Epithelial-mesenchymal transition (EMT) plays an important role in fibrotic diseases. We have previously showed that silica induces EMT in human bronchial epithelial cells (BECs); however, the underlying mechanism...Epithelial-mesenchymal transition (EMT) plays an important role in fibrotic diseases. We have previously showed that silica induces EMT in human bronchial epithelial cells (BECs); however, the underlying mechanism of silica-induced EMT is poorly understood. In the present study, we investigated the role of Snail in silica-induced EMT in human BECs in vitro. Human BECs were treated with silica at various concentrations and incubation times. Then MTr assay, western blot, electrophoretic mobility shift assay (EMSA), and small interfering RNA (siRNA) transfection were performed. We found that silica increased the expression and DNA binding activity of Snail in human BECs. SNAI silica-induced expression siRNA upregulated the siRNA inhibited the of Snail. Moreover, SNAI expression of epithelial marker E-cadherin, but attenuated the expression of mesenchymal marker a-smooth muscle actin and vimentin in silica-stimulated cells. These results suggest that Snail mediates the silica-induced EMT in human BECs.展开更多
Pulp loss is accompanied by the functional impairment of defense,sensory,and nutrition supply.The approach based on endogenous stem cells is a potential strategy for pulp regeneration.However,endogenous stem cell sour...Pulp loss is accompanied by the functional impairment of defense,sensory,and nutrition supply.The approach based on endogenous stem cells is a potential strategy for pulp regeneration.However,endogenous stem cell sources,exogenous regenerative signals,and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells.Therefore,the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration.In in vitro study,we investigated the effects of Wnt3a,transforming growth factor-beta 1,and bone morphogenetic protein 7(BMP7)on human dental pulp stem cells(h-DPSCs)and human umbilical vein endothelial cells.2D and 3D culture systems based on collagen gel,matrigel,and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs.In in vivo study,an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7.We concluded that BMP7promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation.Collagen gel maintained the cell adhesion,cell spreading,and cell viability of h-DPSCs in 2D or 3D culture.The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo.The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.展开更多
Objective:Cancer stem cells(CSCs)have been the focus of several studies because oftheir involvement in cancer initiation and progression.CSCs were identified in 28%to 50%of hepatocellular carcinomas(HCCs).The origin o...Objective:Cancer stem cells(CSCs)have been the focus of several studies because oftheir involvement in cancer initiation and progression.CSCs were identified in 28%to 50%of hepatocellular carcinomas(HCCs).The origin of CSCs is still unclear,but it has been recently suggested that CSCs could originate from the transformation of liver progenitor cells(LPCs)during chronic liver inflammation.展开更多
Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle ce...Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was~25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from~30 kD to~25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.展开更多
The DNA mismatch repair (MMR) system, composed of several proteins such as MLH1, MSH2, MSH6, MSH3,and PMS2, eliminates replication errors and maintains genomic stability. MutS,an MSH2/MSH6 heterodimer,recognizes singl...The DNA mismatch repair (MMR) system, composed of several proteins such as MLH1, MSH2, MSH6, MSH3,and PMS2, eliminates replication errors and maintains genomic stability. MutS,an MSH2/MSH6 heterodimer,recognizes single base mismatches, whereas MutS , an MSH2/MSH3 heterodimer, primarily recognizes 24 bp insertiondeletion loops[1;2].展开更多
Objectives Epidermal growth factor receptor (EGFR)is a receptor protein tyrosine kinase and plays a critical role in the development and function of the heart.Previous studies have demonstrated that EGFR is involved...Objectives Epidermal growth factor receptor (EGFR)is a receptor protein tyrosine kinase and plays a critical role in the development and function of the heart.Previous studies have demonstrated that EGFR is involved in regulating electrical excitability of the heart.The present study was designed to investigate whether EGFR activation would mediate myocardial arrhythmias induced by ischemia/reperfu- sion in anaesthetized rats.Methods and results Myocardial ischemia/reperfusion arrhythmias were induced by 10 min ligation of the left anterior descending coronary artery,followed by a 30 min reperfusion in anaesthetized rats.Incidence and severity of cardiac arrhythmias were significantly reduced by pretreatment with the EGFR kinase inhibitor AG556.Phosphorylation level of myocardial EGFR was increased during ischemia and at early reperfusion.Intramyocardial transfection of EGFR siRNA reduced EGFR mRNA and protein,and decreased the incidence of ventricular fibrillation induced by reperfusion.Interestingly,tyrosine phosphorylation levels of cardiac Na<sup>+</sup> channel(I<sub>Na</sub>) and L-type Ca<sup>2+</sup> channel(I<sub>Ca.l</sub>) were significantly increased at corresponding time points to the alteration of phosphorylated EGFR level during reperfusion.AG556 pretreatment countered the increased tyrosine phosphorylation level of Na<sup>+</sup> and L-type Ca<sup>2+</sup> channels induced by reperfusion.No significant alteration was observed in tyrosine phosphorylation levels of cardiac Kv4.2 and Kir2.1 channels during the cardiac ischemia/reperfusion. Conclusions These results demonstrate for the first time that EGFR plays an important role in the genesis of myocardial ischemia/reperfusion arrhythmias,which is likely mediated at least in part by enhancing tyrosine phosphorylation of cardiac Na<sup>+</sup> and L-type Ca<sup>2+</sup> channels.展开更多
Summary:In this study,we investigated the effects of nucleolin on lipopolysaccharide(LPS)-induced activation of MAPK and NF-KappaB(NF-kB)signaling pathways and secretion of TNF-a,IL-1βand HMGB1 in THP-1 monocytes.Imm...Summary:In this study,we investigated the effects of nucleolin on lipopolysaccharide(LPS)-induced activation of MAPK and NF-KappaB(NF-kB)signaling pathways and secretion of TNF-a,IL-1βand HMGB1 in THP-1 monocytes.Immunofluorescence assay and Western blotting were used to identify the nucleolin expression in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Inactivation of nucleolin was induced by neutralizing antibody against nucleolin.THP-1 monocytes were pretreated with anti-nucleolin antibody for 1 h prior to LPS challenge.The irrelevant IgG group was used as control.Secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1)and activation of MAPK and NF-kB/I-kB signaling pathways were examined to assess the effects of nucleolin on LPS-mediated inflammatory response.Nucleolin existed in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Pretreatment of anti-nucleolin antibody significantly inhibited the LPS-induced secretion of TNF-a,IL-1β and HMGB1.P38,JNK,ERK and NF-κB subunit p65 inhibitors could significantly inhibit the secretion of IL-1β,TNF-a and HMGB1 induced by LPS.Moreover,the phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65)was significantly increased after LPS challenge.In contrast,pretreatment of anti-nucleolin antibody could significantly inhibit the LPS-induced phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).However,the irrelevant IgG,as a negative control,had no effect on LPS-induced secretion of TNF-a and IL-Iβ and phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).We demonstrated that nucleolin mediated the LPS-induced activation of MAPK and NF-κB signaling pathways,and regulated the secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1).展开更多
Although the mechanism of DNA methylationmediated gene silencing is extensively studied, relatively little is known about how promoter methylated genes are protected from transcriptional silencing. SUVH1, an Arabidops...Although the mechanism of DNA methylationmediated gene silencing is extensively studied, relatively little is known about how promoter methylated genes are protected from transcriptional silencing. SUVH1, an Arabidopsis Su(var)3-9 homolog, was previously shown to be required for the expression of a few promoter methylated genes. By chromatin immunoprecipitation combined with sequencing, we demonstrate that SUVH1 binds to methylated genomic loci targeted by RNA-directed DNA methylation. SUVH1 and its homolog SUVH3 function partially redundantly and interact with three DNAJ domain-containing homologs, SDJ1, SDJ2, and SDJ3, thus forming a complex which we named SUVH-SDJ. The SUVH-SDJ complex components are co-localized in a large number of methylated promoters and are required for the expression of a subset of promoter methylated genes. We demonstrate that the SUVHSDJ complex components have transcriptional activation activity. SUVH1 and SUVH3 function synergistically with SDJ1,SDJ2, and SDJ3 and are required for plant viability. This study reveals how the SUVH-SDJ complex protects promoter methylated genes from transcriptional silencing and suggests that the transcriptional activation of promoter methylated genes mediated by the SUVH-SDJ complex may play a critical role in plant growth and development.展开更多
Plants are capable of coordination of their growth and development with ambient temperatures.EARLY FLOWERING3(ELF3), an essential component of the plant circadian clock, is also involved in ambient temperature sensing...Plants are capable of coordination of their growth and development with ambient temperatures.EARLY FLOWERING3(ELF3), an essential component of the plant circadian clock, is also involved in ambient temperature sensing, as well as in inhibiting the expression and protein activity of the thermoresponsive regulator phytochrome interacting factor4(PIF4). The ELF3 activity is subjected to attenuation in response to warm temperature;however,how the protein level of ELF3 is regulated at warm temperature remains less understood. Here, we report that the E3 ligase XB3 ORTHOLOG 5 IN ARABIDOPSIS THALIANA, XBAT35, mediates ELF3 degradation. XBAT35 interacts with ELF3 and ubiquitinates ELF3. Loss-of-function mutation of XBAT35 increases the protein level of ELF3 and confers a short-hypocotyl phenotype under warm temperature conditions. Thus, our findings establish that XBAT35 mediates ELF3 degradation to lift the inhibition of ELF3 on PIF4 for promoting thermoresponsive hypocotyl growth in plants.展开更多
Dear Editor, mTORCI, as a center regulatory hub of metabolism, senses the cellular energy status, nutrition and extracellular stimuli and regulates cell growth, differentiation and functions of immune cells (Powell et...Dear Editor, mTORCI, as a center regulatory hub of metabolism, senses the cellular energy status, nutrition and extracellular stimuli and regulates cell growth, differentiation and functions of immune cells (Powell et al., 2012). Lysosomal localization of key signal comp orients is critical for mTORCI activati on: mTORCI activation requires co-localization of activated Rheb and mTORCI to the lysosome membrane (Buerger et al., 2006). Signals in eluding growth factors, cellular stresses and energy levels act on the disruption the formation of tuberous sclerosis complex (TSC) complex, comprised of TSC1, TSC2 and TBC1D7, which leads to the translocation and activation of Rheb on the lysosome membrane (Dibble et al., 2012). In response to nutrient levels, specifically the availability of amino acids and glucose (Efeyan et al., 2013), mTORCI is recruited to the lysosomal surface by Rag GTPases that are heterodimers of RagA or RagC bound to RagB or RagD. Multiple protein complexes have been implicated in regulation of mTORCI upon nutrient sensing including Ragulator, GATOR1, GATOR2, KICSTOR and vacuolar ATPases (Wolfson et al., 2017). Vacuolar ATPases are large multiple-protein complexes that acidify the lysosome and may mediate additional functions independent of their proton pump activity (Nishi and Forgac, 2002).展开更多
Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment o...Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.展开更多
Photoelectrochemical (PEC) small-molecule oxidation can selectively transform substrates into high-value-added fine chemicals and increase the rate of cathode hydrogen evolution. Nevertheless, achieving high-selectivi...Photoelectrochemical (PEC) small-molecule oxidation can selectively transform substrates into high-value-added fine chemicals and increase the rate of cathode hydrogen evolution. Nevertheless, achieving high-selectivity PEC oxidation of small molecules to produce specific products is a very challenging task. In general, selectivity can be improved by changing the surface catalyticsites of the photoanode and modulating the interfacial environments of the reactions. Herein, recent advances in approaches to improving selective PEC oxidation of small molecules are introduced. We first briefly discuss the basic concept and fundamentals of small-molecule PEC oxidation. The reported approaches to improving the performance of selective PEC oxidation of small molecules are highlighted from two aspects: (1) changing the surface properties of photoanodes by selecting suitable materials or modifying the photoanodes and (2) mediating the oxidation reactions using redox mediators. The PEC oxidation mechanism of these studies is emphasized. We also discuss the challenges in this research direction and offer a perspective on the further development of selective PEC-based small-molecule transformation.展开更多
Hydrogen gas is widely regarded as an ideal green energy carrier and a potential alternative to fossil fuels for coping with the aggravating energy crisis and environmental pollution.Currently,the vast majority of the...Hydrogen gas is widely regarded as an ideal green energy carrier and a potential alternative to fossil fuels for coping with the aggravating energy crisis and environmental pollution.Currently,the vast majority of the world's hydrogen is produced by reforming fossil fuels;however,this hydrogen-making technology is not sustainable or environmentally friendly because ofits high energy consumption and large carbon emissions.Renewables-driven water splitting(2H_(2)0-2H_(2)+0_(2))becomes an extensively studied scheme for sustain-able hydrogen production.Conventional water electrolysis requires an input voltage higher than 1.23 V and forms a gas mixture of H_(2)/O_(2),which results in high electricity consumption,potential safety hazards,and harmful reactive oxygen species.By virtue of the auxiliary redox mediators(RMs)as the robust H^(+)/e^(-)reservoir,decoupled electrolysis splits water at a much lower potential and evolves O_(2)(H_(2)O+RMS_(ox)-O_(2)+H-RMS_(red))and H_(2)(H-RMS_(red)-H_(2)+RMS_(ox))at separate times,rates,and spaces,thus pro-ducing the puretarget hydrogen gas safely.Decoupled electrolysis has accelerated the development ofwater electrolysis technology for H_(2) production.However,itis still lack of a comprehensive and in-depth review in this field based on different types of RMs.This review highlights the basic principles and critical progress of this emerging water electrolysis mode over the past decade.Several representative examples are then dis-played in detail according to the differences in the RMs.The rational choice and design of RMs have also been emphasized.Subsequently,novel applications of decoupled water splitting are briefly discussed,including the manufacture of valuable chemicals,Cl_(2) production,pollutant degradation,and other half-reactions in artificial photosynthesis.Finally,thekey characteristics and disadvantages of each type of mediator are sum-marized in depth.In addition,we present an outlook for future directions in decoupled water splitting.Thus,the flexibility in the design of mediators provides huge space for improving this electrochemical technology.@2024 Science Press and Dalian Institute of Chemical Physics,Chinese Academy of Sciences.Published by ELSEVIER B.V.and Science Press.All rights reserved.展开更多
Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we r...Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we report a multiple redox-mediated linear paired electrolysis system,combining the hydrogen peroxide mediated cathode process with the I2 mediated anode process,and realize the conversion of furfural to furoic acid in both side of the dividedflow cell simultaneously.By reasonably controlling the cathode potential,the undesired water splitting reaction and furfural reduction side reactions are avoided.Under the galvanostatic electrolysis,the two-mediated electrode processes have good compatibility,which reduce the energy consumption by about 22%while improving the electronic efficiency by about 125%.This system provides a green electrochemical synthesis route with commercial prospects.展开更多
Ammonia serves as a crucial chemical raw material and hydrogen energy carrier.Aqueous electrocatalytic nitrogen reduction reaction(NRR),powered by renewable energy,has attracted tremendous interest during the past few...Ammonia serves as a crucial chemical raw material and hydrogen energy carrier.Aqueous electrocatalytic nitrogen reduction reaction(NRR),powered by renewable energy,has attracted tremendous interest during the past few years.Although some achievements have been revealed in aqueous NRR,significant challenges have also been identified.The activity and selectivity are fundamentally limited by nitrogen activation and competitive hydrogen evolution.This review focuses on the hurdles of nitrogen activation and delves into complementary strategies,including materials design and system optimization(reactor,electrolyte,and mediator).Then,it introduces advanced interdisciplinary technologies that have recently emerged for nitrogen activation using high-energy physics such as plasma and triboelectrification.With a better understanding of the corresponding reaction mechanisms in the coming years,these technologies have the potential to be extended in further applications.This review provides further insight into the reaction mechanisms of selectivity and stability of different reaction systems.We then recommend a rigorous and detailed protocol for investigating NRR performance and also highlight several potential research directions in this exciting field,coupling with advanced interdisciplinary applications,in situ/operando characterizations,and theoretical calculations.展开更多
The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant...The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.展开更多
Smart cities are a way for China to construct an innovative and environmentally conscious nation.The paper examines the impact of smart cities on corporate green governance and provides a theoretical foundation for fo...Smart cities are a way for China to construct an innovative and environmentally conscious nation.The paper examines the impact of smart cities on corporate green governance and provides a theoretical foundation for formulating and executing smart city policy in China.Based on panel data from Chinese A-share listed companies in Shanghai and Shenzhen from 2008 to 2020,this study constructs a multiperiod double-difference model to examine the influence of smart cities on corporate green governance.Additionally,it uses a spatial double-difference model to investigate the spatial spillover effect of smart cities on neighboring areas.The findings indicate that smart cities effectively enhance corporate green governance.Analyzing the influencing mechanisms reveals that resource allocation efficiency,technological innovation,management environmental awareness,and regional environmental enforcement efforts act as mediators.Furthermore,the study reveals that the impact of smart cities on promoting corporate green governance is more pronounced in regions with lower levels of marketization and resource-based cities.Moreover,the research explores the spatial spillover effects of smart cities,with an effective radius of approximately 350 km.The optimal spatial correlation zone for green governance of businesses in neighboring areas in relation to smart cities is within a range of 250-350 km.This is manifested by the significant promotion of green governance in neighboring area businesses facilitated by smart cities.展开更多
Background Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry.Multi-omics approaches enable the comprehensive investigation of the complex interactions between ...Background Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry.Multi-omics approaches enable the comprehensive investigation of the complex interactions between mul-tiple layers of information to provide a more holistic view of disease pathogenesis.Therefore,this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data(mRNA and lncRNA),small RNA sequencing data(miRNA)and DNA methylation sequencing data of milk somatic cells from 10 healthy cows and 20 cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus chromogenes.Results Functional investigation of the data sets through gene set analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis,provided further insights into subclin-ical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical mastitis.The abundant genomic and epigenomic signatures with sig-nificant alterations related to subclinical mastitis were observed,including 30,846,2552,1276 and 57 differential methylation haplotype blocks(dMHBs),differentially expressed genes(DEGs),lncRNAs(DELs)and miRNAs(DEMs),respectively.Next,5 factors presenting the principal variation of differential multi-omics signatures were identified.The important roles of Factor 1(DEG,DEM and DEL)and Factor 2(dMHB and DEM),in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed.Each of the omics within Factors 1 and 2 explained about 20%of the source of variation in subclinical mastitis.Also,networks of impor-tant functional gene sets with the involvement of multi-omics signatures were demonstrated,which contributed to a comprehensive view of the possible regulatory mechanisms underlying subclinical mastitis.Furthermore,multi-omics integration enabled the association of the epigenomic regulatory factors(dMHBs,DELs and DEMs)of altered genes in important pathways,such as‘Staphylococcus aureus infection pathway’and‘natural killer cell mediated cyto-toxicity pathway’,etc.,which provides further insights into mastitis regulatory mechanisms.Moreover,few multi-omics signatures(14 dMHBs,25 DEGs,18 DELs and 5 DEMs)were identified as candidate discriminant signatures with capac-ity of distinguishing subclinical mastitis cows from healthy cows.Conclusion The integration of genomic and epigenomic data by multi-omics approaches in this study provided a better understanding of the molecular mechanisms underlying subclinical mastitis and identified multi-omics candidate discriminant signatures for subclinical mastitis,which may ultimately lead to the development of more effective mastitis control and management strategies.展开更多
Objective:The importance of good sleep for energy recovery and overall physical and mental health cannot be overstated.However,the increasing competitiveness of society,diversifying lifestyles,and the rapid spread of ...Objective:The importance of good sleep for energy recovery and overall physical and mental health cannot be overstated.However,the increasing competitiveness of society,diversifying lifestyles,and the rapid spread of the internet and electronic devices have significantly impacted people’s sleep patterns,particularly through bedtime procrastination.Therefore,this study aims to investigate the relationship and underlying mechanisms between sleep determination,anxiety,and bedtime procrastination among the Chinese population.Method:The study utilized data from a national survey—the China Residents’Sleep Condition Survey(November 2021,with 6,037 participants).By constructing mediation and moderation models,it analyzed the relationship and mechanisms between sleep determination and bedtime procrastination,highlighting the dual role of anxiety:as a mediator between sleep determination and bedtime procrastination,and as a moderator of their relationship.Results:There was a negative correlation between sleep determination and bedtime procrastination;anxiety was related to an increase in bedtime procrastination behaviors;In the interplay between sleep determination and pre-bedtime procrastination,the regulatory effect of anxiety is found to be more pronounced than its intermediary role,with anxiety significantly diminishing the inverse relationship between sleep determination and procrastination before bedtime.Conclusion:Bedtime procrastination can lead to sleep issues,thus reducing sleep quality.Enhancing sleep determination or alleviating pre-sleep anxiety can help inhibit bedtime procrastination behaviors.Intervening and reducing bedtime procrastination is one of the effective measures to improve sleep quality.展开更多
BACKGROUND Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis(MHD)that significantly affect their quality of life(QOL).High levels of social support can signif...BACKGROUND Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis(MHD)that significantly affect their quality of life(QOL).High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD.Currently,there is limited research on how social support mediates the relationship between dysphoria,despondency,and overall QOL in patients undergoing MHD.It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD,ultimately enhancing their overall QOL.AIM To investigate the mediating role of social support in relationships between dysphoria,despondency,and QOL among patients undergoing MHD.METHODS Participants comprised 289 patients undergoing MHD,who were selected using a random sampling approach.The Social Support Rating Scale,Self-Rating Anxiety Scale,Self-Rating Depression Scale,and QOL Scale were administered.Correlation analysis was performed to examine the associations between social support,dysphoria,despondency,and QOL in patients undergoing MHD.To assess the mediating impact of social support on dysphoria,despondency,and QOL in patients undergoing MHD,a bootstrap method was applied.RESULTS Significant correlations among social support,dysphoria,despondency,and quality in patients undergoing MHD were observed(all P<0.01).Dysphoria and despondency negatively correlated with social support and QOL(P<0.01).Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD(P<0.05).The direct effect of dysphoria on QOL was statistically significant(P<0.05).Social support mediated the relationship between dysphoria and QOL,and this mediating effect was significant(P<0.05).Similarly,the direct effect of despondency on QOL was significant(P<0.05).Moreover,social support played a mediating role between despondency and QOL,with a significant mediating effect(P<0.05).CONCLUSION These findings suggest that social support plays a significant mediating role in the relationship between dysphoria,despondency,and QOL in patients undergoing MHD.展开更多
基金supported by the National Natural Science Foundation of China(No.30700661,81170023,81470266)China Postdoctoral Science Foundation(2014M562139)Hunan Province Natural Science Foundation(14JJ2041)
文摘Epithelial-mesenchymal transition (EMT) plays an important role in fibrotic diseases. We have previously showed that silica induces EMT in human bronchial epithelial cells (BECs); however, the underlying mechanism of silica-induced EMT is poorly understood. In the present study, we investigated the role of Snail in silica-induced EMT in human BECs in vitro. Human BECs were treated with silica at various concentrations and incubation times. Then MTr assay, western blot, electrophoretic mobility shift assay (EMSA), and small interfering RNA (siRNA) transfection were performed. We found that silica increased the expression and DNA binding activity of Snail in human BECs. SNAI silica-induced expression siRNA upregulated the siRNA inhibited the of Snail. Moreover, SNAI expression of epithelial marker E-cadherin, but attenuated the expression of mesenchymal marker a-smooth muscle actin and vimentin in silica-stimulated cells. These results suggest that Snail mediates the silica-induced EMT in human BECs.
基金supported by grants from the National Key Research and Development Program of China(2021YFA1100603)the Nature Science Foundation of China(82071092)+2 种基金the Fundamental Research Funds for the Central Universities(YJ201878)Key Project of Sichuan province(2019YFS0311,2019YFS0515)Technology Innovation Research and Development Project of Chengdu(2019-YF05-00705-SN)。
文摘Pulp loss is accompanied by the functional impairment of defense,sensory,and nutrition supply.The approach based on endogenous stem cells is a potential strategy for pulp regeneration.However,endogenous stem cell sources,exogenous regenerative signals,and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells.Therefore,the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration.In in vitro study,we investigated the effects of Wnt3a,transforming growth factor-beta 1,and bone morphogenetic protein 7(BMP7)on human dental pulp stem cells(h-DPSCs)and human umbilical vein endothelial cells.2D and 3D culture systems based on collagen gel,matrigel,and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs.In in vivo study,an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7.We concluded that BMP7promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation.Collagen gel maintained the cell adhesion,cell spreading,and cell viability of h-DPSCs in 2D or 3D culture.The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo.The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.
文摘Objective:Cancer stem cells(CSCs)have been the focus of several studies because oftheir involvement in cancer initiation and progression.CSCs were identified in 28%to 50%of hepatocellular carcinomas(HCCs).The origin of CSCs is still unclear,but it has been recently suggested that CSCs could originate from the transformation of liver progenitor cells(LPCs)during chronic liver inflammation.
文摘Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was~25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from~30 kD to~25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.
基金Key Program of National Natural Science Foundation of China (U1432248), National Natural Science Foundation of China (11305226
文摘The DNA mismatch repair (MMR) system, composed of several proteins such as MLH1, MSH2, MSH6, MSH3,and PMS2, eliminates replication errors and maintains genomic stability. MutS,an MSH2/MSH6 heterodimer,recognizes single base mismatches, whereas MutS , an MSH2/MSH3 heterodimer, primarily recognizes 24 bp insertiondeletion loops[1;2].
文摘Objectives Epidermal growth factor receptor (EGFR)is a receptor protein tyrosine kinase and plays a critical role in the development and function of the heart.Previous studies have demonstrated that EGFR is involved in regulating electrical excitability of the heart.The present study was designed to investigate whether EGFR activation would mediate myocardial arrhythmias induced by ischemia/reperfu- sion in anaesthetized rats.Methods and results Myocardial ischemia/reperfusion arrhythmias were induced by 10 min ligation of the left anterior descending coronary artery,followed by a 30 min reperfusion in anaesthetized rats.Incidence and severity of cardiac arrhythmias were significantly reduced by pretreatment with the EGFR kinase inhibitor AG556.Phosphorylation level of myocardial EGFR was increased during ischemia and at early reperfusion.Intramyocardial transfection of EGFR siRNA reduced EGFR mRNA and protein,and decreased the incidence of ventricular fibrillation induced by reperfusion.Interestingly,tyrosine phosphorylation levels of cardiac Na<sup>+</sup> channel(I<sub>Na</sub>) and L-type Ca<sup>2+</sup> channel(I<sub>Ca.l</sub>) were significantly increased at corresponding time points to the alteration of phosphorylated EGFR level during reperfusion.AG556 pretreatment countered the increased tyrosine phosphorylation level of Na<sup>+</sup> and L-type Ca<sup>2+</sup> channels induced by reperfusion.No significant alteration was observed in tyrosine phosphorylation levels of cardiac Kv4.2 and Kir2.1 channels during the cardiac ischemia/reperfusion. Conclusions These results demonstrate for the first time that EGFR plays an important role in the genesis of myocardial ischemia/reperfusion arrhythmias,which is likely mediated at least in part by enhancing tyrosine phosphorylation of cardiac Na<sup>+</sup> and L-type Ca<sup>2+</sup> channels.
基金This work was supported by grants from Bureau of Science and Technology of Changsha,China(No.Kq 1701007)Hunan Natural Science Foundation,China(No.2018JJ6127).
文摘Summary:In this study,we investigated the effects of nucleolin on lipopolysaccharide(LPS)-induced activation of MAPK and NF-KappaB(NF-kB)signaling pathways and secretion of TNF-a,IL-1βand HMGB1 in THP-1 monocytes.Immunofluorescence assay and Western blotting were used to identify the nucleolin expression in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Inactivation of nucleolin was induced by neutralizing antibody against nucleolin.THP-1 monocytes were pretreated with anti-nucleolin antibody for 1 h prior to LPS challenge.The irrelevant IgG group was used as control.Secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1)and activation of MAPK and NF-kB/I-kB signaling pathways were examined to assess the effects of nucleolin on LPS-mediated inflammatory response.Nucleolin existed in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Pretreatment of anti-nucleolin antibody significantly inhibited the LPS-induced secretion of TNF-a,IL-1β and HMGB1.P38,JNK,ERK and NF-κB subunit p65 inhibitors could significantly inhibit the secretion of IL-1β,TNF-a and HMGB1 induced by LPS.Moreover,the phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65)was significantly increased after LPS challenge.In contrast,pretreatment of anti-nucleolin antibody could significantly inhibit the LPS-induced phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).However,the irrelevant IgG,as a negative control,had no effect on LPS-induced secretion of TNF-a and IL-Iβ and phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).We demonstrated that nucleolin mediated the LPS-induced activation of MAPK and NF-κB signaling pathways,and regulated the secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1).
基金supported by grants from National Key Research and Development Program of China (2016YFA0500801)
文摘Although the mechanism of DNA methylationmediated gene silencing is extensively studied, relatively little is known about how promoter methylated genes are protected from transcriptional silencing. SUVH1, an Arabidopsis Su(var)3-9 homolog, was previously shown to be required for the expression of a few promoter methylated genes. By chromatin immunoprecipitation combined with sequencing, we demonstrate that SUVH1 binds to methylated genomic loci targeted by RNA-directed DNA methylation. SUVH1 and its homolog SUVH3 function partially redundantly and interact with three DNAJ domain-containing homologs, SDJ1, SDJ2, and SDJ3, thus forming a complex which we named SUVH-SDJ. The SUVH-SDJ complex components are co-localized in a large number of methylated promoters and are required for the expression of a subset of promoter methylated genes. We demonstrate that the SUVHSDJ complex components have transcriptional activation activity. SUVH1 and SUVH3 function synergistically with SDJ1,SDJ2, and SDJ3 and are required for plant viability. This study reveals how the SUVH-SDJ complex protects promoter methylated genes from transcriptional silencing and suggests that the transcriptional activation of promoter methylated genes mediated by the SUVH-SDJ complex may play a critical role in plant growth and development.
基金project was financially supported by grants from the National Natural Science Foundation of China(31625004 and 31872653)the Zhejiang Provincial Talent Program(2019R52005)+1 种基金the BBSRC(BB/N018540/1)the 111 Project(B14027)。
文摘Plants are capable of coordination of their growth and development with ambient temperatures.EARLY FLOWERING3(ELF3), an essential component of the plant circadian clock, is also involved in ambient temperature sensing, as well as in inhibiting the expression and protein activity of the thermoresponsive regulator phytochrome interacting factor4(PIF4). The ELF3 activity is subjected to attenuation in response to warm temperature;however,how the protein level of ELF3 is regulated at warm temperature remains less understood. Here, we report that the E3 ligase XB3 ORTHOLOG 5 IN ARABIDOPSIS THALIANA, XBAT35, mediates ELF3 degradation. XBAT35 interacts with ELF3 and ubiquitinates ELF3. Loss-of-function mutation of XBAT35 increases the protein level of ELF3 and confers a short-hypocotyl phenotype under warm temperature conditions. Thus, our findings establish that XBAT35 mediates ELF3 degradation to lift the inhibition of ELF3 on PIF4 for promoting thermoresponsive hypocotyl growth in plants.
文摘Dear Editor, mTORCI, as a center regulatory hub of metabolism, senses the cellular energy status, nutrition and extracellular stimuli and regulates cell growth, differentiation and functions of immune cells (Powell et al., 2012). Lysosomal localization of key signal comp orients is critical for mTORCI activati on: mTORCI activation requires co-localization of activated Rheb and mTORCI to the lysosome membrane (Buerger et al., 2006). Signals in eluding growth factors, cellular stresses and energy levels act on the disruption the formation of tuberous sclerosis complex (TSC) complex, comprised of TSC1, TSC2 and TBC1D7, which leads to the translocation and activation of Rheb on the lysosome membrane (Dibble et al., 2012). In response to nutrient levels, specifically the availability of amino acids and glucose (Efeyan et al., 2013), mTORCI is recruited to the lysosomal surface by Rag GTPases that are heterodimers of RagA or RagC bound to RagB or RagD. Multiple protein complexes have been implicated in regulation of mTORCI upon nutrient sensing including Ragulator, GATOR1, GATOR2, KICSTOR and vacuolar ATPases (Wolfson et al., 2017). Vacuolar ATPases are large multiple-protein complexes that acidify the lysosome and may mediate additional functions independent of their proton pump activity (Nishi and Forgac, 2002).
基金supported by the China Scholarship Council(to YW)the Swedish Research Council,No.2018-02601(to MS)+7 种基金the Alzheimer Foundation,No.AF-980695(to MS)the Stockholm County Council,No.RS2020-0731(to MS)the Foundation of Old Servants(to MS)the Gun and Bertil Stohne Foundation(to MS)the?hlén Foundation,No.233055(to MS)The Swedish Fund for Research without Animal Experiments(to MS)the Swedish Dementia Foundation(to MS)the Brain foundation,No.FO2022-0131(to MS)。
文摘Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.
基金the National Natural Science Foundation of China (No. 22136005)the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB36000000).
文摘Photoelectrochemical (PEC) small-molecule oxidation can selectively transform substrates into high-value-added fine chemicals and increase the rate of cathode hydrogen evolution. Nevertheless, achieving high-selectivity PEC oxidation of small molecules to produce specific products is a very challenging task. In general, selectivity can be improved by changing the surface catalyticsites of the photoanode and modulating the interfacial environments of the reactions. Herein, recent advances in approaches to improving selective PEC oxidation of small molecules are introduced. We first briefly discuss the basic concept and fundamentals of small-molecule PEC oxidation. The reported approaches to improving the performance of selective PEC oxidation of small molecules are highlighted from two aspects: (1) changing the surface properties of photoanodes by selecting suitable materials or modifying the photoanodes and (2) mediating the oxidation reactions using redox mediators. The PEC oxidation mechanism of these studies is emphasized. We also discuss the challenges in this research direction and offer a perspective on the further development of selective PEC-based small-molecule transformation.
基金the financial support from the National Natural Science Foundation of China(52002146).
文摘Hydrogen gas is widely regarded as an ideal green energy carrier and a potential alternative to fossil fuels for coping with the aggravating energy crisis and environmental pollution.Currently,the vast majority of the world's hydrogen is produced by reforming fossil fuels;however,this hydrogen-making technology is not sustainable or environmentally friendly because ofits high energy consumption and large carbon emissions.Renewables-driven water splitting(2H_(2)0-2H_(2)+0_(2))becomes an extensively studied scheme for sustain-able hydrogen production.Conventional water electrolysis requires an input voltage higher than 1.23 V and forms a gas mixture of H_(2)/O_(2),which results in high electricity consumption,potential safety hazards,and harmful reactive oxygen species.By virtue of the auxiliary redox mediators(RMs)as the robust H^(+)/e^(-)reservoir,decoupled electrolysis splits water at a much lower potential and evolves O_(2)(H_(2)O+RMS_(ox)-O_(2)+H-RMS_(red))and H_(2)(H-RMS_(red)-H_(2)+RMS_(ox))at separate times,rates,and spaces,thus pro-ducing the puretarget hydrogen gas safely.Decoupled electrolysis has accelerated the development ofwater electrolysis technology for H_(2) production.However,itis still lack of a comprehensive and in-depth review in this field based on different types of RMs.This review highlights the basic principles and critical progress of this emerging water electrolysis mode over the past decade.Several representative examples are then dis-played in detail according to the differences in the RMs.The rational choice and design of RMs have also been emphasized.Subsequently,novel applications of decoupled water splitting are briefly discussed,including the manufacture of valuable chemicals,Cl_(2) production,pollutant degradation,and other half-reactions in artificial photosynthesis.Finally,thekey characteristics and disadvantages of each type of mediator are sum-marized in depth.In addition,we present an outlook for future directions in decoupled water splitting.Thus,the flexibility in the design of mediators provides huge space for improving this electrochemical technology.@2024 Science Press and Dalian Institute of Chemical Physics,Chinese Academy of Sciences.Published by ELSEVIER B.V.and Science Press.All rights reserved.
基金This study is supported by the National Key Research and Development Program of China(2017YFB0307500).
文摘Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we report a multiple redox-mediated linear paired electrolysis system,combining the hydrogen peroxide mediated cathode process with the I2 mediated anode process,and realize the conversion of furfural to furoic acid in both side of the dividedflow cell simultaneously.By reasonably controlling the cathode potential,the undesired water splitting reaction and furfural reduction side reactions are avoided.Under the galvanostatic electrolysis,the two-mediated electrode processes have good compatibility,which reduce the energy consumption by about 22%while improving the electronic efficiency by about 125%.This system provides a green electrochemical synthesis route with commercial prospects.
基金Natural Sciences and Engineering Research Council of Canada (NSERC)Fonds de Recherche du Québec-Nature et Technologies (FRQNT)+3 种基金Centre Québécois sur les Materiaux Fonctionnels (CQMF)Institut National de la Recherche Scientifique (INRS)École de Technologie Supérieure (ÉTS)King Abdullah University of Science and Technology (KAUST)。
文摘Ammonia serves as a crucial chemical raw material and hydrogen energy carrier.Aqueous electrocatalytic nitrogen reduction reaction(NRR),powered by renewable energy,has attracted tremendous interest during the past few years.Although some achievements have been revealed in aqueous NRR,significant challenges have also been identified.The activity and selectivity are fundamentally limited by nitrogen activation and competitive hydrogen evolution.This review focuses on the hurdles of nitrogen activation and delves into complementary strategies,including materials design and system optimization(reactor,electrolyte,and mediator).Then,it introduces advanced interdisciplinary technologies that have recently emerged for nitrogen activation using high-energy physics such as plasma and triboelectrification.With a better understanding of the corresponding reaction mechanisms in the coming years,these technologies have the potential to be extended in further applications.This review provides further insight into the reaction mechanisms of selectivity and stability of different reaction systems.We then recommend a rigorous and detailed protocol for investigating NRR performance and also highlight several potential research directions in this exciting field,coupling with advanced interdisciplinary applications,in situ/operando characterizations,and theoretical calculations.
基金supported by the National Natural Science Foundation of China(Grant No.82173601)Yili&Jiangsu Joint Institute of Health(Grant No.yl2021ms02).
文摘The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.
基金Supported National Social Science Foundation of China[Grant No.18BGL085]Postgraduate Scientific Research Innovation Project of Jiangsu Province[Grant No.KYCX23_0832].
文摘Smart cities are a way for China to construct an innovative and environmentally conscious nation.The paper examines the impact of smart cities on corporate green governance and provides a theoretical foundation for formulating and executing smart city policy in China.Based on panel data from Chinese A-share listed companies in Shanghai and Shenzhen from 2008 to 2020,this study constructs a multiperiod double-difference model to examine the influence of smart cities on corporate green governance.Additionally,it uses a spatial double-difference model to investigate the spatial spillover effect of smart cities on neighboring areas.The findings indicate that smart cities effectively enhance corporate green governance.Analyzing the influencing mechanisms reveals that resource allocation efficiency,technological innovation,management environmental awareness,and regional environmental enforcement efforts act as mediators.Furthermore,the study reveals that the impact of smart cities on promoting corporate green governance is more pronounced in regions with lower levels of marketization and resource-based cities.Moreover,the research explores the spatial spillover effects of smart cities,with an effective radius of approximately 350 km.The optimal spatial correlation zone for green governance of businesses in neighboring areas in relation to smart cities is within a range of 250-350 km.This is manifested by the significant promotion of green governance in neighboring area businesses facilitated by smart cities.
基金The help and support of owners of the dairy farms enrolled in this study is gratefully acknowledged.The financial support from the program of China Scholarship Council during the PhD study of Mengqi Wang in Canada is acknowledged(No.202008880009).
文摘Background Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry.Multi-omics approaches enable the comprehensive investigation of the complex interactions between mul-tiple layers of information to provide a more holistic view of disease pathogenesis.Therefore,this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data(mRNA and lncRNA),small RNA sequencing data(miRNA)and DNA methylation sequencing data of milk somatic cells from 10 healthy cows and 20 cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus chromogenes.Results Functional investigation of the data sets through gene set analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis,provided further insights into subclin-ical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical mastitis.The abundant genomic and epigenomic signatures with sig-nificant alterations related to subclinical mastitis were observed,including 30,846,2552,1276 and 57 differential methylation haplotype blocks(dMHBs),differentially expressed genes(DEGs),lncRNAs(DELs)and miRNAs(DEMs),respectively.Next,5 factors presenting the principal variation of differential multi-omics signatures were identified.The important roles of Factor 1(DEG,DEM and DEL)and Factor 2(dMHB and DEM),in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed.Each of the omics within Factors 1 and 2 explained about 20%of the source of variation in subclinical mastitis.Also,networks of impor-tant functional gene sets with the involvement of multi-omics signatures were demonstrated,which contributed to a comprehensive view of the possible regulatory mechanisms underlying subclinical mastitis.Furthermore,multi-omics integration enabled the association of the epigenomic regulatory factors(dMHBs,DELs and DEMs)of altered genes in important pathways,such as‘Staphylococcus aureus infection pathway’and‘natural killer cell mediated cyto-toxicity pathway’,etc.,which provides further insights into mastitis regulatory mechanisms.Moreover,few multi-omics signatures(14 dMHBs,25 DEGs,18 DELs and 5 DEMs)were identified as candidate discriminant signatures with capac-ity of distinguishing subclinical mastitis cows from healthy cows.Conclusion The integration of genomic and epigenomic data by multi-omics approaches in this study provided a better understanding of the molecular mechanisms underlying subclinical mastitis and identified multi-omics candidate discriminant signatures for subclinical mastitis,which may ultimately lead to the development of more effective mastitis control and management strategies.
文摘Objective:The importance of good sleep for energy recovery and overall physical and mental health cannot be overstated.However,the increasing competitiveness of society,diversifying lifestyles,and the rapid spread of the internet and electronic devices have significantly impacted people’s sleep patterns,particularly through bedtime procrastination.Therefore,this study aims to investigate the relationship and underlying mechanisms between sleep determination,anxiety,and bedtime procrastination among the Chinese population.Method:The study utilized data from a national survey—the China Residents’Sleep Condition Survey(November 2021,with 6,037 participants).By constructing mediation and moderation models,it analyzed the relationship and mechanisms between sleep determination and bedtime procrastination,highlighting the dual role of anxiety:as a mediator between sleep determination and bedtime procrastination,and as a moderator of their relationship.Results:There was a negative correlation between sleep determination and bedtime procrastination;anxiety was related to an increase in bedtime procrastination behaviors;In the interplay between sleep determination and pre-bedtime procrastination,the regulatory effect of anxiety is found to be more pronounced than its intermediary role,with anxiety significantly diminishing the inverse relationship between sleep determination and procrastination before bedtime.Conclusion:Bedtime procrastination can lead to sleep issues,thus reducing sleep quality.Enhancing sleep determination or alleviating pre-sleep anxiety can help inhibit bedtime procrastination behaviors.Intervening and reducing bedtime procrastination is one of the effective measures to improve sleep quality.
基金Supported by the Natural Science Foundation Project of Xinjiang Uygur Autonomous Region,No.2021D01C143.
文摘BACKGROUND Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis(MHD)that significantly affect their quality of life(QOL).High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD.Currently,there is limited research on how social support mediates the relationship between dysphoria,despondency,and overall QOL in patients undergoing MHD.It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD,ultimately enhancing their overall QOL.AIM To investigate the mediating role of social support in relationships between dysphoria,despondency,and QOL among patients undergoing MHD.METHODS Participants comprised 289 patients undergoing MHD,who were selected using a random sampling approach.The Social Support Rating Scale,Self-Rating Anxiety Scale,Self-Rating Depression Scale,and QOL Scale were administered.Correlation analysis was performed to examine the associations between social support,dysphoria,despondency,and QOL in patients undergoing MHD.To assess the mediating impact of social support on dysphoria,despondency,and QOL in patients undergoing MHD,a bootstrap method was applied.RESULTS Significant correlations among social support,dysphoria,despondency,and quality in patients undergoing MHD were observed(all P<0.01).Dysphoria and despondency negatively correlated with social support and QOL(P<0.01).Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD(P<0.05).The direct effect of dysphoria on QOL was statistically significant(P<0.05).Social support mediated the relationship between dysphoria and QOL,and this mediating effect was significant(P<0.05).Similarly,the direct effect of despondency on QOL was significant(P<0.05).Moreover,social support played a mediating role between despondency and QOL,with a significant mediating effect(P<0.05).CONCLUSION These findings suggest that social support plays a significant mediating role in the relationship between dysphoria,despondency,and QOL in patients undergoing MHD.