Bastnaesite flotation typically uses 2-hydroxy-3-naphthyl-hydroxamic acid(H205) as the primary collector.However,the reactivity of the hydroxyl group bonded to the naphthalene ring in H205 also imparts some collecting...Bastnaesite flotation typically uses 2-hydroxy-3-naphthyl-hydroxamic acid(H205) as the primary collector.However,the reactivity of the hydroxyl group bonded to the naphthalene ring in H205 also imparts some collecting ability towards fluorite and dolomite.The design of N-hydroxy-3-methoxy-2-naphthalenecarboxamide(HMNC) replaces this hydroxyl group in H205 with a methoxy group.In the flotation separation of bastnaesite from fluorite and dolomite,HMNC collector outperforms H205 in terms of selectivity.Under identical experimental settings,HMNC achieves higher adsorption amounts on bastnaesite surface compared to fluorite and dolomite,providing HMNC with a superior selectivity.Studies on Ce3+ and La3+ ions dissolution from bastnaesite surface show that after adding HMNC to bastnaesite slurry,dissolved Ce3+ and La3+ ions re-adsorb onto bastnaesite surface.This suggests that HMNC primarily doe s not adsorb onto bastnaesite surface as its anion,but in the form of positively charged Ce-HMNC and La-HMNC complexes.Consequently,the presence of HMNC causes positive shifts in the surface zeta potentials of bastnaesite.After HMNC adsorption on bastnaesite surface,the binding energies of the Ce element undergo significant positive shifts.This suggests that HMNC primarily does not adsorb onto bastnaesite surface by donating electrons to the Ce3+ ions to form chemical bonds.Firstprinciples calculations reveal that HMNC encounters difficulty adsorbing onto fluorite surface via its Nhydroxyamide group.Additionally,the steric hindrance of the methyl group in HMNC's methoxy group further reduces its collecting ability in fluorite flotation.展开更多
To elucidate the mechanisms by which licochalcone A(LA)attenuates influenza A virus(IAV)H3N2-induced macrophage injury through modulation of autophagy and ferroptosis,an established IAV-infected RAW264.7 macrophage mo...To elucidate the mechanisms by which licochalcone A(LA)attenuates influenza A virus(IAV)H3N2-induced macrophage injury through modulation of autophagy and ferroptosis,an established IAV-infected RAW264.7 macrophage model was employed.The optimal LA concentration(15μmol/L)was determined using a Cell Counting Kit-8(CCK-8)assay.Cells were assigned to control,model(IAV),and model+LA(IAV+15μmol/L LA)groups.Mitochondrial ultrastructure was examined by transmission electron microscopy;protein expression related to ferroptosis,autophagy,and the AKT/mTOR pathway was analyzed by Western blotting analysis;intracellular ROS levels were assessed by flow cytometry;cytokine secretion was quantified by ELISA;and levels of MDA,Fe2+,and GSH were synchronously measured.CCK-8 assays demonstrated a marked reduction in cell proliferation in the model group,which was effectively restored following LA treatment(P<0.001).Electron microscopy revealed pronounced mitochondrial swelling,cristae disruption,and vacuolar degeneration in IAV-infected cells,whereas LA intervention substantially alleviated these structural abnormalities.Compared with the control group,the model group exhibited significant downregulation of GPX4 and FTH1 protein expression by 55%and 58%(P<0.001 and P=0.0088,respectively),accompanied by a 26%increase in TP53 expression(P=0.011);these aberrant changes were reversed by LA treatment.In addition,IAV infection resulted in significantly elevated levels of ROS,MDA,and Fe2+,together with a reduction in GSH content.Following LA intervention,ROS,MDA,and Fe2+levels decreased by 29%,41%,and 36%,respectively,while GSH levels increased by 42%(P<0.001,P=0.005,P<0.001,and P=0.001,respectively).The concentrations of IL-6,IL-1β,and TNF-αwere markedly increased in the model group(all P<0.001),whereas LA treatment significantly suppressed their release.Furthermore,IAV infection was associated with reduced expression of p-AKT1,p-mTOR,and the LC3-Ⅱ/LC3-Ⅰratio(P=0.004,P<0.001,and P=0.0097,respectively),along with increased P62 expression(P=0.001);these alterations were significantly reversed by LA,indicating activation of the AKT/mTOR pathway and restoration of autophagic flux.Collectively,these findings demonstrated that LA activated AKT/mTOR signaling to enhance autophagic flux while inhibiting ferroptosis,thereby alleviating IAV-induced mitochondrial damage,oxidative stress,and inflammatory responses in macrophages and ultimately exerting potent anti-influenza effects.展开更多
目的:通过对C3H10T1/2细胞分化为成熟棕色脂肪细胞的培养、诱导分化及鉴定,深入探讨棕色脂肪细胞的生物学特性,为人类棕色脂肪细胞的相关研究提供实验参考与理论依据。方法:C3H10T1/2细胞经细胞接种、培养及诱导分化处理,利用光学显微...目的:通过对C3H10T1/2细胞分化为成熟棕色脂肪细胞的培养、诱导分化及鉴定,深入探讨棕色脂肪细胞的生物学特性,为人类棕色脂肪细胞的相关研究提供实验参考与理论依据。方法:C3H10T1/2细胞经细胞接种、培养及诱导分化处理,利用光学显微镜观察细胞形态变化,并通过油红O染色、免疫荧光法、线粒体探针法以及线粒体电镜技术对分化细胞进行鉴定分析。结果:未分化的C3H10T1/2细胞形态多样,具有突触伸展特征;分化后的细胞逐渐变为圆形或椭圆形,形成环形脂滴;未分化组细胞形态无明显变化。油红O染色显示,未分化组细胞基本无染色,而分化组中约90%的细胞红染,脂滴分布于细胞核周围,吸光度值显著升高(P<0.05)。分化组解偶联蛋白1(uncoupling protein 1,UCP1)、过氧化物酶体增殖激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)辅激活因子1α(PPARγco-activator-1α,PGC-1α)、PPARγ和转录因子PRDM16的相对荧光强度和蛋白表达量显著高于未分化组(P<0.05),且线粒体活性增强。结论:本研究成功诱导C3H10T1/2细胞分化为成熟棕色脂肪细胞,结合细胞形态观察、关键蛋白表达检测及线粒体功能分析进行综合评估,证实了细胞的有效分化及成熟棕色脂肪细胞的功能特性。展开更多
Mono-ubiquitination of histone H2A at lysine 119(H2AK119Ub)is deposited by the Polycomb repressive complex 1(PRC1)and represents an abundant post-translational modification(PTM)of histones.H2AK119Ub is crucially invol...Mono-ubiquitination of histone H2A at lysine 119(H2AK119Ub)is deposited by the Polycomb repressive complex 1(PRC1)and represents an abundant post-translational modification(PTM)of histones.H2AK119Ub is crucially involved in the regulation of a wide range of biological processes,including organization of the genome into distinct functional domains,gene silencing,and the maintenance of cell identities during development,among others.Biochemically,the deposition and removal of H2AK119Ub are tightly controlled in cells owing to a dynamic balance between the specific"writers"(i.e.,PRC1)and"erasers"(i.e.,deubiquitinases(DUBs)such as BAP1 and USP16).Furthermore,the increasing evidence establishes a notion that H2AK119Ub serves as a signal for recruiting specific"readers"(such as JARID2,DNMT3A,RYBP,SSX,and RSF1),which elicit the critical downstream effects such as modulating gene transcription,maintaining genome integrity,and shaping cell identity.This H2AK119Ub-based signaling is often perturbed in human diseases,pointing to a connection between its dysregulation and pathological development.This review is aimed at providing a timely,in-depth analysis of the molecular machinery governing H2AK119Ub,its interactions with other chromatin factors,and its causal role in the onset and progression of diseases,notably cancer.展开更多
基金Project supported by the National Natural Science Foundation of China (52104287,U2067201)
摘要Bastnaesite flotation typically uses 2-hydroxy-3-naphthyl-hydroxamic acid(H205) as the primary collector.However,the reactivity of the hydroxyl group bonded to the naphthalene ring in H205 also imparts some collecting ability towards fluorite and dolomite.The design of N-hydroxy-3-methoxy-2-naphthalenecarboxamide(HMNC) replaces this hydroxyl group in H205 with a methoxy group.In the flotation separation of bastnaesite from fluorite and dolomite,HMNC collector outperforms H205 in terms of selectivity.Under identical experimental settings,HMNC achieves higher adsorption amounts on bastnaesite surface compared to fluorite and dolomite,providing HMNC with a superior selectivity.Studies on Ce3+ and La3+ ions dissolution from bastnaesite surface show that after adding HMNC to bastnaesite slurry,dissolved Ce3+ and La3+ ions re-adsorb onto bastnaesite surface.This suggests that HMNC primarily doe s not adsorb onto bastnaesite surface as its anion,but in the form of positively charged Ce-HMNC and La-HMNC complexes.Consequently,the presence of HMNC causes positive shifts in the surface zeta potentials of bastnaesite.After HMNC adsorption on bastnaesite surface,the binding energies of the Ce element undergo significant positive shifts.This suggests that HMNC primarily does not adsorb onto bastnaesite surface by donating electrons to the Ce3+ ions to form chemical bonds.Firstprinciples calculations reveal that HMNC encounters difficulty adsorbing onto fluorite surface via its Nhydroxyamide group.Additionally,the steric hindrance of the methyl group in HMNC's methoxy group further reduces its collecting ability in fluorite flotation.
摘要To elucidate the mechanisms by which licochalcone A(LA)attenuates influenza A virus(IAV)H3N2-induced macrophage injury through modulation of autophagy and ferroptosis,an established IAV-infected RAW264.7 macrophage model was employed.The optimal LA concentration(15μmol/L)was determined using a Cell Counting Kit-8(CCK-8)assay.Cells were assigned to control,model(IAV),and model+LA(IAV+15μmol/L LA)groups.Mitochondrial ultrastructure was examined by transmission electron microscopy;protein expression related to ferroptosis,autophagy,and the AKT/mTOR pathway was analyzed by Western blotting analysis;intracellular ROS levels were assessed by flow cytometry;cytokine secretion was quantified by ELISA;and levels of MDA,Fe2+,and GSH were synchronously measured.CCK-8 assays demonstrated a marked reduction in cell proliferation in the model group,which was effectively restored following LA treatment(P<0.001).Electron microscopy revealed pronounced mitochondrial swelling,cristae disruption,and vacuolar degeneration in IAV-infected cells,whereas LA intervention substantially alleviated these structural abnormalities.Compared with the control group,the model group exhibited significant downregulation of GPX4 and FTH1 protein expression by 55%and 58%(P<0.001 and P=0.0088,respectively),accompanied by a 26%increase in TP53 expression(P=0.011);these aberrant changes were reversed by LA treatment.In addition,IAV infection resulted in significantly elevated levels of ROS,MDA,and Fe2+,together with a reduction in GSH content.Following LA intervention,ROS,MDA,and Fe2+levels decreased by 29%,41%,and 36%,respectively,while GSH levels increased by 42%(P<0.001,P=0.005,P<0.001,and P=0.001,respectively).The concentrations of IL-6,IL-1β,and TNF-αwere markedly increased in the model group(all P<0.001),whereas LA treatment significantly suppressed their release.Furthermore,IAV infection was associated with reduced expression of p-AKT1,p-mTOR,and the LC3-Ⅱ/LC3-Ⅰratio(P=0.004,P<0.001,and P=0.0097,respectively),along with increased P62 expression(P=0.001);these alterations were significantly reversed by LA,indicating activation of the AKT/mTOR pathway and restoration of autophagic flux.Collectively,these findings demonstrated that LA activated AKT/mTOR signaling to enhance autophagic flux while inhibiting ferroptosis,thereby alleviating IAV-induced mitochondrial damage,oxidative stress,and inflammatory responses in macrophages and ultimately exerting potent anti-influenza effects.
摘要目的:通过对C3H10T1/2细胞分化为成熟棕色脂肪细胞的培养、诱导分化及鉴定,深入探讨棕色脂肪细胞的生物学特性,为人类棕色脂肪细胞的相关研究提供实验参考与理论依据。方法:C3H10T1/2细胞经细胞接种、培养及诱导分化处理,利用光学显微镜观察细胞形态变化,并通过油红O染色、免疫荧光法、线粒体探针法以及线粒体电镜技术对分化细胞进行鉴定分析。结果:未分化的C3H10T1/2细胞形态多样,具有突触伸展特征;分化后的细胞逐渐变为圆形或椭圆形,形成环形脂滴;未分化组细胞形态无明显变化。油红O染色显示,未分化组细胞基本无染色,而分化组中约90%的细胞红染,脂滴分布于细胞核周围,吸光度值显著升高(P<0.05)。分化组解偶联蛋白1(uncoupling protein 1,UCP1)、过氧化物酶体增殖激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)辅激活因子1α(PPARγco-activator-1α,PGC-1α)、PPARγ和转录因子PRDM16的相对荧光强度和蛋白表达量显著高于未分化组(P<0.05),且线粒体活性增强。结论:本研究成功诱导C3H10T1/2细胞分化为成熟棕色脂肪细胞,结合细胞形态观察、关键蛋白表达检测及线粒体功能分析进行综合评估,证实了细胞的有效分化及成熟棕色脂肪细胞的功能特性。
基金supported by the National Cancer Institute(NCI)grants(Nos.R01-CA271603,R01-CA268519,R01-CA296203 and R01-CA268384)Ling Cai by the NCI grants(Nos.R01-CA262903 and R01-CA296203).
摘要Mono-ubiquitination of histone H2A at lysine 119(H2AK119Ub)is deposited by the Polycomb repressive complex 1(PRC1)and represents an abundant post-translational modification(PTM)of histones.H2AK119Ub is crucially involved in the regulation of a wide range of biological processes,including organization of the genome into distinct functional domains,gene silencing,and the maintenance of cell identities during development,among others.Biochemically,the deposition and removal of H2AK119Ub are tightly controlled in cells owing to a dynamic balance between the specific"writers"(i.e.,PRC1)and"erasers"(i.e.,deubiquitinases(DUBs)such as BAP1 and USP16).Furthermore,the increasing evidence establishes a notion that H2AK119Ub serves as a signal for recruiting specific"readers"(such as JARID2,DNMT3A,RYBP,SSX,and RSF1),which elicit the critical downstream effects such as modulating gene transcription,maintaining genome integrity,and shaping cell identity.This H2AK119Ub-based signaling is often perturbed in human diseases,pointing to a connection between its dysregulation and pathological development.This review is aimed at providing a timely,in-depth analysis of the molecular machinery governing H2AK119Ub,its interactions with other chromatin factors,and its causal role in the onset and progression of diseases,notably cancer.