背景与目的目前,肺癌依然是我国发病率和死亡率最高的恶性肿瘤。而在早期肺腺癌(lung adenocarcinoma,LUAD)中,微乳头(micropapillary,MPP)成分尤其常见,且通常表现出高侵袭性,其与早期转移、淋巴浸润的风险以及患者的5年生存率显著相...背景与目的目前,肺癌依然是我国发病率和死亡率最高的恶性肿瘤。而在早期肺腺癌(lung adenocarcinoma,LUAD)中,微乳头(micropapillary,MPP)成分尤其常见,且通常表现出高侵袭性,其与早期转移、淋巴浸润的风险以及患者的5年生存率显著相关。本研究旨在探究以磨玻璃影(ground-glass opacities,GGOs)为特征的早期LUAD中MPP成分和非MPP成分的异同,寻找MPP成分所特有的突变特征,并分析锌指蛋白家族的ZNF469基因与早期LUAD预后以及免疫浸润的关系。方法收集31例LUAD恶性肺结节,采用显微解剖法将其分为成对的MPP和非MPP成分。对早期恶性肺结节组分进行全外显子组测序(whole-exome sequencing,WES),利用maftools、非负矩阵分解(Nonnegative Matrix Factorization,NMF)法、Sigminer等方法进行突变特征分析,以揭示侵袭性LUAD中MPP组分相比于其他肿瘤组织所特有的基因组突变特征。利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)的LUAD数据库中ZNF469的表达情况,探讨其与肺癌预后的关系;利用GeneMANIA数据库以及基因本体(Gene Ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析探索LUAD中与ZNF469相关基因的互作网络及信号通路;利用TIMER和TISIDB数据库分析ZNF469表达与LUAD中免疫细胞浸润水平的相关性。结果MPP成分具有较多的基因组变异,相比于非MPP成分的肿瘤组织,癌症体细胞突变目录(Catalogue of Somatic Mutations in Cancer,COSMIC)的13号突变特征(胞苷脱氨酶家族,APOBEC)是MPP成分所特有的,这提示其参与了MPP成分对LUAD早期侵袭过程的促进作用;并且APOBEC特征高的MPP样本具有更高的肿瘤突变负荷(tumor mutational burden,TMB),提示这些患者更能从免疫治疗中获益。LUAD中突变ZNF469的表达高于正常组织,与LUAD患者的不良预后有关。基因互作网络分析以及GO和KEGG富集分析发现,COL6A1、COL1A1、COL1A2、TGFB2、MMP2、COL8A2、C2CD4C等与ZNF469具有相互作用,且主要与编码胶原蛋白、参与细胞外基质构成有关。ZNF469表达与肿瘤的免疫浸润呈正相关。结论本研究揭示了中国人群侵袭性LUAD中MPP成分的特有突变特征,并发现突变ZNF469的高表达影响LUAD预后与免疫浸润,推测ZNF469可作为LUAD潜在的诊断及预后生物标志物。展开更多
Experiencing urban green and blue spaces(GBSs)can be a nature-based solution to improve mental well-being and cope with negative moods for people exposed to PM2.5 pollution.In this study,a total of 1257 photos were co...Experiencing urban green and blue spaces(GBSs)can be a nature-based solution to improve mental well-being and cope with negative moods for people exposed to PM2.5 pollution.In this study,a total of 1257 photos were collected to recognize their posted emotions of Sina Weibo users from 38 parks in 22 cities in Northeast China in 2021,when atmospheric PM_(2.5)and landscape metrics were evaluated for GBSs of each park.Autumn and winter had heavy atmospheric PM_(2.5)pollutions in resource-dependent cities of Liaoning.Net positive emotions(happy minus sad scores)decreased in larger green spaces.The perception of blue space countered the presentation of sadness only for a limited period over four seasons.High elevation decreased the level of happiness presented in winter.Overall,this study confirms that visiting large urban green spaces at low elevations can benefit the perception of positive sentiments for people exposed to PM_(2.5)in autumn.For planning urban forests in Northeast China,more green spaces should be constructed in cities in southern Jilin province to alleviate air PM_(2.5)pollution and gain better well-being of local people.展开更多
The stability(or instability)of finite sized magnetic island could play a significant role in disruption avoidance or disruption mitigation dynamics.Especially,various current and pressure profile modifications,such a...The stability(or instability)of finite sized magnetic island could play a significant role in disruption avoidance or disruption mitigation dynamics.Especially,various current and pressure profile modifications,such as the current drive and heating caused by electron cyclotron wave,or the radiative cooling and current expulsion caused by the shattered pellet injection could be applied within the island to modify its stability,thus changing the ensuing dynamics.In this study,we calculate the mode structure modification caused by such profile changes within the island using the perturbed equilibrium approach,thus obtain the change of stability criterion Δ′ and assess the corresponding quasi-linear island stability.The positive helical current perturbation is found to always stabilize the island,while the negative one is found to do the opposite,in agreement with previous results.The pressure bump or hole within the island has a more complicated stability impact.In the small island regime,its contribution is monotonic,with pressure bump that tends to stabilize the island while pressure hole destabilizes it.This effect is relatively weak,though,due to the cancellation of the pressure term’s odd parity contribution in the second derivatives of the mode structure.In the large island regime,such cancellation is broken due to the island asymmetry,and the pressure contribution to stability is manifested,which is non-monotonic.The stability analysis in this paper helps to more accurately clarify the expected island response in the presence of profile modifications caused by disruption avoidance or mitigation systems.展开更多
BACKGROUND Antagonists of cannabinoid type 1 receptor(CB1)have been shown to promote body weight loss and improve insulin sensitivity.Cannabinoids decrease adiponectin,and CB1 blocker increase adiponectin.However,the ...BACKGROUND Antagonists of cannabinoid type 1 receptor(CB1)have been shown to promote body weight loss and improve insulin sensitivity.Cannabinoids decrease adiponectin,and CB1 blocker increase adiponectin.However,the mediators of CB1 actions are not well defined.AIM To investigate whether the beneficial effects of CB1 inhibition are,at least in part,mediated by adiponectin.METHODS We compared metabolic and inflammatory phenotypes of wild-type(WT)mice,CB1-null(CB1^(-/-))and CB1/adiponectin double-knockout(DKO)mice.We assessed the insulin sensitivity using insulin tolerance test and glucose tolerance test,and inflammation using flow cytometry analysis of macrophages.RESULTS CB1^(-/-)mice exhibited significantly reduced body weight and fat mass when compared to WT mice.While no significance was found in total daily food intake and locomotor activity,CB1^(-/-)mice showed increased energy expenditure,enhanced thermogenesis in brown adipose tissue(BAT),and improved insulin sensitivity compared to WT mice.DKO showed no difference in body weight,adiposity,nor insulin sensitivity;only showed a modestly elevated thermogenesis in BAT compared to CB1^(-/-)mice.The metabolic phenotype of DKO is largely similar to CB1^(-/-)mice,suggesting that adiponectin is not a key mediator of the metabolic effects of CB1.Interestingly,CB1^(-/-)mice showed reduced pro-inflammatory macrophage polarization in both peritoneal macrophages and adipose tissue macrophages compared to WT mice;in contrast,DKO mice exhibited increased pro-inflammatory macrophage polarization in these macrophages compared to CB1^(-/-)mice,suggesting that adiponectin is an important mediator of the inflammatory effect of CB1.CONCLUSION Our findings reveal that CB1 functions through both adiponectin-dependent and adiponectin-independent mechanisms:CB1 regulates energy metabolism in an adiponectin-independent manner,and inflammation in an adiponectin-dependent manner.The differential effects of adiponectin on CB1-mediated metabolic and inflammatory functions should be taken into consideration in CB1 antagonist utilization.展开更多
Osteoarthritis(OA)is a chronic and degenerative disease with limited clinical options for effective suppression.Recently,significant endeavors have been explored to reveal its pathogenesis and develop treatments again...Osteoarthritis(OA)is a chronic and degenerative disease with limited clinical options for effective suppression.Recently,significant endeavors have been explored to reveal its pathogenesis and develop treatments against OA.Hydrogels,designed with a striking resemblance to the extracellular matrix,offer a biomimetic interaction with biological tissues,presenting a promising avenue for OA amelioration.As a result,biocompatible hydrogels have been erected incorporating on-demand bioactivities to optimize the intra-articular microenvironment,thereby alleviating OA symptoms and fostering the eventual regeneration of articular joints.This review highlights the collaborative objectives underlying the establishment of this tissue microenvironment,encompassing mechanical modulation,anti-inflammation,and tissue regeneration.Specifically,we consolidate recent advances in hydrogel-based biomaterials,serving as the tissue engineering scaffolds to replicate the lubrication properties of natural joints or the bioactive agent-loaded vehicles to combat localized inflammation.Additionally,hydrogels function as cell scaffolds to facilitate the maintenance of cellular homeostasis and contribute to the advancement of cartilage regeneration.Finally,this review outlines the prospective directions for hydrogel-mediated OA therapies.展开更多
Although with the good biological properties,silk fibroin(SF)is immensely restrained in long-distance vascular defect repair due to its relatively fast degradation and inferior mechanical properties.It is necessary to...Although with the good biological properties,silk fibroin(SF)is immensely restrained in long-distance vascular defect repair due to its relatively fast degradation and inferior mechanical properties.It is necessary to construct a multifunctional composite scaffold based on SF.In this study,a novel magnetic SF scaffold(MSFCs)was prepared by an improved infiltration method.Compared with SF scaffold(SFC),MSFCs were found to have better crystallinity,magnetocaloric properties,and mechanical strength,which was ascribed to the rational introduction of iron-based magnetic nanoparticles(MNPs).Moreover,in vivo and in vitro experiments demonstrated that the degradation of MSFCs was significantly extended.The mechanism of delayed degradation was correlated with the dual effect that was the newly formed hydrogen bonds between SFC and MNPs and the complexing to tyrosine(Try)to inhibit hydrolase by internal iron atoms.Besides,theβ-crystallization of protein in MSFCs was increased with the rise of iron concentration,proving the beneficial effect after MNPS doped.Furthermore,although macrophages could phagocytose the released MNPs,it did not affect their function,and even a reasonable level might cause some cytokines to be upregulated.Finally,in vitro and in vivo studies demonstrated that MSFCs showed excellent biocompatibility and the growth promotion effect on CD34-labeled vascular endothelial cells(VECs).In conclusion,we confirm that the doping of MNPs can significantly reduce the degradation of SFC and thus provide an innovative perspective of multifunctional biocomposites for tissue engineering.展开更多
There are some special spaces in which there is no air conditioning or the people are in move,thus exposing people to a hot environment.In this study,portable cooling systems were proposed and their effects on thermal...There are some special spaces in which there is no air conditioning or the people are in move,thus exposing people to a hot environment.In this study,portable cooling systems were proposed and their effects on thermal comfort and work performance were investigated at an air temperature of 32°C.Four conditions were established:cool air towards breathing zone(A),chest and back cooling(B)#combined cooling(C)and no cooling(D).Twenty-eight subjects were exposed to the four conditions in a counterbalanced order.During each exposure they performed tasks and made subjective assessments,while multiple physiological parameters were measured.Compared with no cooling(D),cool air towards breathing zone(A)and chest and back cooling(B)improved work performance by 17.5%and 19.25%,respectively,while decreased the subjects'thermal sensation,skin temperature,and heart rate.When the two cooling systems were combined(C),larger improvements in thermal comfort and work performance were achieved than no cooling(D);the mean thermal sensation rating decreased from 2.4 to 0.7;work performance increased by up to 33%,and physiological parameters including skin temperature,pulse,heart rate and salivary alpha-amylase significantly decreased.The present results suggest that the proposed portable cooling systems could maintain thermal comfort and work performance in a hot environment,while potentially improve air quality for some special spaces.展开更多
Type 2 diabetes mellitus(T2DM)and Alzheimer's disease(AD)share several common pathophysiological features.Rare variants of triggering receptor expressed on myeloid cells 2(TREM2)increase the risk of developing AD,...Type 2 diabetes mellitus(T2DM)and Alzheimer's disease(AD)share several common pathophysiological features.Rare variants of triggering receptor expressed on myeloid cells 2(TREM2)increase the risk of developing AD,suggesting the involvement of TREM2 and innate immunity in AD development.It is still unknown whether TREM2 is related to cognitive impairment in T2DM.Here,we investigated the effects of the hippocampal overexpression of TREM2 on cognitive in long-term high-fat diet(HFD)-fed mice.Male C57BL/6J mice were maintained on HFD for 50 weeks.TREM2 was overexpressed in the hippocampus 36 weeks after HFD feeding using adeno-associated virus vector(AAV)-mediated gene delivery.The results showed that the HFD feeding induced rapid and persistent weight gain,glucose intolerance and significant impairments in learning and memory.Compared with AAV-con,AAV-TREM2 significantly ameliorated cognitive impairment without altering body weight and glucose homeostasis in HFD mice.The overexpression of TREM2 upregulated the synaptic proteins spinophilin,PSD95 and synaptophysin,suggesting the improvement in synaptic transmission.Dendritic complexity and spine density in the CA1 region were rescued after TREM2 overexpression.Furthermore,TREM2 markedly increased the number of iba-1/Arg-1-positive microglia in the hippocampus,suppressed neuroinflammation and microglial activation.In sum,hippocampal TREM2 plays an important role in improving HFD-induced cognitive dysfunction and promoting microglial polarization towards the M2 anti-inflammatory phenotype.Our study also suggests that TREM2 might be a novel target for the intervention of obesity/diabetes-associated cognitive decline.展开更多
SOD-like activity of CeO_(2) nanoparticles(Ce NPs)is driven by Ce^(3+)/Ce^(4+),high oxidative stress can oxidize Ce^(3+) to reduce the ratio of Ce^(3+)/Ce^(4+),inactivating the SOD activity of Ce NPs.Herein,we found A...SOD-like activity of CeO_(2) nanoparticles(Ce NPs)is driven by Ce^(3+)/Ce^(4+),high oxidative stress can oxidize Ce^(3+) to reduce the ratio of Ce^(3+)/Ce^(4+),inactivating the SOD activity of Ce NPs.Herein,we found Au@Ce NPs,assembled by Au NPs and Ce NPs,exhibited high-performance of SOD mimetic enzyme activity even upon the oxidation of H_(2)O_(2).Ce NPs supported by nano-Au can acquire the electrons from Au NPs through the enhanced localized surface plasmon resonance(LSPR),maintaining the stability of Ce^(3+)/Ce^(4+) and SOD-like activity.Meanwhile,Au@Ce NPs retained the peroxidase function and catalase function.As a result,Au@Ce NPs effectively scavenged O_(2·-) and the derived ROS in AML cells,which are the important signaling source that drives AML cell proliferation and accelerates cell cycle progression.When HL-60 cells were treated by Au@Ce NPs,the removal of endogenous ROS signal significantly arrested cell cycle at G1 phase and suppressed the cell proliferation by blocking the mitogen-activated protein kinases(MAPKs)signaling and the Akt/Cyclin D1 cell cycle signaling.Importantly,this treatment strategy showed therapeutic effect for subcutaneous transplantation of AML model as well as a satisfactory result in diminishing the leukocyte infiltration of liver and spleen particularly.Thus,assembled Au@Ce NPs show the high-performance SOD-like activity,promising the potential in treating AML and regulating abnormal ROS in other diseases safely and efficiently.展开更多
A continuous-wave(CW)single-longitudinal-mode(SLM)Raman laser at 1240 nm with power of up to 20.6 W was demonstrated in a free-running diamond Raman oscillator without any axial-mode selection elements.The SLM operati...A continuous-wave(CW)single-longitudinal-mode(SLM)Raman laser at 1240 nm with power of up to 20.6 W was demonstrated in a free-running diamond Raman oscillator without any axial-mode selection elements.The SLM operation was achieved due to the spatial-hole-burning free nature of Raman gain and was maintained at the highest available pump power by suppressing the parasitic stimulated Brillouin scattering(SBS).A folded-cavity design was employed for reducing the perturbing effect of resonances at the pump frequency.At a pump power of 69 W,the maximum Stokes output reached 20.6 W,corresponding to a 30%optical-to-optical conversion efficiency from 1064to 1240 nm.The result shows that parasitic SBS is the main physical process disturbing the SLM operation of Raman oscillator at higher power.In addition,for the first time,the spectral linewidth of a CW SLM diamond Raman laser was resolved using the long-delayed self-heterodyne interferometric method,which is 105 kHz at 20 W.展开更多
Noise exposure is becoming extremely common in urban area,but its specific impact on sleep remains controversial.Considering the limitations of previous researches,a field study which can conduct both horizontal and l...Noise exposure is becoming extremely common in urban area,but its specific impact on sleep remains controversial.Considering the limitations of previous researches,a field study which can conduct both horizontal and longitudinal analysis was designed.Urban participants were tested during two weeks in their homes,and the noise level of bedroom was artificially regulated by changing the status of window and door.During the 1050 test nights in 75 households,noise exposure was reflected from both instrument monitoring at night and perception questionnaire in the morning,and sleep quality was accessed from actigraphy and questionnaire.The analysis results showed that,92.3%of the bedroom acoustic environment did not meet the minimum requirements of Chinese standards,and 87.9%of subjects had ever experienced harmful noise during the test period.Furthermore,sleep quality was affected by noise exposure from the perspective of both physiological and psychological;the duration of rapid eye movement(REM)sleep was significantly(p<0.05)shortened with the increase of sound intensity,the duration of deep sleep shortened and subjective sleep quality worsened significantly(p<0.05)with the increase of acoustic sensation vote.In addition,females were more sensitive to noise exposure and their subjective sleep quality was more likely to be influenced by emotions.This study has important implications for acoustic environment design of bedrooms in cities,and suggested more attention should be paid to the anxiety caused by noise exposure.展开更多
With tin diselenide(SnSe2)film as a saturable absorber(SA),the passively Q-switched self-frequency doubling(SFD)lasers were realized in Nd^3+:ReCa4O(BO3)3(Re=Y,Gd)crystals.For Nd:YCa4O(BO3)3 crystal,the maximum averag...With tin diselenide(SnSe2)film as a saturable absorber(SA),the passively Q-switched self-frequency doubling(SFD)lasers were realized in Nd^3+:ReCa4O(BO3)3(Re=Y,Gd)crystals.For Nd:YCa4O(BO3)3 crystal,the maximum average output power at 532 nm was 19.6 mW,and the corresponding pulse repetition frequency,pulse duration,single pulse energy,and peak power were 17.6 kHz,91.9 ns,1.1μJ,and 12.1 W,respectively.For Nd:GdCa4 O(BO3)3 crystal,these values were 14.5 mW,22.1 kHz,48.7 ns,0.66μJ,and 13.5 W.展开更多
This is the IET Cyber-systems and Robotics special issue of Autonomous systems:Navigation,learning,and control.Autonomous systems,as very important representatives of Artificial Intelligence technologies,combine mecha...This is the IET Cyber-systems and Robotics special issue of Autonomous systems:Navigation,learning,and control.Autonomous systems,as very important representatives of Artificial Intelligence technologies,combine mechanical and electronic hardware,operating system,low-level dynamic control,and high-level intelligent decision components to address challenges that demand high-level autonomy and ma-chine intelligence.展开更多
文摘背景与目的目前,肺癌依然是我国发病率和死亡率最高的恶性肿瘤。而在早期肺腺癌(lung adenocarcinoma,LUAD)中,微乳头(micropapillary,MPP)成分尤其常见,且通常表现出高侵袭性,其与早期转移、淋巴浸润的风险以及患者的5年生存率显著相关。本研究旨在探究以磨玻璃影(ground-glass opacities,GGOs)为特征的早期LUAD中MPP成分和非MPP成分的异同,寻找MPP成分所特有的突变特征,并分析锌指蛋白家族的ZNF469基因与早期LUAD预后以及免疫浸润的关系。方法收集31例LUAD恶性肺结节,采用显微解剖法将其分为成对的MPP和非MPP成分。对早期恶性肺结节组分进行全外显子组测序(whole-exome sequencing,WES),利用maftools、非负矩阵分解(Nonnegative Matrix Factorization,NMF)法、Sigminer等方法进行突变特征分析,以揭示侵袭性LUAD中MPP组分相比于其他肿瘤组织所特有的基因组突变特征。利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)的LUAD数据库中ZNF469的表达情况,探讨其与肺癌预后的关系;利用GeneMANIA数据库以及基因本体(Gene Ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析探索LUAD中与ZNF469相关基因的互作网络及信号通路;利用TIMER和TISIDB数据库分析ZNF469表达与LUAD中免疫细胞浸润水平的相关性。结果MPP成分具有较多的基因组变异,相比于非MPP成分的肿瘤组织,癌症体细胞突变目录(Catalogue of Somatic Mutations in Cancer,COSMIC)的13号突变特征(胞苷脱氨酶家族,APOBEC)是MPP成分所特有的,这提示其参与了MPP成分对LUAD早期侵袭过程的促进作用;并且APOBEC特征高的MPP样本具有更高的肿瘤突变负荷(tumor mutational burden,TMB),提示这些患者更能从免疫治疗中获益。LUAD中突变ZNF469的表达高于正常组织,与LUAD患者的不良预后有关。基因互作网络分析以及GO和KEGG富集分析发现,COL6A1、COL1A1、COL1A2、TGFB2、MMP2、COL8A2、C2CD4C等与ZNF469具有相互作用,且主要与编码胶原蛋白、参与细胞外基质构成有关。ZNF469表达与肿瘤的免疫浸润呈正相关。结论本研究揭示了中国人群侵袭性LUAD中MPP成分的特有突变特征,并发现突变ZNF469的高表达影响LUAD预后与免疫浸润,推测ZNF469可作为LUAD潜在的诊断及预后生物标志物。
基金funded by the Department of Science and Technology of Jilin Province (20190303126SF)the Project of Beihua University (320121060)+1 种基金National Natural Science Foundation of China (31771695 and 31971464)Fundamental Research Funds for the Central Universities (0919/140124)。
文摘Experiencing urban green and blue spaces(GBSs)can be a nature-based solution to improve mental well-being and cope with negative moods for people exposed to PM2.5 pollution.In this study,a total of 1257 photos were collected to recognize their posted emotions of Sina Weibo users from 38 parks in 22 cities in Northeast China in 2021,when atmospheric PM_(2.5)and landscape metrics were evaluated for GBSs of each park.Autumn and winter had heavy atmospheric PM_(2.5)pollutions in resource-dependent cities of Liaoning.Net positive emotions(happy minus sad scores)decreased in larger green spaces.The perception of blue space countered the presentation of sadness only for a limited period over four seasons.High elevation decreased the level of happiness presented in winter.Overall,this study confirms that visiting large urban green spaces at low elevations can benefit the perception of positive sentiments for people exposed to PM_(2.5)in autumn.For planning urban forests in Northeast China,more green spaces should be constructed in cities in southern Jilin province to alleviate air PM_(2.5)pollution and gain better well-being of local people.
基金Project supported by the National MCF Energy Research and Development Program of China (Grant No. 2019YFE03010001)the National Natural Science Foundation of China (Grant No. 11905004)
文摘The stability(or instability)of finite sized magnetic island could play a significant role in disruption avoidance or disruption mitigation dynamics.Especially,various current and pressure profile modifications,such as the current drive and heating caused by electron cyclotron wave,or the radiative cooling and current expulsion caused by the shattered pellet injection could be applied within the island to modify its stability,thus changing the ensuing dynamics.In this study,we calculate the mode structure modification caused by such profile changes within the island using the perturbed equilibrium approach,thus obtain the change of stability criterion Δ′ and assess the corresponding quasi-linear island stability.The positive helical current perturbation is found to always stabilize the island,while the negative one is found to do the opposite,in agreement with previous results.The pressure bump or hole within the island has a more complicated stability impact.In the small island regime,its contribution is monotonic,with pressure bump that tends to stabilize the island while pressure hole destabilizes it.This effect is relatively weak,though,due to the cancellation of the pressure term’s odd parity contribution in the second derivatives of the mode structure.In the large island regime,such cancellation is broken due to the island asymmetry,and the pressure contribution to stability is manifested,which is non-monotonic.The stability analysis in this paper helps to more accurately clarify the expected island response in the presence of profile modifications caused by disruption avoidance or mitigation systems.
基金Supported by the NIH,No.DK118334 and No.AG064869and the BrightFocus,No.A2019630S(to Sun Y).
文摘BACKGROUND Antagonists of cannabinoid type 1 receptor(CB1)have been shown to promote body weight loss and improve insulin sensitivity.Cannabinoids decrease adiponectin,and CB1 blocker increase adiponectin.However,the mediators of CB1 actions are not well defined.AIM To investigate whether the beneficial effects of CB1 inhibition are,at least in part,mediated by adiponectin.METHODS We compared metabolic and inflammatory phenotypes of wild-type(WT)mice,CB1-null(CB1^(-/-))and CB1/adiponectin double-knockout(DKO)mice.We assessed the insulin sensitivity using insulin tolerance test and glucose tolerance test,and inflammation using flow cytometry analysis of macrophages.RESULTS CB1^(-/-)mice exhibited significantly reduced body weight and fat mass when compared to WT mice.While no significance was found in total daily food intake and locomotor activity,CB1^(-/-)mice showed increased energy expenditure,enhanced thermogenesis in brown adipose tissue(BAT),and improved insulin sensitivity compared to WT mice.DKO showed no difference in body weight,adiposity,nor insulin sensitivity;only showed a modestly elevated thermogenesis in BAT compared to CB1^(-/-)mice.The metabolic phenotype of DKO is largely similar to CB1^(-/-)mice,suggesting that adiponectin is not a key mediator of the metabolic effects of CB1.Interestingly,CB1^(-/-)mice showed reduced pro-inflammatory macrophage polarization in both peritoneal macrophages and adipose tissue macrophages compared to WT mice;in contrast,DKO mice exhibited increased pro-inflammatory macrophage polarization in these macrophages compared to CB1^(-/-)mice,suggesting that adiponectin is an important mediator of the inflammatory effect of CB1.CONCLUSION Our findings reveal that CB1 functions through both adiponectin-dependent and adiponectin-independent mechanisms:CB1 regulates energy metabolism in an adiponectin-independent manner,and inflammation in an adiponectin-dependent manner.The differential effects of adiponectin on CB1-mediated metabolic and inflammatory functions should be taken into consideration in CB1 antagonist utilization.
基金National Key Research and Development Program of China,Grant/Award Number:2022YFB380440003National Natural Science Foundation of China,Grant/Award Number:32271385China Postdoctoral Science Foundation,Grant/Award Number:2022M721194。
文摘Osteoarthritis(OA)is a chronic and degenerative disease with limited clinical options for effective suppression.Recently,significant endeavors have been explored to reveal its pathogenesis and develop treatments against OA.Hydrogels,designed with a striking resemblance to the extracellular matrix,offer a biomimetic interaction with biological tissues,presenting a promising avenue for OA amelioration.As a result,biocompatible hydrogels have been erected incorporating on-demand bioactivities to optimize the intra-articular microenvironment,thereby alleviating OA symptoms and fostering the eventual regeneration of articular joints.This review highlights the collaborative objectives underlying the establishment of this tissue microenvironment,encompassing mechanical modulation,anti-inflammation,and tissue regeneration.Specifically,we consolidate recent advances in hydrogel-based biomaterials,serving as the tissue engineering scaffolds to replicate the lubrication properties of natural joints or the bioactive agent-loaded vehicles to combat localized inflammation.Additionally,hydrogels function as cell scaffolds to facilitate the maintenance of cellular homeostasis and contribute to the advancement of cartilage regeneration.Finally,this review outlines the prospective directions for hydrogel-mediated OA therapies.
基金The work was supported by the National Key Research and Development Program of China(2017YFA0104302)the National Natural Science Foundation of China(61821002,51832001 and 31800843).
文摘Although with the good biological properties,silk fibroin(SF)is immensely restrained in long-distance vascular defect repair due to its relatively fast degradation and inferior mechanical properties.It is necessary to construct a multifunctional composite scaffold based on SF.In this study,a novel magnetic SF scaffold(MSFCs)was prepared by an improved infiltration method.Compared with SF scaffold(SFC),MSFCs were found to have better crystallinity,magnetocaloric properties,and mechanical strength,which was ascribed to the rational introduction of iron-based magnetic nanoparticles(MNPs).Moreover,in vivo and in vitro experiments demonstrated that the degradation of MSFCs was significantly extended.The mechanism of delayed degradation was correlated with the dual effect that was the newly formed hydrogen bonds between SFC and MNPs and the complexing to tyrosine(Try)to inhibit hydrolase by internal iron atoms.Besides,theβ-crystallization of protein in MSFCs was increased with the rise of iron concentration,proving the beneficial effect after MNPS doped.Furthermore,although macrophages could phagocytose the released MNPs,it did not affect their function,and even a reasonable level might cause some cytokines to be upregulated.Finally,in vitro and in vivo studies demonstrated that MSFCs showed excellent biocompatibility and the growth promotion effect on CD34-labeled vascular endothelial cells(VECs).In conclusion,we confirm that the doping of MNPs can significantly reduce the degradation of SFC and thus provide an innovative perspective of multifunctional biocomposites for tissue engineering.
基金This work was supported by the National Natural Science Foundation of China(No.51778359 and No.51478260)the State Key Laboratory of Air Conditioning Equipment and System Energy Conservation(No.ACSKL2018KT04)。
文摘There are some special spaces in which there is no air conditioning or the people are in move,thus exposing people to a hot environment.In this study,portable cooling systems were proposed and their effects on thermal comfort and work performance were investigated at an air temperature of 32°C.Four conditions were established:cool air towards breathing zone(A),chest and back cooling(B)#combined cooling(C)and no cooling(D).Twenty-eight subjects were exposed to the four conditions in a counterbalanced order.During each exposure they performed tasks and made subjective assessments,while multiple physiological parameters were measured.Compared with no cooling(D),cool air towards breathing zone(A)and chest and back cooling(B)improved work performance by 17.5%and 19.25%,respectively,while decreased the subjects'thermal sensation,skin temperature,and heart rate.When the two cooling systems were combined(C),larger improvements in thermal comfort and work performance were achieved than no cooling(D);the mean thermal sensation rating decreased from 2.4 to 0.7;work performance increased by up to 33%,and physiological parameters including skin temperature,pulse,heart rate and salivary alpha-amylase significantly decreased.The present results suggest that the proposed portable cooling systems could maintain thermal comfort and work performance in a hot environment,while potentially improve air quality for some special spaces.
基金This work was supported by the National Natural Science Foundation of China(No.81871222,81570763 and 81270947,to XX)the Fundamental Science and Advanced Technology Research of Chongqing(Major Project,No.CSTC2015jcyjB0146)the National Program on Key Basic Research Project(973 Program)of China(973 Program,No.2012CB517505,to XX).
文摘Type 2 diabetes mellitus(T2DM)and Alzheimer's disease(AD)share several common pathophysiological features.Rare variants of triggering receptor expressed on myeloid cells 2(TREM2)increase the risk of developing AD,suggesting the involvement of TREM2 and innate immunity in AD development.It is still unknown whether TREM2 is related to cognitive impairment in T2DM.Here,we investigated the effects of the hippocampal overexpression of TREM2 on cognitive in long-term high-fat diet(HFD)-fed mice.Male C57BL/6J mice were maintained on HFD for 50 weeks.TREM2 was overexpressed in the hippocampus 36 weeks after HFD feeding using adeno-associated virus vector(AAV)-mediated gene delivery.The results showed that the HFD feeding induced rapid and persistent weight gain,glucose intolerance and significant impairments in learning and memory.Compared with AAV-con,AAV-TREM2 significantly ameliorated cognitive impairment without altering body weight and glucose homeostasis in HFD mice.The overexpression of TREM2 upregulated the synaptic proteins spinophilin,PSD95 and synaptophysin,suggesting the improvement in synaptic transmission.Dendritic complexity and spine density in the CA1 region were rescued after TREM2 overexpression.Furthermore,TREM2 markedly increased the number of iba-1/Arg-1-positive microglia in the hippocampus,suppressed neuroinflammation and microglial activation.In sum,hippocampal TREM2 plays an important role in improving HFD-induced cognitive dysfunction and promoting microglial polarization towards the M2 anti-inflammatory phenotype.Our study also suggests that TREM2 might be a novel target for the intervention of obesity/diabetes-associated cognitive decline.
基金funded in part with the National Key Research and Development Program of China(2017YFA0205502,2017YFA0205501)the National Natural Science Foundation of China(82073804)+3 种基金Shandong Provincial Natural Science Foundation of China(ZR2020QE091)Scientific research foundation of Nanjing Health Commission(YKK20232)the the Fundamental Research Funds for the Central Universities(2242018K3DN30)supported by the Open Research Fund of State Key Laboratory of Bioelectronics Southeast University.
文摘SOD-like activity of CeO_(2) nanoparticles(Ce NPs)is driven by Ce^(3+)/Ce^(4+),high oxidative stress can oxidize Ce^(3+) to reduce the ratio of Ce^(3+)/Ce^(4+),inactivating the SOD activity of Ce NPs.Herein,we found Au@Ce NPs,assembled by Au NPs and Ce NPs,exhibited high-performance of SOD mimetic enzyme activity even upon the oxidation of H_(2)O_(2).Ce NPs supported by nano-Au can acquire the electrons from Au NPs through the enhanced localized surface plasmon resonance(LSPR),maintaining the stability of Ce^(3+)/Ce^(4+) and SOD-like activity.Meanwhile,Au@Ce NPs retained the peroxidase function and catalase function.As a result,Au@Ce NPs effectively scavenged O_(2·-) and the derived ROS in AML cells,which are the important signaling source that drives AML cell proliferation and accelerates cell cycle progression.When HL-60 cells were treated by Au@Ce NPs,the removal of endogenous ROS signal significantly arrested cell cycle at G1 phase and suppressed the cell proliferation by blocking the mitogen-activated protein kinases(MAPKs)signaling and the Akt/Cyclin D1 cell cycle signaling.Importantly,this treatment strategy showed therapeutic effect for subcutaneous transplantation of AML model as well as a satisfactory result in diminishing the leukocyte infiltration of liver and spleen particularly.Thus,assembled Au@Ce NPs show the high-performance SOD-like activity,promising the potential in treating AML and regulating abnormal ROS in other diseases safely and efficiently.
基金supported by the National Natural Science Foundation of China(No.62005073)the Program of the State Key Laboratory of Crystal Materials(No.KF2101)+3 种基金the National Key Research and Development Program of China(No.2020YFC2200300)the Program of the State Key Laboratory of Quantum Optics and Quantum Optics Devices(No.KF202207)the Research Funds of Hangzhou Institute for Advanced Study(No.2022ZZ01006)the Hangzhou Agricultural and Social Development initiative Design Project(No.2022ZDSJ0846).
文摘A continuous-wave(CW)single-longitudinal-mode(SLM)Raman laser at 1240 nm with power of up to 20.6 W was demonstrated in a free-running diamond Raman oscillator without any axial-mode selection elements.The SLM operation was achieved due to the spatial-hole-burning free nature of Raman gain and was maintained at the highest available pump power by suppressing the parasitic stimulated Brillouin scattering(SBS).A folded-cavity design was employed for reducing the perturbing effect of resonances at the pump frequency.At a pump power of 69 W,the maximum Stokes output reached 20.6 W,corresponding to a 30%optical-to-optical conversion efficiency from 1064to 1240 nm.The result shows that parasitic SBS is the main physical process disturbing the SLM operation of Raman oscillator at higher power.In addition,for the first time,the spectral linewidth of a CW SLM diamond Raman laser was resolved using the long-delayed self-heterodyne interferometric method,which is 105 kHz at 20 W.
基金This work was supported by the ASHRAE project 1837-RP“Effects of ventilation in sleeping environments”,2019–2022 and by the National Natural Science Foundation of China(52078291).
文摘Noise exposure is becoming extremely common in urban area,but its specific impact on sleep remains controversial.Considering the limitations of previous researches,a field study which can conduct both horizontal and longitudinal analysis was designed.Urban participants were tested during two weeks in their homes,and the noise level of bedroom was artificially regulated by changing the status of window and door.During the 1050 test nights in 75 households,noise exposure was reflected from both instrument monitoring at night and perception questionnaire in the morning,and sleep quality was accessed from actigraphy and questionnaire.The analysis results showed that,92.3%of the bedroom acoustic environment did not meet the minimum requirements of Chinese standards,and 87.9%of subjects had ever experienced harmful noise during the test period.Furthermore,sleep quality was affected by noise exposure from the perspective of both physiological and psychological;the duration of rapid eye movement(REM)sleep was significantly(p<0.05)shortened with the increase of sound intensity,the duration of deep sleep shortened and subjective sleep quality worsened significantly(p<0.05)with the increase of acoustic sensation vote.In addition,females were more sensitive to noise exposure and their subjective sleep quality was more likely to be influenced by emotions.This study has important implications for acoustic environment design of bedrooms in cities,and suggested more attention should be paid to the anxiety caused by noise exposure.
基金supported by the Natural Science Foundation of Shandong Province(No.ZR2017MF031)
文摘With tin diselenide(SnSe2)film as a saturable absorber(SA),the passively Q-switched self-frequency doubling(SFD)lasers were realized in Nd^3+:ReCa4O(BO3)3(Re=Y,Gd)crystals.For Nd:YCa4O(BO3)3 crystal,the maximum average output power at 532 nm was 19.6 mW,and the corresponding pulse repetition frequency,pulse duration,single pulse energy,and peak power were 17.6 kHz,91.9 ns,1.1μJ,and 12.1 W,respectively.For Nd:GdCa4 O(BO3)3 crystal,these values were 14.5 mW,22.1 kHz,48.7 ns,0.66μJ,and 13.5 W.
文摘This is the IET Cyber-systems and Robotics special issue of Autonomous systems:Navigation,learning,and control.Autonomous systems,as very important representatives of Artificial Intelligence technologies,combine mechanical and electronic hardware,operating system,low-level dynamic control,and high-level intelligent decision components to address challenges that demand high-level autonomy and ma-chine intelligence.
