper, pesticides, and shampoos;. It is readily absorbed, but poorly eliminated, with the elimination half-life of approximately 5 years;.Hence, there have been concerns regarding its potential damage to human health. Some studies展开更多
To evaluate the long-term consequence of repetitive mild traumatic brain injury （mTBI） on bone, mTBI was induced in 10-week-old female C57BL/6J mice using a weight drop model, once per day for 4 consecutive days at ...To evaluate the long-term consequence of repetitive mild traumatic brain injury （mTBI） on bone, mTBI was induced in 10-week-old female C57BL/6J mice using a weight drop model, once per day for 4 consecutive days at different drop heights （0.5, 1 and 1.5 m） and the skeletal phenotype was evaluated at different time points after the impact. In vivo micro-CT （μ-CT） analysis of the tibial metaphysis at 2, 8 and 12 weeks after the impact revealed a 5%-32% reduction in trabecular bone mass. Histomorphometric analyses showed a reduced bone formation rate in the secondary spongiosa ofl.5 m impacted mice at 12 weeks post impact. Apparent modulus （bone strength）, was reduced by 30% （P 〈 0.05） at the proximal tibial metaphysis in the 1.5 m drop height group at 2 and 8 weeks post impact. Ex vivo μ-CT analysis of the fifth lumbar vertebra revealed a significant reduction in trabecular bone mass at 12 weeks of age in all three drop height groups. Serum levels of osteocalcin were decreased by 22%, 15%, and 19% in the 0.5, 1.0 and 1.5 m drop height groups, respectively, at 2 weeks post impact. Serum IGF-I levels were reduced by 18%-32% in mTBI mice compared to control mice at 2 weeks post impact. Serum osteocalcin and IGF-I levels correlated with trabecular BV/TV （r2 = 0.14 and 0.16, P 〈 0.05）. In conclusion, repetitive mTBI exerts significant negative effects on the trabecular bone microarchitecture and bone mechanical properties by influencing osteoblast function via reduced endocrine IGF-I actions.展开更多
We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcri...We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase Ⅱ. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase Ⅱ and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.展开更多
CRISPR-Cas system has been widely adapted as a platform for genome editing in various eukaryotic organisms, including zebrafish（Cong et al., 2013; Hwang et al., 2013）. One of the important applications of CRISPR-Cas...CRISPR-Cas system has been widely adapted as a platform for genome editing in various eukaryotic organisms, including zebrafish（Cong et al., 2013; Hwang et al., 2013）. One of the important applications of CRISPR-Cas9 system is to produce double-strand DNA breaks（DSBs） at targeted sites with guide RNA（gRNA）.展开更多
Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer’s disease （AD）. Exposure to lead during the critical phase of brain development has been linked with mental retardatio...Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer’s disease （AD）. Exposure to lead during the critical phase of brain development has been linked with mental retardation and hypophrenia in later life.展开更多
Modern technology has witnessed milestone achievements in the telecommunication industry.However,the widespread application of telecommunication technology is believed to heighten electromagnetic field(EMF)‘pollution...Modern technology has witnessed milestone achievements in the telecommunication industry.However,the widespread application of telecommunication technology is believed to heighten electromagnetic field(EMF)‘pollution’in our environment[1]and subject living organisms to various sources of electromagnetic emissions.These emissions include;microwaves.展开更多
Traumatic cerebral or spinal cord injury induced by military,traffic,and sports accidents,falls or environmental and anthropogenic catastrophes are among main causes of people mortality and disability,especially in yo...Traumatic cerebral or spinal cord injury induced by military,traffic,and sports accidents,falls or environmental and anthropogenic catastrophes are among main causes of people mortality and disability,especially in young and middle age men（Kobeissy,2015）.Axon transection,or axotomy,occurs in wounds and during surgery.展开更多
In the process of oxidative phosphorylation, protons are pumped into the intermembrane space to establish the mitochondrial membrane potential (MMP). Relying on the electrochemical gradient, protons can return to the ...In the process of oxidative phosphorylation, protons are pumped into the intermembrane space to establish the mitochondrial membrane potential (MMP). Relying on the electrochemical gradient, protons can return to the matrix through the ATP synthase complex with ATP generation. MitoQ, a lipophilic cation drug, can be bsorbed to the inner mitochondrial membrane with the cationic moiety staying at the intermembrane space[1].展开更多
The effects of chitosan treatment and inoculation on dry rot in tubers and slices of potato were studied. The results showed that chitosan treatment significantly reduced the lesion diameter of potato inoculated with ...The effects of chitosan treatment and inoculation on dry rot in tubers and slices of potato were studied. The results showed that chitosan treatment significantly reduced the lesion diameter of potato inoculated with Fusarium sulphureum. The treatment at 0.25% showed the best effect. Chitosan at 0.25% increased the activities of peroxidase and polyphenoloxidase, and the contents of flavonoid compounds and lignin in tissues. Increased activities of 13-1,3-glucanase, and phenylalanine ammonialyase were observed, but there were no significant differences between the treated and the control. These findings suggested that the effects of chitosan could be associated with the induced resistance against Fusarium dry rot in potato.展开更多
文摘The published article titled“MicroRNA-98-5p Inhibits Cell Proliferation and Induces Cell Apoptosis in Hepatocellular Carcinoma via Targeting IGF2BP1”has been retracted from Oncology Research,Vol.25,No.7,2017,pp.1117–1127.
文摘It is well known that transition metal sulfides(TMS)(i.e.,NiS_(2))undergo electrochemical reconstructions to generate highly active Ni_(3)S_(2) during the process of hydrogen evolution reaction(HER)under overpotentials of<500 mV.However,at higher overpotentials,Ni_(3)S_(2) can theoretically be further restructured into Ni and thus form Ni/Ni_(3)S_(2) heterogeneous interface structures,which may provide opportunities to further enhance HER activity of NiS_(2).Here,we selected NiS_(2) as a model electrocatalyst and investigated the influence of the reconstruction results induced from regular to ultrahigh overpotentials on its electrocatalytic hydrogen precipitation performance.The experimental results showed that the most significant enhancement of hydrogen precipitation performance was obtained for the NiS_(2)@CC-900(900 means 900 mV overpotential)sample after the ultra-high overpotential induced reconstruction.Compared with the initial overpotential of 161 mV(10 mA cm^(-2)),the overpotential of the reconstructed sample reduced by 67 mV(42%).The characterization results showed that an ultra-high overpotential of 900 mV induced deep reconstruction of NiS_(2),formed highly reactive Ni/Ni_(3)S_(2) heterogeneous interfaces,which is more conducive to improved HER performance and match well with theoretical calculations results.We demonstrated ultrahigh overpotential was an effective strategy to induce NiS_(2) deeply reconstruction and significantly improve its HER performance,and this strategy was also applicable to CoS_(2) and FeS_(2).This study provides an extremely simple and universal pathway for the reasonable construction of efficient electrocatalysts by induced TMS deeply reconstruction.
基金Supported by the Changzhou Science and Techology Program,No.CJ20241048Changzhou High-Level Medical Talents Training Project,No.2022CZBJ105+1 种基金Development Foundation of the Affiliated Hospital of Xuzhou Medical University,No.XYFC202304 and No.XYFM202307The Open Project of Jiangsu Provincial Key Laboratory of Laboratory Medicine,No.JSKLM-Z-2024-002.
文摘BACKGROUND The progression of non-alcoholic fatty liver disease(NAFLD)to non-alcoholic steatohepatitis(NASH)and liver fibrosis remains poorly understood,though liver sinusoidal endothelial cells(LSECs)are thought to play a central role in disease pathogenesis.AIM To investigate the role of TSC22D1 in NAFLD fibrosis through its regulation of LSEC dysfunction and macrophage polarization.METHODS We analysed single-cell transcriptomic data(GSE129516)from NASH and normal INTRODUCTION Non-alcoholic fatty liver disease(NAFLD)is a global health issue associated with increasing rates of obesity and metabolic syndrome.NAFLD encompasses a spectrum of conditions,ranging from simple steatosis to more severe manifestations such as non-alcoholic steatohepatitis(NASH),fibrosis,cirrhosis,and hepatocellular carcinoma.Liver fibrosis represents a critical stage in NAFLD progression because of its strong association with impaired liver function,progression to end-stage liver disease,and increased disease-related mortality[1].The pathogenesis of NAFLD is multifactorial and involves complex interactions between genetic predispositions,insulin resistance,dietary factors,and chronic inflammation[2].Liver sinusoidal endothelial cells(LSECs),which are highly specialized endothelial cells lining the hepatic sinusoids,critically contribute to both the pathogenesis and progression of NAFLD[3,4].In NAFLD,LSECs undergo structural alterations such as reduced fenestrations,which impair hepatic microcirculation and hinder the exchange of lipids and other substances,thereby promoting lipid accumulation in hepatocytes[5].Furthermore,dysfunctional LSECs exacerbate hepatic inflammation and fibrogenesis by releasing pro-inflammatory cytokines and fibrogenic mediators,such as transforming growth factor-β(TGF-β).These factors activate hepatic stellate cells(HSCs),resulting in the pathological accumulation of extracellular matrix components[6].LSECs are also highly susceptible to oxidative stress,further aggravating hepatic injury[7,8].Importantly,LSECs influence macrophage polarization by producing chemotactic and immunomodulatory factors,thereby promoting the recruitment and activation of M1-type pro-inflammatory CONCLUSION In conclusion,this study provides a comprehensive understanding of the role of TSC22D1 in the pathogenesis of NAFLD fibrosis.We elucidated the mechanisms through which TSC22D1 drives LSEC microvascularization and EndMT,as well as its role in promoting the secretion of TWEAK,which induces macrophage polarization towards the M1 phenotype.These findings offer novel insights into the pathophysiology of NAFLD,particularly the interplay between endothelial dysfunction,inflammation,and fibrosis.Importantly,our results highlight the potential of TSC22D1 as a therapeutic target for NAFLD.Future research should focus on validating these mechanisms in human clinical cohorts and deve-loping targeted interventions,such as TSC22D1 inhibitors or modulators of the TWEAK/FN14 signalling pathway,to translate these findings into effective treatments for NAFLD progression to fibrosis.
基金the financial support of the National Center for Scientific and Technical Research(CNRST)through the‘PhD-Associate Scholarship-PASS’program。
文摘We theoretically investigate the magnomechanically induced transparency phenomenon,Fano resonance and the slow-fast light effect in the situation where an atomic ensemble is placed inside the hybrid cavity of an optomagnomechanical system.The system is driven by dual optical and phononic drives.We show double magnomechanically induced transparency in the probe output spectrum by exploiting the phonon-photon coupling strength.Then,we study the effects of the decay rate of the cavity and the atomic ensemble on magnomechanically induced transparency.In addition,we demonstrate that effective detuning of the cavity field frequency changes the transparency window from a symmetrical to an asymmetrical profile,resembling Fano resonances.Further,the fast and slow light effects in the system are explored.We show that the slow light profile is enhanced by adjusting the phonon-photon coupling strength.This result may have potential applications in quantum information processing and communication.
基金supported by Cancer Institute NSW CDF fellowship (YZ)Cure Cancer Foundation of Australia (YZ)+3 种基金Cancer Council New South Wales (MJS, YZ, HZ, and CRD)Prostate Cancer Foundation of Australia (MJS, YZ, HZ, and CRD)NH and MRC Early Career Fellowship 596870 (YZ)German Research Foundation HO 5109/2-1 and HO 5109/2-2 (KH)
文摘Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihydroxy-vitamin D [1,25（OH）2D] are mediated through binding to the vitamin D receptor （VDR）. Here, we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation in vitro. Implantation of these VDR knockdown cells into the mammary fat pad （MDA-MB-231）, subcutaneously （PC3） or intra-tibially （both cell lines） in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls. These growth-retarding effects of VDR knockdown occur in the presence and absence of vitamin D and are independent of whether cells were grown in bone or soft tissues. Transcriptome analysis of VDR knockdown and non-target control cell lines demonstrated that loss of the VDR was associated with significant attenuation in the Wnt/0-catenin signaling pathway. In particular, cytoplasmic and nuclear β-catenin protein levels were reduced with a corresponding downregulation of downstream genes such as Axin2, Cyclin D1, interleukin-6 （IL-6）, and IL-8. Stabilization of 0-catenin using the GSK-3β inhibitor BIO partly reversed the growth-retarding effects of VDR knockdown. Our results indicate that the unliganded VDR possesses hitherto unknown functions to promote breast and prostate cancer growth, which appear to be operational not only within but also outside the bone environment. These novel functions contrast with the known anti-proliferative nuclear actions of the liganded VDR and may represent targets for new diagnostic and therapeutic approaches in breast and prostate cancer.
基金supported by Natural Science Foundation of Jiangsu Province(BK2011049)Jiangsu"333"Projects in Jiangsu Province(BK201140032)Innovation Fund ofYangzhou University(2012CXJ085)
文摘The mortality of cancer patients has considerably improved due to progress in surgery, chemotherapy and radiotherapy. However, some types of cancers, such as melanoma, remain refractory to conventional strategies. Although melanoma accounts for only 4% of all dermatological malignancies, it is responsible for 80% of mortalities from skin tumors[11. The reported survival rate of melanoma over 5 years is not yet encouraging due to its chemo-resistance and rapid metastasis. Therefore, it is necessary to develop new drugs with potent activity and weak side-effect against melanoma.
基金supported by the National Natural Science Foundation of China (81471037 and 81770841)the "Six Kinds of Talents Summit" of Jiangsu Province, China (SWYY-051)+1 种基金Basic Research Program of Education Department of Jiangsu Province, China (14KJA180006)the Program for New Technology of Clinical Diagnosis and Treatment at Nantong (MS22016024)
文摘Dear Editor,Cognitive impairment is a hallmark of neurodegenerative disorders such as Alzheimer’s disease（AD）and Parkinson’s disease.Growing evidence has demonstrated that cognitive impairment is closely associated with insulin resistance.
基金supported by Elam M. and Georgina E.Hack Memorial Research Funds,Department of Periodontics,University of Washington,Seattle,WA,USAsupported by WVCTSI funds,West Virginia University,Morgantown,WV,USA
文摘Toll-like receptor （TLR）-mediated inflammatory response could negatively affect bone metabolism. In this study, we determined how osteogenesis is regulated during inflammatory responses that are downstream of TLR signaling. Human primary osteoblasts were cultured in collagen gels. Pam3CSK4 （P3C） and Escherichia coli lipopolysaccharide （EcLPS） were used as TLR2 and TLR4 ligand respectively. Porphyromonas gingivalis LPS having TLR2 activity with either TLR4 agonism （Pg1690） or TLR4 antagonism （Pg1449） and mutant E. coli LPS （LPxE/LPxF/WSK） were used. IL-lp, SH2-containing inositol phosphatase-1 （SHIP1） that has regulatory roles in osteogenesis, alkaline phosphatase and mineralization were analyzed. 3α-Aminocholestane （3AC） was used to inhibit SHIP1. Our results suggest that osteoblasts stimulated by P3C, poorly induced IL-1β but strongly upregulated SHIP1 and enhanced osteogenic mediators. On the contrary, EcLPS significantly induced IL-1β and osteogenic mediators were not induced. While Pg1690 downmodulated osteogenic mediators, Pg1449 enhanced osteogenic responses, suggesting that TLR4 signaling annuls osteogenesis even with TLR2 activity. Interestingly, mutant E. coli LPS that induces weak inflammation upregulated osteogenesis, but SHIP1 was not induced. Moreover, inhibiting SHIP1 significantly upregulated TLR2-mediated inflammatory response and downmodulated osteogenesis. In conclusion, these results suggest that induction of weak inflammatory response through TLR2 （with SHIP1 activity） and mutant TLR4 ligands could enhance osteogenesis.
基金Council for Scientific and Industrial Research (CSIR),New Delhi for providing the fellowshipthe Defence Institute of Physiology & Allied Sciences (DIPAS),the Defence Research & Development Organisation (DRDO),Government of India,for their consecutive financial support
文摘Present study deals with the straight impact of hypobaric hypoxia on the quantity and composition of some predominant fecal microflora and its functional aspects. For that, isolated fecal contents of rat were exposed to two different simulated air pressures （70 kPa and 40 kPa） for different time durations （1, 3, and 5 h） and the bacterial community composition was compared with normobaric groups （101.3 kPa）. It was found that the total anaerobes, Escherichio coli, Enterbocters spp., Bi^idobocterium spp., CIostridium spp. were increased whereas total aerobes were decreased at both hypobaric treatments. The increased number of amplicon was detected in the pressure-treated groups than the control that clearly mentioned the disruption of microbiota structure at different simulated hypobaric-hypoxia. The amylase, protease, tannase, 13-glucuronidase, and alkaline phosphatase activities were increased at these atmospheric pressures. Thus, the present investigation demonstrates that the hypobaric hypoxia is an important environmental factor which can strongly modulate the composition of intestinal flora as well as microfiora-derived functional aspects.
基金supported by grants from the National Basic Research Program of China(2010CB834202)The National Natural Science Foundation of China(10835011)the Scientific Technology Research Projects of Gansu Province(0702NKDA045,0806RJYA020)
文摘Microtubules are involved in a variety of cellular functions such as cell division, intracellular transport, maintenance of cell polarity and flagella and ciliary motility. The heterogeneity of tubulin and microtubule-associated proteins is responsible for these different microtubule functions. Many studies have confirmed that the structure and function of the different α-tubulin and β-tubulin subunits can affect the microtubule. The sperm axoneme microtubule has linear fiber filaments which are polymerized by heterodimeric a and β-tubulin, each with a molecular mass of approximately 50 kD[1].
基金supported by NSFC (the National Natural Science Foundation of China) [81273126, 30972454]the Key Project of Guangdong Natural Science Foundation [S2012020010903]+2 种基金the Project of Shenzhen Basic Research Plan [JCYJ20120616 154222545]the Upgrade Scheme of Shenzhen Municipal Key Laboratory [CXB201005260068A]Medical Scientific Research Foundation of Guangdong Province (A2012577)
文摘Trichloroethylene （TCE） is a major pollutant that affects both occupational and general environments. The liver is an important target organ of TCEE. Substantial efforts and remarkable progress into understanding TCE cytotoxicity have been made in cultured liver cells. However, the molecular mechanisms by which TCE induces hepatotoxicity are not well understood. SET （also known as protein phosphatase 2A inhibitor, 12PP2A, or template-activating factor-I, TAF-D is a nuclear protein that regulates histone modification, gene transcription, DNA replication, nucleosome assembly,
基金supported by awards from National Natural Science Foundation of China [No.81703260]the Education Department of Jiangsu Province [No.16KJB330010]+2 种基金the Science and Technology Department of Jiangsu Province [No.BK20160227]the China Postdoctoral Science Foundation funded project [No.2016M601892]the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(PAPD)
文摘Perfluorooctane sulfonate （PFOS） is a class of stable organic compounds with wide industrial,commercial, and consumer applications, such as in textiles, paper, pesticides, and shampoos;. It is readily absorbed, but poorly eliminated, with the elimination half-life of approximately 5 years;.Hence, there have been concerns regarding its potential damage to human health. Some studies
基金supported by funding from a Veterans Administration BLR&D merit review grant 1–101-BX-002717 to Dr Subburaman Mohan
文摘To evaluate the long-term consequence of repetitive mild traumatic brain injury （mTBI） on bone, mTBI was induced in 10-week-old female C57BL/6J mice using a weight drop model, once per day for 4 consecutive days at different drop heights （0.5, 1 and 1.5 m） and the skeletal phenotype was evaluated at different time points after the impact. In vivo micro-CT （μ-CT） analysis of the tibial metaphysis at 2, 8 and 12 weeks after the impact revealed a 5%-32% reduction in trabecular bone mass. Histomorphometric analyses showed a reduced bone formation rate in the secondary spongiosa ofl.5 m impacted mice at 12 weeks post impact. Apparent modulus （bone strength）, was reduced by 30% （P 〈 0.05） at the proximal tibial metaphysis in the 1.5 m drop height group at 2 and 8 weeks post impact. Ex vivo μ-CT analysis of the fifth lumbar vertebra revealed a significant reduction in trabecular bone mass at 12 weeks of age in all three drop height groups. Serum levels of osteocalcin were decreased by 22%, 15%, and 19% in the 0.5, 1.0 and 1.5 m drop height groups, respectively, at 2 weeks post impact. Serum IGF-I levels were reduced by 18%-32% in mTBI mice compared to control mice at 2 weeks post impact. Serum osteocalcin and IGF-I levels correlated with trabecular BV/TV （r2 = 0.14 and 0.16, P 〈 0.05）. In conclusion, repetitive mTBI exerts significant negative effects on the trabecular bone microarchitecture and bone mechanical properties by influencing osteoblast function via reduced endocrine IGF-I actions.
文摘We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase Ⅱ. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase Ⅱ and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.
基金supported by the funding from the Science and Technology Program of Shenzhen (JCYJ20150924110425180 and JCYJ20151030170755264)
文摘CRISPR-Cas system has been widely adapted as a platform for genome editing in various eukaryotic organisms, including zebrafish（Cong et al., 2013; Hwang et al., 2013）. One of the important applications of CRISPR-Cas9 system is to produce double-strand DNA breaks（DSBs） at targeted sites with guide RNA（gRNA）.
基金supported by the National Natural Science Foundation of China(NSFC),No.31201878,81172716,and U1204804Post Doctoral Foundation of China,No.2015M572109Post Doctoral Fund of Henan province,No.2014049
文摘Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer’s disease （AD）. Exposure to lead during the critical phase of brain development has been linked with mental retardation and hypophrenia in later life.
文摘Modern technology has witnessed milestone achievements in the telecommunication industry.However,the widespread application of telecommunication technology is believed to heighten electromagnetic field(EMF)‘pollution’in our environment[1]and subject living organisms to various sources of electromagnetic emissions.These emissions include;microwaves.
基金Supported by the Ministry of Education and Science of Russia grants 6.4951.2017/6.7 and 6.6З24.2017/8.9
文摘Traumatic cerebral or spinal cord injury induced by military,traffic,and sports accidents,falls or environmental and anthropogenic catastrophes are among main causes of people mortality and disability,especially in young and middle age men（Kobeissy,2015）.Axon transection,or axotomy,occurs in wounds and during surgery.
基金Key Program of National Natural Science Foundation of China (U1432248), National Natural Science Foundation of China (11505245), Western Talent Program of Chinese Academy of Sciences (Y460040XB0)
文摘In the process of oxidative phosphorylation, protons are pumped into the intermembrane space to establish the mitochondrial membrane potential (MMP). Relying on the electrochemical gradient, protons can return to the matrix through the ATP synthase complex with ATP generation. MitoQ, a lipophilic cation drug, can be bsorbed to the inner mitochondrial membrane with the cationic moiety staying at the intermembrane space[1].
文摘The effects of chitosan treatment and inoculation on dry rot in tubers and slices of potato were studied. The results showed that chitosan treatment significantly reduced the lesion diameter of potato inoculated with Fusarium sulphureum. The treatment at 0.25% showed the best effect. Chitosan at 0.25% increased the activities of peroxidase and polyphenoloxidase, and the contents of flavonoid compounds and lignin in tissues. Increased activities of 13-1,3-glucanase, and phenylalanine ammonialyase were observed, but there were no significant differences between the treated and the control. These findings suggested that the effects of chitosan could be associated with the induced resistance against Fusarium dry rot in potato.
