Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studie...Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.展开更多
In this paper,the density functional theory has been used to perform a comparative theoretical study of water monomer,dimer,trimer,and bilayer adsorptions on the Be(0001) surface.In our calculations,the adsorbed water...In this paper,the density functional theory has been used to perform a comparative theoretical study of water monomer,dimer,trimer,and bilayer adsorptions on the Be(0001) surface.In our calculations,the adsorbed water molecules are energetically favoured adsorbed on the atop sites,and the dimer adsorption is found to be the most stable with a peak adsorption energy of ～ 437 meV.Further analyses have revealed that the essential bonding interaction between the water monomer and the metal substrate is the hybridization of the water 3a 1-like molecular orbital with the (s,p z) orbitals of the surface beryllium atoms.While in the case of the water dimer adsorption,the 1b 1-like orbital of the H2O molecule plays a dominant role.展开更多
Background: The motivation of birds to proceed with migration is associated with both endogenous and exogenous factors. According to their migratory situation and to the characteristics of stopover sites, birds might ...Background: The motivation of birds to proceed with migration is associated with both endogenous and exogenous factors. According to their migratory situation and to the characteristics of stopover sites, birds might exhibit migratory motivation differently among sites. Although migratory motivation of migrating birds has been well studied in many species, the investigation of the same species in different migratory situations and at different stopover sites is still limited. We predicted that birds at different stopover sites could differ in migratory disposition, including expression of migratory restlessness and responses to environmental cues.Methods: Here we compared migration motivation and orientation of Great Knots(Calidris tenuirostris) at two stopo ver sites, Chongming Dongtan in the south Yellow Sea, which is a temporary rest site, and Yalujiang Estuary Wetland in the north Yellow Sea, which is a critical refuelling site, during northward migration. Modified Emlen funnels, with thermal paper inside to record scratches of the birds, were used to detect activity(intensity and direction) of birds. Environmental conditions, including wind direction and speed, cloud cover, tide condition, times of the day(before and after sunset) were recorded during experiments. Generalized linear models were used to detect the effects of endogenous and exogenous factors on the migratory motivation of the birds.Results: In the south Yellow Sea, the migratory activity intensity of Great Knots was positively related to wind assistance. In the north Yellow Sea, where birds exhibited higher intensity of migratory activity than in the south, the intensity increased and the motivation to initiate migration grew stronger as the season advanced. The Great Knots exhibited wind-related orientation behaviour in the funnels at both sites.Conclusions: The results suggest that the intensity of migratory motivation differed between the two sites. Departure decisions of Great Knots appear to be affected mainly by external factors at the temporary rest site in the south Yellow Sea but possibly by endogenous factors at the final pre-breeding refuelling site in the north Yellow Sea.展开更多
Cholesterol-core nanoparticles(LDE) have been shown to be recognized by low-density lipoprotein receptors(LDLR) after administration;therefore,LDE is an ideal vehicle to deliver drug with targeting property.Paclitaxel...Cholesterol-core nanoparticles(LDE) have been shown to be recognized by low-density lipoprotein receptors(LDLR) after administration;therefore,LDE is an ideal vehicle to deliver drug with targeting property.Paclitaxel,when incorporated into LDE,promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR.Here,we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR.Nineteen LDLR knockout male mice were fed 1%cholesterol for 12 weeks.Then,12 animals received 4-weekly intraperitoneal LDE-paclitaxel(4 mg/kg) while 7 controls received saline solution.On week 12 and 16,in vivo MRI of the aortic roots was performed.Aorta macroscopy was made after euthanasia.Reduction of atherosclerotic lesions was observed.LDE-paclitaxel treatment resulted in reduction of wall area(14%)and stenosis(22%) by MRI and 33%by macroscopy.Thus,LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.展开更多
The degradation mechanism of GaN-based near-ultraviolet(NUV,320-400 nm)light emitting diodes(LEDs)with low-indium content under electrical stress is studied from the aspect of defects.A decrease in the optical power a...The degradation mechanism of GaN-based near-ultraviolet(NUV,320-400 nm)light emitting diodes(LEDs)with low-indium content under electrical stress is studied from the aspect of defects.A decrease in the optical power and an increase in the leakage current are observed after electrical stress.The defect behaviors are characterized using deep level transient spectroscopy(DLTS)measurement under different filling pulse widths.After stress,the concentration of defects with the energy level of 0.47-0.56 eV increases,accompanied by decrease in the concentration of 0.72-0.84 eV defects.Combing the defect energy level with the increased yellow luminescence in photoluminescence spectra,the device degradation can be attributed to the activation of the gallium vacancy and oxygen related complex defect along dislocation,which was previously passivated with hydrogen.This study reveals the evolution process of defects under electrical stress and their spatial location,laying a foundation for manufacture of GaN-based NUV LEDs with high reliability.展开更多
Hepatic ischemia–reperfusion(IR)injury is a serious clinical problem that complicates liver resection and transplantation.Despite recent advances in understanding of the pathophysiology of hepatic IR injury,effective...Hepatic ischemia–reperfusion(IR)injury is a serious clinical problem that complicates liver resection and transplantation.Despite recent advances in understanding of the pathophysiology of hepatic IR injury,effective interventions and therapeutics are still lacking.Here,we examined the role of transient receptor potential melastatin 2(TRPM2),a Ca^(2+)-permeable,non-selective cation channel,in mediating hepatic IR injury.Our data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction,inflammation,and cell death in mice.Moreover,RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related pathways.Consistently,as a ferroptosis inducer,(1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 inhibitor suppressed this.Interestingly,TRPM2-mediated calcium influx caused mitochondrial calcium accumulation via the mitochondrial Ca^(2+)-selective uniporter and increased the expression level of arachidonate 12-lipoxygenase(ALOX12),which results in mitochondrial lipid peroxidation during hepatic IR injury.Furthermore,hepatic IR injury-induced ferroptosis was obviously relieved by a TRPM2 inhibitor or calcium depletion,both in vitro and in vivo.Collectively,these findings demonstrate a crucial role for TRPM2-mediated ferroptosis in hepatic IR injury via increased Ca^(2+)-induced ALOX12 expression,indicating that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy for hepatic IR injury-related diseases,such as during liver resection and transplantation.展开更多
基金supported by Technological Innovation 2030-Major Projects of Brain Science and Brain-like Research(Grant No.:2022zD0206200)the Natural Science Foundation of China(Grant Nos.:31872796,82030108 to W.Yang,32071102 to P.Yu)+3 种基金the National Major Special Project on New Drug Innovation of China(Grant No.:2018ZX09711001-004-005)the key research and development program of Ningxia Hui Autonomous Region(Grant No.:2019BFH02003)Fundamental Research Funds for the Central Universities of China(Grant No.:2016QNA7002 to P.Yu)Zhejiang Provincial Natural Science Foundation(Grant No.:LR16H090001 to W.Yang).
文摘Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.
基金Project supported by the National Natural Science Foundation of China(Grant No.11074217)
文摘In this paper,the density functional theory has been used to perform a comparative theoretical study of water monomer,dimer,trimer,and bilayer adsorptions on the Be(0001) surface.In our calculations,the adsorbed water molecules are energetically favoured adsorbed on the atop sites,and the dimer adsorption is found to be the most stable with a peak adsorption energy of ～ 437 meV.Further analyses have revealed that the essential bonding interaction between the water monomer and the metal substrate is the hybridization of the water 3a 1-like molecular orbital with the (s,p z) orbitals of the surface beryllium atoms.While in the case of the water dimer adsorption,the 1b 1-like orbital of the H2O molecule plays a dominant role.
基金supported by the National Basic Research Program of China(2013CB430404)National Natural Science Foundation of China(31071939 and 31572280)+3 种基金the State Scholarship Fund of China(201206100060)supported by a Project Grant(621-2010-5584)from the Swedish Research Councila Linnaeus grant to the Centre for Animal Movement Research(CAn Move)from the Swedish Research Council(349-2007-8690)Lund University
文摘Background: The motivation of birds to proceed with migration is associated with both endogenous and exogenous factors. According to their migratory situation and to the characteristics of stopover sites, birds might exhibit migratory motivation differently among sites. Although migratory motivation of migrating birds has been well studied in many species, the investigation of the same species in different migratory situations and at different stopover sites is still limited. We predicted that birds at different stopover sites could differ in migratory disposition, including expression of migratory restlessness and responses to environmental cues.Methods: Here we compared migration motivation and orientation of Great Knots(Calidris tenuirostris) at two stopo ver sites, Chongming Dongtan in the south Yellow Sea, which is a temporary rest site, and Yalujiang Estuary Wetland in the north Yellow Sea, which is a critical refuelling site, during northward migration. Modified Emlen funnels, with thermal paper inside to record scratches of the birds, were used to detect activity(intensity and direction) of birds. Environmental conditions, including wind direction and speed, cloud cover, tide condition, times of the day(before and after sunset) were recorded during experiments. Generalized linear models were used to detect the effects of endogenous and exogenous factors on the migratory motivation of the birds.Results: In the south Yellow Sea, the migratory activity intensity of Great Knots was positively related to wind assistance. In the north Yellow Sea, where birds exhibited higher intensity of migratory activity than in the south, the intensity increased and the motivation to initiate migration grew stronger as the season advanced. The Great Knots exhibited wind-related orientation behaviour in the funnels at both sites.Conclusions: The results suggest that the intensity of migratory motivation differed between the two sites. Departure decisions of Great Knots appear to be affected mainly by external factors at the temporary rest site in the south Yellow Sea but possibly by endogenous factors at the final pre-breeding refuelling site in the north Yellow Sea.
基金provided by a grant from Boston University,United States,Fundacao de Amparo à Pesquisa do Estado de Sao Paulo(FAPESP),Sao PauloConselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq),Brasília,Brazila scholarship from Coordena??o de Aperfeicoamento de Pessoal de Nível Superior-CAPES
文摘Cholesterol-core nanoparticles(LDE) have been shown to be recognized by low-density lipoprotein receptors(LDLR) after administration;therefore,LDE is an ideal vehicle to deliver drug with targeting property.Paclitaxel,when incorporated into LDE,promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR.Here,we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR.Nineteen LDLR knockout male mice were fed 1%cholesterol for 12 weeks.Then,12 animals received 4-weekly intraperitoneal LDE-paclitaxel(4 mg/kg) while 7 controls received saline solution.On week 12 and 16,in vivo MRI of the aortic roots was performed.Aorta macroscopy was made after euthanasia.Reduction of atherosclerotic lesions was observed.LDE-paclitaxel treatment resulted in reduction of wall area(14%)and stenosis(22%) by MRI and 33%by macroscopy.Thus,LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.
基金supported by the National Natural Science Foundation of China(Grant Nos.62104180,61974115,11690042,61634005,61974111,12035019,and 61904142)the Fundamental Research Funds for the Central Universities(Grant No.XJS221106)the Key Research and Development Program of Shaanxi,China(Grant No.2020ZDLGY03-05)。
文摘The degradation mechanism of GaN-based near-ultraviolet(NUV,320-400 nm)light emitting diodes(LEDs)with low-indium content under electrical stress is studied from the aspect of defects.A decrease in the optical power and an increase in the leakage current are observed after electrical stress.The defect behaviors are characterized using deep level transient spectroscopy(DLTS)measurement under different filling pulse widths.After stress,the concentration of defects with the energy level of 0.47-0.56 eV increases,accompanied by decrease in the concentration of 0.72-0.84 eV defects.Combing the defect energy level with the increased yellow luminescence in photoluminescence spectra,the device degradation can be attributed to the activation of the gallium vacancy and oxygen related complex defect along dislocation,which was previously passivated with hydrogen.This study reveals the evolution process of defects under electrical stress and their spatial location,laying a foundation for manufacture of GaN-based NUV LEDs with high reliability.
基金the National Key Research and Development Project[2017YFC0110802]the Zhejiang Province Key Research and Development Project[2020C01059,2020]+4 种基金the Natural Science Foundation of China[82030108,31872796,81874059,32071102,and 82102105]the Natural Science Foundation of Zhejiang Province[LQ22H160017]the Zhejiang Engineering Research Center of Cognitive Healthcare[2017E10011]the National Key Scientific Instrument and Equipment Development Project[81827804]the China Postdoctoral Science Foundation[2021M702825].
文摘Hepatic ischemia–reperfusion(IR)injury is a serious clinical problem that complicates liver resection and transplantation.Despite recent advances in understanding of the pathophysiology of hepatic IR injury,effective interventions and therapeutics are still lacking.Here,we examined the role of transient receptor potential melastatin 2(TRPM2),a Ca^(2+)-permeable,non-selective cation channel,in mediating hepatic IR injury.Our data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction,inflammation,and cell death in mice.Moreover,RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related pathways.Consistently,as a ferroptosis inducer,(1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 inhibitor suppressed this.Interestingly,TRPM2-mediated calcium influx caused mitochondrial calcium accumulation via the mitochondrial Ca^(2+)-selective uniporter and increased the expression level of arachidonate 12-lipoxygenase(ALOX12),which results in mitochondrial lipid peroxidation during hepatic IR injury.Furthermore,hepatic IR injury-induced ferroptosis was obviously relieved by a TRPM2 inhibitor or calcium depletion,both in vitro and in vivo.Collectively,these findings demonstrate a crucial role for TRPM2-mediated ferroptosis in hepatic IR injury via increased Ca^(2+)-induced ALOX12 expression,indicating that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy for hepatic IR injury-related diseases,such as during liver resection and transplantation.
