DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expressi...DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expression in BC using RNA-seq data from 1,082 BC patient samples in the TCGA dataset and 67 BC cell lines in the CCLE database(Supplementary material 1).展开更多
Inflammatory diseases are often chronic and recurrent,and current treatments do not typically remove underlying disease drivers1.T cells participate in a wide range of inflammatory diseases such as psoriasis2,Crohn...Inflammatory diseases are often chronic and recurrent,and current treatments do not typically remove underlying disease drivers1.T cells participate in a wide range of inflammatory diseases such as psoriasis2,Crohn's disease3,oesophagitis4 and multiple sclerosis5,6,and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence,in part by forming persistent pathogenic memory.Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities7.Chronic rhinosinusitis affects more than 10%of the general population8.Among these patients,20-25%would develop nasal polyps,which often require repeated surgical resections owing to a high incidence of recurrence9.Whereas abundant T cells infiltrate the nasal polyps tissue10,11,T cell subsets that drive the disease pathology and promote recurrence are not fully understood.By comparing T cell repertoires in nasal polyp tissues obtained from consecutive surgeries,here we report that persistent CD8^(+)T cell clones carrying effector memory-like features colonize the mucosal tissue during disease recurrence,and these cells characteristically express the tryptase Granzyme K(GZMK).We find that GZMK cleaves many complement components,including C2,C3,C4 and C5,that collectively contribute to the activation of the complement cascade.GZMK-expressing CD8^(+)T cells participate in organized tertiary lymphoid structures,and tissue GZMK levels predict the disease severity and comorbidities better than well-established biomarkers such as eosinophilia and tissue interleukin-5.Using a mouse asthma model,we further show that GZMK-expressing CD8^(+)T cells exacerbate the disease in a manner dependent on the proteolytic activity of GZMK and complements.Genetic ablation or pharmacological inhibition of GZMK after the disease onset markedly alleviates tissue pathology and restores lung function.Our work identifies a pathogenic CD8^(+)memory T cell subset that promotes tissue inflammation and recurrent airway diseases by the effector molecule GZMK and suggests GZMK as a potential therapeutic target.展开更多
Traumatic brain injury(TBI)remains a prominent global cause of mortality and disability,accounting for an estimated 69 million new cases annually[1].Both civilian and military populations face substantial health chall...Traumatic brain injury(TBI)remains a prominent global cause of mortality and disability,accounting for an estimated 69 million new cases annually[1].Both civilian and military populations face substantial health challenges due to TBI,particularly in military settings,where combat-related injuries introduce unique considerations for prevalence and management[2].Despite notable advancements in acute care,our comprehension of the complex pathophysiological mechanisms underlying the long-term eff ects of TBI remains inadequate[3].Although the initial mechanical impact triggers the cascade of injury,it is often the subsequent neuroinfl ammatory processes that propel progressive neuronal damage and lead to long-term neurological impairments[4,5].展开更多
[Objective] The aim was to establish the BHK-21 stable cell lines expressing T7 RNAP and GFP.[Method]T7 RNAP gene was amplified from E.coli BL21（DE3）and inserted into FG12 vector.The lenti-virus recombinant plasmid ...[Objective] The aim was to establish the BHK-21 stable cell lines expressing T7 RNAP and GFP.[Method]T7 RNAP gene was amplified from E.coli BL21（DE3）and inserted into FG12 vector.The lenti-virus recombinant plasmid FG12-T7 RNAP plasmid was obtained via identification with double enzymes digestion and gene sequencing.The transient expressed T7 RNAP protein was determined by WB in 293T cells transfected with FG12-T7 RNAP plasmid.The recombinant FG12-RNAP lenti-virus was packaged up by transfecting the 293 cells with the recombinant vector FG12-RNAP and the helper plasmids via lipofectamine-2000,which was then used to infect BHK-21 cells.The positive cell clones were obtained after continuous screening by GFP.The expression of T7 RNAP gene was confirmed by Western blot.[Result]The cell line stably expressing the T7 RNAP gene was established by Western blot.[Conclusion]T7 RNAP gene could be stably expressed in eukaryotic cells and it provided a good platform to rescue RNA virus in vivo.展开更多
Local culture resources were excavated and expressed in environmental landscape section of ‘Miaojiang ·Yujinyuan’ residential plot in Taijiang County of Guizhou Province, with lusheng, Bronze drum and national ...Local culture resources were excavated and expressed in environmental landscape section of ‘Miaojiang ·Yujinyuan’ residential plot in Taijiang County of Guizhou Province, with lusheng, Bronze drum and national architecture as design elements. Making environmental landscape of residential plot, where the minority nationality lived in, possess culture agreement and emotion arrangement.展开更多
A Tibetan art form bridges the past and present and connects cultures around the world.THANGKA,a unique form of Tibetan sacred painting,is gaining prominence globally due to its vibrant colors,exquisite craftsmanship,...A Tibetan art form bridges the past and present and connects cultures around the world.THANGKA,a unique form of Tibetan sacred painting,is gaining prominence globally due to its vibrant colors,exquisite craftsmanship,and profound religious and cultural significance.With the acceleration of globalization,this symbol of Tibetan culture that combines artistic expression with spirituality has become a bridge for cultural exchange between the East and the West.Recently,China Today spoke to Yixi Puncog,art collector and council member of the China Association for Preservation and Development of Tibetan Culture,to learn more about Thangka art,its role in international exchange,and how it is enhancing China’s cultural soft power.展开更多
Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for sign...Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.展开更多
Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
Cultures are different between western countries and China,and people's ways of expressing their love are also different.Thes edifferences badly influence well communication between lovers and family members.By co...Cultures are different between western countries and China,and people's ways of expressing their love are also different.Thes edifferences badly influence well communication between lovers and family members.By comparing the different ways of expressing love between western people and Chinese,this paper tries to make readers deeply recognize and make use of the differences of expressing love.展开更多
文摘DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expression in BC using RNA-seq data from 1,082 BC patient samples in the TCGA dataset and 67 BC cell lines in the CCLE database(Supplementary material 1).
文摘Inflammatory diseases are often chronic and recurrent,and current treatments do not typically remove underlying disease drivers1.T cells participate in a wide range of inflammatory diseases such as psoriasis2,Crohn's disease3,oesophagitis4 and multiple sclerosis5,6,and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence,in part by forming persistent pathogenic memory.Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities7.Chronic rhinosinusitis affects more than 10%of the general population8.Among these patients,20-25%would develop nasal polyps,which often require repeated surgical resections owing to a high incidence of recurrence9.Whereas abundant T cells infiltrate the nasal polyps tissue10,11,T cell subsets that drive the disease pathology and promote recurrence are not fully understood.By comparing T cell repertoires in nasal polyp tissues obtained from consecutive surgeries,here we report that persistent CD8^(+)T cell clones carrying effector memory-like features colonize the mucosal tissue during disease recurrence,and these cells characteristically express the tryptase Granzyme K(GZMK).We find that GZMK cleaves many complement components,including C2,C3,C4 and C5,that collectively contribute to the activation of the complement cascade.GZMK-expressing CD8^(+)T cells participate in organized tertiary lymphoid structures,and tissue GZMK levels predict the disease severity and comorbidities better than well-established biomarkers such as eosinophilia and tissue interleukin-5.Using a mouse asthma model,we further show that GZMK-expressing CD8^(+)T cells exacerbate the disease in a manner dependent on the proteolytic activity of GZMK and complements.Genetic ablation or pharmacological inhibition of GZMK after the disease onset markedly alleviates tissue pathology and restores lung function.Our work identifies a pathogenic CD8^(+)memory T cell subset that promotes tissue inflammation and recurrent airway diseases by the effector molecule GZMK and suggests GZMK as a potential therapeutic target.
基金supported by the National Natural Science Foundation of China(82102645)the Guangdong Basic and Applied Basic Research Foundation(2021A1515011042)the China Postdoctoral Science Foundation(2019M662995).
文摘Traumatic brain injury(TBI)remains a prominent global cause of mortality and disability,accounting for an estimated 69 million new cases annually[1].Both civilian and military populations face substantial health challenges due to TBI,particularly in military settings,where combat-related injuries introduce unique considerations for prevalence and management[2].Despite notable advancements in acute care,our comprehension of the complex pathophysiological mechanisms underlying the long-term eff ects of TBI remains inadequate[3].Although the initial mechanical impact triggers the cascade of injury,it is often the subsequent neuroinfl ammatory processes that propel progressive neuronal damage and lead to long-term neurological impairments[4,5].
基金Supported by National Transgenic Major Program of China(2009ZX08007-006B)the National Natural Science Foundation of China(31072160)+2 种基金Science and Technique Foundation of Shandong Province(2009GG20002032)Natural Science Foundation of Shandong Province(Y2008D20)an Open Issue of State Key Laboratory of Veterinary Biotechnology Fund(SKLVBF200806)~~
文摘[Objective] The aim was to establish the BHK-21 stable cell lines expressing T7 RNAP and GFP.[Method]T7 RNAP gene was amplified from E.coli BL21（DE3）and inserted into FG12 vector.The lenti-virus recombinant plasmid FG12-T7 RNAP plasmid was obtained via identification with double enzymes digestion and gene sequencing.The transient expressed T7 RNAP protein was determined by WB in 293T cells transfected with FG12-T7 RNAP plasmid.The recombinant FG12-RNAP lenti-virus was packaged up by transfecting the 293 cells with the recombinant vector FG12-RNAP and the helper plasmids via lipofectamine-2000,which was then used to infect BHK-21 cells.The positive cell clones were obtained after continuous screening by GFP.The expression of T7 RNAP gene was confirmed by Western blot.[Result]The cell line stably expressing the T7 RNAP gene was established by Western blot.[Conclusion]T7 RNAP gene could be stably expressed in eukaryotic cells and it provided a good platform to rescue RNA virus in vivo.
文摘Local culture resources were excavated and expressed in environmental landscape section of ‘Miaojiang ·Yujinyuan’ residential plot in Taijiang County of Guizhou Province, with lusheng, Bronze drum and national architecture as design elements. Making environmental landscape of residential plot, where the minority nationality lived in, possess culture agreement and emotion arrangement.
文摘A Tibetan art form bridges the past and present and connects cultures around the world.THANGKA,a unique form of Tibetan sacred painting,is gaining prominence globally due to its vibrant colors,exquisite craftsmanship,and profound religious and cultural significance.With the acceleration of globalization,this symbol of Tibetan culture that combines artistic expression with spirituality has become a bridge for cultural exchange between the East and the West.Recently,China Today spoke to Yixi Puncog,art collector and council member of the China Association for Preservation and Development of Tibetan Culture,to learn more about Thangka art,its role in international exchange,and how it is enhancing China’s cultural soft power.
基金supported by the National Natural Science Foundation of China(NSFC/RGC/JRF N_HKU735/21)Research Grant Council of Hong Kong,China(17102120,17108821,17103922,C1024-22GF,C7074-21G)+1 种基金Health and Medical Research Fund(HMRF 09200966)(to CSWL)FRQS Postdoctoral Fellowship(to AHKF).
文摘Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
文摘Cultures are different between western countries and China,and people's ways of expressing their love are also different.Thes edifferences badly influence well communication between lovers and family members.By comparing the different ways of expressing love between western people and Chinese,this paper tries to make readers deeply recognize and make use of the differences of expressing love.
