Understanding microbial-host interactions in the oral cavity is essential for elucidating oral disease pathogenesis and its systemic implications.In vitro bacteria-host cell coculture models have enabled fundamental s...Understanding microbial-host interactions in the oral cavity is essential for elucidating oral disease pathogenesis and its systemic implications.In vitro bacteria-host cell coculture models have enabled fundamental studies to characterize bacterial infection and host responses in a reductionist yet reproducible manner.However,existing in vitro coculture models fail to establish conditions that are suitable for the growth of both mammalian cells and anaerobes,thereby hindering a comprehensive understanding of their interactions.Here,we present an asymmetric gas coculture system that simulates the oral microenvironment by maintaining distinct normoxic and anaerobic conditions for gingival epithelial cells and anaerobic bacteria,respectively.Using a key oral pathobiont,Fusobacterium nucleatum,as the primary test bed,we demonstrate that the system preserves bacterial viability and supports the integrity of telomerase-immortalized gingival keratinocytes.Compared to conventional models,this system enhanced bacterial invasion,elevated intracellular bacterial loads,and elicited more robust host pro-inflammatory responses,including increased secretion of CXCL10,IL-6,and IL-8.In addition,the model enabled precise evaluation of antibiotic efficacy against intracellular pathogens.Finally,we validate the ability of the asymmetric system to support the proliferation of a more oxygen-sensitive oral pathobiont,Porphyromonas gingivalis.These results underscore the utility of this coculture platform for studying oral microbial pathogenesis and screening therapeutics,offering a physiologically relevant approach to advance oral and systemic health research.展开更多
Viruses,the most diverse of all biological entities,are ubiquitous and can influence nearly all life forms on Earth[1].The preliminary pathway through which viruses affect microbialmetabolism and evolution is viral in...Viruses,the most diverse of all biological entities,are ubiquitous and can influence nearly all life forms on Earth[1].The preliminary pathway through which viruses affect microbialmetabolism and evolution is viral infection[2].There are two distinct infection modes for viruses interacting with prokaryotes,namely temperate and virulent lifestyles[3].Virulent viruses trigger their hosts’death by lysis once they invade the host cells[2],whereas temperate viruses can replicate alongside their host inthe lysogenic cycle until a lytic cycle is induced[2,3].It has beenreported that viral lifestyles are key determinants of virusencoded auxiliary metabolic genes(AMGs)that are crucial toolboxes for viruses to reprogram host metabolisms[4].An in-depthinvestigation of virus-microbe infection modes over a broad geographical scale is thus vital for understanding the potential effectsof viruses on the microbial community and biogeochemical cycles.展开更多
The first discovery of bacterial Extracellular Vesicles(bEVs)was made in the Gram-negative bacterium Escherichia coli in the 1960s.1 The secretion of vesicles by Gram-positive bacteria was not uncovered until the 1990...The first discovery of bacterial Extracellular Vesicles(bEVs)was made in the Gram-negative bacterium Escherichia coli in the 1960s.1 The secretion of vesicles by Gram-positive bacteria was not uncovered until the 1990s because the thick cell wall was seen as a physical barrier to their release.2 It is now evident that in all domains of life,bacteria secrete spherical membrane vesicles ranging in diameter from 20 to 400 nm(Figure 1A).展开更多
INTRODUCTION Tuberculosis(TB)remains a widespread and serious infectious disease caused by the chronic pathogen Mycobacterium tuberculosis(Mtb),leading to approximately 10 million new cases and 1.5 million deaths annu...INTRODUCTION Tuberculosis(TB)remains a widespread and serious infectious disease caused by the chronic pathogen Mycobacterium tuberculosis(Mtb),leading to approximately 10 million new cases and 1.5 million deaths annually[1].Notably,the continuous emergence of drug-resistantMtb strains and co-infection with human immunodeficiency virus(HIV)further pose significant challenges to TB prevention and treatment,necessitating an innovative breakthrough in TB control.Vaccination is the most economical and effective approach to preventing and controlling infectious diseases.However,Bacillus Calmette-Guérin(BCG)is currently the only licensed vaccine available for TB,protecting meningeal and disseminated TB in children,but failing to protect adolescents and adults,who are the primary transmitters of TB.Moreover,BCG cannot prevent the progression of latent TB infection(LTBI)to active TB,and its protective efficacy wanes over time[2,3].Against this backdrop,efforts to develop more effective TB vaccines have been ongoing.展开更多
The intratumor microbiome,one of the hallmarks of cancer,plays a crucial role in cancer progression through its interaction with the host.However,the underlying mechanisms remain poorly understood.In this study,six pu...The intratumor microbiome,one of the hallmarks of cancer,plays a crucial role in cancer progression through its interaction with the host.However,the underlying mechanisms remain poorly understood.In this study,six publicly available single-cell transcriptomic lung cancer datasets(comprising 178 samples)from multiple centers(Shanghai,New York,Seoul)were integrated to investigate the heterogeneity of host-microbiome interactions at the single-cell level using single-cell analysis of host-microbiome interactions(SAHMI).The results indicate that primary tumor tissues have a high proportion of fungi-associated cells,whereas metastatic brain tissues predominantly contain bacteria-associated cells.There are also distinct microbial distributions across cell types.Notably,the presence of specific bacteria significantly influences the transcriptome of resident host cells,including T cells and macrophages,by modulating pathways related to ribosomal RNA(rRNA)processing,cellular responses to stress and stimuli,and RNA and protein metabolism.Finally,specific cell-associated bacteria are significantly correlated with clinical features,such as lung cancer stages and smoking frequency.These single-cell insights into microbiome-host interactions improve current understanding about lung cancer development and progression and offer potential micro-ecological and diagnostic insights.展开更多
Aromatic nitro compounds present substantial health and environmental concerns due to their toxic nature and potential explosive properties.Consequently,the development of host–vip molecular recognition systems for...Aromatic nitro compounds present substantial health and environmental concerns due to their toxic nature and potential explosive properties.Consequently,the development of host–vip molecular recognition systems for these compounds serves a dual-purpose:enabling the fabrication of high-performance sensors for detection and guiding the design of efficient adsorbents for environmental remediation.This study investigated the host–vip recognition behavior of perethylated pillar[n]arenes toward two aromatic nitro molecules,1-chloro-2,4-dinitrobenzene and picric acid.Various techniques including^(1)H NMR,2D NOESY NMR,and UV-vis spectroscopy were employed to explore the binding behavior between pillararenes and aromatic nitro vips in solution.Moreover,valuable single crystal structures were obtained to elucidate the distinct solid-state assembly behaviors of these vips with different pillararenes.The assembled solid-state supramolecular structures observed encompassed a 1:1 host–vip inclusion complex,an external binding complex,and an exo-wall tessellation complex.Furthermore,based on the findings from these systems,a pillararene-based test paper was developed for efficient picric acid detection,and the removal of picric acid from solution was also achieved using pillararenes powder.This research provides novel insights into the development of diverse host–vip systems toward hazardous compounds,offering potential applications in environmental protection and explosive detection domains.展开更多
The first event in viral infection is the attachment of a virus to specific receptors on the host cell surface. This will trigger conformational changes of the viral surface protein. For
With constant economic development and continuous improvement of living standards in Northeast China,rural tourism,as a new type of tourism,is increasingly favored. From the perspective of symbolic interaction theory,...With constant economic development and continuous improvement of living standards in Northeast China,rural tourism,as a new type of tourism,is increasingly favored. From the perspective of symbolic interaction theory,taking the current situation of rural tourism in Northeast China as an example,this paper explained the semiotic significance between hosts and vips in rural tourism. It established the evaluation indicators for authentic symbolic perception of rural tourism. Also,combined with the theories of sociology and anthropology,it studied the interaction between hosts and tourists of rural tourism in Northeast China.展开更多
Ralstonia solanacearum is an important model phytopathogenic bacterium that causes bacterial wilt disease on many plant species and leads to serious economic losses. The interactions between R. solanacearum and host p...Ralstonia solanacearum is an important model phytopathogenic bacterium that causes bacterial wilt disease on many plant species and leads to serious economic losses. The interactions between R. solanacearum and host plants have become a model system for the study of plants and pathogens interactions. This paper reviews the advances on the molecular mechanisms between R. solanacearum and hosts interaction including the formation of plant innate immunity, the suppression of plant innate immunity by this pathogen and the activation of effector-triggered immunity. Furthermore, we made a prospect on how to utilize the interaction mechanism between R. solanacearum and hosts to control the disease.展开更多
Luminescent metal-organic frameworks(MOFs)have garnered significant attention due to their structural tunability and potential applications in solid-state lighting,bioimaging,sensing,anticounterfeiting,and other field...Luminescent metal-organic frameworks(MOFs)have garnered significant attention due to their structural tunability and potential applications in solid-state lighting,bioimaging,sensing,anticounterfeiting,and other fields.Nevertheless,due to the tendency of1,4-benzenedicarboxylic acid(BDC)to rotate within the framework,MOFs composed of it exhibit significant non-radiative energy dissipation and thus impair the emissive properties.In this study,efficient luminescence of MIL-140A nanocrystals(NCs)with BDC rotors as ligands is achieved by pressure treatment strategy.Pressure treatment effectively modulates the pore structure of the framework,enhancing the interactions between the N,N-dimethylformamide vip molecules and the BDC ligands.The enhanced host-vip interaction contributes to the structural rigidity of the MOF,thereby suppressing the rotation-induced excited-state energy loss.As a result,the pressure-treated MIL-140A NCs displayed bright blue-light emission,with the photoluminescence quantum yield increasing from an initial 6.8%to 69.2%.This study developed an effective strategy to improve the luminescence performance of rotor ligand MOFs,offers a new avenue for the rational design and synthesis of MOFs with superior luminescent properties.展开更多
Helicobacter pylori (H.pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently.A well-choreographed equilibrium between the bacterial effectors and host resp...Helicobacter pylori (H.pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently.A well-choreographed equilibrium between the bacterial effectors and host responses permits microbial persistence and health of the host,but confers a risk for serious diseases including gastric cancer.During its long coexistence with humans,H.pylori has developed complex strategies to limit the degree and extent of gastric mucosal damage and in? ammation,as well as immune effector activity.The present editorial thus aims to introduce and comment on major advances in the rapidly developing area of H.pylori/human gastric mucosa interaction (and its pathological sequelae),which is the result of millennia of co-evolution of,and thus of reciprocal knowledge between,the pathogen and its human host.展开更多
The bitterness of a drug is a major challenge for patient acceptability and compliance,especially for children.Due to the toxicity of medication,a human taste panel test has certain limitations.Atomoxetine hydrochlori...The bitterness of a drug is a major challenge for patient acceptability and compliance,especially for children.Due to the toxicity of medication,a human taste panel test has certain limitations.Atomoxetine hydrochloride(HCl),which is used for the treatment of attention deficit/hyperactivity disorder(ADHD),has an extremely bitter taste.The aim of this work is to quantitatively predict the bitterness of atomoxetine HCl by a biosensor system.Based on the mechanism of detection of the electronic tongue(Etongue),the bitterness of atomoxetine HCl was evaluated,and it was found that its bitterness was similar to that of quinine HCl.The bitterness threshold of atomoxetine HCl was 8.61μg/ml based on the Change of membrane Potential caused by Adsorption(CPA)value of the BT0 sensor.In this study,the taste-masking efficiency of 2-hydroxypropyl-β-cyclodextrin(HP-β-CyD)was assessed by Euclidean distances on a principle component analysis(PCA)map with the SA402B Taste Sensing System,and the host–vip interactions were investigated by differential scanning calorimetry(DSC),powder X-ray diffraction(XRD),nuclear magnetic resonance(NMR)spectroscopy and scanning electron microscopy(SEM).Biosensor evaluation and characterization of the inclusion complex indicated that atomoxetine HCl could actively react with 2-hydroxypropyl-β-cyclodextrin.展开更多
Tuberculosis(TB)is one of the deadliest infectious diseases in the world.The meta-bolic disease type 2 diabetes(T2D)significantly increases the risk of developing ac-tive TB.Effective new TB vaccine candidates and nov...Tuberculosis(TB)is one of the deadliest infectious diseases in the world.The meta-bolic disease type 2 diabetes(T2D)significantly increases the risk of developing ac-tive TB.Effective new TB vaccine candidates and novel therapeutic interventions are required to meet the challenges of global TB eradication.Recent evidence suggests that the microbiota plays a significant role in how the host responds to infection,in-jury and neoplastic changes.Animal models that closely reflect human physiology are crucial in assessing new treatments and to decipher the underlying immunological defects responsible for increased TB susceptibility in comorbid patients.In this study,using a diet-induced murine T2D model that reflects the etiopathogenesis of clinical T2D and increased TB susceptibility,we investigated how the intestinal microbiota may impact the development of T2D,and how the gut microbial composition changes following a very low-dose aerosol infection with Mycobacterium tuberculosis(Mtb).Our data revealed a substantial intestinal microbiota dysbiosis in T2D mice compared to non-diabetic animals.The observed differences were comparable to previous clini-cal reports in TB patients,in which it was shown that Mtb infection causes rapid loss of microbial diversity.Furthermore,diversity index and principle component analyses demonstrated distinct clustering of Mtb-infected non-diabetic mice vs.Mtb-infected T2D mice.Our findings support a broad applicability of T2D mice as a tractable small animal model for studying distinct immune parameters,microbiota and the immune-metabolome of TB/T2D comorbidity.This model may also enable answers to be found to critical outstanding questions about targeted interventions of the gut mi-crobiota and the gut-lung axis.展开更多
Parasitic plants and their hosts communicate through haustorial connections.Nutrient deficiency is a common stress for plants,yet little is known about whether and how host plants and parasites communicate during adap...Parasitic plants and their hosts communicate through haustorial connections.Nutrient deficiency is a common stress for plants,yet little is known about whether and how host plants and parasites communicate during adaptation to such nutrient stresses.In this study,we used transcriptomics and proteomics to analyze how soybean(Glycine max)and its parasitizing dodder(Cuscuta australis)respond to nitrate and phosphate deficiency(-N and-P).After-N and-P treatment,the soybean and dodder plants exhibited substantial changes of transcriptome and proteome,although soybean plants showed very few transcriptional responses to-P and dodder did not show any transcriptional changes to either-N or-P.Importantly,large-scale interplant transport of mRNAs and proteins was detected.Although the mobile mRNAs only comprised at most 0.2%of the transcriptomes,the foreign mobile proteins could reach 6.8%of the total proteins,suggesting that proteins may be the major forms of interplant communications.Furthermore,the interplant mobility of macromolecules was specifically affected by the nutrient regimes and the transport of these macromolecules was very likely independently regulated.This study provides new insight into the communication between host plants and parasites under stress conditions.展开更多
The major innate immune cell types involved in tuberculosis(TB)infection are macrophages,dendritic cells(DCs),neutrophils and natural killer(NK)cells.These immune cells recognize the TB-causing pathogen Mycobacterium ...The major innate immune cell types involved in tuberculosis(TB)infection are macrophages,dendritic cells(DCs),neutrophils and natural killer(NK)cells.These immune cells recognize the TB-causing pathogen Mycobacterium tuberculosis(Mtb)through various pattern recognition receptors(PRRs),including but not limited to Toll-like receptors(TLRs),Nod-like receptors(NLRs)and C-type lectin receptors(CLRs).Upon infection by Mtb,the host orchestrates multiple signaling cascades via the PRRs to launch a variety of innate immune defense functions such as phagocytosis,autophagy,apoptosis and inflammasome activation.In contrast,Mtb utilizes numerous exquisite strategies to evade or circumvent host innate immunity.Here we discuss recent research on major host innate immune cells,PRR signaling,and the cellular functions involved in Mtb infection,with a specific focus on the host’s innate immune defense and Mtb immune evasion.A better understanding of the molecular mechanisms underlying host–pathogen interactions could provide a rational basis for the development of effective anti-TB therapeutics.展开更多
MicroRNAs （miRNAs） were discovered two decades ago, yet there is still a great need for further studies elucidating their genesis and targeting in different phyla. Since experimental discovery and validation of miRN...MicroRNAs （miRNAs） were discovered two decades ago, yet there is still a great need for further studies elucidating their genesis and targeting in different phyla. Since experimental discovery and validation of miRNAs is difficult, computational predictions are indispensable and today most computational approaches employ machine learning. Toxoplasma gondii, a parasite residing within the cells of its hosts like human, uses miRNAs for its post-transcriptional gene reg- ulation. It may also regulate its hosts＇ gene expression, which has been shown in brain cancer. Since previous studies have shown that overexpressed miRNAs within the host are causal for disease onset, we hypothesized that T. gondii could export miRNAs into its host cell. We computationally predicted all hairpins from the genome of T. gondii and used mouse and human models to filter possible candidates. These were then further compared to known miRNAs in human and rodents and their expression was examined for T. gondii grown in mouse and human hosts, respectively. We found that among the millions of potential hairpins in T. gondii, only a few thousand pass filtering using a human or mouse model and that even fewer of those are expressed. Since they are expressed and differentially expressed in rodents and human, we suggest that there is a chance that T. gondii may export miRNAs into its hosts for direct regulation.展开更多
Amplified chirality and Förster resonance energy transfer(FRET)-assisted chirality transfer frommolecular to nanoscale level have been shown to play a vital role in co-assembled nanohelix for potential energy tra...Amplified chirality and Förster resonance energy transfer(FRET)-assisted chirality transfer frommolecular to nanoscale level have been shown to play a vital role in co-assembled nanohelix for potential energy transfer in biological systems.Herein,we have constructed a chiral host–vip complex donor system for chiral amplification via induced chirality of pillar[5]arene host and loaded it with an achiral dye acceptor to demonstrate how chirality-assisted excitation energy transfer occurred in the supramolecular nanohelix system in an aqueous medium.展开更多
Enteroviruses(EVs)are human pathogens commonly observed in children aged 0–5 years and adults.EV infections usually cause the common cold and hand-foot-and-mouth disease;however,more severe infections can result in m...Enteroviruses(EVs)are human pathogens commonly observed in children aged 0–5 years and adults.EV infections usually cause the common cold and hand-foot-and-mouth disease;however,more severe infections can result in multiorgan complications,such as polio,aseptic meningitis,and myocarditis.The molecular mechanisms by which enteroviruses cause these diseases are still poorly understood,but accumulating evidence points to two enterovirus proteases,2Apro and 3Cpro,as the key players in pathogenesis.The 2Apro performs post-translational proteolytic processing of viral polyproteins and cleaves several host factors to evade antiviral immune responses and promote viral replication.It was also discovered that coxsackievirus-induced cardiomyopathy was caused by 2Apro-mediated cleavage of dystrophin in cardiomyocytes,indicating that cellular protein proteolysis may play a key role in enterovirus-associated diseases.Therefore,studies of 2Apro could reveal additional substrates that may be associated with specific diseases.Here,we discuss the genetic and structural properties of 2Apro and review how the protease antagonizes innate immune responses to promote viral replication,as well as novel substrates and mechanisms for 2Apro.We also summarize the current approaches for identifying the substrates of 2Apro to discover novel mechanisms relating to certain diseases.展开更多
In recent years,many studies have focused on the interaction between host genes and microbiota and their mutual influence(Bonder et al.,2016;Goodrich et al.,2014;Rothschild et al.,2018;Wang et al.,2016;Zhang et al.,20...In recent years,many studies have focused on the interaction between host genes and microbiota and their mutual influence(Bonder et al.,2016;Goodrich et al.,2014;Rothschild et al.,2018;Wang et al.,2016;Zhang et al.,2019).Host genetic variation influences the composition of the microbial community,for instance in inflammatory bowel disease,host genetic susceptibilities induce pathological shifts in microbiome composition.展开更多
In a recent publication in Nature,Sakoguchi et al.reveal a long-sought missing link between pathogen-derived ligands and activating human natural killer(NK)cell receptors.1 The study identifies a clade of Plasmodium f...In a recent publication in Nature,Sakoguchi et al.reveal a long-sought missing link between pathogen-derived ligands and activating human natural killer(NK)cell receptors.1 The study identifies a clade of Plasmodium falciparum(P.falciparum)repetitive interspersed family(RIFIN)proteins that not only bind to the inhibitory KIR2DL1 receptor but,strikingly,also engage the activating KIR2DS1 receptor,thereby offering new insight into NK cell regulation in malaria and expanding our understanding of host–pathogen interaction in innate immune responses.展开更多
基金supported by National Science Foundation CAREER (2238972)National Institute of Dental and Craniofacial Research awards (R03DE031329 and R01DE030943)The Translational Tissue Modeling Laboratory is supported by the University of Michigan (Center for Gastrointestinal Research,Office of the Dean, Comprehensive Cancer Center, and the Departments of Pathology, Pharmacology, and Internal Medicine) with additional funding from the Endowment for Basic Sciences
文摘Understanding microbial-host interactions in the oral cavity is essential for elucidating oral disease pathogenesis and its systemic implications.In vitro bacteria-host cell coculture models have enabled fundamental studies to characterize bacterial infection and host responses in a reductionist yet reproducible manner.However,existing in vitro coculture models fail to establish conditions that are suitable for the growth of both mammalian cells and anaerobes,thereby hindering a comprehensive understanding of their interactions.Here,we present an asymmetric gas coculture system that simulates the oral microenvironment by maintaining distinct normoxic and anaerobic conditions for gingival epithelial cells and anaerobic bacteria,respectively.Using a key oral pathobiont,Fusobacterium nucleatum,as the primary test bed,we demonstrate that the system preserves bacterial viability and supports the integrity of telomerase-immortalized gingival keratinocytes.Compared to conventional models,this system enhanced bacterial invasion,elevated intracellular bacterial loads,and elicited more robust host pro-inflammatory responses,including increased secretion of CXCL10,IL-6,and IL-8.In addition,the model enabled precise evaluation of antibiotic efficacy against intracellular pathogens.Finally,we validate the ability of the asymmetric system to support the proliferation of a more oxygen-sensitive oral pathobiont,Porphyromonas gingivalis.These results underscore the utility of this coculture platform for studying oral microbial pathogenesis and screening therapeutics,offering a physiologically relevant approach to advance oral and systemic health research.
基金supported by the National Key Research and Development Program of China(2022YFF0801901 and 2022YFF0801903)the National Natural Science Foundation of China(32425004)the New Cornerstone Science Foundation through the XPLORER PRIZE.
文摘Viruses,the most diverse of all biological entities,are ubiquitous and can influence nearly all life forms on Earth[1].The preliminary pathway through which viruses affect microbialmetabolism and evolution is viral infection[2].There are two distinct infection modes for viruses interacting with prokaryotes,namely temperate and virulent lifestyles[3].Virulent viruses trigger their hosts’death by lysis once they invade the host cells[2],whereas temperate viruses can replicate alongside their host inthe lysogenic cycle until a lytic cycle is induced[2,3].It has beenreported that viral lifestyles are key determinants of virusencoded auxiliary metabolic genes(AMGs)that are crucial toolboxes for viruses to reprogram host metabolisms[4].An in-depthinvestigation of virus-microbe infection modes over a broad geographical scale is thus vital for understanding the potential effectsof viruses on the microbial community and biogeochemical cycles.
基金supported by the Agence Nationale de la Recherche(ELISE-ANR-21-CE42)the European Union(grant agreement no.101135402,Mobiles project)the Department MICA of INRAE(Velib project).
文摘The first discovery of bacterial Extracellular Vesicles(bEVs)was made in the Gram-negative bacterium Escherichia coli in the 1960s.1 The secretion of vesicles by Gram-positive bacteria was not uncovered until the 1990s because the thick cell wall was seen as a physical barrier to their release.2 It is now evident that in all domains of life,bacteria secrete spherical membrane vesicles ranging in diameter from 20 to 400 nm(Figure 1A).
基金supported by the National Key Research and Development Program of China(2022YFC2302900 and 2021YFA1300200 to C.H.L.and J.W.)the National Natural Science Foundation of China(82330069 to C.H.L.and 82372653 to J.W.)+4 种基金the State Key Laboratory of Medical Proteomics(SKLPK202001,SKLPO202003,and SKLP-X202401 to C.H.L.)the CAS Project for Young Scientists in Basic Research(YSBR-010 to J.W.)Youth Innovation Promotion Association CAS(Y2022036 to J.W.)Shenzhen Medical Research Fund(B2302035 to C.H.L.)Guangzhou National Laboratory(GZNL2024A01023 to C.H.L.).
文摘INTRODUCTION Tuberculosis(TB)remains a widespread and serious infectious disease caused by the chronic pathogen Mycobacterium tuberculosis(Mtb),leading to approximately 10 million new cases and 1.5 million deaths annually[1].Notably,the continuous emergence of drug-resistantMtb strains and co-infection with human immunodeficiency virus(HIV)further pose significant challenges to TB prevention and treatment,necessitating an innovative breakthrough in TB control.Vaccination is the most economical and effective approach to preventing and controlling infectious diseases.However,Bacillus Calmette-Guérin(BCG)is currently the only licensed vaccine available for TB,protecting meningeal and disseminated TB in children,but failing to protect adolescents and adults,who are the primary transmitters of TB.Moreover,BCG cannot prevent the progression of latent TB infection(LTBI)to active TB,and its protective efficacy wanes over time[2,3].Against this backdrop,efforts to develop more effective TB vaccines have been ongoing.
基金funding from the MOST Key R&D Program of China(Grant numbers 2022YFC2304703 and 2020YFA0907200)the Natural Science Foundation of China(Grant numbers 32270202 and 62372286)+2 种基金Program of Shanghai Academic/Technology Research Leader(Grant number 23XD1422300)Science and Technology Innovation Plan of Shanghai(Grant number 23JC1403200)Innovative research team of high-level local universities in Shanghai are greatly appreciated by all the authors.
文摘The intratumor microbiome,one of the hallmarks of cancer,plays a crucial role in cancer progression through its interaction with the host.However,the underlying mechanisms remain poorly understood.In this study,six publicly available single-cell transcriptomic lung cancer datasets(comprising 178 samples)from multiple centers(Shanghai,New York,Seoul)were integrated to investigate the heterogeneity of host-microbiome interactions at the single-cell level using single-cell analysis of host-microbiome interactions(SAHMI).The results indicate that primary tumor tissues have a high proportion of fungi-associated cells,whereas metastatic brain tissues predominantly contain bacteria-associated cells.There are also distinct microbial distributions across cell types.Notably,the presence of specific bacteria significantly influences the transcriptome of resident host cells,including T cells and macrophages,by modulating pathways related to ribosomal RNA(rRNA)processing,cellular responses to stress and stimuli,and RNA and protein metabolism.Finally,specific cell-associated bacteria are significantly correlated with clinical features,such as lung cancer stages and smoking frequency.These single-cell insights into microbiome-host interactions improve current understanding about lung cancer development and progression and offer potential micro-ecological and diagnostic insights.
基金supported by the fundamental research funds of Zhejiang Sci-Tech University(No.22212286-Y)the Natural Science Foundation of Zhejiang Province(No.LQ24B040003)。
文摘Aromatic nitro compounds present substantial health and environmental concerns due to their toxic nature and potential explosive properties.Consequently,the development of host–vip molecular recognition systems for these compounds serves a dual-purpose:enabling the fabrication of high-performance sensors for detection and guiding the design of efficient adsorbents for environmental remediation.This study investigated the host–vip recognition behavior of perethylated pillar[n]arenes toward two aromatic nitro molecules,1-chloro-2,4-dinitrobenzene and picric acid.Various techniques including^(1)H NMR,2D NOESY NMR,and UV-vis spectroscopy were employed to explore the binding behavior between pillararenes and aromatic nitro vips in solution.Moreover,valuable single crystal structures were obtained to elucidate the distinct solid-state assembly behaviors of these vips with different pillararenes.The assembled solid-state supramolecular structures observed encompassed a 1:1 host–vip inclusion complex,an external binding complex,and an exo-wall tessellation complex.Furthermore,based on the findings from these systems,a pillararene-based test paper was developed for efficient picric acid detection,and the removal of picric acid from solution was also achieved using pillararenes powder.This research provides novel insights into the development of diverse host–vip systems toward hazardous compounds,offering potential applications in environmental protection and explosive detection domains.
文摘The first event in viral infection is the attachment of a virus to specific receptors on the host cell surface. This will trigger conformational changes of the viral surface protein. For
基金Supported by Student Innovation Project of University of Science and Technology Liaoning in 2017(201710146000016)
文摘With constant economic development and continuous improvement of living standards in Northeast China,rural tourism,as a new type of tourism,is increasingly favored. From the perspective of symbolic interaction theory,taking the current situation of rural tourism in Northeast China as an example,this paper explained the semiotic significance between hosts and vips in rural tourism. It established the evaluation indicators for authentic symbolic perception of rural tourism. Also,combined with the theories of sociology and anthropology,it studied the interaction between hosts and tourists of rural tourism in Northeast China.
基金Supported by Fundamental Research Funds for the Central Universities(110201202002)
文摘Ralstonia solanacearum is an important model phytopathogenic bacterium that causes bacterial wilt disease on many plant species and leads to serious economic losses. The interactions between R. solanacearum and host plants have become a model system for the study of plants and pathogens interactions. This paper reviews the advances on the molecular mechanisms between R. solanacearum and hosts interaction including the formation of plant innate immunity, the suppression of plant innate immunity by this pathogen and the activation of effector-triggered immunity. Furthermore, we made a prospect on how to utilize the interaction mechanism between R. solanacearum and hosts to control the disease.
基金supported by the National Key R&D Program of China(Grant No.2023YFA1406200)the National Natural Science Foundation of China(No.12274177 and 12304261)the China Postdoctoral Science Foundation(No.2024M751076)。
文摘Luminescent metal-organic frameworks(MOFs)have garnered significant attention due to their structural tunability and potential applications in solid-state lighting,bioimaging,sensing,anticounterfeiting,and other fields.Nevertheless,due to the tendency of1,4-benzenedicarboxylic acid(BDC)to rotate within the framework,MOFs composed of it exhibit significant non-radiative energy dissipation and thus impair the emissive properties.In this study,efficient luminescence of MIL-140A nanocrystals(NCs)with BDC rotors as ligands is achieved by pressure treatment strategy.Pressure treatment effectively modulates the pore structure of the framework,enhancing the interactions between the N,N-dimethylformamide vip molecules and the BDC ligands.The enhanced host-vip interaction contributes to the structural rigidity of the MOF,thereby suppressing the rotation-induced excited-state energy loss.As a result,the pressure-treated MIL-140A NCs displayed bright blue-light emission,with the photoluminescence quantum yield increasing from an initial 6.8%to 69.2%.This study developed an effective strategy to improve the luminescence performance of rotor ligand MOFs,offers a new avenue for the rational design and synthesis of MOFs with superior luminescent properties.
基金Supported by University of Pavia(Fondo d'Ateneo per la Ricercato Ricci V)+1 种基金Second University of Naples(CIRANAD to Romano M)
文摘Helicobacter pylori (H.pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently.A well-choreographed equilibrium between the bacterial effectors and host responses permits microbial persistence and health of the host,but confers a risk for serious diseases including gastric cancer.During its long coexistence with humans,H.pylori has developed complex strategies to limit the degree and extent of gastric mucosal damage and in? ammation,as well as immune effector activity.The present editorial thus aims to introduce and comment on major advances in the rapidly developing area of H.pylori/human gastric mucosa interaction (and its pathological sequelae),which is the result of millennia of co-evolution of,and thus of reciprocal knowledge between,the pathogen and its human host.
基金Support received from the National Major Scientific and Technological Special Project for“Significant New Drugs Development”during the Thirteenth Five-year Plan Period,P.R.China(2018ZX09721003-002-004)the Major Research Project of Shandong Province,P.R.China(2018GSF118004)the Key Research and Development Program of Shandong Province,P.R.China(2018CXGC1411)for their support and encouragement in carrying out this work.
文摘The bitterness of a drug is a major challenge for patient acceptability and compliance,especially for children.Due to the toxicity of medication,a human taste panel test has certain limitations.Atomoxetine hydrochloride(HCl),which is used for the treatment of attention deficit/hyperactivity disorder(ADHD),has an extremely bitter taste.The aim of this work is to quantitatively predict the bitterness of atomoxetine HCl by a biosensor system.Based on the mechanism of detection of the electronic tongue(Etongue),the bitterness of atomoxetine HCl was evaluated,and it was found that its bitterness was similar to that of quinine HCl.The bitterness threshold of atomoxetine HCl was 8.61μg/ml based on the Change of membrane Potential caused by Adsorption(CPA)value of the BT0 sensor.In this study,the taste-masking efficiency of 2-hydroxypropyl-β-cyclodextrin(HP-β-CyD)was assessed by Euclidean distances on a principle component analysis(PCA)map with the SA402B Taste Sensing System,and the host–vip interactions were investigated by differential scanning calorimetry(DSC),powder X-ray diffraction(XRD),nuclear magnetic resonance(NMR)spectroscopy and scanning electron microscopy(SEM).Biosensor evaluation and characterization of the inclusion complex indicated that atomoxetine HCl could actively react with 2-hydroxypropyl-β-cyclodextrin.
基金the National Health and Medical Research Council(NHMRC)through a CJ Martin Biomedical Early Career Fellowship(grant number APP1052764)a Career Development Fellowship(grant number APP1140709)+2 种基金a New Investigator Project Grant(grant num-ber APP1120808)an Australian Institute of Tropical Health and Medicine(AITHM)Capacity Building Grant(grant number 15031)to A.K&NKHDS was supported by an AITHM scholarship.
文摘Tuberculosis(TB)is one of the deadliest infectious diseases in the world.The meta-bolic disease type 2 diabetes(T2D)significantly increases the risk of developing ac-tive TB.Effective new TB vaccine candidates and novel therapeutic interventions are required to meet the challenges of global TB eradication.Recent evidence suggests that the microbiota plays a significant role in how the host responds to infection,in-jury and neoplastic changes.Animal models that closely reflect human physiology are crucial in assessing new treatments and to decipher the underlying immunological defects responsible for increased TB susceptibility in comorbid patients.In this study,using a diet-induced murine T2D model that reflects the etiopathogenesis of clinical T2D and increased TB susceptibility,we investigated how the intestinal microbiota may impact the development of T2D,and how the gut microbial composition changes following a very low-dose aerosol infection with Mycobacterium tuberculosis(Mtb).Our data revealed a substantial intestinal microbiota dysbiosis in T2D mice compared to non-diabetic animals.The observed differences were comparable to previous clini-cal reports in TB patients,in which it was shown that Mtb infection causes rapid loss of microbial diversity.Furthermore,diversity index and principle component analyses demonstrated distinct clustering of Mtb-infected non-diabetic mice vs.Mtb-infected T2D mice.Our findings support a broad applicability of T2D mice as a tractable small animal model for studying distinct immune parameters,microbiota and the immune-metabolome of TB/T2D comorbidity.This model may also enable answers to be found to critical outstanding questions about targeted interventions of the gut mi-crobiota and the gut-lung axis.
基金supported by the National Natural Science Foundation of China (31970274 (J.W.), 32170272 (X.W.), 32100251 (J.Z.), 32000179 (Y.X.))the Special Research Assistant of Chinese Academy of Sciences (J.Z. and Y.X.), China Postdoctoral Science Foundation (2022M713224 (J.Z.))+6 种基金the Strategic Priority Research Program of Chinese Academy of Sciences (XDPB16 (J.W.))the Yunnan Innovation Team Project (202105AE160013 (J.W.))CAS “Light of West China” Program (G.S.)Yunnan Revitalization Talent Support Program “Young Talents” Project (XDYC-QNRC-2022-0301 (J.Z.), XDYC-QNRC-2022-0001 (G.S.))the General and Key Project of the Applied Basic Research Program of Yunnan (202001AS070021(J.W.))Yunnan Fundamental Research Projects-General Project (202101AT070457 (S.L.))Yunnan Fundamental Research Projects-Youth Talent Project (202101AU070021(S.L.))
文摘Parasitic plants and their hosts communicate through haustorial connections.Nutrient deficiency is a common stress for plants,yet little is known about whether and how host plants and parasites communicate during adaptation to such nutrient stresses.In this study,we used transcriptomics and proteomics to analyze how soybean(Glycine max)and its parasitizing dodder(Cuscuta australis)respond to nitrate and phosphate deficiency(-N and-P).After-N and-P treatment,the soybean and dodder plants exhibited substantial changes of transcriptome and proteome,although soybean plants showed very few transcriptional responses to-P and dodder did not show any transcriptional changes to either-N or-P.Importantly,large-scale interplant transport of mRNAs and proteins was detected.Although the mobile mRNAs only comprised at most 0.2%of the transcriptomes,the foreign mobile proteins could reach 6.8%of the total proteins,suggesting that proteins may be the major forms of interplant communications.Furthermore,the interplant mobility of macromolecules was specifically affected by the nutrient regimes and the transport of these macromolecules was very likely independently regulated.This study provides new insight into the communication between host plants and parasites under stress conditions.
基金the National Key Research and Development Program of China(Grant Nos.2017YFA0505900 and 2017YFD0500300)the National Basic Research Programs of China(Grant No.2014CB74440)+2 种基金the National Natural Science Foundation of China(Grant Nos.81371769 and 81571954)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDPB03)the Youth Innovation Promotion Association CAS(Grant No.Y12A027BB2).
文摘The major innate immune cell types involved in tuberculosis(TB)infection are macrophages,dendritic cells(DCs),neutrophils and natural killer(NK)cells.These immune cells recognize the TB-causing pathogen Mycobacterium tuberculosis(Mtb)through various pattern recognition receptors(PRRs),including but not limited to Toll-like receptors(TLRs),Nod-like receptors(NLRs)and C-type lectin receptors(CLRs).Upon infection by Mtb,the host orchestrates multiple signaling cascades via the PRRs to launch a variety of innate immune defense functions such as phagocytosis,autophagy,apoptosis and inflammasome activation.In contrast,Mtb utilizes numerous exquisite strategies to evade or circumvent host innate immunity.Here we discuss recent research on major host innate immune cells,PRR signaling,and the cellular functions involved in Mtb infection,with a specific focus on the host’s innate immune defense and Mtb immune evasion.A better understanding of the molecular mechanisms underlying host–pathogen interactions could provide a rational basis for the development of effective anti-TB therapeutics.
基金supported by the Scientific and Technological Research Council of Turkey (Grant No. 113E326) awarded to JA
文摘MicroRNAs （miRNAs） were discovered two decades ago, yet there is still a great need for further studies elucidating their genesis and targeting in different phyla. Since experimental discovery and validation of miRNAs is difficult, computational predictions are indispensable and today most computational approaches employ machine learning. Toxoplasma gondii, a parasite residing within the cells of its hosts like human, uses miRNAs for its post-transcriptional gene reg- ulation. It may also regulate its hosts＇ gene expression, which has been shown in brain cancer. Since previous studies have shown that overexpressed miRNAs within the host are causal for disease onset, we hypothesized that T. gondii could export miRNAs into its host cell. We computationally predicted all hairpins from the genome of T. gondii and used mouse and human models to filter possible candidates. These were then further compared to known miRNAs in human and rodents and their expression was examined for T. gondii grown in mouse and human hosts, respectively. We found that among the millions of potential hairpins in T. gondii, only a few thousand pass filtering using a human or mouse model and that even fewer of those are expressed. Since they are expressed and differentially expressed in rodents and human, we suggest that there is a chance that T. gondii may export miRNAs into its hosts for direct regulation.
基金supported by the National Natural Science Foundation of China for the Sino-German Mobility Program(grant no.M-0411)the Natural Science Foundation of Jiangsu Province(grant nos.BK20211179 and BK20200432)the Fundamental Research Funds for the Central Universities(grant no.NS2021040).
文摘Amplified chirality and Förster resonance energy transfer(FRET)-assisted chirality transfer frommolecular to nanoscale level have been shown to play a vital role in co-assembled nanohelix for potential energy transfer in biological systems.Herein,we have constructed a chiral host–vip complex donor system for chiral amplification via induced chirality of pillar[5]arene host and loaded it with an achiral dye acceptor to demonstrate how chirality-assisted excitation energy transfer occurred in the supramolecular nanohelix system in an aqueous medium.
基金supported by the National Key Research and Development Program of China (Project No.2021YFC2302003).
文摘Enteroviruses(EVs)are human pathogens commonly observed in children aged 0–5 years and adults.EV infections usually cause the common cold and hand-foot-and-mouth disease;however,more severe infections can result in multiorgan complications,such as polio,aseptic meningitis,and myocarditis.The molecular mechanisms by which enteroviruses cause these diseases are still poorly understood,but accumulating evidence points to two enterovirus proteases,2Apro and 3Cpro,as the key players in pathogenesis.The 2Apro performs post-translational proteolytic processing of viral polyproteins and cleaves several host factors to evade antiviral immune responses and promote viral replication.It was also discovered that coxsackievirus-induced cardiomyopathy was caused by 2Apro-mediated cleavage of dystrophin in cardiomyocytes,indicating that cellular protein proteolysis may play a key role in enterovirus-associated diseases.Therefore,studies of 2Apro could reveal additional substrates that may be associated with specific diseases.Here,we discuss the genetic and structural properties of 2Apro and review how the protease antagonizes innate immune responses to promote viral replication,as well as novel substrates and mechanisms for 2Apro.We also summarize the current approaches for identifying the substrates of 2Apro to discover novel mechanisms relating to certain diseases.
基金the National Key Research and Development Program of China (2018YFC2000504, 2017YFD0500503 and 2017YFD0501000)the National Natural Science Foundation of China (81770434 and 81370906)the National Program on Key Basic Research Project of China (973 Program) (2007CB513007 and 2013CB531406)。
文摘In recent years,many studies have focused on the interaction between host genes and microbiota and their mutual influence(Bonder et al.,2016;Goodrich et al.,2014;Rothschild et al.,2018;Wang et al.,2016;Zhang et al.,2019).Host genetic variation influences the composition of the microbial community,for instance in inflammatory bowel disease,host genetic susceptibilities induce pathological shifts in microbiome composition.
文摘In a recent publication in Nature,Sakoguchi et al.reveal a long-sought missing link between pathogen-derived ligands and activating human natural killer(NK)cell receptors.1 The study identifies a clade of Plasmodium falciparum(P.falciparum)repetitive interspersed family(RIFIN)proteins that not only bind to the inhibitory KIR2DL1 receptor but,strikingly,also engage the activating KIR2DS1 receptor,thereby offering new insight into NK cell regulation in malaria and expanding our understanding of host–pathogen interaction in innate immune responses.
