Abstract Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the...Abstract Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hip- pocampal extracellular glutamate level induced by nalox- one （2 mg/kg, i.p.） precipitation. Agmatine （20 mg/kg, s.c.） administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synapto- somes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agrnatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors （NMDARs） was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine pre- vented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including mod- ulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.展开更多
Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induct...Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD:transforming growth factor-β1(TGF-β1),fibrin,sodium tetradecyl sulfate(STS)combined with TGF-β1,and polidocanol(POL)combined with TGF-β1.The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature.The STS+TGF-β1 combination resulted in both histological and morphological alterations,but with a high incidence of localized necrosis that led to animal death.The POL+TGF-β1 combination produced pathological changes and curvature comparable to STS+TGF-β1 and led to fewer complications.In conclusion,fibrin,STS+TGF-β1,and POL+TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats.The POL+TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.展开更多
Lung cancer,particularly non-small cell lung cancer(NSCLC),remains a leading cause of cancer-related death globally,and a significant number of patients develop brain metastasis(BM)as the disease progresses.The presen...Lung cancer,particularly non-small cell lung cancer(NSCLC),remains a leading cause of cancer-related death globally,and a significant number of patients develop brain metastasis(BM)as the disease progresses.The presence of BM,which affects up to 60%of patients with NSCLC,is correlated with an unfavorable prognosis and markedly decreased quality of life.Standard treatment options for BMs,such as whole-brain radiation therapy and surgery,have displayed limited efficacy in controlling disease progression,and they can cause significant neurocognitive side effects.Stereotactic radiotherapy(SRT),including stereotactic radiosurgery,fractionated SRT,and stereotactic body radiotherapy,represents an advanced and precise approach for treating BM that minimizes damage to surrounding healthy tissues.This review highlights recent advances in the application of SRT for treating BM of NSCLC,focusing on its underlying biological principles and mechanisms of action as well as the quality standards necessary for effective SRT implementation.The ability of SRT to deliver substantial radiation doses in a precisely targeted manner has resulted in better local tumor management,fewer side effects,and increased patient survival rates.Future research is crucial to improve SRT procedures and successfully incorporate them into multimodal therapy plans for patients with NSCLC and BM.展开更多
Mapping human footprint(HF)is crucial for understanding the cumulative anthropogenic pressures on the envi-ronment.However,its effectiveness is often hampered by the absence of fine-scale,high-quality spatio-temporal ...Mapping human footprint(HF)is crucial for understanding the cumulative anthropogenic pressures on the envi-ronment.However,its effectiveness is often hampered by the absence of fine-scale,high-quality spatio-temporal datasets.Addressing this gap,we present the first annual HF maps for the Qingzang Plateau(QP)from 1990 to 2020,at a 100 m×100 m resolution,boasting an accuracy exceeding 80%.Our findings reveal that the QP’s human-induced modifications were relatively low,with a median HF of 3.39 in 2020,significantly lower than the global average of 7.56.The northeast and mid-south regions of the QP emerged as hotspots for anthropogenic impact.Notably,over two-thirds(68.2%)of the QP registered an HF score below 4,classifying them as largely intact.However,the QP’s average HF score has escalated more swiftly than the global mean(0.0348/yr vs.0.0186/yr),particularly in the last decade,indicating escalating human pressures.In terms of stability,montane grasslands and shrublands comprised 75.1%of moderately or highly altered biomes in 2020.In contrast,tropical and subtropical moist broadleaf forests witnessed the most substantial HF increases.Encouragingly,26.29%of the QP experienced HF reductions over the past thirty years,highlighting potential conservation opportunities.展开更多
Safety,high protein content,and the numerous health benefits make Spirulina an outstanding source of bioactive peptides.Peptides from Spirulina,which exhibit antioxidant,anti-inflammatory,and antihypertensive effects,...Safety,high protein content,and the numerous health benefits make Spirulina an outstanding source of bioactive peptides.Peptides from Spirulina,which exhibit antioxidant,anti-inflammatory,and antihypertensive effects,may assist in the management of cardiovascular diseases(CVDs).Here,we present the optimization of enzyme-digested hydrolysates derived from Spirulina sp.by using response surface methodology(RSM).We also evaluated the biological activity of Spirulina protein hydrolysates(SPHs)in contributing to the amelioration of hypertension and associated cardiovascular diseases.Our findings suggest that Spirulina protein extracts contain a complex proteinaceous composition with phycocyanin being the dominant protein,as evidenced by both SDS-PAGE and LC-MS/MS profiling.Alkaline protease,protease K,andα-chymotrypsin exhibited a substantial hydrolytic effect on Spirulina protein,taking into account their degree of hydrolysis(DH),peptide yield,and molecular weight distribution.Single-factor experiments identified pH,temperature,and enzyme/substrate ratio as the key factors influencing DH.Moreover,optimal hydrolysis conditions for the proteases were determined via RSM,leading to a considerable enhancement of the actual DH.Bioassays showed that SPHs have strong antioxidant activity against various free radicals,with a higher ability to scavenge hydroxyl radicals.Furthermore,SPHs inhibited macrophage nitric oxide secretion and significantly inhibited angiotensin I-converting enzyme in vitro at 400μg/mL.It is worth noting that SPHs prepared with protease K exhibited a potent anti-hypertensive effect in vivo.The findings indicate the potential usefulness of including dietary SPHs in preventing hypertension and associated CVDs.This research could be valuable in guiding the development of health-promoting foods within the Spirulina industry.展开更多
We demonstrate a bipolar graphene/F_(16)CuPc synaptic transistor(GFST)with matched p-type and n-type bipolar properties,which emulates multiplexed neurotransmission of the release of two excitatory neurotransmitters i...We demonstrate a bipolar graphene/F_(16)CuPc synaptic transistor(GFST)with matched p-type and n-type bipolar properties,which emulates multiplexed neurotransmission of the release of two excitatory neurotransmitters in graphene and F_(16)CuPc channels,separately.This process facilitates fast-switching plasticity by altering charge carriers in the separated channels.The complementary neural network for image recognition of Fashion-MNIST dataset was constructed using the matched relative amplitude and plasticity properties of the GFST dominated by holes or electrons to improve the weight regulation and recognition accuracy,achieving a pattern recognition accuracy of 83.23%.These results provide new insights to the construction of future neuromorphic systems.展开更多
Carbon nanotubes(CNTs)are widely used in various fields owing to their unique properties.In this study,three different types of nitrogen-doped CNT heterojunctions were constructed:parallel-doped(PCNT),vertically doped...Carbon nanotubes(CNTs)are widely used in various fields owing to their unique properties.In this study,three different types of nitrogen-doped CNT heterojunctions were constructed:parallel-doped(PCNT),vertically doped(VCNT),and mesh-doped(MCNT).Non-equilibrium molecular dynamics(NEMD)simulations were conducted to investigate their heat flux and thermal rectification(TR)effects.The results show that heat flux preferentially flows from nitrogen-doped regions to undoped regions,exhibiting distinct thermal rectification behavior,with PCNT showing the most pronounced effect.Interestingly,the TR ratio of the zigzag PCNT is significantly higher than that of the armchair PCNT.Subsequently,we examined the effects of system length and diameter on the TR ratio of the PCNT and found that the TR ratio increases and then decreases with increasing model length.In addition,the effect of defect density on the heat flux of the PCNT is peculiar.The phonon density of states,phonon dispersion,participation ratio,and phonon spectral heat flux were analyzed to elucidate the thermal transport behavior of phonons in the nanotubes.This study provides insights into the development and design of nitrogen-doped CNT thermal rectifiers.展开更多
Clinical diagnosis and treatment of malignant tumor bone metastasesOverview Bone is the most common place of metastases in ad-vanced malignant diseases. Constant improvement in the treatment of malignant tumors has r...Clinical diagnosis and treatment of malignant tumor bone metastasesOverview Bone is the most common place of metastases in ad-vanced malignant diseases. Constant improvement in the treatment of malignant tumors has resulted in prolonged survival time, and so as an increased incidence of osseous metastases and skeletal complications.展开更多
Objective This paper is to explore the DNA repair mechanism of immune adaptive response （AR） induced by low dose radiation （LDR）, the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic su...Objective This paper is to explore the DNA repair mechanism of immune adaptive response （AR） induced by low dose radiation （LDR）, the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic subunit （DNA-PKcs） and PARP-1 genes in the LDR-induced AR in EL-4 cells. Methods The apoptosis and cell cycle progression of EL-4 cells were detected by flow cytometry in 12 h after the cells received the pre-exposure of 0.075 Gy X-rays （inductive dose, D 1） and the succeeding high dose irradiation （challenge dose, D2; 1.0, 1.5, and 2.0 Gy X-rays, respectively） with or without wortmannin （inhibitor of ATM and DNA-PK） and 3-aminobenzamid （inhibitor of PARP-1）. And the protein expressions and mRNA levels related to these genes were detected with flow cytometry and reverse transcription-polymerase chain reaction in 12 h after irradiation with D2. Results The mRNA and protein expressions of p53 and PARP-1 in EL-4 cells in the D1 ＋ D2 groups were much lower than those in the D2 groups, and those of PARP-1 in the 3-AB ＋ D2 and the 3-AB ＋ D1 ＋ D2 groups were much lower than those in the D2 and the D1 ＋ D2 groups. The percentage of apoptotic EL-4 cells in the 3-AB ＋ D1 ＋ D2 groups was much higher than that in the D1 ＋ D2 groups, that in the G0/G1 and the G2 ＋ M phases was much higher, and that in the S phase were much lower. Although the ATM and DNA-PKcs mRNA and protein expressions in wortmannin ＋ D1 ＋ D2 groups were much lower than those in the D1 ＋ D2 groups, there were no significant changes in the apoptosis and cell cycle progression between the wortmannin ＋ D1 ＋ D2 and the D1 ＋ D2 groups. Conclusion PARP-1 and p53 might play important roles in AR induced by LDR.展开更多
基金supported by grants from the National Basic Research Development Program of China (2015CB553504)the National Natural Science Foundation of China (30930040 and 81102426)a Project of the National Science and Technology Support Program of China(2012BAI01B07)
文摘Abstract Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hip- pocampal extracellular glutamate level induced by nalox- one （2 mg/kg, i.p.） precipitation. Agmatine （20 mg/kg, s.c.） administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synapto- somes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agrnatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors （NMDARs） was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine pre- vented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including mod- ulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.
基金supported by the National Natural Science Foundation of China(grant No.81971380 and No.82301822).
文摘Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD:transforming growth factor-β1(TGF-β1),fibrin,sodium tetradecyl sulfate(STS)combined with TGF-β1,and polidocanol(POL)combined with TGF-β1.The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature.The STS+TGF-β1 combination resulted in both histological and morphological alterations,but with a high incidence of localized necrosis that led to animal death.The POL+TGF-β1 combination produced pathological changes and curvature comparable to STS+TGF-β1 and led to fewer complications.In conclusion,fibrin,STS+TGF-β1,and POL+TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats.The POL+TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
基金Supported by the National Key Research and Development Program of China,No.2022YFE0110200Project of Science and Technology Department of Jilin Province,No.20240501002GH and No.YDZJ202102CXJD020+3 种基金Jilin University Norman Bethune Medical Department“Medicine+X”Project,No.2022JBGS04Project of Development and Reform Commission of Jilin Province,No.2021C023Department of Human Resources and Social Security Project of Jilin Province20th Batch of Innovation and Entrepreneurship Talent Funding Project of Jilin Province.
文摘Lung cancer,particularly non-small cell lung cancer(NSCLC),remains a leading cause of cancer-related death globally,and a significant number of patients develop brain metastasis(BM)as the disease progresses.The presence of BM,which affects up to 60%of patients with NSCLC,is correlated with an unfavorable prognosis and markedly decreased quality of life.Standard treatment options for BMs,such as whole-brain radiation therapy and surgery,have displayed limited efficacy in controlling disease progression,and they can cause significant neurocognitive side effects.Stereotactic radiotherapy(SRT),including stereotactic radiosurgery,fractionated SRT,and stereotactic body radiotherapy,represents an advanced and precise approach for treating BM that minimizes damage to surrounding healthy tissues.This review highlights recent advances in the application of SRT for treating BM of NSCLC,focusing on its underlying biological principles and mechanisms of action as well as the quality standards necessary for effective SRT implementation.The ability of SRT to deliver substantial radiation doses in a precisely targeted manner has resulted in better local tumor management,fewer side effects,and increased patient survival rates.Future research is crucial to improve SRT procedures and successfully incorporate them into multimodal therapy plans for patients with NSCLC and BM.
基金supported by the National Natural Science Foun-dation of China(Grant No.42071238)the Second Qingzang Plateau Scientific Expedition and Research Program(STEP)(Grant No.2019QZKK0402).
文摘Mapping human footprint(HF)is crucial for understanding the cumulative anthropogenic pressures on the envi-ronment.However,its effectiveness is often hampered by the absence of fine-scale,high-quality spatio-temporal datasets.Addressing this gap,we present the first annual HF maps for the Qingzang Plateau(QP)from 1990 to 2020,at a 100 m×100 m resolution,boasting an accuracy exceeding 80%.Our findings reveal that the QP’s human-induced modifications were relatively low,with a median HF of 3.39 in 2020,significantly lower than the global average of 7.56.The northeast and mid-south regions of the QP emerged as hotspots for anthropogenic impact.Notably,over two-thirds(68.2%)of the QP registered an HF score below 4,classifying them as largely intact.However,the QP’s average HF score has escalated more swiftly than the global mean(0.0348/yr vs.0.0186/yr),particularly in the last decade,indicating escalating human pressures.In terms of stability,montane grasslands and shrublands comprised 75.1%of moderately or highly altered biomes in 2020.In contrast,tropical and subtropical moist broadleaf forests witnessed the most substantial HF increases.Encouragingly,26.29%of the QP experienced HF reductions over the past thirty years,highlighting potential conservation opportunities.
基金Supported by the Science and Technology Project of Fujian Province(Nos.2023T3034,2020N3011)the Innovation Academy for Drug Discovery and DevelopmentChinese Academy of Sciences。
文摘Safety,high protein content,and the numerous health benefits make Spirulina an outstanding source of bioactive peptides.Peptides from Spirulina,which exhibit antioxidant,anti-inflammatory,and antihypertensive effects,may assist in the management of cardiovascular diseases(CVDs).Here,we present the optimization of enzyme-digested hydrolysates derived from Spirulina sp.by using response surface methodology(RSM).We also evaluated the biological activity of Spirulina protein hydrolysates(SPHs)in contributing to the amelioration of hypertension and associated cardiovascular diseases.Our findings suggest that Spirulina protein extracts contain a complex proteinaceous composition with phycocyanin being the dominant protein,as evidenced by both SDS-PAGE and LC-MS/MS profiling.Alkaline protease,protease K,andα-chymotrypsin exhibited a substantial hydrolytic effect on Spirulina protein,taking into account their degree of hydrolysis(DH),peptide yield,and molecular weight distribution.Single-factor experiments identified pH,temperature,and enzyme/substrate ratio as the key factors influencing DH.Moreover,optimal hydrolysis conditions for the proteases were determined via RSM,leading to a considerable enhancement of the actual DH.Bioassays showed that SPHs have strong antioxidant activity against various free radicals,with a higher ability to scavenge hydroxyl radicals.Furthermore,SPHs inhibited macrophage nitric oxide secretion and significantly inhibited angiotensin I-converting enzyme in vitro at 400μg/mL.It is worth noting that SPHs prepared with protease K exhibited a potent anti-hypertensive effect in vivo.The findings indicate the potential usefulness of including dietary SPHs in preventing hypertension and associated CVDs.This research could be valuable in guiding the development of health-promoting foods within the Spirulina industry.
基金supported by the Shenzhen Science and Technology Program(No.JCYJ20210324121002008)the National Science Fund for Distinguished Young Scholars of China(No.T2125005)+5 种基金the National Key R&D Program of China(Nos.2022YFE0198200,2022YFA1204500,and 2022YFA1204504)the Natural Science Foundation of Tianjin(Nos.22JCYBJC01290 and 23JCQNJC01440)the Key Project of Natural Science Foundation of Tianjin(No.22JCZDJC00120)the Fundamental Research Funds for the Central Universities,Nankai University(Nos.BEG124901 and BEG124401)the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515110319)the Key Science and Technology Program of Henan Province(No.242102210171).
文摘We demonstrate a bipolar graphene/F_(16)CuPc synaptic transistor(GFST)with matched p-type and n-type bipolar properties,which emulates multiplexed neurotransmission of the release of two excitatory neurotransmitters in graphene and F_(16)CuPc channels,separately.This process facilitates fast-switching plasticity by altering charge carriers in the separated channels.The complementary neural network for image recognition of Fashion-MNIST dataset was constructed using the matched relative amplitude and plasticity properties of the GFST dominated by holes or electrons to improve the weight regulation and recognition accuracy,achieving a pattern recognition accuracy of 83.23%.These results provide new insights to the construction of future neuromorphic systems.
基金supported by the National Natural Science Foundation of China(Grant No.52476071)the Natural Science Foundation of Hebei Province(Grant No.A2024502008).
文摘Carbon nanotubes(CNTs)are widely used in various fields owing to their unique properties.In this study,three different types of nitrogen-doped CNT heterojunctions were constructed:parallel-doped(PCNT),vertically doped(VCNT),and mesh-doped(MCNT).Non-equilibrium molecular dynamics(NEMD)simulations were conducted to investigate their heat flux and thermal rectification(TR)effects.The results show that heat flux preferentially flows from nitrogen-doped regions to undoped regions,exhibiting distinct thermal rectification behavior,with PCNT showing the most pronounced effect.Interestingly,the TR ratio of the zigzag PCNT is significantly higher than that of the armchair PCNT.Subsequently,we examined the effects of system length and diameter on the TR ratio of the PCNT and found that the TR ratio increases and then decreases with increasing model length.In addition,the effect of defect density on the heat flux of the PCNT is peculiar.The phonon density of states,phonon dispersion,participation ratio,and phonon spectral heat flux were analyzed to elucidate the thermal transport behavior of phonons in the nanotubes.This study provides insights into the development and design of nitrogen-doped CNT thermal rectifiers.
文摘Clinical diagnosis and treatment of malignant tumor bone metastasesOverview Bone is the most common place of metastases in ad-vanced malignant diseases. Constant improvement in the treatment of malignant tumors has resulted in prolonged survival time, and so as an increased incidence of osseous metastases and skeletal complications.
基金supported by the National Natural Science Foundation of China(30570546 and 30870747)the Natural Science Foundation of Jilin Province (20090458 and 201015183)+1 种基金the Young Teachers Innovative Foundation of Jilin University(421010043430)the Young Scholars Research Foundation Program of China-Japan Union Hospital(2009)
文摘Objective This paper is to explore the DNA repair mechanism of immune adaptive response （AR） induced by low dose radiation （LDR）, the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic subunit （DNA-PKcs） and PARP-1 genes in the LDR-induced AR in EL-4 cells. Methods The apoptosis and cell cycle progression of EL-4 cells were detected by flow cytometry in 12 h after the cells received the pre-exposure of 0.075 Gy X-rays （inductive dose, D 1） and the succeeding high dose irradiation （challenge dose, D2; 1.0, 1.5, and 2.0 Gy X-rays, respectively） with or without wortmannin （inhibitor of ATM and DNA-PK） and 3-aminobenzamid （inhibitor of PARP-1）. And the protein expressions and mRNA levels related to these genes were detected with flow cytometry and reverse transcription-polymerase chain reaction in 12 h after irradiation with D2. Results The mRNA and protein expressions of p53 and PARP-1 in EL-4 cells in the D1 ＋ D2 groups were much lower than those in the D2 groups, and those of PARP-1 in the 3-AB ＋ D2 and the 3-AB ＋ D1 ＋ D2 groups were much lower than those in the D2 and the D1 ＋ D2 groups. The percentage of apoptotic EL-4 cells in the 3-AB ＋ D1 ＋ D2 groups was much higher than that in the D1 ＋ D2 groups, that in the G0/G1 and the G2 ＋ M phases was much higher, and that in the S phase were much lower. Although the ATM and DNA-PKcs mRNA and protein expressions in wortmannin ＋ D1 ＋ D2 groups were much lower than those in the D1 ＋ D2 groups, there were no significant changes in the apoptosis and cell cycle progression between the wortmannin ＋ D1 ＋ D2 and the D1 ＋ D2 groups. Conclusion PARP-1 and p53 might play important roles in AR induced by LDR.
