Theaflavins from black tea effectively improve insulin secretion in obesity and diabetes,but the molecular mechanisms are unclear.Here,the palmitic acid(PA)-induced pancreaticβ-TC-6 cells and high fat-/high glucose-i...Theaflavins from black tea effectively improve insulin secretion in obesity and diabetes,but the molecular mechanisms are unclear.Here,the palmitic acid(PA)-induced pancreaticβ-TC-6 cells and high fat-/high glucose-induced zebrafish were used.The effects of theaflavin-3,3'-digallate(TF3)on glucolipotoxicityinduced insulin secretion dysfunction,ferroptosis and endoplasmic reticulum(ER)stress were investigated by a variety of molecular biological approaches,inductively coupled plasma-mass spectrometry(ICP-MS),transmission electron microscopy(TEM)and widely targeted metabolomics analysis.TF3 was found to potently inhibit glucolipotoxicity-induced insulin secretion dysfunction and ferroptosis inβ-TC-6 cells and zebrafish,with increasing glutathione peroxidase 4(GPX4)expression,suppressing lipid peroxidation and iron accumulation and protecting mitochondria.Additionally,TF3 attenuated ER stress by regulating 3 unfolded protein response(UPR)pathways inβ-TC-6 cells,and significantly modulated linoleic acid metabolism and L-kynurenine signalling in zebrafish.The expression of sarcoplasmic/endoplasmic reticulum calcium ATPase 2(SERCA2)was obviously enhanced by TF3.Thapsigargin,a SERCA2 inhibitor,remarkably reversed the effects of TF3 on insulin production,ferroptosis,ER stress and the kynurenine signalling.Together,this work revealed the critical role of SERCA2 in ferroptosis regulation,and demonstrated TF3 targeted SERCA2 to inhibit ER stress and ferropto sis,thereby protectingβ-cell secretory function from glucolipotoxicity.展开更多
Cubic boron nitride(cBN)with high hardness,thermal conductivity,wear resistance,and chemical inertness has become the most promising abrasive and machining material.Due to the difficulty of fabricating pure cBN body,g...Cubic boron nitride(cBN)with high hardness,thermal conductivity,wear resistance,and chemical inertness has become the most promising abrasive and machining material.Due to the difficulty of fabricating pure cBN body,generally,some binders are incorporated among cBN particles to prepare polycrystalline cubic boron nitride(PcBN).Hence,the binders play a critical factor to the performances of PcBN composites.In this study,the PcBN composites with three binder systems containing ceramic and metal phases were fabricated by spark plasma sintering(SPS)from 1400 to 1700℃.The sintering behaviors and mechanical properties of the composites were investigated.Results show that the effect of binder formulas on mechanical properties mainly related to the compactness,mechanical performances,and thermal expansion coefficient of binder phases,which affect the carrying capacity of the composites and the bonding strength between binder phases and cBN particles.The PcBN composite with SiAlON phase as binder presented optimal flexural strength(465±29 MPa)and fracture toughness(5.62±0.37 MPa·m^(1/2)),attributing to the synergistic effect similar to transgranular and intergranular fractures.Meanwhile,the excellent mechanical properties can be maintained a comparable level when the temperature even rises to 800℃.Due to the weak bonding strength and high porosity,the PcBN composites with Al_(2)O_(3)–ZrO_(2)(3Y)and Al–Ti binder systems exhibited inferior mechanical properties.The possible mechanisms to explain these results were also analyzed.展开更多
High-entropy carbides are a nascent group of ceramics that are promising for high-temperature applications due to the combination of good stability,high hardness(H),high strength,and superior creep resistance that the...High-entropy carbides are a nascent group of ceramics that are promising for high-temperature applications due to the combination of good stability,high hardness(H),high strength,and superior creep resistance that they display.Due to high melting points and low lattice diffusion coefficients,however,the high-entropy carbides are usually difficult to consolidate to a nearly full density.To cope with this challenge,herein,binary carbides including TiC,V_(8)C_(7),NbC,Mo_(2)C,and WC with different carbon stoichiometry were used to prepare dense high-entropy(TiVNbMoW)C_(4.375),and the influence of carbon vacancy on formation ability and mechanical properties of carbon-deficient high-entropy(TiVNbMoW)C_(4.375) were investigated.Intriguingly,although the starting binary carbides have different crystal structures and carbon stoichiometry,the as-prepared high-entropy material showed a rock-salt structure with a relatively high density(98.1%)and good mechanical properties with hardness of 19.4±0.4 GPa and fracture toughness(KIC)of 4.02 MPa·m^(1/2).More importantly,the high-entropy(TiVNbMoW)C_(4.375) exhibited low coefficient of friction(COF)at room temperature(RT)and 800℃.Wear rate(W)gradually increased with the temperature rising,which were attributed to the formation of low-hardness oxidation films at high temperatures to aggravate wear.At 800℃,lubricating films formed from sufficient oxidation products of V_(2)O_(5) and MoO_(3) effectively improved tribological behavior of the high-entropy(TiVNbMoW)C_(4.375).Wear mechanisms were mainly abrasive wear resulting from grain pullout and brittle fracture as well as oxidation wear generated from high-temperature reactions.These results are useful as valuable guidance and reference to the synthesis of high-entropy ceramics(HECs)for sliding parts under high-temperature serving conditions.展开更多
基金supported by National Natural Science Foundation of China(32272303)Natural Science Foundation of Zhejiang Province,China(LY21C200010)。
文摘Theaflavins from black tea effectively improve insulin secretion in obesity and diabetes,but the molecular mechanisms are unclear.Here,the palmitic acid(PA)-induced pancreaticβ-TC-6 cells and high fat-/high glucose-induced zebrafish were used.The effects of theaflavin-3,3'-digallate(TF3)on glucolipotoxicityinduced insulin secretion dysfunction,ferroptosis and endoplasmic reticulum(ER)stress were investigated by a variety of molecular biological approaches,inductively coupled plasma-mass spectrometry(ICP-MS),transmission electron microscopy(TEM)and widely targeted metabolomics analysis.TF3 was found to potently inhibit glucolipotoxicity-induced insulin secretion dysfunction and ferroptosis inβ-TC-6 cells and zebrafish,with increasing glutathione peroxidase 4(GPX4)expression,suppressing lipid peroxidation and iron accumulation and protecting mitochondria.Additionally,TF3 attenuated ER stress by regulating 3 unfolded protein response(UPR)pathways inβ-TC-6 cells,and significantly modulated linoleic acid metabolism and L-kynurenine signalling in zebrafish.The expression of sarcoplasmic/endoplasmic reticulum calcium ATPase 2(SERCA2)was obviously enhanced by TF3.Thapsigargin,a SERCA2 inhibitor,remarkably reversed the effects of TF3 on insulin production,ferroptosis,ER stress and the kynurenine signalling.Together,this work revealed the critical role of SERCA2 in ferroptosis regulation,and demonstrated TF3 targeted SERCA2 to inhibit ER stress and ferropto sis,thereby protectingβ-cell secretory function from glucolipotoxicity.
基金This work was supported by the National Natural Science Foundation of China(No.51775534)the West Light Foundation of the Chinese Academy of Sciences(2019)the LICP Cooperation Foundation for Young Scholars(No.HZJJ21-07).
文摘Cubic boron nitride(cBN)with high hardness,thermal conductivity,wear resistance,and chemical inertness has become the most promising abrasive and machining material.Due to the difficulty of fabricating pure cBN body,generally,some binders are incorporated among cBN particles to prepare polycrystalline cubic boron nitride(PcBN).Hence,the binders play a critical factor to the performances of PcBN composites.In this study,the PcBN composites with three binder systems containing ceramic and metal phases were fabricated by spark plasma sintering(SPS)from 1400 to 1700℃.The sintering behaviors and mechanical properties of the composites were investigated.Results show that the effect of binder formulas on mechanical properties mainly related to the compactness,mechanical performances,and thermal expansion coefficient of binder phases,which affect the carrying capacity of the composites and the bonding strength between binder phases and cBN particles.The PcBN composite with SiAlON phase as binder presented optimal flexural strength(465±29 MPa)and fracture toughness(5.62±0.37 MPa·m^(1/2)),attributing to the synergistic effect similar to transgranular and intergranular fractures.Meanwhile,the excellent mechanical properties can be maintained a comparable level when the temperature even rises to 800℃.Due to the weak bonding strength and high porosity,the PcBN composites with Al_(2)O_(3)–ZrO_(2)(3Y)and Al–Ti binder systems exhibited inferior mechanical properties.The possible mechanisms to explain these results were also analyzed.
基金supported by the National Natural Science Foundation of China (51902317)the Key Research Program of the Chinese Academy of Sciences (XDPB24)+1 种基金the State Key Laboratory of New Ceramic and Fine Processing Tsinghua University (KF201911)the Key Research and Development Project of Gansu Province (20YF8GA001).
文摘High-entropy carbides are a nascent group of ceramics that are promising for high-temperature applications due to the combination of good stability,high hardness(H),high strength,and superior creep resistance that they display.Due to high melting points and low lattice diffusion coefficients,however,the high-entropy carbides are usually difficult to consolidate to a nearly full density.To cope with this challenge,herein,binary carbides including TiC,V_(8)C_(7),NbC,Mo_(2)C,and WC with different carbon stoichiometry were used to prepare dense high-entropy(TiVNbMoW)C_(4.375),and the influence of carbon vacancy on formation ability and mechanical properties of carbon-deficient high-entropy(TiVNbMoW)C_(4.375) were investigated.Intriguingly,although the starting binary carbides have different crystal structures and carbon stoichiometry,the as-prepared high-entropy material showed a rock-salt structure with a relatively high density(98.1%)and good mechanical properties with hardness of 19.4±0.4 GPa and fracture toughness(KIC)of 4.02 MPa·m^(1/2).More importantly,the high-entropy(TiVNbMoW)C_(4.375) exhibited low coefficient of friction(COF)at room temperature(RT)and 800℃.Wear rate(W)gradually increased with the temperature rising,which were attributed to the formation of low-hardness oxidation films at high temperatures to aggravate wear.At 800℃,lubricating films formed from sufficient oxidation products of V_(2)O_(5) and MoO_(3) effectively improved tribological behavior of the high-entropy(TiVNbMoW)C_(4.375).Wear mechanisms were mainly abrasive wear resulting from grain pullout and brittle fracture as well as oxidation wear generated from high-temperature reactions.These results are useful as valuable guidance and reference to the synthesis of high-entropy ceramics(HECs)for sliding parts under high-temperature serving conditions.
