The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. ...The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of nonimmune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct proinflammatory mediators. Excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in IBD.The effects determine pathologic changes,which may sustain chronic intestinal inflammation and also underlie specific disease phenotypes.In addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers,research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.展开更多
BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer treatme...BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer treatments.However,inducing a purposeful synergistic response between conventional therapies and the immune system remains evasive.The release of damage associated molecular patterns(DAMPs)is indicative of immunogenic cell death and propagation of established immune responses.However,there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma(OAC)or by immune cells themselves.AIM To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic cancer.METHODS We investigated the levels of immunogenic cell death-associated DAMPs,calreticulin(CRT)and HMGB1 using an OAC isogenic model of radioresistance.DAMP expression was also assessed directly using ex vivo cancer patient T cells(n=10)and within tumour biopsies(n=9)both pre and post-treatment with clinically relevant chemo(radio)therapeutics.RESULTS Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in vitro.Significantly increased frequencies of T cell DAMP expression in OAC patients were observed following chemo-(radio)therapy,which was significantly higher in tumour tissue compared with peripheral blood.Patients with high expression of HMGB1 had a significantly better tumour regression grade(TRG 1-2)compared to low expressors.CONCLUSION In conclusion,OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors,which correlated with tumour regression grade and lymphatic invasion.It also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.展开更多
BACKGROUND Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for ch...BACKGROUND Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for cholangiocarcinoma treatment but their efficacy against cholangiocarcinoma was low. We suggest how such antitumor activity can be increased using cell lysates derived from an honokioltreated cholangiocarcinoma cell line (KKU-213L5). AIM To increase antitumour activity of DCs pulsed with cell lysates derived from honokiol-treated cholangiocarcinoma cell line (KKU-213L5). METHODS The effect of honokiol, a phenolic compound isolated from Magnolia officinalis, on choangiocarcinoma cells was investigated in terms of the cytotoxicity and the expression of damage-associated molecular patterns (DAMPs). DCs were loaded with tumour cell lysates derived from honokiol-treated cholangiocarcinoma cells their efficacy including induction of T lymphocyte proliferation, proinflammatory cytokine production and cytotoxicity effect on target cholangiocarcinoma cells were evaluated. RESULTS Honokiol can effectively activate cholangiocarcinoma apoptosis and increase the release of damage-associated molecular patterns. DCs loaded with cell lysates derived from honokiol-treated tumour cells enhanced priming and stimulated T lymphocyte proliferation and type I cytokine production. T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated tumour cells significantly increased specific killing of human cholangiocarcinoma cells compared to those associated with DCs pulsed with cell lysates of untreated cholangiocarcinoma cells. CONCLUSION The present findings suggested that honokiol was able to enhance the immunogenicity of cholangiocarcinoma cells associated with increased effectiveness of DC-based vaccine formulation. Treatment of tumour cells with honokiol offers a promising approach as an ex vivo DC-based anticancer vaccine.展开更多
All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli.The immune system activates when damaged or injured cells release damage‐associated molecul...All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli.The immune system activates when damaged or injured cells release damage‐associated molecular patterns(DAMPs).In addition to well‐characterized DAMPs such as high‐mobility group box 1 and adenosine triphosphate,studies on new classes of DAMPs have emerged.Here,we review recent reports of a new class of isoprenoid‐derived DAMPs,including farnesyl pyrophosphate and geranylgeranyl pyrophosphate,both of which are pivotal metabolic inter-mediates of the mevalonate pathway.We also explore the roles of old and new DAMPs in autoimmune diseases that result from dysregulated inflammation.The findings highlight that understanding the functional mechanisms of DAMPs is important to enrich the DAMP family and decipher their immunoregulatory mechanisms to provide new therapeutics for the prevention and treatment of autoimmune diseases.展开更多
A molecular study based on COI, 16S and 28S genes reveals that a batch of specimens(7 males and 4 females) of Dysphaea Selys, 1853 collected from central Vietnam,which include different color patterns of wings and bod...A molecular study based on COI, 16S and 28S genes reveals that a batch of specimens(7 males and 4 females) of Dysphaea Selys, 1853 collected from central Vietnam,which include different color patterns of wings and body, and were originally identified as three different species, are all the same species. This study implies that, in some group of Odonata,identification only depending on color pattern may be unreliable, no matter what huge variations there are.展开更多
BACKGROUND Periodontitis is a chronic inflammation of periodontal supporting tissue caused by local factors. Periodontal surgery can change the gene expression of peripheral blood mononuclear cells. However, little is...BACKGROUND Periodontitis is a chronic inflammation of periodontal supporting tissue caused by local factors. Periodontal surgery can change the gene expression of peripheral blood mononuclear cells. However, little is known about the potential mechanism of surgical treatment for periodontitis. AIM To explore the potential molecular mechanism of surgical treatment for periodontitis. METHODS First, based on the expression profiles of genes related to surgical treatment for periodontitis, a set of expression disorder modules related to surgical treatment for periodontitis were obtained by enrichment analysis. Subsequently, based on crosstalk analysis, we proved that there was a significant crosstalk relationship between module 3 and module 5. Finally, based on predictive analysis of multidimensional regulators, we identified a series of regulatory factors, such as endogenous genes, non-coding RNAs (ncRNAs), and transcription factors, which have potential regulatory effects on periodontitis. RESULTS A total of 337 genes related to surgical treatment for periodontitis were obtained, and 3896 genes related to periodontitis were amplified. Eight expression modules of periodontitis were obtained, involving the aggregation of 2672 gene modules. These modules are mainly involved in G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger, and adenylate cyclasemodulating G-protein coupled receptor signaling pathway. In addition, eight endogenous genes (including EGF, RPS27A, and GNB3) were screened by network connectivity analysis. Finally, based on this set of potential dysfunction modules, 94 transcription factors (including NFKB1, SP1, and STAT3) and 1198 ncRNAs (including MALAT1, CRNDE, and ANCR) were revealed. These core regulators are thought to be involved in the potential molecular mechanism of periodontitis after surgical treatment. CONCLUSION Based on the results of this study, we can show biologists and pharmacists a new idea to reveal the potential molecular mechanism of surgical treatment for periodontitis, and provide valuable reference for follow-up treatment programs.展开更多
Crystal patterns in ultrathin films of six poly（ethylene oxide） fractions with molecular weights from 25000 to 932000 g/mol were characterized within crystallization temperature range from 20 ℃to 60℃. Labyrinthine...Crystal patterns in ultrathin films of six poly（ethylene oxide） fractions with molecular weights from 25000 to 932000 g/mol were characterized within crystallization temperature range from 20 ℃to 60℃. Labyrinthine, dendritic and faceted crystal patterns were observed in different temperature ranges, and then labyrinthine-to-dendritic and dendritic-to- faceted transition temperatures T_L-D and T_D-F were quantitatively identified. Their molecular weight dependences are T_L-D（M_w） = T_L-D（∞） -K_L-D/M_w, where T_L-D（∞） = 38.2 ℃ and K_L-D = 253000 ℃.g/mol and T_D-F（M_w） = T_D-F（∞） -K_D-F/M_w, where T_D-F（∞） = 54.7 ℃ and K_D-F= 27000 ℃.g/mol. Quasi two-dimensional blob models were proposed to provide empirical explanations of the molecular weight dependences. The labyrinthine-to-dendritic transition is attributed to a molecular diffusion process change from a local-diffusion to diffusion-limited-aggregation （DLA） and a polymer chain with M_w ≈253000 g/mol within a blob can join crystals independently. The dendritic-to-faceted transition is attributed to a turnover of the pattern formation mechanism from DLA to crystallization control, and a polymer chain with a M_w ≈27000 g/tool as an independent blob crosses to a depletion zone to join crystals. These molecular weight dependences reveal a macromolecular effect on the crystal pattern formation and selection of crystalline polymers.展开更多
Molecular dynamics simulations are performed to study the nanoindentation models of monolayer suspended graphene and graphyne. Fullerenes are selected as indenters. Our results show that Young＇s modulus of monolayer-...Molecular dynamics simulations are performed to study the nanoindentation models of monolayer suspended graphene and graphyne. Fullerenes are selected as indenters. Our results show that Young＇s modulus of monolayer-thick graphyne is almost half of that of graphene, which is estimated to be 0.50 TPa. The mechanical properties of graphene and graphyne are different in the presence of strain. A pre-tension has an important effect on the mechanical properties of a membrane. Both the pre-tension and Young＇s modulus plots demonstrate index behavior. The toughness of graphyne is stronger than that of graphene due to Young＇s modulus magnitude. Young＇s moduli of graphene and graphyne are almost independent of the size ratio of indenter to membrane.展开更多
High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex...High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.展开更多
Herbivorous insects and pathogens cause severe damage to rice tissues,affecting yield and grain quality.Damaged cells trigger downstream defense responses through various signals.Extracellular ATP(eATP),a signaling mo...Herbivorous insects and pathogens cause severe damage to rice tissues,affecting yield and grain quality.Damaged cells trigger downstream defense responses through various signals.Extracellular ATP(eATP),a signaling molecule released during mechanical cell damage,is considered a constitutive damage-associated molecular pattern(DAMP),which is crucial for initiating plant defense responses.Thus,understanding how rice plants cope with DAMPs such as eATP is essential.Here,we found that exogenous ATP affected rice growth and development,cell wall composition,chloroplast development,and cell death.Subsequent global transcriptome analysis revealed that several pathways were involved in the eATP response,including genes related to cell surface receptors,cell wall organization,chlorophyll biosynthesis,heat and temperature stimulation,epigenetic regulation,and reactive oxygen species metabolism.Cell surface receptors,including members of the lectin receptor-like kinases(LecRKs),were found to participate in the eATP response.We further investigated ATP-induced genes in T-DNA activation mutants of OsLecRKs,demonstrating their involvement in eATP signaling in rice.This study confirms a DAMP-mediated transcriptional response in plants and provides novel candidates for advancing resistant rice breeding against insect herbivores and pathogens.展开更多
Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive imm...Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.展开更多
基金Supported by the Brazilian research foundations Fundacao de Amparo à Pesquisa do Estado do Rio de Janeiro--FAPERJ,No.E26/202.781/2017Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq,No.302401/2016-4
文摘The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of nonimmune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct proinflammatory mediators. Excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in IBD.The effects determine pathologic changes,which may sustain chronic intestinal inflammation and also underlie specific disease phenotypes.In addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers,research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.
文摘BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer treatments.However,inducing a purposeful synergistic response between conventional therapies and the immune system remains evasive.The release of damage associated molecular patterns(DAMPs)is indicative of immunogenic cell death and propagation of established immune responses.However,there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma(OAC)or by immune cells themselves.AIM To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic cancer.METHODS We investigated the levels of immunogenic cell death-associated DAMPs,calreticulin(CRT)and HMGB1 using an OAC isogenic model of radioresistance.DAMP expression was also assessed directly using ex vivo cancer patient T cells(n=10)and within tumour biopsies(n=9)both pre and post-treatment with clinically relevant chemo(radio)therapeutics.RESULTS Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in vitro.Significantly increased frequencies of T cell DAMP expression in OAC patients were observed following chemo-(radio)therapy,which was significantly higher in tumour tissue compared with peripheral blood.Patients with high expression of HMGB1 had a significantly better tumour regression grade(TRG 1-2)compared to low expressors.CONCLUSION In conclusion,OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors,which correlated with tumour regression grade and lymphatic invasion.It also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.
基金the grant from the Thailand Research Fund,No.BRG6180010Naresuan University Research Grant,No.R2561B001
文摘BACKGROUND Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for cholangiocarcinoma treatment but their efficacy against cholangiocarcinoma was low. We suggest how such antitumor activity can be increased using cell lysates derived from an honokioltreated cholangiocarcinoma cell line (KKU-213L5). AIM To increase antitumour activity of DCs pulsed with cell lysates derived from honokiol-treated cholangiocarcinoma cell line (KKU-213L5). METHODS The effect of honokiol, a phenolic compound isolated from Magnolia officinalis, on choangiocarcinoma cells was investigated in terms of the cytotoxicity and the expression of damage-associated molecular patterns (DAMPs). DCs were loaded with tumour cell lysates derived from honokiol-treated cholangiocarcinoma cells their efficacy including induction of T lymphocyte proliferation, proinflammatory cytokine production and cytotoxicity effect on target cholangiocarcinoma cells were evaluated. RESULTS Honokiol can effectively activate cholangiocarcinoma apoptosis and increase the release of damage-associated molecular patterns. DCs loaded with cell lysates derived from honokiol-treated tumour cells enhanced priming and stimulated T lymphocyte proliferation and type I cytokine production. T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated tumour cells significantly increased specific killing of human cholangiocarcinoma cells compared to those associated with DCs pulsed with cell lysates of untreated cholangiocarcinoma cells. CONCLUSION The present findings suggested that honokiol was able to enhance the immunogenicity of cholangiocarcinoma cells associated with increased effectiveness of DC-based vaccine formulation. Treatment of tumour cells with honokiol offers a promising approach as an ex vivo DC-based anticancer vaccine.
基金The authors acknowledge support from the Tsinghua University Spring Breeze Fund,Center for Life Sciences,and Institute for Immunology,Tsinghua University,and grants from the Ministry of Science and Technology of China(2021YFC2300500 and 2021YFC2302403)National Natural Science Foundation of China(32141004,81825010,81730043,and 81621002).
文摘All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli.The immune system activates when damaged or injured cells release damage‐associated molecular patterns(DAMPs).In addition to well‐characterized DAMPs such as high‐mobility group box 1 and adenosine triphosphate,studies on new classes of DAMPs have emerged.Here,we review recent reports of a new class of isoprenoid‐derived DAMPs,including farnesyl pyrophosphate and geranylgeranyl pyrophosphate,both of which are pivotal metabolic inter-mediates of the mevalonate pathway.We also explore the roles of old and new DAMPs in autoimmune diseases that result from dysregulated inflammation.The findings highlight that understanding the functional mechanisms of DAMPs is important to enrich the DAMP family and decipher their immunoregulatory mechanisms to provide new therapeutics for the prevention and treatment of autoimmune diseases.
基金supported by the National Natural Science Foundation of China(31572299)a grant from the Ministry of Science and Technology of China(2015FY210300)
文摘A molecular study based on COI, 16S and 28S genes reveals that a batch of specimens(7 males and 4 females) of Dysphaea Selys, 1853 collected from central Vietnam,which include different color patterns of wings and body, and were originally identified as three different species, are all the same species. This study implies that, in some group of Odonata,identification only depending on color pattern may be unreliable, no matter what huge variations there are.
文摘BACKGROUND Periodontitis is a chronic inflammation of periodontal supporting tissue caused by local factors. Periodontal surgery can change the gene expression of peripheral blood mononuclear cells. However, little is known about the potential mechanism of surgical treatment for periodontitis. AIM To explore the potential molecular mechanism of surgical treatment for periodontitis. METHODS First, based on the expression profiles of genes related to surgical treatment for periodontitis, a set of expression disorder modules related to surgical treatment for periodontitis were obtained by enrichment analysis. Subsequently, based on crosstalk analysis, we proved that there was a significant crosstalk relationship between module 3 and module 5. Finally, based on predictive analysis of multidimensional regulators, we identified a series of regulatory factors, such as endogenous genes, non-coding RNAs (ncRNAs), and transcription factors, which have potential regulatory effects on periodontitis. RESULTS A total of 337 genes related to surgical treatment for periodontitis were obtained, and 3896 genes related to periodontitis were amplified. Eight expression modules of periodontitis were obtained, involving the aggregation of 2672 gene modules. These modules are mainly involved in G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger, and adenylate cyclasemodulating G-protein coupled receptor signaling pathway. In addition, eight endogenous genes (including EGF, RPS27A, and GNB3) were screened by network connectivity analysis. Finally, based on this set of potential dysfunction modules, 94 transcription factors (including NFKB1, SP1, and STAT3) and 1198 ncRNAs (including MALAT1, CRNDE, and ANCR) were revealed. These core regulators are thought to be involved in the potential molecular mechanism of periodontitis after surgical treatment. CONCLUSION Based on the results of this study, we can show biologists and pharmacists a new idea to reveal the potential molecular mechanism of surgical treatment for periodontitis, and provide valuable reference for follow-up treatment programs.
基金financially supported by the National Science Foundation of China(No.20874053)
文摘Crystal patterns in ultrathin films of six poly（ethylene oxide） fractions with molecular weights from 25000 to 932000 g/mol were characterized within crystallization temperature range from 20 ℃to 60℃. Labyrinthine, dendritic and faceted crystal patterns were observed in different temperature ranges, and then labyrinthine-to-dendritic and dendritic-to- faceted transition temperatures T_L-D and T_D-F were quantitatively identified. Their molecular weight dependences are T_L-D（M_w） = T_L-D（∞） -K_L-D/M_w, where T_L-D（∞） = 38.2 ℃ and K_L-D = 253000 ℃.g/mol and T_D-F（M_w） = T_D-F（∞） -K_D-F/M_w, where T_D-F（∞） = 54.7 ℃ and K_D-F= 27000 ℃.g/mol. Quasi two-dimensional blob models were proposed to provide empirical explanations of the molecular weight dependences. The labyrinthine-to-dendritic transition is attributed to a molecular diffusion process change from a local-diffusion to diffusion-limited-aggregation （DLA） and a polymer chain with M_w ≈253000 g/mol within a blob can join crystals independently. The dendritic-to-faceted transition is attributed to a turnover of the pattern formation mechanism from DLA to crystallization control, and a polymer chain with a M_w ≈27000 g/tool as an independent blob crosses to a depletion zone to join crystals. These molecular weight dependences reveal a macromolecular effect on the crystal pattern formation and selection of crystalline polymers.
基金Supported by the National Natural Science Foundation of China under Grant No 11274262the Natural Science Foundation of Hunan Province under Grand No 14JJ2046the Program for Changjiang Scholars and Innovative Research Team in Universities under Grant No IRT13093
文摘Molecular dynamics simulations are performed to study the nanoindentation models of monolayer suspended graphene and graphyne. Fullerenes are selected as indenters. Our results show that Young＇s modulus of monolayer-thick graphyne is almost half of that of graphene, which is estimated to be 0.50 TPa. The mechanical properties of graphene and graphyne are different in the presence of strain. A pre-tension has an important effect on the mechanical properties of a membrane. Both the pre-tension and Young＇s modulus plots demonstrate index behavior. The toughness of graphyne is stronger than that of graphene due to Young＇s modulus magnitude. Young＇s moduli of graphene and graphyne are almost independent of the size ratio of indenter to membrane.
基金supported by a grant of the M.D.-Ph.D./Medical Scientist Training Program through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(to HK)+3 种基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSITMinistry of Science and ICT)(NRF2019R1A5A2026045 and NRF-2021R1F1A1061819)a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HR21C1003)New Faculty Research Fund of Ajou University School of Medicine(to JYC)。
文摘High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.
基金supported by the Brain Pool Program funded by the Ministry of Science and Information and Communication Technology through the National Research Foundation of Korea(Grant Nos.2022H1D3A2A01096185 and RS-2024-00410063)the Basic Science Research Program through the National Research Foundation of Korea(Grant No.RS-2023-00247376)+4 种基金the Cooperative Research Program for Agriculture Science and Technology Development,Korea(Grant No.RS-2022-RD010386)US National Science Foundation Plant Genome Program(Grant No.IOS-2048410)the US National Institute of General Medical Sciences of the National Institutes of Health(Grant No.R01GM121445)US Department of Agriculture’s National Institute of Food and Agriculture(Grant No.USDA-AFRI-2023-67013-39896)the National Science Foundation(Grant No.IOS-PGRP-2348319).
文摘Herbivorous insects and pathogens cause severe damage to rice tissues,affecting yield and grain quality.Damaged cells trigger downstream defense responses through various signals.Extracellular ATP(eATP),a signaling molecule released during mechanical cell damage,is considered a constitutive damage-associated molecular pattern(DAMP),which is crucial for initiating plant defense responses.Thus,understanding how rice plants cope with DAMPs such as eATP is essential.Here,we found that exogenous ATP affected rice growth and development,cell wall composition,chloroplast development,and cell death.Subsequent global transcriptome analysis revealed that several pathways were involved in the eATP response,including genes related to cell surface receptors,cell wall organization,chlorophyll biosynthesis,heat and temperature stimulation,epigenetic regulation,and reactive oxygen species metabolism.Cell surface receptors,including members of the lectin receptor-like kinases(LecRKs),were found to participate in the eATP response.We further investigated ATP-induced genes in T-DNA activation mutants of OsLecRKs,demonstrating their involvement in eATP signaling in rice.This study confirms a DAMP-mediated transcriptional response in plants and provides novel candidates for advancing resistant rice breeding against insect herbivores and pathogens.
基金Supported by Shenzhen Medical Research Fund,No.D2301010Shenzhen Science and Technology Program,No.RCYX20231211090346060。
文摘Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.
