The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain f...The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.展开更多
Type 2 diabetes mellitus(T2DM)is a lifelong condition and a grave threat to human health.Innovative efforts to relieve its detrimental effects are acutely needed.The sine qua non in T2DM management is consistent adher...Type 2 diabetes mellitus(T2DM)is a lifelong condition and a grave threat to human health.Innovative efforts to relieve its detrimental effects are acutely needed.The sine qua non in T2DM management is consistent adherence to a prudent lifestyle and nutrition,combined with aerobic and resistance exercise regimens,together repeatedly shown to lead to complete reversal and even longterm remission.Non-adherence to the above lifestyle adjustments condemns any treatment effort and ultimately the patient to a grim fate.It is thus imperative that every study evaluating the effects of innovative interventions in T2DM objectively compares the novel treatment modality to lifestyle modifications,preferably through double-blind controlled randomization,before claiming efficacy.展开更多
As naturally sourced proteins,peanut proteins have garnered significant attention from the food industry,owing to their numerous advantages,such as easy extraction,non-pungency,and high bioavailability.Furthermore,pea...As naturally sourced proteins,peanut proteins have garnered significant attention from the food industry,owing to their numerous advantages,such as easy extraction,non-pungency,and high bioavailability.Furthermore,peanut proteins are highly digestible in the gastrointestinal tract and boast a high net protein utilization rate,making them an appealing protein source in food products and a promising alternative to animal protein.In this paper,the recent works on the extraction method,modification method,and application of peanut proteins were reviewed.Both advantages and disadvantages of current extraction and modification were discussed.Recently updated information about peanut protein research was summarized.Based on these,the prospection of peanut proteins research was presented,which may be instructive for future research in this field.Future research is still needed for accessible modification methods to develop the functional properties of peanut proteins.展开更多
Epigenetic modifications modulate conformational structure of chromatin and consequently gene expression by enzyme-mediated chemical modifications of DNA and histones.The activities of epigenetic modifying enzymes dep...Epigenetic modifications modulate conformational structure of chromatin and consequently gene expression by enzyme-mediated chemical modifications of DNA and histones.The activities of epigenetic modifying enzymes depend on many co-substrates and cofactors,such as 2-oxoglutarate(2-OG),iron,S-adenosylmethionine(SAM),nicotinamide adenine dinucleotide(NAD+),flavin adenine dinucleotide(FAD),and acetyl-CoA.These factors are inter-connecting molecules that integrate cellular nutrient metabolism and redox homeostasis,two key regulators of cell proliferation,cell survival,and cell functions.Dysregulation of such delicate regulatory network has been implicated in many pathological conditions and also been increasingly recognized as an emerging mechanism responsible for environmental pollutant-induced adverse effects.In this review,we first summarize DNA and histone modifying enzymes and their essential factors,then discuss the metabolic sources and the redox regulatory roles of these enzymatic factors,and finally elaborate the mechanisms of how targeting such factors by environmental pollutants influences epigenetic regulation and perturbs cellular functions.展开更多
Epigenetics focuses on DNA methylation,histone modification,chromatin remodeling,noncoding RNAs,and other gene regulation mechanisms beyond the DNA sequence.In the past decade,epigenetic modifications have drawn more ...Epigenetics focuses on DNA methylation,histone modification,chromatin remodeling,noncoding RNAs,and other gene regulation mechanisms beyond the DNA sequence.In the past decade,epigenetic modifications have drawn more attention as they participate in the development and progression of diabetic retinopathy despite tight control of glucose levels.The underlying mechanisms of epigenetic modifications in diabetic retinopathy still urgently need to be elucidated.The diabetic condition facilitates epigenetic changes and influences target gene expression.In this review,we summarize the involvement of epigenetic modifications and metabolic memory in the development and progression of diabetic retinopathy and propose novel insights into the treatment of diabetic retinopathy.展开更多
As the number of patients suffering from cardiovascular diseases and peripheral vascular diseases rises,the constraints of autologous transplantation remain unavoidable.As a result,artificial vascular grafts must be d...As the number of patients suffering from cardiovascular diseases and peripheral vascular diseases rises,the constraints of autologous transplantation remain unavoidable.As a result,artificial vascular grafts must be developed.Adhesion of proteins,platelets and bacteria on implants can result in stenosis,thrombus formation,and postoperative infection,which can be fatal for an implantation.Polyurethane,as a commonly used biomaterial,has been modified in various ways to deal with the adhesions of proteins,platelets,and bacteria and to stimulate endothelium adhesion.In this review,we briefly summarize the mechanisms behind adhesions,overview the current strategies of surface modifications of polyurethane biomaterials used in vascular grafts,and highlight the challenges that need to be addressed in future studies,aiming to gain a more profound understanding of how to develop artificial polyurethane vascular grafts with an enhanced implantation success rate and reduced side effect.展开更多
Atmospheric pressure plasma jet shows great potential for polymer film processing. The electrode geometry is the key factor to determine discharge characteristics and film modification of jets. In this paper, we compa...Atmospheric pressure plasma jet shows great potential for polymer film processing. The electrode geometry is the key factor to determine discharge characteristics and film modification of jets. In this paper, we compared the discharge characteristics and the film modifications of atmospheric pressure plasma jets with needle-ring electrode(NRE) and doublering electrode(DRE). The results show that jet with NRE has stronger electric field intensity and higher discharge power,making it present more reactive oxygen particles and higher electron temperature, but its discharge stability is insufficient.In contrast, the jet with DRE has uniform electric field distribution of lower field intensity, which allows it to maintain stable discharge over a wide range of applied voltages. Besides, the modification results show that the treatment efficiency of PET film by NRE is higher than that by DRE. These results provide a suitable atmospheric pressure plasma jets device selection scheme for polymer film processing process.展开更多
The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to th...The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR NAs to proteins that control mR NA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.展开更多
Replication of hepatitis C virus(HCV)depends on the interaction of viral proteins with various host cellular proteins and signalling pathways.Similar to cellular proteins,post-translational modifications(PTMs)of HCV p...Replication of hepatitis C virus(HCV)depends on the interaction of viral proteins with various host cellular proteins and signalling pathways.Similar to cellular proteins,post-translational modifications(PTMs)of HCV proteins are essential for proper protein function and regulation,thus,directly affecting viral life cycle and the generation of infectious virus particles.Cleavage of the HCV polyprotein by cellular and viral proteases into more than 10 proteins represents an early protein modification step after translation of the HCV positivestranded RNA genome.The key modifications include the regulated intramembranous proteolytic cleavage of core protein,disulfide bond formation of core,glycosylation of HCV envelope proteins E1 and E2,methylation of nonstructural protein 3(NS3),biotinylation of NS4A,ubiquitination of NS5B and phosphorylation of core and NS5B.Other modifications like ubiquitination of core and palmitoylation of core and NS4B proteins have been reported as well.For some modifications such as phosphorylation of NS3 and NS5A and acetylation of NS3,we have limited understanding of their effects on HCV replication and pathogenesis while the impact of other modifications is far from clear.In this review,we summarize the available information on PTMs of HCV proteins and discuss their relevance to HCV replication and pathogenesis.展开更多
BACKGROUND Pancreatic cancer(PC)is one of the deadliest malignancies with an alarming mortality rate.Despite significant advancement in diagnostics and therapeutics,early diagnosis remains elusive causing poor prognos...BACKGROUND Pancreatic cancer(PC)is one of the deadliest malignancies with an alarming mortality rate.Despite significant advancement in diagnostics and therapeutics,early diagnosis remains elusive causing poor prognosis,marred by mutations and epigenetic modifications in key genes which contribute to disease progression.AIM To evaluate the various biological tumor markers collectively for early diagnosis which could act as prognostic biomarkers and helps in future therapeutics of PC in Kashmir valley.METHODS A total of 50 confirmed PC cases were included in the study to evaluate the levels of carbohydrate antigen 19-9(CA 19-9),tissue polypeptide specific antigen(TPS),carcinoembryonic antigen(CEA),vascular endothelial growth factor-A(VEGF-A),and epidermal growth factor receptor(EGFR).Mutational analysis was performed to evaluate the mutations in Kirsten rat sarcoma(KRAS),Breast cancer type 2(BRCA-2),and deleted in pancreatic cancer-4(DPC-4)genes.However,epigenetic modifications(methylation of CpG islands)were performed in the promoter regions of cyclin-dependent kinase inhibitor 2A(p16;CDKN2A),MutL homolog 1(hMLH1),and Ras association domain-containing protein 1(RASSF1A)genes.RESULTS We found significantly elevated levels of biological markers CA 19-9(P≤0.05),TPS(P≤0.05),CEA(P≤0.001),and VEGF(P≤0.001).Molecular genetic analysis revealed that KRAS gene mutation is predominant in codon 12(16 subjects,P≤0.05),and 13(12 subjects,P≤0.05).However,we did not find a mutation in DPC-4(1203G>T)and BRCA-2(617delT)genes.Furthermore,epigenetic modification revealed that CpG methylation in 21(P≤0.05)and 4 subjects in the promoter regions of the p16 and hMLH1 gene,respectively.CONCLUSION In conclusion,CA 19-9,TPS,CEA,and VEGF levels were significantly elevated and collectively have potential as diagnostic and prognostic markers in PC.Global data of mutation in the KRAS gene commonly in codon 12 and rare in codon 13 could augment the predisposition towards PC.Additionally,methylation of the p16 gene could also modulate transcription of genes thereby increasing the predisposition and susceptibility towards PC.展开更多
Objective:To validate the eighth edition of the AJCC staging system in patients with pancreatic adenocarcinoma receiving only stereotactic body radiation therapy and chemotherapy,and to propose modifications to improv...Objective:To validate the eighth edition of the AJCC staging system in patients with pancreatic adenocarcinoma receiving only stereotactic body radiation therapy and chemotherapy,and to propose modifications to improve prognostic accuracy.Methods:Patients with pathologically confirmed pancreatic adenocarcinoma without metastasis who were undergoing only chemoradiotherapy were included and staged according to the seventh and eighth editions of the AJCC staging system.Meanwhile,another group of stage T4 patients from the above enrollment with only portal vein involvement with or without tumor thrombi(PV±PVTT)were retrieved for survival comparisons.Modifications were proposed according to the survival comparisons.A cohort from the SEER database was used for external validation of the modified staging system.Results:A total of 683 patients were included.Patients with N2 or N1 but different T stages had significantly different survival outcomes according to the eighth edition.The survival of patients with(PV±PVTT)was comparable to that of patients with T4 tumors.The concordance index of the seventh and eighth editions,and the modified staging system was 0.744(95%CI:0.718—0.769),0.750(95%CI:0.725—0.775),and 0.788(95%CI:0.762-0.813),respectively.For external validation,the concordance index was 0.744(95%CI:0.718-0.770),0.750(95%CI:0.724-0.776),and 0.788(95%CI:0.762-0.814),respectively.Conclusions:The modified staging system is suggested to have the m ost accurate prognostic value.Hence,PV土PVTT should be added to the definition of T4 tumors regardless of tumor size.Patients with N2 or N1 in different T stages could be regrouped into different substages.Additionally,stage III should be subclassified into IIIA(T3N 2 and T4N 0)and IIIB(T4N 1-2).展开更多
Layered double hydroxides are one class or kind of 2 D layered materials that are considered promising for use in the supercapacitor.Although there have been many studies on the structure,composition,properties,and el...Layered double hydroxides are one class or kind of 2 D layered materials that are considered promising for use in the supercapacitor.Although there have been many studies on the structure,composition,properties,and electrode fabrication of layered double hydroxides,none summarize the effects of various modification methods on the structure and performance of layered double hydroxides in the supercapacitor.In a bid to fill this gap,in this review,we summarize the progress of modification methods such as exfoliation,intercalation,vacancy,doping,phase transformation,and composition regulation of layered double hydroxides in the field of the supercapacitor and put forward some opinions regarding the progress of research on the methods used in modifying the layered double hydroxides.展开更多
The 57 kDa antigen recognized by the Ki-1 antibody,is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7%identity and 67.4%similarity with serpin mRNA binding protein 1,which is also named C...The 57 kDa antigen recognized by the Ki-1 antibody,is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7%identity and 67.4%similarity with serpin mRNA binding protein 1,which is also named CGI-55,or plasminogen activator inhibitor type-1-RNA binding protein-1,indicating that they might be paralog proteins,possibly with similar or redundant functions in human cells.Through the identification of their protein interactomes,both regulatory proteins have been functionally implicated in transcriptional regulation,mRNA metabolism,specifically RNA splicing,the regulation of mRNA stability,especially,in the context of the progesterone hormone response,and the DNA damage response.Both proteins also show a complex pattern of post-translational modifications,involving Ser/Thr phosphorylation,mainly through protein kinase C,arginine methylation and SUMOylation,suggesting that their functions and locations are highly regulated.Furthermore,they show a highly dynamic cellular localization pattern with localizations in both the cytoplasm and nucleus as well as punctuated localizations in both granular cytoplasmic protein bodies,upon stress,and nuclear splicing speckles.Several reports in the literature show altered expressions of both regulatory proteins in a series of cancers as well as mutations in their genes that may contribute to tumorigenesis.This review highlights important aspects of the structure,interactome,post-translational modifications,sub-cellular localization and function of both regulatory proteins and further discusses their possible functions and their potential as tumor markers in different cancer settings.展开更多
Single-crystal cathodes(SCCs)are promising substitute materials for polycrystal cathodes(PCCs)in lithium-ion batteries(LIBs),because of their unique ordered structure,excellent cycling stability and high safety perfor...Single-crystal cathodes(SCCs)are promising substitute materials for polycrystal cathodes(PCCs)in lithium-ion batteries(LIBs),because of their unique ordered structure,excellent cycling stability and high safety performance.Cathode materials with layered(LiCoO_(2),LiNi_xCo_yMnzO_(2),LiNi_xCo_yAl_(2)O_(2))and spinel structure(LiMn_(2)O_(4),LiNi_(0.5)Mn_(1.5)O_(4))show a relatively stable electrochemical performance,but still lack of sufficient attention in research field.In this review,we begin with the definition,structural features and electrochemical advantages of SCCs.Common SCCs synthesis methods and the thermodynamic growth mechanism of SCCs with oriented facet exposure are summarized in the following part.Then we introduce the problems and challenges of SCCs faced and the corresponding modification strategies.Finally,the industrialization progress of SCCs is brifly outlined.We intend to tease out the difficulties and advances of SCCs to provide insights for future development of high-performance SCCs for practical LIBs.展开更多
This study was intended to understand how smallholder farmers’modifications improved agroforestry technologies’usability in Uganda’s Mt.Elgon region.We used a case study approach to understand how smallholder farm...This study was intended to understand how smallholder farmers’modifications improved agroforestry technologies’usability in Uganda’s Mt.Elgon region.We used a case study approach to understand how smallholder farmers’contextual realities informed their modifications and enhanced the usability of agroforestry technologies.Data was collected over four months of frequent and regular interaction with the cases using formal and informal methods that included in-depth interviews,conversations,discussions,and direct observations.Emerging themes and patterns were identified from the comprehensively reduced data.In addition,respondents’direct quotes were used to emphasize the reasons for the modifications.The findings showed that smallholder farmers modified the recommended technologies to suit their biophysical and socio-economic realities.Differences and similarities in modifications existed among cases across the agroforestry technologies.The modifications were mainly done to diversify tree uses,optimize space utilization,and minimize production costs for farming households.These findings imply a need to critically examine the smallholder farmers’modifications to make agroforestry technologies applicable and compliant to their contexts.This will inform the re-invention of technologies that will quickly diffuse into the community for broader impact.Findings also emphasize the need to rethink the linear model of technology transfer mainly applied in agroforestry technology development and dissemination because it offers limited space for the much-needed feedback from smallholder farmers.展开更多
The influence of different modification methods on the surface properties of indium-tin-oxide (ITO) electrodes were investigated by measurements of chemical composition,surface roughness,sheet resistance,contact angle...The influence of different modification methods on the surface properties of indium-tin-oxide (ITO) electrodes were investigated by measurements of chemical composition,surface roughness,sheet resistance,contact angle and surface free energy.Experimental results demonstrate that oxygen plasma treatment more effectively optimizes the surface properties of ITO electrodes compared with the other treatments.Furthermore,the polymer light-emitting electrochemical cells (PLECs) with the differently treated ITO substrates as device electrodes were fabricated and characterized.It is found that oxygen plasma treatment on the ITO electrode enhances injection current,luminance and efficiency,thereby improves the device characteristics of the PLECs.展开更多
Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or dela...Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or delay the progression of AMD more efficiently.Until now,the pathogenesis of AMD has remained unclear,limiting the development of the novel therapy.Bruch’s membrane(BM)goes through remarkable changes in AMD,playing a significant role during the disease course.The main aim of this review is to present the crucial processes that occur at the level of BM,with special consideration of the lipid accumulation and protein modifications.Besides,some therapies targeted at these molecules and the construction of BM in tissue engineering of retinal pigment epithelium(RPE)cells transplantation were listed.Hopefully,this review may provide a reference for researchers engaged in pathogenesis or management on AMD.展开更多
In the present work, computational analyses were applied to study the subcellular localiza-tion and posttranslational modifications of hu-man prion proteins (PrPs). The tentative location of prion protein was determin...In the present work, computational analyses were applied to study the subcellular localiza-tion and posttranslational modifications of hu-man prion proteins (PrPs). The tentative location of prion protein was determined to be in the nu-cleolus inside the nucleus by the following bio-informatics tools: Hum-PLoc, Euk-PLoc and Nuc-PLoc. Based on our results signal peptides with average of 22 base pairs in N-terminal were identified in human PrPs. This theoretical study demonstrates that PrP is post-translationally modified by: 1) attachment of two N-linked complex carbohydrate moieties (N181 and N197), 2) attachmet of glycosylphosphatidylinositol (GPI) at serine 230 and 3) formation of two di-sulfide bonds between “6–22” and “179–214” cysteines. Furthermore, ten protein kinase phosphorylation sites were predicted in human PrP. The above-noted phosphorylation was car-ried out by PKC and CK2. By using bioinfor-matics tools, we have shown that computation-ally human PrPs locate particularly into the nu-cleolus.展开更多
Pineapple Leaf Fibre (PALF) is one of the natural fibres that have high potential in the industry. Natural fibres have become the main alternative source for reinforced polymer composites. The objective of this study ...Pineapple Leaf Fibre (PALF) is one of the natural fibres that have high potential in the industry. Natural fibres have become the main alternative source for reinforced polymer composites. The objective of this study is to observe the effect of chemical treatments using Sodium Hydroxide (NaOH) solution, Zinc chloride, Acetic Anhydride and Nitric acid on the mechanical properties of pineapple leaf fibre reinforced polypropylene composites. The tensile test was conducted by using the ASTM D638-10 to obtain the tensile strength (TS) and Young’s modulus (YM), Flexural properties were conducted to determine the flexural strength (FS) and flexural modulus (FM) of the reinforced composites using the ASTM D256-10 method, and impact test was conducted to determine the impact strength (IS) of the reinforced composites using the Izod ASTM D790-17 method. From the results obtained, the composites with surface modified PALF fillers show enhanced mechanical properties over the untreated PALF fillers in this order;for TS untreated composite C3H6O3 3. For YM untreated composite 3 C3H6O3 3 3H6O3. For FM, untreated reinforced PALF/PP composites C3H6O3 3. For IS, the untreated reinforced PALF/PP composites 3 C3H6O3. SEM analysis was carried out on the PALF before the compounding to analyze the effect of the surface modification agents.展开更多
In this work,surface modification of a Mg-4Sm-2Al-0.5Mn alloy with high current pulse electron beam(HCPEB)under different number of pulses were investigated.The evolution in microstructure,composition and phase compon...In this work,surface modification of a Mg-4Sm-2Al-0.5Mn alloy with high current pulse electron beam(HCPEB)under different number of pulses were investigated.The evolution in microstructure,composition and phase components and properties in the surface layer before and after HCPEB treatment were characterized.It was found that the Al 11 Sm 3 and Al 2 Sm phases in the surface layer were gradually dissolved during HCPEB treatment,leading to the formation of a chemical homogeneous melted layers.Besides,deformation bands were formed in the treated layer due to the thermal stress generated during treatment.After 15 pulses treatment,the surface hardness increases to the maximum value of about 62.2 HV,about 61.2%higher than that of the untreated state.Electrochemical results show that the 15 pulses treated sample presents the best corrosion resistance in the 3.5wt%NaCl water solution by showing the highest corrosion potential(E_(corr))of-1.339V SEC and the lowest corrosion current density(I_(corr))of 1.48×10^(-6)A·cm^(-2).The results prove that the surface properties of the Mg-4Sm-2Al-0.5Mn alloy can be significantly improved by the HCPEB treatments under proper conditions.展开更多
基金supported by the Natural Science Foundation Project of China(81820108015,82201683)China Postdoctoral Science Foundation(2021M693926,2020TQ0393,2020M683634XB)+1 种基金Chongqing Science&Technology Commission(cstc2021jcyj-bshX0150,cstc2021jcyj-bshX0201)Special Funding for Chongqing Postdoctoral Research Projects(2021XMT001)。
文摘The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.
文摘Type 2 diabetes mellitus(T2DM)is a lifelong condition and a grave threat to human health.Innovative efforts to relieve its detrimental effects are acutely needed.The sine qua non in T2DM management is consistent adherence to a prudent lifestyle and nutrition,combined with aerobic and resistance exercise regimens,together repeatedly shown to lead to complete reversal and even longterm remission.Non-adherence to the above lifestyle adjustments condemns any treatment effort and ultimately the patient to a grim fate.It is thus imperative that every study evaluating the effects of innovative interventions in T2DM objectively compares the novel treatment modality to lifestyle modifications,preferably through double-blind controlled randomization,before claiming efficacy.
基金the Natural Science Foundation of Shandong Province[grant number ZR2020QC218]Key R&D plan of Shandong Province[grant number 2019YYSP005]+2 种基金Major Science and Technology Projects of Shandong Province[grant number2019JZZY010722]Qingdao Municipal Science and Technology Benefit People Project[grant number 20-3-4-34-nsh]Breeding Plan of Shandong Provincial Qingchuang Research Team[grant number 2021-Innovation Team of Functional Plant Protein-Based Food]。
文摘As naturally sourced proteins,peanut proteins have garnered significant attention from the food industry,owing to their numerous advantages,such as easy extraction,non-pungency,and high bioavailability.Furthermore,peanut proteins are highly digestible in the gastrointestinal tract and boast a high net protein utilization rate,making them an appealing protein source in food products and a promising alternative to animal protein.In this paper,the recent works on the extraction method,modification method,and application of peanut proteins were reviewed.Both advantages and disadvantages of current extraction and modification were discussed.Recently updated information about peanut protein research was summarized.Based on these,the prospection of peanut proteins research was presented,which may be instructive for future research in this field.Future research is still needed for accessible modification methods to develop the functional properties of peanut proteins.
基金This work is funded by National Natural Science Foundation of China(No.81773466)to W.H,and by Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease(No.DXWL2023-06)to W.X.
文摘Epigenetic modifications modulate conformational structure of chromatin and consequently gene expression by enzyme-mediated chemical modifications of DNA and histones.The activities of epigenetic modifying enzymes depend on many co-substrates and cofactors,such as 2-oxoglutarate(2-OG),iron,S-adenosylmethionine(SAM),nicotinamide adenine dinucleotide(NAD+),flavin adenine dinucleotide(FAD),and acetyl-CoA.These factors are inter-connecting molecules that integrate cellular nutrient metabolism and redox homeostasis,two key regulators of cell proliferation,cell survival,and cell functions.Dysregulation of such delicate regulatory network has been implicated in many pathological conditions and also been increasingly recognized as an emerging mechanism responsible for environmental pollutant-induced adverse effects.In this review,we first summarize DNA and histone modifying enzymes and their essential factors,then discuss the metabolic sources and the redox regulatory roles of these enzymatic factors,and finally elaborate the mechanisms of how targeting such factors by environmental pollutants influences epigenetic regulation and perturbs cellular functions.
基金supported by the National Natural Science Foundation of China,No.82171062(to JFZ)Aier Eye Hospital Group Scientific Research Fund,No.AF2101D8(to LMG).
文摘Epigenetics focuses on DNA methylation,histone modification,chromatin remodeling,noncoding RNAs,and other gene regulation mechanisms beyond the DNA sequence.In the past decade,epigenetic modifications have drawn more attention as they participate in the development and progression of diabetic retinopathy despite tight control of glucose levels.The underlying mechanisms of epigenetic modifications in diabetic retinopathy still urgently need to be elucidated.The diabetic condition facilitates epigenetic changes and influences target gene expression.In this review,we summarize the involvement of epigenetic modifications and metabolic memory in the development and progression of diabetic retinopathy and propose novel insights into the treatment of diabetic retinopathy.
基金supported by the National High Level Hospital Clinical Research Funding:2022-PUMCH-A-191.
文摘As the number of patients suffering from cardiovascular diseases and peripheral vascular diseases rises,the constraints of autologous transplantation remain unavoidable.As a result,artificial vascular grafts must be developed.Adhesion of proteins,platelets and bacteria on implants can result in stenosis,thrombus formation,and postoperative infection,which can be fatal for an implantation.Polyurethane,as a commonly used biomaterial,has been modified in various ways to deal with the adhesions of proteins,platelets,and bacteria and to stimulate endothelium adhesion.In this review,we briefly summarize the mechanisms behind adhesions,overview the current strategies of surface modifications of polyurethane biomaterials used in vascular grafts,and highlight the challenges that need to be addressed in future studies,aiming to gain a more profound understanding of how to develop artificial polyurethane vascular grafts with an enhanced implantation success rate and reduced side effect.
基金Project supported by the National Natural Science Foundation of China (Grant No. 11565003)the Jiangxi Province Academic Degree and Postgraduate Education and Teaching Reform Research Project (Grant No. JXYJG-2022-180)the Scientific Research Base Project of Gannan Normal University (Grant No. 22wdxt01)。
文摘Atmospheric pressure plasma jet shows great potential for polymer film processing. The electrode geometry is the key factor to determine discharge characteristics and film modification of jets. In this paper, we compared the discharge characteristics and the film modifications of atmospheric pressure plasma jets with needle-ring electrode(NRE) and doublering electrode(DRE). The results show that jet with NRE has stronger electric field intensity and higher discharge power,making it present more reactive oxygen particles and higher electron temperature, but its discharge stability is insufficient.In contrast, the jet with DRE has uniform electric field distribution of lower field intensity, which allows it to maintain stable discharge over a wide range of applied voltages. Besides, the modification results show that the treatment efficiency of PET film by NRE is higher than that by DRE. These results provide a suitable atmospheric pressure plasma jets device selection scheme for polymer film processing process.
基金Supported by Ministerio de Ciencia Innovación y Universidades,No.SAF2017-82436R and SAF2016-75004RComunidad de Madrid,No.S2017/BMD-3686+2 种基金Fundación Ramón Areces,No.2016/CIVP18A3864Instituto de Salud Carlos Ⅲby Fondos FEDER,No.Cibercv and Ciberehd
文摘The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR NAs to proteins that control mR NA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.
基金Supported by Canadian Institutes of Health Research,Saskatchewan Health Research Foundation,and Natural Sciences and Engineering Research Council of Canada
文摘Replication of hepatitis C virus(HCV)depends on the interaction of viral proteins with various host cellular proteins and signalling pathways.Similar to cellular proteins,post-translational modifications(PTMs)of HCV proteins are essential for proper protein function and regulation,thus,directly affecting viral life cycle and the generation of infectious virus particles.Cleavage of the HCV polyprotein by cellular and viral proteases into more than 10 proteins represents an early protein modification step after translation of the HCV positivestranded RNA genome.The key modifications include the regulated intramembranous proteolytic cleavage of core protein,disulfide bond formation of core,glycosylation of HCV envelope proteins E1 and E2,methylation of nonstructural protein 3(NS3),biotinylation of NS4A,ubiquitination of NS5B and phosphorylation of core and NS5B.Other modifications like ubiquitination of core and palmitoylation of core and NS4B proteins have been reported as well.For some modifications such as phosphorylation of NS3 and NS5A and acetylation of NS3,we have limited understanding of their effects on HCV replication and pathogenesis while the impact of other modifications is far from clear.In this review,we summarize the available information on PTMs of HCV proteins and discuss their relevance to HCV replication and pathogenesis.
文摘BACKGROUND Pancreatic cancer(PC)is one of the deadliest malignancies with an alarming mortality rate.Despite significant advancement in diagnostics and therapeutics,early diagnosis remains elusive causing poor prognosis,marred by mutations and epigenetic modifications in key genes which contribute to disease progression.AIM To evaluate the various biological tumor markers collectively for early diagnosis which could act as prognostic biomarkers and helps in future therapeutics of PC in Kashmir valley.METHODS A total of 50 confirmed PC cases were included in the study to evaluate the levels of carbohydrate antigen 19-9(CA 19-9),tissue polypeptide specific antigen(TPS),carcinoembryonic antigen(CEA),vascular endothelial growth factor-A(VEGF-A),and epidermal growth factor receptor(EGFR).Mutational analysis was performed to evaluate the mutations in Kirsten rat sarcoma(KRAS),Breast cancer type 2(BRCA-2),and deleted in pancreatic cancer-4(DPC-4)genes.However,epigenetic modifications(methylation of CpG islands)were performed in the promoter regions of cyclin-dependent kinase inhibitor 2A(p16;CDKN2A),MutL homolog 1(hMLH1),and Ras association domain-containing protein 1(RASSF1A)genes.RESULTS We found significantly elevated levels of biological markers CA 19-9(P≤0.05),TPS(P≤0.05),CEA(P≤0.001),and VEGF(P≤0.001).Molecular genetic analysis revealed that KRAS gene mutation is predominant in codon 12(16 subjects,P≤0.05),and 13(12 subjects,P≤0.05).However,we did not find a mutation in DPC-4(1203G>T)and BRCA-2(617delT)genes.Furthermore,epigenetic modification revealed that CpG methylation in 21(P≤0.05)and 4 subjects in the promoter regions of the p16 and hMLH1 gene,respectively.CONCLUSION In conclusion,CA 19-9,TPS,CEA,and VEGF levels were significantly elevated and collectively have potential as diagnostic and prognostic markers in PC.Global data of mutation in the KRAS gene commonly in codon 12 and rare in codon 13 could augment the predisposition towards PC.Additionally,methylation of the p16 gene could also modulate transcription of genes thereby increasing the predisposition and susceptibility towards PC.
基金grants from the Special Project of Ministry of Science and Technology(Grant No.2017 YFC0113104)We thank Dr.Jiuhong Chen for helpful comments,Dr.Fabienne Hirigoyenberry and Dr.Huijun Chen,for language editing and LinkDoc for their constructive advice in patient follow-up.
文摘Objective:To validate the eighth edition of the AJCC staging system in patients with pancreatic adenocarcinoma receiving only stereotactic body radiation therapy and chemotherapy,and to propose modifications to improve prognostic accuracy.Methods:Patients with pathologically confirmed pancreatic adenocarcinoma without metastasis who were undergoing only chemoradiotherapy were included and staged according to the seventh and eighth editions of the AJCC staging system.Meanwhile,another group of stage T4 patients from the above enrollment with only portal vein involvement with or without tumor thrombi(PV±PVTT)were retrieved for survival comparisons.Modifications were proposed according to the survival comparisons.A cohort from the SEER database was used for external validation of the modified staging system.Results:A total of 683 patients were included.Patients with N2 or N1 but different T stages had significantly different survival outcomes according to the eighth edition.The survival of patients with(PV±PVTT)was comparable to that of patients with T4 tumors.The concordance index of the seventh and eighth editions,and the modified staging system was 0.744(95%CI:0.718—0.769),0.750(95%CI:0.725—0.775),and 0.788(95%CI:0.762-0.813),respectively.For external validation,the concordance index was 0.744(95%CI:0.718-0.770),0.750(95%CI:0.724-0.776),and 0.788(95%CI:0.762-0.814),respectively.Conclusions:The modified staging system is suggested to have the m ost accurate prognostic value.Hence,PV土PVTT should be added to the definition of T4 tumors regardless of tumor size.Patients with N2 or N1 in different T stages could be regrouped into different substages.Additionally,stage III should be subclassified into IIIA(T3N 2 and T4N 0)and IIIB(T4N 1-2).
基金The authors gratefully acknowledge the financial support provided by the project of Technological Innovation and Application Development in Chongqing(cstc2019jscxmsxm0378)the National Natural Science Foundation of China(Grant No.21576034 and 51908092)+1 种基金the State Education Ministry and Fundamental Research Funds for the Central Universities(2019CDQYCL042,2019CDXYCL0031,106112017CDJXSYY0001,2018CDYJSY0055,106112017CDJQJ138802,106112017CDJSK04XK11,and 2018CDQYCL0027)the Joint Funds of the National Natural Science Foundation of China-Guangdong(Grant No.U1801254).
文摘Layered double hydroxides are one class or kind of 2 D layered materials that are considered promising for use in the supercapacitor.Although there have been many studies on the structure,composition,properties,and electrode fabrication of layered double hydroxides,none summarize the effects of various modification methods on the structure and performance of layered double hydroxides in the supercapacitor.In a bid to fill this gap,in this review,we summarize the progress of modification methods such as exfoliation,intercalation,vacancy,doping,phase transformation,and composition regulation of layered double hydroxides in the field of the supercapacitor and put forward some opinions regarding the progress of research on the methods used in modifying the layered double hydroxides.
基金Supported by the “Conselho Nacional de Desenvolvimento Cientifico e Tecnológico”,Grant No.302534/2017-2the “Fundacao de Amparo a Pesquisa do Estado de Sao Paulo”(FAPESP,Grant 2014/21700-3,to JK)
文摘The 57 kDa antigen recognized by the Ki-1 antibody,is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7%identity and 67.4%similarity with serpin mRNA binding protein 1,which is also named CGI-55,or plasminogen activator inhibitor type-1-RNA binding protein-1,indicating that they might be paralog proteins,possibly with similar or redundant functions in human cells.Through the identification of their protein interactomes,both regulatory proteins have been functionally implicated in transcriptional regulation,mRNA metabolism,specifically RNA splicing,the regulation of mRNA stability,especially,in the context of the progesterone hormone response,and the DNA damage response.Both proteins also show a complex pattern of post-translational modifications,involving Ser/Thr phosphorylation,mainly through protein kinase C,arginine methylation and SUMOylation,suggesting that their functions and locations are highly regulated.Furthermore,they show a highly dynamic cellular localization pattern with localizations in both the cytoplasm and nucleus as well as punctuated localizations in both granular cytoplasmic protein bodies,upon stress,and nuclear splicing speckles.Several reports in the literature show altered expressions of both regulatory proteins in a series of cancers as well as mutations in their genes that may contribute to tumorigenesis.This review highlights important aspects of the structure,interactome,post-translational modifications,sub-cellular localization and function of both regulatory proteins and further discusses their possible functions and their potential as tumor markers in different cancer settings.
基金supported by the National Natural Science Foundation of China(52001171,21835004,51901104,22020102002,51801105 and 52101226)the National Key R&D Program of China(2017YFA0206700 and 2018YFB1502101)+1 种基金the NCC Fund(NCC2020FH03)the 111 Project from the Ministry of Education of China(B12015)。
文摘Single-crystal cathodes(SCCs)are promising substitute materials for polycrystal cathodes(PCCs)in lithium-ion batteries(LIBs),because of their unique ordered structure,excellent cycling stability and high safety performance.Cathode materials with layered(LiCoO_(2),LiNi_xCo_yMnzO_(2),LiNi_xCo_yAl_(2)O_(2))and spinel structure(LiMn_(2)O_(4),LiNi_(0.5)Mn_(1.5)O_(4))show a relatively stable electrochemical performance,but still lack of sufficient attention in research field.In this review,we begin with the definition,structural features and electrochemical advantages of SCCs.Common SCCs synthesis methods and the thermodynamic growth mechanism of SCCs with oriented facet exposure are summarized in the following part.Then we introduce the problems and challenges of SCCs faced and the corresponding modification strategies.Finally,the industrialization progress of SCCs is brifly outlined.We intend to tease out the difficulties and advances of SCCs to provide insights for future development of high-performance SCCs for practical LIBs.
基金the German Academic Exchange Service(DAAD),ICRAF and NARO for funding this research。
文摘This study was intended to understand how smallholder farmers’modifications improved agroforestry technologies’usability in Uganda’s Mt.Elgon region.We used a case study approach to understand how smallholder farmers’contextual realities informed their modifications and enhanced the usability of agroforestry technologies.Data was collected over four months of frequent and regular interaction with the cases using formal and informal methods that included in-depth interviews,conversations,discussions,and direct observations.Emerging themes and patterns were identified from the comprehensively reduced data.In addition,respondents’direct quotes were used to emphasize the reasons for the modifications.The findings showed that smallholder farmers modified the recommended technologies to suit their biophysical and socio-economic realities.Differences and similarities in modifications existed among cases across the agroforestry technologies.The modifications were mainly done to diversify tree uses,optimize space utilization,and minimize production costs for farming households.These findings imply a need to critically examine the smallholder farmers’modifications to make agroforestry technologies applicable and compliant to their contexts.This will inform the re-invention of technologies that will quickly diffuse into the community for broader impact.Findings also emphasize the need to rethink the linear model of technology transfer mainly applied in agroforestry technology development and dissemination because it offers limited space for the much-needed feedback from smallholder farmers.
文摘The influence of different modification methods on the surface properties of indium-tin-oxide (ITO) electrodes were investigated by measurements of chemical composition,surface roughness,sheet resistance,contact angle and surface free energy.Experimental results demonstrate that oxygen plasma treatment more effectively optimizes the surface properties of ITO electrodes compared with the other treatments.Furthermore,the polymer light-emitting electrochemical cells (PLECs) with the differently treated ITO substrates as device electrodes were fabricated and characterized.It is found that oxygen plasma treatment on the ITO electrode enhances injection current,luminance and efficiency,thereby improves the device characteristics of the PLECs.
文摘Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or delay the progression of AMD more efficiently.Until now,the pathogenesis of AMD has remained unclear,limiting the development of the novel therapy.Bruch’s membrane(BM)goes through remarkable changes in AMD,playing a significant role during the disease course.The main aim of this review is to present the crucial processes that occur at the level of BM,with special consideration of the lipid accumulation and protein modifications.Besides,some therapies targeted at these molecules and the construction of BM in tissue engineering of retinal pigment epithelium(RPE)cells transplantation were listed.Hopefully,this review may provide a reference for researchers engaged in pathogenesis or management on AMD.
文摘In the present work, computational analyses were applied to study the subcellular localiza-tion and posttranslational modifications of hu-man prion proteins (PrPs). The tentative location of prion protein was determined to be in the nu-cleolus inside the nucleus by the following bio-informatics tools: Hum-PLoc, Euk-PLoc and Nuc-PLoc. Based on our results signal peptides with average of 22 base pairs in N-terminal were identified in human PrPs. This theoretical study demonstrates that PrP is post-translationally modified by: 1) attachment of two N-linked complex carbohydrate moieties (N181 and N197), 2) attachmet of glycosylphosphatidylinositol (GPI) at serine 230 and 3) formation of two di-sulfide bonds between “6–22” and “179–214” cysteines. Furthermore, ten protein kinase phosphorylation sites were predicted in human PrP. The above-noted phosphorylation was car-ried out by PKC and CK2. By using bioinfor-matics tools, we have shown that computation-ally human PrPs locate particularly into the nu-cleolus.
文摘Pineapple Leaf Fibre (PALF) is one of the natural fibres that have high potential in the industry. Natural fibres have become the main alternative source for reinforced polymer composites. The objective of this study is to observe the effect of chemical treatments using Sodium Hydroxide (NaOH) solution, Zinc chloride, Acetic Anhydride and Nitric acid on the mechanical properties of pineapple leaf fibre reinforced polypropylene composites. The tensile test was conducted by using the ASTM D638-10 to obtain the tensile strength (TS) and Young’s modulus (YM), Flexural properties were conducted to determine the flexural strength (FS) and flexural modulus (FM) of the reinforced composites using the ASTM D256-10 method, and impact test was conducted to determine the impact strength (IS) of the reinforced composites using the Izod ASTM D790-17 method. From the results obtained, the composites with surface modified PALF fillers show enhanced mechanical properties over the untreated PALF fillers in this order;for TS untreated composite C3H6O3 3. For YM untreated composite 3 C3H6O3 3 3H6O3. For FM, untreated reinforced PALF/PP composites C3H6O3 3. For IS, the untreated reinforced PALF/PP composites 3 C3H6O3. SEM analysis was carried out on the PALF before the compounding to analyze the effect of the surface modification agents.
基金This work was supported by the National Natural Science Foundations of China(No.51271121,51471109).
文摘In this work,surface modification of a Mg-4Sm-2Al-0.5Mn alloy with high current pulse electron beam(HCPEB)under different number of pulses were investigated.The evolution in microstructure,composition and phase components and properties in the surface layer before and after HCPEB treatment were characterized.It was found that the Al 11 Sm 3 and Al 2 Sm phases in the surface layer were gradually dissolved during HCPEB treatment,leading to the formation of a chemical homogeneous melted layers.Besides,deformation bands were formed in the treated layer due to the thermal stress generated during treatment.After 15 pulses treatment,the surface hardness increases to the maximum value of about 62.2 HV,about 61.2%higher than that of the untreated state.Electrochemical results show that the 15 pulses treated sample presents the best corrosion resistance in the 3.5wt%NaCl water solution by showing the highest corrosion potential(E_(corr))of-1.339V SEC and the lowest corrosion current density(I_(corr))of 1.48×10^(-6)A·cm^(-2).The results prove that the surface properties of the Mg-4Sm-2Al-0.5Mn alloy can be significantly improved by the HCPEB treatments under proper conditions.
