Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pa...Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pandemic in early 2022.At present,the lethal mouse model for the study of SARS-CoV-2 needs supplementation,and the alterations in neutrophils and monocytes caused by different strains remain to be elucidated.Methods:Human ACE2 transgenic mice were inoculated with the SARS-CoV-2 proto-type and Omicron BA.1,respectively.The pathogenicity of the two strains was evalu-ated by observing clinical symptoms,viral load and pathology.Complete blood count,immunohistochemistry and flow cytometry were performed to detect the alterations of neutrophils and monocytes caused by the two strains.Results:Our findings revealed that Omicron BA.1 exhibited significantly lower vir-ulence compared to the SARS-CoV-2 prototype in the mouse model.Additionally,we observed a significant increase in the proportion of neutrophils late in infection with the SARS-CoV-2 prototype and Omicron BA.1.We found that the proportion of monocytes increased at first and then decreased.The trends in the changes in the proportions of neutrophils and monocytes induced by the two strains were similar.Conclusion:Our study provides valuable insights into the utility of mouse models for simulating the severe disease of SARS-CoV-2 prototype infection and the milder manifestation associated with Omicron BA.1.SARS-CoV-2 prototype and Omicron BA.1 resulted in similar trends in the changes in neutrophils and monocytes.展开更多
A new class of phosphor samples,denoted as Ba_(1-x)Al_(2)Ge_(2)O_(8):xEu^(2+)(BAGO:xEu^(2+))was synthesized using a Pechini-type sol-gel technique and subsequent thermal reduction in CO atmosphere.The morphology and s...A new class of phosphor samples,denoted as Ba_(1-x)Al_(2)Ge_(2)O_(8):xEu^(2+)(BAGO:xEu^(2+))was synthesized using a Pechini-type sol-gel technique and subsequent thermal reduction in CO atmosphere.The morphology and structural characteristics of both the BAGO host lattice and the Eu^(2+)ions activated BAGO phosphors were investigated through field-emission scanning electron microscopy and X-ray diffractometry analyses,respectively.The BAGO host lattice has micro-sized particles and the Rietveld refinement reveals the presence of a monoclinic crystal phase,characterized by the space group I2/c(No.15).Introducing Eu^(2+)ions into Ba^(2+)sites under CO condition reduces the particle size,switching from microscale to nanoscale.Within the near-ultraviolet spectrum(353 nm),the BAGO:xEu^(2+)phosphors exhibit a broadband bluish-green photoluminescence(PL)emission characterized by a peak band at 492 nm.This phenomenon is attributed to the 4f^(6)5d^(1)→4f^(7) electronic transition.The BAGO:0.02Eu^(2+)phosphor shows the strongest bluish-green PL emission,and a co mprehensive description of the concentration quenching mechanism between Eu^(2+)ions is revealed.Additionally,the thermal stability of the optimized BAGO:0.02Eu^(2+)phosphor was investigated,and its activation energy was estimated.Therefore,the synthesized bluish-green BAGO:0.02Eu^(2+)phosphor holds the promise of being a novel and potential candidate for utilization in white light-emitting diode applications.展开更多
Since the outbreak of COVID-19,with the emergence of a series of novel coronavirus variants of different types,COVID-19 has continued to spread across the globe,posing a huge threat to the lives and health of people a...Since the outbreak of COVID-19,with the emergence of a series of novel coronavirus variants of different types,COVID-19 has continued to spread across the globe,posing a huge threat to the lives and health of people around the world and posing a severe challenge to global public health security.Recently,the World Health Organization(WHO)announced that novel coronavirus variant strain"Omicron"subtype variant strain BA.2 has been found in 57 countries and regions.It has higher vaccine and antibody tolerance and is more infectious than omicron(B.1.1.529).In this paper,we briefly review the recent studies on the omicron subtype variant strain BA.2.展开更多
Objective:The luminal androgen receptor(LAR)subtype of triple-negative breast cancer(TNBC)differentiation displays low proliferation yet strong metastatic potential and a poor chemotherapy response.This study aimed to...Objective:The luminal androgen receptor(LAR)subtype of triple-negative breast cancer(TNBC)differentiation displays low proliferation yet strong metastatic potential and a poor chemotherapy response.This study aimed to define the molecular basis of the LAR subtype and identify actionable therapeutic targets.Methods:Comprehensive multi-omic analyses were performed on the FUSCC-TNBC cohort,integrating whole-exome sequencing,RNA sequencing,and functional validation in vitro and in vivo.Somatic mutation profiling,gene set enrichment analysis(GSEA),and weighted gene co-expression network analysis(WGCNA)were used to define genomic and transcriptomic signatures.A machine learning model using the Mime1 package was applied to derive a senescence-associated prognostic signature(LAR-S)and validation in external cohorts.Immune deconvolution was performed to decipher the tumor microenvironment.Functional assays,patient-derived organoids(PDOs),and TS/V mouse models were used to evaluate therapeutic responses to senescence-modulating agent and immunotherapy combinations.Results:The LAR subtype was enriched for PIK3CA,PTEN,and ERBB2 kinase domain mutations.Functional studies confirmed ERBB2 variants(e.g.,V777L and E698_P699delinsA)as oncogenic drivers conferring sensitivity to neratinib.Transcriptomic analyses revealed a dominant cellular senescence program associated with immune suppression.The LAR-S signature stratified survival across cohorts and predicted immunotherapy resistance.Targeting cellular senescence inhibited LAR subtype organoid growth and when combined with anti-PD-1 therapy synergistically suppressed tumor growth in vivo.Conclusions:The LAR subtype harbors two therapeutic vulnerabilities:ERBB2 mutation-driven kinase activation;and senescencemediated immune evasion.The LAR-S signature enables precise patient stratification and supports senescence-targeted and immunotherapy combination strategies as promising approaches for this refractory TNBC subtype.展开更多
基金supported by Beijing Natural Science Foundation(Grant No.Z210014)National Natural Science Foundation of China(Grant No.32070543)+1 种基金National Key Research and Development Project of China(Grant No.2022YFC2303404)CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2022-12M-CoV19-002)
文摘Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pandemic in early 2022.At present,the lethal mouse model for the study of SARS-CoV-2 needs supplementation,and the alterations in neutrophils and monocytes caused by different strains remain to be elucidated.Methods:Human ACE2 transgenic mice were inoculated with the SARS-CoV-2 proto-type and Omicron BA.1,respectively.The pathogenicity of the two strains was evalu-ated by observing clinical symptoms,viral load and pathology.Complete blood count,immunohistochemistry and flow cytometry were performed to detect the alterations of neutrophils and monocytes caused by the two strains.Results:Our findings revealed that Omicron BA.1 exhibited significantly lower vir-ulence compared to the SARS-CoV-2 prototype in the mouse model.Additionally,we observed a significant increase in the proportion of neutrophils late in infection with the SARS-CoV-2 prototype and Omicron BA.1.We found that the proportion of monocytes increased at first and then decreased.The trends in the changes in the proportions of neutrophils and monocytes induced by the two strains were similar.Conclusion:Our study provides valuable insights into the utility of mouse models for simulating the severe disease of SARS-CoV-2 prototype infection and the milder manifestation associated with Omicron BA.1.SARS-CoV-2 prototype and Omicron BA.1 resulted in similar trends in the changes in neutrophils and monocytes.
基金Project supported by the National Research Foundation of Korea Grant funded by the Korean government(MSIP)(2018R1A6A1A03025708)。
文摘A new class of phosphor samples,denoted as Ba_(1-x)Al_(2)Ge_(2)O_(8):xEu^(2+)(BAGO:xEu^(2+))was synthesized using a Pechini-type sol-gel technique and subsequent thermal reduction in CO atmosphere.The morphology and structural characteristics of both the BAGO host lattice and the Eu^(2+)ions activated BAGO phosphors were investigated through field-emission scanning electron microscopy and X-ray diffractometry analyses,respectively.The BAGO host lattice has micro-sized particles and the Rietveld refinement reveals the presence of a monoclinic crystal phase,characterized by the space group I2/c(No.15).Introducing Eu^(2+)ions into Ba^(2+)sites under CO condition reduces the particle size,switching from microscale to nanoscale.Within the near-ultraviolet spectrum(353 nm),the BAGO:xEu^(2+)phosphors exhibit a broadband bluish-green photoluminescence(PL)emission characterized by a peak band at 492 nm.This phenomenon is attributed to the 4f^(6)5d^(1)→4f^(7) electronic transition.The BAGO:0.02Eu^(2+)phosphor shows the strongest bluish-green PL emission,and a co mprehensive description of the concentration quenching mechanism between Eu^(2+)ions is revealed.Additionally,the thermal stability of the optimized BAGO:0.02Eu^(2+)phosphor was investigated,and its activation energy was estimated.Therefore,the synthesized bluish-green BAGO:0.02Eu^(2+)phosphor holds the promise of being a novel and potential candidate for utilization in white light-emitting diode applications.
基金The 940th Hospital Intra-Hospital Fund Project(No.20yjky020)the Huoshenshan Hospital Research Fund General Project(No.HSS-217)。
文摘Since the outbreak of COVID-19,with the emergence of a series of novel coronavirus variants of different types,COVID-19 has continued to spread across the globe,posing a huge threat to the lives and health of people around the world and posing a severe challenge to global public health security.Recently,the World Health Organization(WHO)announced that novel coronavirus variant strain"Omicron"subtype variant strain BA.2 has been found in 57 countries and regions.It has higher vaccine and antibody tolerance and is more infectious than omicron(B.1.1.529).In this paper,we briefly review the recent studies on the omicron subtype variant strain BA.2.
基金funding from the Ministry of Science and Technology of China(Grant Nos.2023YFF1205003,2023YFF0613304,and 2023YFC3402504)the National Key R&D Program of China(Grant No.2023YFF0613300,2023YFF1205003)the National Natural Science Foundation of China(Grant Nos.82473499,82272957,and 82303735).
文摘Objective:The luminal androgen receptor(LAR)subtype of triple-negative breast cancer(TNBC)differentiation displays low proliferation yet strong metastatic potential and a poor chemotherapy response.This study aimed to define the molecular basis of the LAR subtype and identify actionable therapeutic targets.Methods:Comprehensive multi-omic analyses were performed on the FUSCC-TNBC cohort,integrating whole-exome sequencing,RNA sequencing,and functional validation in vitro and in vivo.Somatic mutation profiling,gene set enrichment analysis(GSEA),and weighted gene co-expression network analysis(WGCNA)were used to define genomic and transcriptomic signatures.A machine learning model using the Mime1 package was applied to derive a senescence-associated prognostic signature(LAR-S)and validation in external cohorts.Immune deconvolution was performed to decipher the tumor microenvironment.Functional assays,patient-derived organoids(PDOs),and TS/V mouse models were used to evaluate therapeutic responses to senescence-modulating agent and immunotherapy combinations.Results:The LAR subtype was enriched for PIK3CA,PTEN,and ERBB2 kinase domain mutations.Functional studies confirmed ERBB2 variants(e.g.,V777L and E698_P699delinsA)as oncogenic drivers conferring sensitivity to neratinib.Transcriptomic analyses revealed a dominant cellular senescence program associated with immune suppression.The LAR-S signature stratified survival across cohorts and predicted immunotherapy resistance.Targeting cellular senescence inhibited LAR subtype organoid growth and when combined with anti-PD-1 therapy synergistically suppressed tumor growth in vivo.Conclusions:The LAR subtype harbors two therapeutic vulnerabilities:ERBB2 mutation-driven kinase activation;and senescencemediated immune evasion.The LAR-S signature enables precise patient stratification and supports senescence-targeted and immunotherapy combination strategies as promising approaches for this refractory TNBC subtype.
