This study aimed to investigate the dose-effect of iron on growth performance,antioxidant function.intestinal morphology,and mRNA expression of jejunal tight junction protein in 1-to21-d-old yellow-feathered broilers....This study aimed to investigate the dose-effect of iron on growth performance,antioxidant function.intestinal morphology,and mRNA expression of jejunal tight junction protein in 1-to21-d-old yellow-feathered broilers.A total of 7201-d-old yellow-feathered maleb roilers were allocated to 9 treatments with 8 replicate cages of 10 birds per cage.The dietary treatments were consisted of a basal diet(contained 79.6 mg Fe kg^(-1))supplemented with 0,20,40,60,80,160,320,640,and 1,280 mg Fe kg^(-1)in the form of FeSO_(4)·7H_(2)O.Compared with the birds in the control group,birds supplemented with 20mg Fe kg^(-1)had higher average daily gain(ADG)(P<0.0001).Adding 640 and 1,280 mg Fe kg^(-1)significantly decreased ADG(P<0.0001)and average daily feed intake(ADFI)(P<0.0001)compared with supplementation of 20mg Fe kg^(-1).Malondialdehyde(MDA)concentration in plasma and duodenum increased linearly(P<0.0001),but MDA concentration in liver and jejunum increased linearly(P<0.05)or quadratically(P<0.05)with increased dietary Fe concentration.The villus height(VH)in duodenum and jejunum,and the ratio of villus height to crypt depth(V/C)in duodenum decreased linearly(P?0.05)as dietary Feincreased.As dietary Fe increased,the jejunal relative mRNA abundance of claudin-1 decreased linearly(P=0.001),but the jejunal relative mRNA abundance of zona occludens-1(ZO-1)and occludin decreased linearly(P?0.05)or quadratically(P?0.05).Compared with the supplementation of 20 mg Fe kg^(-1),the supplementation of640 mg Fe kg^(-1)or higher increased(P?0.05)MDA concentrations in plasma,duodenum,and jejunum,decreased VH in the duodenum and jejunum,and the addition of 1,280 mg Fe kg^(-1)reduced(P?0.05)the jejunal tight junction protein(claudin-1,ZO-1,occludin)mRNA abundance.In summary,640 mg of supplemental Fe kg^(-1)or greater was associated with decreased growth performance,increased oxidative stress,disrupted intestinal morphology,and reduced mRNA expression of jejunal tight junction protein.展开更多
BACKGROUND Enhancing awareness and use of pre-exposure prophylaxis(PrEP)and postexposure prophylaxis(PEP)is vital to curb human immunodeficiency virus(HIV)spread.High-risk behaviors prevalent among sexually transmitte...BACKGROUND Enhancing awareness and use of pre-exposure prophylaxis(PrEP)and postexposure prophylaxis(PEP)is vital to curb human immunodeficiency virus(HIV)spread.High-risk behaviors prevalent among sexually transmitted infection clinic outpatients underscore the need for increased PrEP/PEP education in this group.AIM To investigate the effects of both onsite and online health education on the knowledge of,and willingness to use,PrEP and PEP among individuals receiving PEP services.METHODS Participants were drawn from a cohort study on PEP service intervention at an STD/AIDS outpatient clinic in designated HIV/AIDS hospitals in Beijing,conducted from January 1 to June 30,2022.Health education was provided both onsite and online during follow-up.Surveys assessing knowledge of,and willingness to use,PrEP/PEP were administered at baseline and again at 24 wk post-intervention.RESULTS A total of 112 participants were enrolled in the study;105 completed the follow-up at week 24.The percentage of participants with adequate knowledge of,and willingness to use,PrEP significantly increased from 65.2%and 69.6%at baseline to 83.8%and 82.9%at the end of the intervention(both P<0.05).Similarly,those with adequate knowledge of,and willingness to use,PEP increased from 74.1%and 77.7%at baseline to 92.4%and 89.5%at week 24(P<0.05).Being between 31 years and 40 years of age,having a postgraduate degree or higher,and reporting a monthly expenditure of RMB 5000 or more were found to be significantly associated with knowledge of PrEP and PEP(both P<0.05).CONCLUSION The findings show that both onsite and online health education significantly improved the knowledge of,and increased willingness to use,PrEP and PEP in individuals utilizing PEP services.展开更多
胎儿型肺腺癌(fetal adenocarcinoma of the lung,FLAC)是一种罕见的肺部肿瘤。FLAC分为低级别FLAC(low-grade FLAC,L-FLAC)和高级别FLAC(high-grade FLAC,H-FLAC),两者在临床病理特征、生物学行为和临床结局方面有所不同。大多数H-FLA...胎儿型肺腺癌(fetal adenocarcinoma of the lung,FLAC)是一种罕见的肺部肿瘤。FLAC分为低级别FLAC(low-grade FLAC,L-FLAC)和高级别FLAC(high-grade FLAC,H-FLAC),两者在临床病理特征、生物学行为和临床结局方面有所不同。大多数H-FLAC患者是重度吸烟的中年人。本研究描述了1例罕见的非吸烟年轻男性患者,其最初表现为头顶肿块,最终被诊断为H-FLAC。本文旨在增进对FLAC的了解和认识,提高对该疾病的重视,以防止该疾病漏诊与误诊,加强早期识别、精准诊断,从而推进后续的有效治疗、改善预后。展开更多
[Objectives]To observe the effect of Xianlinggubao Capsule on osteoporotic vertebral compression fracture(OVCF)in rabbits and the influence mechanism of the repair of fractures.[Methods]Female June age 30 rabbits were...[Objectives]To observe the effect of Xianlinggubao Capsule on osteoporotic vertebral compression fracture(OVCF)in rabbits and the influence mechanism of the repair of fractures.[Methods]Female June age 30 rabbits were randomly divided into control group,model control group and Xianlinggubao group.After bilateral ovariectomy,the model control group and Xianlinggubao group were injected with dexamethasone continuously for 4 weeks,and then the OVCF compound model was established by surgery.The Xianlinggubao group was treated with Xianlinggubao at a dose of 300 mg/(kg·d)for 60 d,while the blank control group and the model control group were treated with the same amount of normal saline for 60 d.The number of blood vessels and the expression of bone morphogenetic protein-2(BMP-2)were detected by immunohistochemical staining and the bone mineral density(BMD)in the callus of the third lumbar fracture area of rabbits was measured.The content of serum phosphorus(P),alkaline phosphatase(ALP)and total calcium(TCa)in rabbit venous blood were measured by automatic biochemical analyzer.The content of vascular endothelial growth factor(VEGF)and platelet-derived growth factor(PDGF)in rabbit venous blood were measured by ELISA kit.[Results]The number of blood vessels and the expression of BMP-2 in the callus of the third lumbar fracture area of rabbits was high in Xianlinggubao group,the content of serum P,ALP,TCa,VEGF and PDGF was obviously increased,BMD was obviously increased,the bone microstructure of the third lumbar vertebrae fracture area of rabbits was basically restored.Compared with the model control group(P<0.05),the difference was statistically significant.[Conclusions]Xianlinggubao Capsule can increase calcium and phosphorus deposition,promote the formation of blood vessels in the fracture area of OVCF in rabbits,and have a strong repair effect on OVCF in rabbits.展开更多
Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex s...Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.展开更多
Zirconium hydride(ZrH_(2)) is an ideal neutron moderator material. However, radiation effect significantly changes its properties, which affect its behavior and the lifespan of the reactor. The threshold energy of dis...Zirconium hydride(ZrH_(2)) is an ideal neutron moderator material. However, radiation effect significantly changes its properties, which affect its behavior and the lifespan of the reactor. The threshold energy of displacement is an important quantity of the number of radiation defects produced, which helps us to predict the evolution of radiation defects in ZrH_(2).Molecular dynamics(MD) and ab initio molecular dynamics(AIMD) are two main methods of calculating the threshold energy of displacement. The MD simulations with empirical potentials often cannot accurately depict the transitional states that lattice atoms must surpass to reach an interstitial state. Additionally, the AIMD method is unable to perform largescale calculation, which poses a computational challenge beyond the simulation range of density functional theory. Machine learning potentials are renowned for their high accuracy and efficiency, making them an increasingly preferred choice for molecular dynamics simulations. In this work, we develop an accurate potential energy model for the ZrH_(2) system by using the deep-potential(DP) method. The DP model has a high degree of agreement with first-principles calculations for the typical defect energy and mechanical properties of the ZrH_(2) system, including the basic bulk properties, formation energy of point defects, as well as diffusion behavior of hydrogen and zirconium. By integrating the DP model with Ziegler–Biersack–Littmark(ZBL) potential, we can predict the threshold energy of displacement of zirconium and hydrogen in ε-ZrH_(2).展开更多
The mechanical properties and failure mechanism of lightweight aggregate concrete(LWAC)is a hot topic in the engineering field,and the relationship between its microstructure and macroscopic mechanical properties is a...The mechanical properties and failure mechanism of lightweight aggregate concrete(LWAC)is a hot topic in the engineering field,and the relationship between its microstructure and macroscopic mechanical properties is also a frontier research topic in the academic field.In this study,the image processing technology is used to establish a micro-structure model of lightweight aggregate concrete.Through the information extraction and processing of the section image of actual light aggregate concrete specimens,the mesostructural model of light aggregate concrete with real aggregate characteristics is established.The numerical simulation of uniaxial tensile test,uniaxial compression test and three-point bending test of lightweight aggregate concrete are carried out using a new finite element method-the base force element method respectively.Firstly,the image processing technology is used to produce beam specimens,uniaxial compression specimens and uniaxial tensile specimens of light aggregate concrete,which can better simulate the aggregate shape and random distribution of real light aggregate concrete.Secondly,the three-point bending test is numerically simulated.Thirdly,the uniaxial compression specimen generated by image processing technology is numerically simulated.Fourth,the uniaxial tensile specimen generated by image processing technology is numerically simulated.The mechanical behavior and damage mode of the specimen during loading were analyzed.The results of numerical simulation are compared and analyzed with those of relevant experiments.The feasibility and correctness of the micromodel established in this study for analyzing the micromechanics of lightweight aggregate concrete materials are verified.Image processing technology has a broad application prospect in the field of concrete mesoscopic damage analysis.展开更多
Animal body size variation is of particular interest in evolutionary biology,but the genetic basis remains largely unknown.Previous studies have shown the presence of two parallel evolutionary genetic clusters within ...Animal body size variation is of particular interest in evolutionary biology,but the genetic basis remains largely unknown.Previous studies have shown the presence of two parallel evolutionary genetic clusters within the fish genus Epinephelus with evident divergence in body size,providing an excellent opportunity to investigate the genetic basis of body size variation in vertebrates.Herein,we performed phylotranscriptomic analysis and reconstructed the phylogeny of 13 epinephelids originating from the South China Sea.Two genetic clades with an estimated divergence time of approximately 15.4 million years ago were correlated with large and small body size,respectively.A total of 180 rapidly evolving genes and two positively selected genes were identified between the two groups.Functional enrichment analyses of these candidate genes revealed distinct enrichment categories between the two groups.These pathways and genes may play important roles in body size variation in groupers through complex regulatory networks.Based on our results,we speculate that the ancestors of the two divergent groups of groupers may have adapted to different environments through habitat selection,leading to genetic variations in metabolic patterns,organ development,and lifespan,resulting in body size divergence between the two locally adapted populations.These findings provide important insights into the genetic mechanisms underlying body size variation in groupers and species differentiation.展开更多
Bats,notable as the only flying mammals,serve as natural reservoir hosts for various highly pathogenic viruses in humans(e.g.,SARS-CoV and Ebola virus).Furthermore,bats exhibit an unparalleled longevity among mammals ...Bats,notable as the only flying mammals,serve as natural reservoir hosts for various highly pathogenic viruses in humans(e.g.,SARS-CoV and Ebola virus).Furthermore,bats exhibit an unparalleled longevity among mammals relative to their size,particularly the Myotis bats,which can live up to 40 years.However,the mechanisms underlying these distinctive traits remain incompletely understood.In our prior research,we demonstrated that bats exhibit dampened STING-interferon activation,potentially conferring upon them the capacity to mitigate virus-or aging-induced inflammation.To substantiate this hypothesis,we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING(MdSTING)into the mouse genome.We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process.Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice,as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines,immunopathology,and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo.These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner.Although the underlying mechanism awaits further study,this research has critical implications for bat longevity research,potentially contributing to our comprehension of healthy aging in humans.展开更多
The high-speed train transmission system,experiencing both the internal excitation originating from gear meshing and the external excitation originating from the wheel-rail interaction,exhibits complex dynamic behavio...The high-speed train transmission system,experiencing both the internal excitation originating from gear meshing and the external excitation originating from the wheel-rail interaction,exhibits complex dynamic behavior in the actual service environment.This paper focuses on the gearbox in the high-speed train to carry out the bench test,in which various operat-ing conditions(torques and rotation speeds)were set up and the excitation condition covering both internal and external was created.Acceleration responses on multiple positions of the gearbox were acquired in the test and the vibration behavior of the gearbox was studied.Meanwhile,a stochastic excitation modal test was also carried out on the test bench under different torques,and the modal parameter of the gearbox was identified.Finally,the sweep frequency response of the gearbox under gear meshing excitation was analyzed through dynamic modeling.The results showed that the torque has an attenuating effect on the amplitude of gear meshing frequency on the gearbox,and the effect of external excitation on the gearbox vibration cannot be ignored,especially under the rated operating condition.It was also found that the torque affects the modal param-eter of the gearbox significantly.The torque has a great effect on both the gear meshing stiffness and the bearing stiffness in the transmission system,which is the inherent reason for the changed modal characteristics observed in the modal test and affects the vibration behavior of the gearbox consequently.展开更多
Objectives:To investigate whether the protective actions of ginsenoside Rb1(Rb1)on astrocytes are mediated through the G_(s)-type G-protein-coupled receptor(GPCR-G_(s)).Methods:Primary astrocyte cultures derived from ...Objectives:To investigate whether the protective actions of ginsenoside Rb1(Rb1)on astrocytes are mediated through the G_(s)-type G-protein-coupled receptor(GPCR-G_(s)).Methods:Primary astrocyte cultures derived from neonatal mouse brain were used.Astrocyte injury was induced via oxygen-glucose deprivation/re-oxygenation(OGD/R).Cell morphology,viability,lactate dehydrogenase(LDH)leakage,apoptosis,glutamate uptake,and brain-derived neurotrophic factor(BDNF)secretion were assessed to gauge cell survival and functionality.Western blot was used to investigate the cyclic adenosine monophosphate(cAMP)and protein kinase B(Akt)signaling pathways.GPCR-G_(s)-specific inhibitors and molecular docking were used to identify target receptors.Results:Rb1 at concentrations ranging from 0.8 to 5μM did not significantly affect the viability,glutamate uptake,or BDNF secretion in normal astrocytes.OGD/R reduced astrocyte viability,increasing their LDH leakage and apoptosis rate.It also decreased glutamate uptake and BDNF secretion by these cells.Rb1 had protective effects of astrocytes challenged by OGD/R,by improving viability,reducing apoptosis,and enhancing glutamate uptake and BDNF secretion.Additionally,Rb1 activated the cAMP and Akt pathways in these cells.When the GPCR-G_(s) inhibitor NF449 was introduced,the protective effects of Rb1 completely disappeared,and its activation of cAMP and Akt signaling pathways was significantly inhibited.Conclusion:Rb1 protects against astrocytes from OGD/R-induced injury through GPCR-G_(s) mediation.展开更多
As a potential endocrine-disrupting chemical,bisphenol F(BPF)may cause nonalcoholic fatty liver disease(NAFLD)-like changes,but the mechanisms under its pathogenesis as well as the intervention strategies remain uncle...As a potential endocrine-disrupting chemical,bisphenol F(BPF)may cause nonalcoholic fatty liver disease(NAFLD)-like changes,but the mechanisms under its pathogenesis as well as the intervention strategies remain unclear.Using the electron microscopy technology,along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays,we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells,accompanied by an increased total level of triglycerides.At the molecular level,the lipogenesis-associated mRNAs and proteins,including acetyl-CoA carboxylase,fatty acid synthase,stearoyl-CoA desaturase-1,peroxisome proliferator-activated receptor gamma,and CCAAT-enhancer-binding proteins,increased significantly via the AMP-activated protein kinase(AMPK)-mammalian target of rapamycin(mTOR)signaling regulation in both in vitro and in vivo studies.Furthermore,the immunofluorescence results also showed the robust lipogenesis induced by BPF,evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei.To investigate the intervention strategies for BPF-induced NAFLD-like changes,we demonstrated that bellidifolin,isolated and purified from Swertia chirayita,significantly attenuated BPF-induced lipid droplet deposition in HepG2 cells and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins.Therefore,the present study elucidates the mechanisms underlying the BPF-induced lipid accumulation in HepG2 cells,while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.展开更多
基金supported by the National Natural Science Foundation of China(31501977)the Sichuan Provincial Key R&D Project China(22ZDYF0194)the Double World-Class Project of Southwest Minzu University China(XM2023010)。
文摘This study aimed to investigate the dose-effect of iron on growth performance,antioxidant function.intestinal morphology,and mRNA expression of jejunal tight junction protein in 1-to21-d-old yellow-feathered broilers.A total of 7201-d-old yellow-feathered maleb roilers were allocated to 9 treatments with 8 replicate cages of 10 birds per cage.The dietary treatments were consisted of a basal diet(contained 79.6 mg Fe kg^(-1))supplemented with 0,20,40,60,80,160,320,640,and 1,280 mg Fe kg^(-1)in the form of FeSO_(4)·7H_(2)O.Compared with the birds in the control group,birds supplemented with 20mg Fe kg^(-1)had higher average daily gain(ADG)(P<0.0001).Adding 640 and 1,280 mg Fe kg^(-1)significantly decreased ADG(P<0.0001)and average daily feed intake(ADFI)(P<0.0001)compared with supplementation of 20mg Fe kg^(-1).Malondialdehyde(MDA)concentration in plasma and duodenum increased linearly(P<0.0001),but MDA concentration in liver and jejunum increased linearly(P<0.05)or quadratically(P<0.05)with increased dietary Fe concentration.The villus height(VH)in duodenum and jejunum,and the ratio of villus height to crypt depth(V/C)in duodenum decreased linearly(P?0.05)as dietary Feincreased.As dietary Fe increased,the jejunal relative mRNA abundance of claudin-1 decreased linearly(P=0.001),but the jejunal relative mRNA abundance of zona occludens-1(ZO-1)and occludin decreased linearly(P?0.05)or quadratically(P?0.05).Compared with the supplementation of 20 mg Fe kg^(-1),the supplementation of640 mg Fe kg^(-1)or higher increased(P?0.05)MDA concentrations in plasma,duodenum,and jejunum,decreased VH in the duodenum and jejunum,and the addition of 1,280 mg Fe kg^(-1)reduced(P?0.05)the jejunal tight junction protein(claudin-1,ZO-1,occludin)mRNA abundance.In summary,640 mg of supplemental Fe kg^(-1)or greater was associated with decreased growth performance,increased oxidative stress,disrupted intestinal morphology,and reduced mRNA expression of jejunal tight junction protein.
基金This study received ethical approval from the ethics committee of Beijing Youan Hospital,Capital Medical University[No.(2021)078]the research was implemented in strict conformity with the guidelines outlined in the Declaration of Helsinki.
文摘BACKGROUND Enhancing awareness and use of pre-exposure prophylaxis(PrEP)and postexposure prophylaxis(PEP)is vital to curb human immunodeficiency virus(HIV)spread.High-risk behaviors prevalent among sexually transmitted infection clinic outpatients underscore the need for increased PrEP/PEP education in this group.AIM To investigate the effects of both onsite and online health education on the knowledge of,and willingness to use,PrEP and PEP among individuals receiving PEP services.METHODS Participants were drawn from a cohort study on PEP service intervention at an STD/AIDS outpatient clinic in designated HIV/AIDS hospitals in Beijing,conducted from January 1 to June 30,2022.Health education was provided both onsite and online during follow-up.Surveys assessing knowledge of,and willingness to use,PrEP/PEP were administered at baseline and again at 24 wk post-intervention.RESULTS A total of 112 participants were enrolled in the study;105 completed the follow-up at week 24.The percentage of participants with adequate knowledge of,and willingness to use,PrEP significantly increased from 65.2%and 69.6%at baseline to 83.8%and 82.9%at the end of the intervention(both P<0.05).Similarly,those with adequate knowledge of,and willingness to use,PEP increased from 74.1%and 77.7%at baseline to 92.4%and 89.5%at week 24(P<0.05).Being between 31 years and 40 years of age,having a postgraduate degree or higher,and reporting a monthly expenditure of RMB 5000 or more were found to be significantly associated with knowledge of PrEP and PEP(both P<0.05).CONCLUSION The findings show that both onsite and online health education significantly improved the knowledge of,and increased willingness to use,PrEP and PEP in individuals utilizing PEP services.
文摘胎儿型肺腺癌(fetal adenocarcinoma of the lung,FLAC)是一种罕见的肺部肿瘤。FLAC分为低级别FLAC(low-grade FLAC,L-FLAC)和高级别FLAC(high-grade FLAC,H-FLAC),两者在临床病理特征、生物学行为和临床结局方面有所不同。大多数H-FLAC患者是重度吸烟的中年人。本研究描述了1例罕见的非吸烟年轻男性患者,其最初表现为头顶肿块,最终被诊断为H-FLAC。本文旨在增进对FLAC的了解和认识,提高对该疾病的重视,以防止该疾病漏诊与误诊,加强早期识别、精准诊断,从而推进后续的有效治疗、改善预后。
基金Supported by Shiyan Taihe Hospital Project(2021JJXM084)General Project of Hubei Provincial Health and Health Commission(ZY2021M006).
文摘[Objectives]To observe the effect of Xianlinggubao Capsule on osteoporotic vertebral compression fracture(OVCF)in rabbits and the influence mechanism of the repair of fractures.[Methods]Female June age 30 rabbits were randomly divided into control group,model control group and Xianlinggubao group.After bilateral ovariectomy,the model control group and Xianlinggubao group were injected with dexamethasone continuously for 4 weeks,and then the OVCF compound model was established by surgery.The Xianlinggubao group was treated with Xianlinggubao at a dose of 300 mg/(kg·d)for 60 d,while the blank control group and the model control group were treated with the same amount of normal saline for 60 d.The number of blood vessels and the expression of bone morphogenetic protein-2(BMP-2)were detected by immunohistochemical staining and the bone mineral density(BMD)in the callus of the third lumbar fracture area of rabbits was measured.The content of serum phosphorus(P),alkaline phosphatase(ALP)and total calcium(TCa)in rabbit venous blood were measured by automatic biochemical analyzer.The content of vascular endothelial growth factor(VEGF)and platelet-derived growth factor(PDGF)in rabbit venous blood were measured by ELISA kit.[Results]The number of blood vessels and the expression of BMP-2 in the callus of the third lumbar fracture area of rabbits was high in Xianlinggubao group,the content of serum P,ALP,TCa,VEGF and PDGF was obviously increased,BMD was obviously increased,the bone microstructure of the third lumbar vertebrae fracture area of rabbits was basically restored.Compared with the model control group(P<0.05),the difference was statistically significant.[Conclusions]Xianlinggubao Capsule can increase calcium and phosphorus deposition,promote the formation of blood vessels in the fracture area of OVCF in rabbits,and have a strong repair effect on OVCF in rabbits.
基金suppor ted by the National Key Research and Development Program of China(2022YFA1104800)the Beijing Nova Program(20220484100)+6 种基金the National Natural Science Foundation of China(81873939)the Open Research Fund of State Key Laboratory of Cardiovascular Disease,Fuwai Hospital(2022KF-04)the Clinical Medicine Plus X-Young Scholars Projec t,Pek ing Universit y(PKU2022LCXQ003)the Emerging Engineering InterdisciplinaryYoung Scholars Project,Peking University,the Fundamental Research Funds for the Central Universities(PKU2023XGK011)the Open Research Fund of State Key Laboratory of Digital Medical Engineering,Southeast University(2023K-01)the Open Research Fund of Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease,Beijing,China(DXWL2023-01)the Science and Technology Bureau Foundation Application Project of Changzhou(CJ20220118)。
文摘Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.
基金Project supported by the Joint Fund of the National Natural Science Foundation of China–“Ye Qisun”Science Fund(Grant No.U2341251)。
文摘Zirconium hydride(ZrH_(2)) is an ideal neutron moderator material. However, radiation effect significantly changes its properties, which affect its behavior and the lifespan of the reactor. The threshold energy of displacement is an important quantity of the number of radiation defects produced, which helps us to predict the evolution of radiation defects in ZrH_(2).Molecular dynamics(MD) and ab initio molecular dynamics(AIMD) are two main methods of calculating the threshold energy of displacement. The MD simulations with empirical potentials often cannot accurately depict the transitional states that lattice atoms must surpass to reach an interstitial state. Additionally, the AIMD method is unable to perform largescale calculation, which poses a computational challenge beyond the simulation range of density functional theory. Machine learning potentials are renowned for their high accuracy and efficiency, making them an increasingly preferred choice for molecular dynamics simulations. In this work, we develop an accurate potential energy model for the ZrH_(2) system by using the deep-potential(DP) method. The DP model has a high degree of agreement with first-principles calculations for the typical defect energy and mechanical properties of the ZrH_(2) system, including the basic bulk properties, formation energy of point defects, as well as diffusion behavior of hydrogen and zirconium. By integrating the DP model with Ziegler–Biersack–Littmark(ZBL) potential, we can predict the threshold energy of displacement of zirconium and hydrogen in ε-ZrH_(2).
基金supported by the National Science Foundation of China(10972015,11172015)the Beijing Natural Science Foundation(8162008).
文摘The mechanical properties and failure mechanism of lightweight aggregate concrete(LWAC)is a hot topic in the engineering field,and the relationship between its microstructure and macroscopic mechanical properties is also a frontier research topic in the academic field.In this study,the image processing technology is used to establish a micro-structure model of lightweight aggregate concrete.Through the information extraction and processing of the section image of actual light aggregate concrete specimens,the mesostructural model of light aggregate concrete with real aggregate characteristics is established.The numerical simulation of uniaxial tensile test,uniaxial compression test and three-point bending test of lightweight aggregate concrete are carried out using a new finite element method-the base force element method respectively.Firstly,the image processing technology is used to produce beam specimens,uniaxial compression specimens and uniaxial tensile specimens of light aggregate concrete,which can better simulate the aggregate shape and random distribution of real light aggregate concrete.Secondly,the three-point bending test is numerically simulated.Thirdly,the uniaxial compression specimen generated by image processing technology is numerically simulated.Fourth,the uniaxial tensile specimen generated by image processing technology is numerically simulated.The mechanical behavior and damage mode of the specimen during loading were analyzed.The results of numerical simulation are compared and analyzed with those of relevant experiments.The feasibility and correctness of the micromodel established in this study for analyzing the micromechanics of lightweight aggregate concrete materials are verified.Image processing technology has a broad application prospect in the field of concrete mesoscopic damage analysis.
基金supported by the National Natural Science Foundation of China (32273136,31872572)Agriculture Research System of China (ARS-47)+1 种基金Science and Technology Planning Project of Guangdong Province (2023B1212060023)Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai) (SML2023SP201)。
文摘Animal body size variation is of particular interest in evolutionary biology,but the genetic basis remains largely unknown.Previous studies have shown the presence of two parallel evolutionary genetic clusters within the fish genus Epinephelus with evident divergence in body size,providing an excellent opportunity to investigate the genetic basis of body size variation in vertebrates.Herein,we performed phylotranscriptomic analysis and reconstructed the phylogeny of 13 epinephelids originating from the South China Sea.Two genetic clades with an estimated divergence time of approximately 15.4 million years ago were correlated with large and small body size,respectively.A total of 180 rapidly evolving genes and two positively selected genes were identified between the two groups.Functional enrichment analyses of these candidate genes revealed distinct enrichment categories between the two groups.These pathways and genes may play important roles in body size variation in groupers through complex regulatory networks.Based on our results,we speculate that the ancestors of the two divergent groups of groupers may have adapted to different environments through habitat selection,leading to genetic variations in metabolic patterns,organ development,and lifespan,resulting in body size divergence between the two locally adapted populations.These findings provide important insights into the genetic mechanisms underlying body size variation in groupers and species differentiation.
基金supported by the China Natural Science Foundation for Outstanding Scholars(82325032)Self-Supporting Program of Guangzhou Laboratory(SRPG22-001)。
文摘Bats,notable as the only flying mammals,serve as natural reservoir hosts for various highly pathogenic viruses in humans(e.g.,SARS-CoV and Ebola virus).Furthermore,bats exhibit an unparalleled longevity among mammals relative to their size,particularly the Myotis bats,which can live up to 40 years.However,the mechanisms underlying these distinctive traits remain incompletely understood.In our prior research,we demonstrated that bats exhibit dampened STING-interferon activation,potentially conferring upon them the capacity to mitigate virus-or aging-induced inflammation.To substantiate this hypothesis,we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING(MdSTING)into the mouse genome.We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process.Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice,as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines,immunopathology,and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo.These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner.Although the underlying mechanism awaits further study,this research has critical implications for bat longevity research,potentially contributing to our comprehension of healthy aging in humans.
基金The authors are grateful for the financial support from the National Key Research and Development Program of China(Grant No.2021YFB3400701)the Fundamental Research Funds for the Central Universities(Science and technology leading talent team project,Grant No.2022JBQY007).
文摘The high-speed train transmission system,experiencing both the internal excitation originating from gear meshing and the external excitation originating from the wheel-rail interaction,exhibits complex dynamic behavior in the actual service environment.This paper focuses on the gearbox in the high-speed train to carry out the bench test,in which various operat-ing conditions(torques and rotation speeds)were set up and the excitation condition covering both internal and external was created.Acceleration responses on multiple positions of the gearbox were acquired in the test and the vibration behavior of the gearbox was studied.Meanwhile,a stochastic excitation modal test was also carried out on the test bench under different torques,and the modal parameter of the gearbox was identified.Finally,the sweep frequency response of the gearbox under gear meshing excitation was analyzed through dynamic modeling.The results showed that the torque has an attenuating effect on the amplitude of gear meshing frequency on the gearbox,and the effect of external excitation on the gearbox vibration cannot be ignored,especially under the rated operating condition.It was also found that the torque affects the modal param-eter of the gearbox significantly.The torque has a great effect on both the gear meshing stiffness and the bearing stiffness in the transmission system,which is the inherent reason for the changed modal characteristics observed in the modal test and affects the vibration behavior of the gearbox consequently.
基金supported by the grant International Cooperation Project of Prevention and Treatment of Major Diseases with Chinese Medicine(GZYYGJ2021047)the High-end Experts Support Program from the Ministry of Science and Technology(DL 2021110001L)the Basic Research Funds from the Ministry of Education(1000061223731).
文摘Objectives:To investigate whether the protective actions of ginsenoside Rb1(Rb1)on astrocytes are mediated through the G_(s)-type G-protein-coupled receptor(GPCR-G_(s)).Methods:Primary astrocyte cultures derived from neonatal mouse brain were used.Astrocyte injury was induced via oxygen-glucose deprivation/re-oxygenation(OGD/R).Cell morphology,viability,lactate dehydrogenase(LDH)leakage,apoptosis,glutamate uptake,and brain-derived neurotrophic factor(BDNF)secretion were assessed to gauge cell survival and functionality.Western blot was used to investigate the cyclic adenosine monophosphate(cAMP)and protein kinase B(Akt)signaling pathways.GPCR-G_(s)-specific inhibitors and molecular docking were used to identify target receptors.Results:Rb1 at concentrations ranging from 0.8 to 5μM did not significantly affect the viability,glutamate uptake,or BDNF secretion in normal astrocytes.OGD/R reduced astrocyte viability,increasing their LDH leakage and apoptosis rate.It also decreased glutamate uptake and BDNF secretion by these cells.Rb1 had protective effects of astrocytes challenged by OGD/R,by improving viability,reducing apoptosis,and enhancing glutamate uptake and BDNF secretion.Additionally,Rb1 activated the cAMP and Akt pathways in these cells.When the GPCR-G_(s) inhibitor NF449 was introduced,the protective effects of Rb1 completely disappeared,and its activation of cAMP and Akt signaling pathways was significantly inhibited.Conclusion:Rb1 protects against astrocytes from OGD/R-induced injury through GPCR-G_(s) mediation.
基金supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.21KJA330002)Natural Science Foundation of Jiangsu Province(Grant No.BK20211252)+3 种基金Young and Middle-aged Academic Leaders of the"Blue Project"in Jiangsu Universities(2022-2)Jiangsu Health and Family Planning Commission Medical Research Program(Grant No.Z2018035)Project of Public Health Research Center of Jiangnan University(Grant No.JUPH201842)Natural Science Foundation of Nanjing University of Chinese Medicine(Grant No.XZR2020021).
文摘As a potential endocrine-disrupting chemical,bisphenol F(BPF)may cause nonalcoholic fatty liver disease(NAFLD)-like changes,but the mechanisms under its pathogenesis as well as the intervention strategies remain unclear.Using the electron microscopy technology,along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays,we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells,accompanied by an increased total level of triglycerides.At the molecular level,the lipogenesis-associated mRNAs and proteins,including acetyl-CoA carboxylase,fatty acid synthase,stearoyl-CoA desaturase-1,peroxisome proliferator-activated receptor gamma,and CCAAT-enhancer-binding proteins,increased significantly via the AMP-activated protein kinase(AMPK)-mammalian target of rapamycin(mTOR)signaling regulation in both in vitro and in vivo studies.Furthermore,the immunofluorescence results also showed the robust lipogenesis induced by BPF,evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei.To investigate the intervention strategies for BPF-induced NAFLD-like changes,we demonstrated that bellidifolin,isolated and purified from Swertia chirayita,significantly attenuated BPF-induced lipid droplet deposition in HepG2 cells and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins.Therefore,the present study elucidates the mechanisms underlying the BPF-induced lipid accumulation in HepG2 cells,while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.