Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strateg...Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strategy of anti-obesity by dissipating energy as heat.However,drugs based on adipose tissue thermogenesis have not been successfully approved yet.In current study,we found that black tea extract(BTE)obtained by patentauthorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity,improvement of adipose distribution,and glucose metabolism improvement in diet-induced obesity mice.Mechanismly,anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1(UCP1),especially visceral adipose tissue(VAT)with browning resistance.Specifically,utilizing in silico approach of network pharmacology and molecular docking,we identified carbonic anhydrase 2(CA2)in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B(AKT)signaling pathway linked CA2 and UCP1.Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation.Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway,which could be developed as promising anti-obesity agent with good safety and efficacy.展开更多
Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmac...Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.展开更多
Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Me...Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Methods:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling pathways.We enrolled 241 HCC patients who underwent liver transplantation from three centers.Tissue microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung metastasis.Results:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of HCC.The expression of TNF was degraded in comparison to that in para-tumor tissues(P<0.001).The expression of key receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(P<0.001).TNF and TNFR1 showed no relationship with patients’outcomes,whereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival(OS)and increased recurrence risk(5-year OS rate:31.9%vs.62.5%,P<0.001).Notably,elevated TNFR2 levels were also associated with an increased risk of post-transplant lung metastasis(hazard ratio:1.146;P<0.001).Cox regression analysis revealed that TNFR2,Hangzhou criteria,age,and hepatitis B surface antigen were independent risk factors for post-transplant lung metastasis,and a novel nomogram was established accordingly.The nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan criteria.Conclusions:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantation for HCC.展开更多
Catalytic oxidation of CH_(4) has been proved to be an attractive option for landfill gas(LFG) upgrading.However, coking of catalysts in catalytic LFG deoxygen has been clearly observed in industrial applications. In ...Catalytic oxidation of CH_(4) has been proved to be an attractive option for landfill gas(LFG) upgrading.However, coking of catalysts in catalytic LFG deoxygen has been clearly observed in industrial applications. In this regard, it is necessary to investigate whether coke deposition originates from CH_(4) or volatile organic compounds present in LFG, and the influence of coke deposition on catalytic performance. Herein,we evaluate the LFG deoxygen on Pt/γ-Al_(2)O_(3) catalyst in simulated LFG(CH_(4), CO_(2), O_(2), N_(2)) and its co-feed with representative volatile organic compounds, ethylbenzene, toluene, benzene and cyclohexane. The results show that the coking of the catalyst is originated from volatile organic compounds rather than CH_(4). The Pt/γ-Al_(2)O_(3) catalyst does not deactivate during LFG deoxygen process, even significant amount of coke deposited, up to 18.15%(mass). Characterization analyses reveal that although coke deposition overall covers the catalyst surface, resulting in mesopores blockage and a reduced number of accessible Pt sites, however, the coke formed, H-rich carbonaceous components, behaves as counterpart for O_(2) elimination. Besides, the coke deposited is mainly filamentous. Thus, coke formation has little negative effect on the overall catalytic performance of Pt/γ-Al_(2)O_(3) catalyst ultimately. The results obtained in this work are helpful for the rational design of robust Pt based catalysts for LFG deoxygen without undue attention to their coking properties, and also favor the innovation of more attractive purification scheme configurations.展开更多
Interacting multiple models is the hotspot in the research of maneuvering target models at present. A hierarchical idea is introduced into IMM algorithm. The method is that the whole models are organized as two levels...Interacting multiple models is the hotspot in the research of maneuvering target models at present. A hierarchical idea is introduced into IMM algorithm. The method is that the whole models are organized as two levels to co-work, and each cell model is an improved ＂current＂ statistical model. In the improved model, a kind of nonlinear fuzzy membership function is presented to get over the limitation of original model, which can not track weak maneuvering target precisely. At last, simulation experiments prove the efficient of the novel algorithm compared to interacting multiple model and hierarchical interacting multiple model based original ＂current＂ statistical model in tracking precision.展开更多
BACKGROUND：Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.O...BACKGROUND：Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.OBJECTIVE：To observe the effects of adult endogenous neurogenesis on cognitive function repair and regeneration of neural progenitor cells following varying graded traumatic hippocampal injury to determine the significance of endogenous neurogenesis in the repair of brain injury.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment was performed at the Key Laboratory of Injuries,Variations and Regeneration of Nervous System,Tianjin Medical University General Hospital,from February to October 2009.MATERIALS：Mouse anti-rat 5-bromodeoxyuridine （BrdU） and neuronal nuclei （NeuN） monoclonal antibodies were purchased from Millipore Corporation,USA.METHODS：A total of 45 Wistar rats were randomly assigned to three groups.Mild and severe injury groups were respectively subjected to （182 ± 2） kPa and （284 ± 4） kPa lateral fluid percussion to establish models of brain injury,and the control group was subjected to surgery with no lateral fluid percussion.MAIN OUTCOME MEASURES：Cognitive function was estimated using the Morris water maze.Proliferation,survival,and differentiation of newly generated cells in the injured hippocampus were observed through the use of immunofluorescent staining.RESULTS：At 7 days post-injury,the number of BrdU＋ cells in the hippocampal dentate gyrus significantly increased in the mild and severe injury groups compared with the control group （P〈0.01）.At 61 days post-injury,the number of BrdU7NeuN＋ cells in the hippocampal dentate gyrus was significantly greater in the mild injury group compared with the severe injury and control groups （P〈 0.01）.In addition,the control group exhibited the greatest proportion of surviving cells that differentiated into mature neurons compared with the injury groups （P〈 0.01）.Moreover,at 61 days post-injury,cognitive function in rats with mild injury recovered to normal levels,whereas the severe injury group exhibited cognitive deficits （P〈 0.01）.CONCLUSION：Traumatic brain injury may be a stimulation factor for proliferation of neural progenitor cells in the adult hippocampus but severe brain trauma does not lead to an increased number of newly generated cells.Endogenous adult neurogenesis repairs neurological functions to an extent.However,recovery of neurological function remains limited following severe traumatic brain injury.展开更多
Converting low-grade waste heat into usable electricity and storing it simultaneously requires a new technology that realize the directional migration of electrons or ions under temperature difference and enrichment o...Converting low-grade waste heat into usable electricity and storing it simultaneously requires a new technology that realize the directional migration of electrons or ions under temperature difference and enrichment on the electrodes.Although the urgent demand of energy conversion-storage(ECS)has emerged in the field of wearable electronic,achieving the integrated bi-functional device remains challenge due to the different mechanisms of electrical transportation and storage.Here,we report an ionic thermoelectric supercapacitor that relies on the synergistic functions of thermoelectricity and supercapacitor in the thermoelectric ionogel electrolyte and high-performance hydrogel electrodes to enhance the ECS performance under a thermal gradient.The thermoelectric electrolyte is composed of polyacrylamide hydrogel and sodium carboxymethyl cellulose(PMSC),possessing cross-linked network with excellent cation selectivity,while the ionic thermoelectric properties are further improved in the presence of NaCl.The corresponding Seebeck coefficient and ionic conductivity of the NaCl–PMSC electrolyte reach 17.1 mV K^(-1)and 26.8 mS cm^(-1),respectively.Owing to good stretchability of both gel-based electrolyte and electrode,the fullstretchable integrated ECS device,termed ionic thermoelectric supercapacitor,presents promising thermal-charge storage capability(~1.3 mC,ΔT≈10 K),thus holds promise for wearable energy harvesting.展开更多
Emerging wireless community cloud enables usergenerated video content to be shared and consumed in a social context. However, the nature of shared wireless medium and timevarying channels seriously limits the quality ...Emerging wireless community cloud enables usergenerated video content to be shared and consumed in a social context. However, the nature of shared wireless medium and timevarying channels seriously limits the quality of service(QoS), partially owing to the lack of mechanisms for effectively utilizing multi-rate channel resources. In this paper, the joint optimization of admission control and rate adaptation is proposed, resulting in a bandwidth-aware rate-adaptive admission control(BRAC) scheme to provide bandwidth guarantee for sharing social multimedia contents. The analytical approach leads to the following major contributions:(1) a bandwidth-aware rate selection(BRS) algorithm to optimally meet the bandwidth requirement of the data session and channel conditions at the physical layer;(2) a routing-coupled rate adaption and admission control algorithm to admit data sessions with bandwidth guarantee. Moreover, extensive numerical simulations suggest that BRAC is efficient and effective in meeting the bandwidth requirements for sharing social multimedia contents. These insights will shed light on communication system implementation for multimedia content sharing over multirate wireless community cloud.展开更多
Polyhydroxyalkanoates(PHAs)are diversiform biopolyesters with a similar structure and different side chain groups,synthesized by a variety of microorganism.Due to their excellent biodegradability and biocompatibility,...Polyhydroxyalkanoates(PHAs)are diversiform biopolyesters with a similar structure and different side chain groups,synthesized by a variety of microorganism.Due to their excellent biodegradability and biocompatibility,PHAs have been used for many applications,including medical implants,antibacterial agents and bioengineering.Nano-architecture is an emerging area for the use of PHAs.This review summarizes the current status and challenges of PHAs-based particles on the micro-and nano-scale,including their production,degradation,biological safety,and surface functionalization.We also focus on the applications of PHA particles in drug delivery systems,environment protection,tissue engi-neering,vaccine engineering,food science,biotechnology and cosmetics.Finally,the future development trends of PHAs-based particles are prospected.展开更多
Tumor biomarkers,the substances which are produced by tumors or the body’s responses to tumors during tumorigenesis and progression,have been demonstrated to possess critical and encouraging value in screening and ea...Tumor biomarkers,the substances which are produced by tumors or the body’s responses to tumors during tumorigenesis and progression,have been demonstrated to possess critical and encouraging value in screening and early diagnosis,prognosis prediction,recurrence detection,and therapeutic efficacy monitoring of cancers.Over the past decades,continuous progress has been made in exploring and discovering novel,sensitive,specific,and accurate tumor biomarkers,which has significantly promoted personalized medicine and improved the outcomes of cancer patients,especially advances in molecular biology technologies developed for the detection of tumor biomarkers.Herein,we summarize the discovery and development of tumor biomarkers,including the history of tumor biomarkers,the conventional and innovative technologies used for biomarker discovery and detection,the classification of tumor biomarkers based on tissue origins,and the application of tumor biomarkers in clinical cancer management.In particular,we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies.We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field.Collectively,the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine,broaden horizons in future research directions,and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.展开更多
Energy status is linked to the production of reactive oxygen species(ROS)in macrophages,which is elevated in obesity.However,it is unclear how ROS production is upregulated in macrophages in response to energy overloa...Energy status is linked to the production of reactive oxygen species(ROS)in macrophages,which is elevated in obesity.However,it is unclear how ROS production is upregulated in macrophages in response to energy overload for mediating the development of obesity.Here,we show that the Rab-GTPase activating protein(Rab GAP)TBC1D1,a substrate of the energy sensor AMP-activated protein kinase(AMPK),is a critical regulator of macrophage ROS production and consequent adipose inflammation for obesity development.TBC1D1 deletion decreases,whereas an energy overload-mimetic non-phosphorylatable TBC1D1^(S231A)Amutation increases,ROS production and M1-like polarization in macrophages.Mechanistically,TBC1D1 and its downstream target Rab8a form an energy-responsive complex with NOX2 for ROS generation.Transplantation of TBC1D1^(S231A)bone marrow aggravates diet-induced obesity whereas treatment with an ultra-stable Tt SOD for removal of ROS selectively in macrophages alleviates both TBC1D1~(S231A)mutation-and diet-induced obesity.Our findings therefore have implications for drug discovery to combat obesity.展开更多
The adenosine subfamily G protein-coupled receptors A_(2A)R and A_(2B)R have been identified as promising cancer immunotherapy candidates.One of the A_(2A)R/A_(2B)R dual antagonists,AB928,has progressed to a phaseⅡcl...The adenosine subfamily G protein-coupled receptors A_(2A)R and A_(2B)R have been identified as promising cancer immunotherapy candidates.One of the A_(2A)R/A_(2B)R dual antagonists,AB928,has progressed to a phaseⅡclinical trial to treat rectal cancer.However,the precise mechanism underlying its dual-antagonistic properties remains elusive.Herein,we report crystal structures of the A_(2A)R complexed with AB928 and a selective A_(2A)R antagonist 2-118.The structures revealed a common binding mode on A_(2A)R,wherein the ligands established extensive interactions with residues from the orthosteric and secondary pockets.In contrast,the cAMP assay and A_(2A)R and A_(2B)R molecular dynamics simulations indicated that the ligands adopted distinct binding modes on A_(2B)R.Detailed analysis of their chemical structures suggested that AB928 readily adapted to the A_(2B)R pocket,while 2-118 did not due to intrinsic differences.This disparity potentially accounted for the difference in inhibitory efficacy between A_(2B)R and A_(2A)R.This study serves as a valuable structural template for the future development of selective or dual inhibitors targeting A_(2A)R/A_(2B)R for cancer therapy.展开更多
The human face is a valuable biomarker of aging,but the collection and use of its image raise significant privacy concerns.Here we present an approach for facial data masking that preserves age-related features using ...The human face is a valuable biomarker of aging,but the collection and use of its image raise significant privacy concerns.Here we present an approach for facial data masking that preserves age-related features using coordinate-wise monotonic transformations.We first develop a deep learning model that estimates age directly from non-registered face point clouds with high accuracy and generalizability.We show that the model learns a highly indistinguishable mapping using faces treated with coordinate-wise monotonic transformations,indicating that the relative positioning of facial information is a low-level biomarker of facial aging.Through visual perception tests and computational3D face verification experiments,we demonstrate that transformed faces are significantly more difficult to perceive for human but not for machines,except when only the face shape information is accessible.Our study leads to a facial data protection guideline that has the potential to broaden public access to face datasets with minimized privacy risks.展开更多
Studies have suggested that the nucleus accumbens(NAc)is implicated in the pathophysiology of major depression;however,the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depressi...Studies have suggested that the nucleus accumbens(NAc)is implicated in the pathophysiology of major depression;however,the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated.Here,we identified a specific reduction of cyclic adenosine monophosphate(cAMP)in the subset of dopamine D1 receptor medium spiny neurons(D1-MSNs)in the NAc that promoted stress susceptibility,while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors.Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons(D2-MSNs)of depressed mice,however,the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs.We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration,but not a lower dose.The fast onset property of crocin was verified through multicenter studies.Moreover,crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN.These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc,and provide a potential rapid antidepressant drug candidate,crocin.展开更多
基金funded by National Natural Science Foundation of China(NSFC 82070877)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M-JB-010,2021-I2M-1-005)The National High Technology Research and Development Program of China(2017YFE0112900).
文摘Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strategy of anti-obesity by dissipating energy as heat.However,drugs based on adipose tissue thermogenesis have not been successfully approved yet.In current study,we found that black tea extract(BTE)obtained by patentauthorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity,improvement of adipose distribution,and glucose metabolism improvement in diet-induced obesity mice.Mechanismly,anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1(UCP1),especially visceral adipose tissue(VAT)with browning resistance.Specifically,utilizing in silico approach of network pharmacology and molecular docking,we identified carbonic anhydrase 2(CA2)in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B(AKT)signaling pathway linked CA2 and UCP1.Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation.Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway,which could be developed as promising anti-obesity agent with good safety and efficacy.
基金supported by the National Key R&D Program of China(Grant No.:2022YFA0806400)the CAMS Innovation Fund for Medical Sciences(Grant Nos.:2022-I2M-1-028,2022-I2M-2-002,and 2021-I2M-1-007)+1 种基金the National Natural Science Foundation of China(Grant Nos.:81973290 and 82173888)Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study,China(Grant No.:Z141102004414062)。
文摘Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.
基金the National Key Research and Development Program of China(No.2021YFA1100500)the Major Research Plan of the National Natural Science Foundation of China(No.92159202)+2 种基金the Key Research&Development Plan of Zhejiang Province(No.2019C03050),the Key Research&Development Plan of Zhejiang Province(No.2021C03118)National S&T Major Project(No.2017ZX10203205)the Health Science&Technology Plan of Zhejiang Province(No.2022RC060)。
文摘Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Methods:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling pathways.We enrolled 241 HCC patients who underwent liver transplantation from three centers.Tissue microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung metastasis.Results:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of HCC.The expression of TNF was degraded in comparison to that in para-tumor tissues(P<0.001).The expression of key receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(P<0.001).TNF and TNFR1 showed no relationship with patients’outcomes,whereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival(OS)and increased recurrence risk(5-year OS rate:31.9%vs.62.5%,P<0.001).Notably,elevated TNFR2 levels were also associated with an increased risk of post-transplant lung metastasis(hazard ratio:1.146;P<0.001).Cox regression analysis revealed that TNFR2,Hangzhou criteria,age,and hepatitis B surface antigen were independent risk factors for post-transplant lung metastasis,and a novel nomogram was established accordingly.The nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan criteria.Conclusions:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantation for HCC.
基金the financial supports from the National Natural Science Foundation of China (22076077, 21577060)Jiangsu Science and Technology Department (BK20191256)Analysis & Test Fund of Nanjing University。
文摘Catalytic oxidation of CH_(4) has been proved to be an attractive option for landfill gas(LFG) upgrading.However, coking of catalysts in catalytic LFG deoxygen has been clearly observed in industrial applications. In this regard, it is necessary to investigate whether coke deposition originates from CH_(4) or volatile organic compounds present in LFG, and the influence of coke deposition on catalytic performance. Herein,we evaluate the LFG deoxygen on Pt/γ-Al_(2)O_(3) catalyst in simulated LFG(CH_(4), CO_(2), O_(2), N_(2)) and its co-feed with representative volatile organic compounds, ethylbenzene, toluene, benzene and cyclohexane. The results show that the coking of the catalyst is originated from volatile organic compounds rather than CH_(4). The Pt/γ-Al_(2)O_(3) catalyst does not deactivate during LFG deoxygen process, even significant amount of coke deposited, up to 18.15%(mass). Characterization analyses reveal that although coke deposition overall covers the catalyst surface, resulting in mesopores blockage and a reduced number of accessible Pt sites, however, the coke formed, H-rich carbonaceous components, behaves as counterpart for O_(2) elimination. Besides, the coke deposited is mainly filamentous. Thus, coke formation has little negative effect on the overall catalytic performance of Pt/γ-Al_(2)O_(3) catalyst ultimately. The results obtained in this work are helpful for the rational design of robust Pt based catalysts for LFG deoxygen without undue attention to their coking properties, and also favor the innovation of more attractive purification scheme configurations.
基金This work was supported by National Key Research and Development Program of China(2016YFB0301101)Key Science and Technology Program of Beijing Municipal Commission of Education,China(KZ201810005005).
文摘Interacting multiple models is the hotspot in the research of maneuvering target models at present. A hierarchical idea is introduced into IMM algorithm. The method is that the whole models are organized as two levels to co-work, and each cell model is an improved ＂current＂ statistical model. In the improved model, a kind of nonlinear fuzzy membership function is presented to get over the limitation of original model, which can not track weak maneuvering target precisely. At last, simulation experiments prove the efficient of the novel algorithm compared to interacting multiple model and hierarchical interacting multiple model based original ＂current＂ statistical model in tracking precision.
基金the National Natural Science Foundation of China,No. 30973090the Natural Science Foundation of Tianjin,No.09JCZDJC17200
文摘BACKGROUND：Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.OBJECTIVE：To observe the effects of adult endogenous neurogenesis on cognitive function repair and regeneration of neural progenitor cells following varying graded traumatic hippocampal injury to determine the significance of endogenous neurogenesis in the repair of brain injury.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment was performed at the Key Laboratory of Injuries,Variations and Regeneration of Nervous System,Tianjin Medical University General Hospital,from February to October 2009.MATERIALS：Mouse anti-rat 5-bromodeoxyuridine （BrdU） and neuronal nuclei （NeuN） monoclonal antibodies were purchased from Millipore Corporation,USA.METHODS：A total of 45 Wistar rats were randomly assigned to three groups.Mild and severe injury groups were respectively subjected to （182 ± 2） kPa and （284 ± 4） kPa lateral fluid percussion to establish models of brain injury,and the control group was subjected to surgery with no lateral fluid percussion.MAIN OUTCOME MEASURES：Cognitive function was estimated using the Morris water maze.Proliferation,survival,and differentiation of newly generated cells in the injured hippocampus were observed through the use of immunofluorescent staining.RESULTS：At 7 days post-injury,the number of BrdU＋ cells in the hippocampal dentate gyrus significantly increased in the mild and severe injury groups compared with the control group （P〈0.01）.At 61 days post-injury,the number of BrdU7NeuN＋ cells in the hippocampal dentate gyrus was significantly greater in the mild injury group compared with the severe injury and control groups （P〈 0.01）.In addition,the control group exhibited the greatest proportion of surviving cells that differentiated into mature neurons compared with the injury groups （P〈 0.01）.Moreover,at 61 days post-injury,cognitive function in rats with mild injury recovered to normal levels,whereas the severe injury group exhibited cognitive deficits （P〈 0.01）.CONCLUSION：Traumatic brain injury may be a stimulation factor for proliferation of neural progenitor cells in the adult hippocampus but severe brain trauma does not lead to an increased number of newly generated cells.Endogenous adult neurogenesis repairs neurological functions to an extent.However,recovery of neurological function remains limited following severe traumatic brain injury.
基金financial support by the National Natural Science Foundation of China(No.51873033 and No.52073057)the Fundamental Research Funds for the Central Universities(2232020A-01 and 2232019A3-02)+3 种基金DHU Distinguished Young Professor Program(LZB2019002)Shanghai Rising-Star Program(20QA1400300)the Fundamental Research Funds for the Central University and Graduate Student Innovation Fund of Donghua University(CUSFDH-D-2020033)State Key Laboratory for Space Power Sources Technology(No.YF07050117F0768)。
文摘Converting low-grade waste heat into usable electricity and storing it simultaneously requires a new technology that realize the directional migration of electrons or ions under temperature difference and enrichment on the electrodes.Although the urgent demand of energy conversion-storage(ECS)has emerged in the field of wearable electronic,achieving the integrated bi-functional device remains challenge due to the different mechanisms of electrical transportation and storage.Here,we report an ionic thermoelectric supercapacitor that relies on the synergistic functions of thermoelectricity and supercapacitor in the thermoelectric ionogel electrolyte and high-performance hydrogel electrodes to enhance the ECS performance under a thermal gradient.The thermoelectric electrolyte is composed of polyacrylamide hydrogel and sodium carboxymethyl cellulose(PMSC),possessing cross-linked network with excellent cation selectivity,while the ionic thermoelectric properties are further improved in the presence of NaCl.The corresponding Seebeck coefficient and ionic conductivity of the NaCl–PMSC electrolyte reach 17.1 mV K^(-1)and 26.8 mS cm^(-1),respectively.Owing to good stretchability of both gel-based electrolyte and electrode,the fullstretchable integrated ECS device,termed ionic thermoelectric supercapacitor,presents promising thermal-charge storage capability(~1.3 mC,ΔT≈10 K),thus holds promise for wearable energy harvesting.
基金sponsored by the following funds:the National Natural Science Foundation of China(No.61502381)the Fundamental Research Funds for the Central Universities(No.xjj2015065)the China Post Doctoral Science Foundation(No.2015M570836)
文摘Emerging wireless community cloud enables usergenerated video content to be shared and consumed in a social context. However, the nature of shared wireless medium and timevarying channels seriously limits the quality of service(QoS), partially owing to the lack of mechanisms for effectively utilizing multi-rate channel resources. In this paper, the joint optimization of admission control and rate adaptation is proposed, resulting in a bandwidth-aware rate-adaptive admission control(BRAC) scheme to provide bandwidth guarantee for sharing social multimedia contents. The analytical approach leads to the following major contributions:(1) a bandwidth-aware rate selection(BRS) algorithm to optimally meet the bandwidth requirement of the data session and channel conditions at the physical layer;(2) a routing-coupled rate adaption and admission control algorithm to admit data sessions with bandwidth guarantee. Moreover, extensive numerical simulations suggest that BRAC is efficient and effective in meeting the bandwidth requirements for sharing social multimedia contents. These insights will shed light on communication system implementation for multimedia content sharing over multirate wireless community cloud.
基金supported by Grants from Key Science and Technology Plan Projects in Zigong (grant No.2022ZCNKY07)National Natural Science Foundation of China (grant No.31900950)Jiangxi Provincial Natural Science Foundation (grant No.20212BAB214048).
文摘Polyhydroxyalkanoates(PHAs)are diversiform biopolyesters with a similar structure and different side chain groups,synthesized by a variety of microorganism.Due to their excellent biodegradability and biocompatibility,PHAs have been used for many applications,including medical implants,antibacterial agents and bioengineering.Nano-architecture is an emerging area for the use of PHAs.This review summarizes the current status and challenges of PHAs-based particles on the micro-and nano-scale,including their production,degradation,biological safety,and surface functionalization.We also focus on the applications of PHA particles in drug delivery systems,environment protection,tissue engi-neering,vaccine engineering,food science,biotechnology and cosmetics.Finally,the future development trends of PHAs-based particles are prospected.
基金supported by 135 Project for Disciplines of Excellence of West China Hospital Sichuan University(ZYGD23011)National Natural Sciences Foundation of China(882272716)Natural Sciences Foundation of Sichuan(2022NSFSC0053).
文摘Tumor biomarkers,the substances which are produced by tumors or the body’s responses to tumors during tumorigenesis and progression,have been demonstrated to possess critical and encouraging value in screening and early diagnosis,prognosis prediction,recurrence detection,and therapeutic efficacy monitoring of cancers.Over the past decades,continuous progress has been made in exploring and discovering novel,sensitive,specific,and accurate tumor biomarkers,which has significantly promoted personalized medicine and improved the outcomes of cancer patients,especially advances in molecular biology technologies developed for the detection of tumor biomarkers.Herein,we summarize the discovery and development of tumor biomarkers,including the history of tumor biomarkers,the conventional and innovative technologies used for biomarker discovery and detection,the classification of tumor biomarkers based on tissue origins,and the application of tumor biomarkers in clinical cancer management.In particular,we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies.We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field.Collectively,the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine,broaden horizons in future research directions,and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.
基金the Ministry of Science and Technology of China(Grant Nos.2018YFA0801100 and 2021YFF0702100)the National Natural Science Foundation of China(Grant Nos.32025019 and 31970719 to S.C.,31971067)the Fundamental Research Funds for the Central Universities(021414380533,021414380505)for financial support。
文摘Energy status is linked to the production of reactive oxygen species(ROS)in macrophages,which is elevated in obesity.However,it is unclear how ROS production is upregulated in macrophages in response to energy overload for mediating the development of obesity.Here,we show that the Rab-GTPase activating protein(Rab GAP)TBC1D1,a substrate of the energy sensor AMP-activated protein kinase(AMPK),is a critical regulator of macrophage ROS production and consequent adipose inflammation for obesity development.TBC1D1 deletion decreases,whereas an energy overload-mimetic non-phosphorylatable TBC1D1^(S231A)Amutation increases,ROS production and M1-like polarization in macrophages.Mechanistically,TBC1D1 and its downstream target Rab8a form an energy-responsive complex with NOX2 for ROS generation.Transplantation of TBC1D1^(S231A)bone marrow aggravates diet-induced obesity whereas treatment with an ultra-stable Tt SOD for removal of ROS selectively in macrophages alleviates both TBC1D1~(S231A)mutation-and diet-induced obesity.Our findings therefore have implications for drug discovery to combat obesity.
基金supported by the National Key Research and Development Program of China(2018YFA0507001)the Basic Research Program of Science and Technology Commission of Shanghai Municipality(21JC1402400)+1 种基金the National Natural Science Foundation of China(32171215,81972828,82172644,82273857 and 81830083)the National Key Scientific Infrastructure for Translational Medicine(Shanghai)(TMSK-2021-120)。
文摘The adenosine subfamily G protein-coupled receptors A_(2A)R and A_(2B)R have been identified as promising cancer immunotherapy candidates.One of the A_(2A)R/A_(2B)R dual antagonists,AB928,has progressed to a phaseⅡclinical trial to treat rectal cancer.However,the precise mechanism underlying its dual-antagonistic properties remains elusive.Herein,we report crystal structures of the A_(2A)R complexed with AB928 and a selective A_(2A)R antagonist 2-118.The structures revealed a common binding mode on A_(2A)R,wherein the ligands established extensive interactions with residues from the orthosteric and secondary pockets.In contrast,the cAMP assay and A_(2A)R and A_(2B)R molecular dynamics simulations indicated that the ligands adopted distinct binding modes on A_(2B)R.Detailed analysis of their chemical structures suggested that AB928 readily adapted to the A_(2B)R pocket,while 2-118 did not due to intrinsic differences.This disparity potentially accounted for the difference in inhibitory efficacy between A_(2B)R and A_(2A)R.This study serves as a valuable structural template for the future development of selective or dual inhibitors targeting A_(2A)R/A_(2B)R for cancer therapy.
基金supported by the National Natural Science Foundation of China(92049302,92374207,32088101,32330017)the National Key Research and Development Program of China(2020YFA0804000)。
文摘The human face is a valuable biomarker of aging,but the collection and use of its image raise significant privacy concerns.Here we present an approach for facial data masking that preserves age-related features using coordinate-wise monotonic transformations.We first develop a deep learning model that estimates age directly from non-registered face point clouds with high accuracy and generalizability.We show that the model learns a highly indistinguishable mapping using faces treated with coordinate-wise monotonic transformations,indicating that the relative positioning of facial information is a low-level biomarker of facial aging.Through visual perception tests and computational3D face verification experiments,we demonstrate that transformed faces are significantly more difficult to perceive for human but not for machines,except when only the face shape information is accessible.Our study leads to a facial data protection guideline that has the potential to broaden public access to face datasets with minimized privacy risks.
基金supported by National Natural Science Foundation of China(No.82104278)Leading Technology Foundation Research Project of Jiangsu Province(No.BK20192005,China)+4 种基金National Key Project of Science and Technology for Innovation Drugs of China(No.2017ZX09301013)CAMS Innovation Fund for Medical Sciences(CIFMS,No.2021-I2M-5-011,China)Sanming Project of Medicine in Shenzhen(No.SZSM201801060,China)Project of State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.SKLNMKF202203,China)National Innovation and Entrepreneurship Training Program for Undergraduate,China Pharmaceutical University(Nos.2023103161381 and 2023103161287,China)。
文摘Studies have suggested that the nucleus accumbens(NAc)is implicated in the pathophysiology of major depression;however,the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated.Here,we identified a specific reduction of cyclic adenosine monophosphate(cAMP)in the subset of dopamine D1 receptor medium spiny neurons(D1-MSNs)in the NAc that promoted stress susceptibility,while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors.Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons(D2-MSNs)of depressed mice,however,the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs.We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration,but not a lower dose.The fast onset property of crocin was verified through multicenter studies.Moreover,crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN.These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc,and provide a potential rapid antidepressant drug candidate,crocin.
