Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is ...Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.展开更多
We work within a Winterberg framework where space, i.e., the vacuum, consists of a two component superfluid/super-solid made up of a vast assembly (sea) of positive and negative mass Planck particles, called planckion...We work within a Winterberg framework where space, i.e., the vacuum, consists of a two component superfluid/super-solid made up of a vast assembly (sea) of positive and negative mass Planck particles, called planckions. These material particles interact indirectly, and have very strong restoring forces keeping them a finite distance apart from each other within their respective species. Because of their mass compensating effect, the vacuum appears massless, charge-less, without pressure, net energy density or entropy. In addition, we consider two varying G models, where G, is Newton’s constant, and G<sup>-1</sup>, increases with an increase in cosmological time. We argue that there are at least two competing models for the quantum vacuum within such a framework. The first follows a strict extension of Winterberg’s model. This leads to nonsensible results, if G increases, going back in cosmological time, as the length scale inherent in such a model will not scale properly. The second model introduces a different length scale, which does scale properly, but keeps the mass of the Planck particle as, ± the Planck mass. Moreover we establish a connection between ordinary matter, dark matter, and dark energy, where all three mass densities within the Friedman equation must be interpreted as residual vacuum energies, which only surface, once aggregate matter has formed, at relatively low CMB temperatures. The symmetry of the vacuum will be shown to be broken, because of the different scaling laws, beginning with the formation of elementary particles. Much like waves on an ocean where positive and negative planckion mass densities effectively cancel each other out and form a zero vacuum energy density/zero vacuum pressure surface, these positive mass densities are very small perturbations (anomalies) about the mean. This greatly alleviates, i.e., minimizes the cosmological constant problem, a long standing problem associated with the vacuum.展开更多
Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
Satellite communications, pivotal for global connectivity, are increasingly converging with cutting-edge mobile networks, notably 5G, B5G, and 6G. This amalgamation heralds the promise of universal, high-velocity comm...Satellite communications, pivotal for global connectivity, are increasingly converging with cutting-edge mobile networks, notably 5G, B5G, and 6G. This amalgamation heralds the promise of universal, high-velocity communication, yet it is not without its challenges. Paramount concerns encompass spectrum allocation, the harmonization of network architectures, and inherent latency issues in satellite transmissions. Potential mitigations, such as dynamic spectrum sharing and the deployment of edge computing, are explored as viable solutions. Looking ahead, the advent of quantum communications within satellite frameworks and the integration of AI spotlight promising research trajectories. These advancements aim to foster a seamless and synergistic coexistence between satellite communications and next-gen mobile networks.展开更多
Perennial grass-legume mixtures have been extensively used to restore degraded grasslands,increasing grassland productivity and forage quality.Tillage is crucial for seedbed preparation and sustainable weed management...Perennial grass-legume mixtures have been extensively used to restore degraded grasslands,increasing grassland productivity and forage quality.Tillage is crucial for seedbed preparation and sustainable weed management for the establishment of grass-legume mixtures.However,a common concern is that intensive tillage may alter soil characteristics,leading to losses in soil organic carbon(SOC).We investigated the plant community composition,SOC,soil microbial biomass carbon(MBC),soil enzyme activities,and soil properties in long-term perennial grass-legume mixtures under two different tillage intensities(once and twice)as well as in a fenced grassland(FG).The establishment of grass-legume mixtures increased plant species diversity and plant community coverage,compared with FG.Compared with once tilled grassland(OTG),twice tilled grassland(TTG)enhanced the coverage of high-quality leguminous forage species by 380.3%.Grass-legume mixtures with historical tillage decreased SOC and dissolved organic carbon(DOC)concentrations,whereas soil MBC concentrations in OTG and TTG increased by 16.0%and 16.4%,respectively,compared with FG.TTG significantly decreased the activity of N-acetyl-β-D-glucosaminidase(NAG)by 72.3%,whereas soil enzymeβ-glucosidase(βG)in OTG and TTG increased by 55.9%and 27.3%,respectively,compared with FG.Correlation analysis indicated a close association of the increase in MBC andβG activities with the rapid decline in SOC.This result suggested that MBC was a key driving factor in soil carbon storage dynamics,potentially accelerating soil carbon cycling and facilitating biogeochemical cycling.The establishment of grass-legume mixtures effectively improves forage quality and boosts plant diversity,thereby facilitating the restoration of degraded grasslands.Although tillage assists in establishing legume-grass mixtures by controlling weeds,it accelerates microbial activity and organic carbon decomposition.Our findings provide a foundation for understanding the process and effectiveness of restoration management in degraded grasslands.展开更多
Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are inv...Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.展开更多
BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes p...BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes play a significant role in the development of diverse tumors.AIM To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus.The study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and PLA2G12B.Gene Set Enrichment Analysis was utilized to pinpoint associated pathways.Moreover,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was evaluated.RESULTS PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals.Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients.Additionally,the study delineated pathways and miRNAs associated with these genes.CONCLUSION Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA.The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.展开更多
Communicating on millimeter wave(mmWave)bands is ushering in a new epoch of mobile communication which provides the availability of 10 Gbps high data rate transmission.However,mmWave links are easily prone to short tr...Communicating on millimeter wave(mmWave)bands is ushering in a new epoch of mobile communication which provides the availability of 10 Gbps high data rate transmission.However,mmWave links are easily prone to short transmission range communication because of the serious free space path loss and the blockage by obstacles.To overcome these challenges,highly directional beams are exploited to achieve robust links by hybrid beamforming.Accurately aligning the transmitter and receiver beams,i.e.beam training,is vitally important to high data rate transmission.However,it may cause huge overhead which has negative effects on initial access,handover,and tracking.Besides,the mobility patterns of users are complicated and dynamic,which may cause tracking error and large tracking latency.An efficient beam tracking method has a positive effect on sustaining robust links.This article provides an overview of the beam training and tracking technologies on mmWave bands and reveals the insights for future research in the 6th Generation(6G)mobile network.Especially,some open research problems are proposed to realize fast,accurate,and robust beam training and tracking.We hope that this survey provides guidelines for the researchers in the area of mmWave communications.展开更多
G protein-coupled receptors(GPCRs)are crucial players in various physiological processes,making them attractive candidates for drug discovery.However,traditional approaches to GPCR ligand discovery are time-consuming ...G protein-coupled receptors(GPCRs)are crucial players in various physiological processes,making them attractive candidates for drug discovery.However,traditional approaches to GPCR ligand discovery are time-consuming and resource-intensive.The emergence of artificial intelligence(AI)methods has revolutionized the field of GPCR ligand discovery and has provided valuable tools for accelerating the identification and optimization of GPCR ligands.In this study,we provide guidelines for effectively utilizing AI methods for GPCR ligand discovery,including data collation and representation,model selection,and specific applications.First,the online resources that are instrumental in GPCR ligand discovery were summarized,including databases and repositories that contain valuable GPCR-related information and ligand data.Next,GPCR and ligand representation schemes that can convert data into computer-readable formats were introduced.Subsequently,the key applications of AI methods in the different stages of GPCR drug discovery were discussed,ranging from GPCR function prediction to ligand design and agonist identification.Furthermore,an AI-driven multi-omics integration strategy for GPCR ligand discovery that combines information from various omics disciplines was proposed.Finally,the challenges and future directions of the application of AI in GPCR research were deliberated.In conclusion,continued advancements in AI techniques coupled with interdisciplina ry collaborations will offer great potential for improving the efficiency of GPCR ligand discovery.展开更多
Significant technological trends are impacting health care,from consumerisation,datafication,circular economy,and platformization of services.Web 3.0,or the Internet of Value,enables direct peer-to-peer value exchange...Significant technological trends are impacting health care,from consumerisation,datafication,circular economy,and platformization of services.Web 3.0,or the Internet of Value,enables direct peer-to-peer value exchange,opening up new business models that will impact health care.Among the many technologies that will also be part of the healthcare transformation is artificial intelligence,which shocked the world with the debut of ChatGPT in 2022.This opinion piece will explore how AI underpins the health transformation and,far from being an enemy of health,is the critical friend health care has been waiting for.展开更多
The infamous type Ⅳ failure within the fine-grained heat-affected zone (FGHAZ) in G115 steel weldments seriously threatens the safe operation of ultra-supercritical (USC) power plants.In this work,the traditional the...The infamous type Ⅳ failure within the fine-grained heat-affected zone (FGHAZ) in G115 steel weldments seriously threatens the safe operation of ultra-supercritical (USC) power plants.In this work,the traditional thermo-mechanical treatment was modified via the replacement of hot-rolling with cold rolling,i.e.,normalizing,cold rolling,and tempering (NCT),which was developed to improve the creep strength of the FGHAZ in G115 steel weldments.The NCT treatment effectively promoted the dissolution of preformed M_(23)C_(6)particles and relieved the boundary segregation of C and Cr during welding thermal cycling,which accelerated the dispersed reprecipitation of M_(23)C_(6) particles within the fresh reaustenitized grains during post-weld heat treatment.In addition,the precipitation of Cu-rich phases and MX particles was promoted evidently due to the deformation-induced dislocations.As a result,the interacting actions between precipitates,dislocations,and boundaries during creep were reinforced considerably.Following this strategy,the creep rupture life of the FGHAZ in G115 steel weldments can be prolonged by 18.6%,which can further push the application of G115 steel in USC power plants.展开更多
In Beyond the Fifth Generation(B5G)heterogeneous edge networks,numerous users are multiplexed on a channel or served on the same frequency resource block,in which case the transmitter applies coding and the receiver u...In Beyond the Fifth Generation(B5G)heterogeneous edge networks,numerous users are multiplexed on a channel or served on the same frequency resource block,in which case the transmitter applies coding and the receiver uses interference cancellation.Unfortunately,uncoordinated radio resource allocation can reduce system throughput and lead to user inequity,for this reason,in this paper,channel allocation and power allocation problems are formulated to maximize the system sum rate and minimum user achievable rate.Since the construction model is non-convex and the response variables are high-dimensional,a distributed Deep Reinforcement Learning(DRL)framework called distributed Proximal Policy Optimization(PPO)is proposed to allocate or assign resources.Specifically,several simulated agents are trained in a heterogeneous environment to find robust behaviors that perform well in channel assignment and power allocation.Moreover,agents in the collection stage slow down,which hinders the learning of other agents.Therefore,a preemption strategy is further proposed in this paper to optimize the distributed PPO,form DP-PPO and successfully mitigate the straggler problem.The experimental results show that our mechanism named DP-PPO improves the performance over other DRL methods.展开更多
This study presents a layered generalization ensemble model for next generation radio mobiles,focusing on supervised channel estimation approaches.Channel estimation typically involves the insertion of pilot symbols w...This study presents a layered generalization ensemble model for next generation radio mobiles,focusing on supervised channel estimation approaches.Channel estimation typically involves the insertion of pilot symbols with a well-balanced rhythm and suitable layout.The model,called Stacked Generalization for Channel Estimation(SGCE),aims to enhance channel estimation performance by eliminating pilot insertion and improving throughput.The SGCE model incorporates six machine learning methods:random forest(RF),gradient boosting machine(GB),light gradient boosting machine(LGBM),support vector regression(SVR),extremely randomized tree(ERT),and extreme gradient boosting(XGB).By generating meta-data from five models(RF,GB,LGBM,SVR,and ERT),we ensure accurate channel coefficient predictions using the XGB model.To validate themodeling performance,we employ the leave-one-out cross-validation(LOOCV)approach,where each observation serves as the validation set while the remaining observations act as the training set.SGCE performances’results demonstrate higher mean andmedian accuracy compared to the separatedmodel.SGCE achieves an average accuracy of 98.4%,precision of 98.1%,and the highest F1-score of 98.5%,accurately predicting channel coefficients.Furthermore,our proposedmethod outperforms prior traditional and intelligent techniques in terms of throughput and bit error rate.SGCE’s superior performance highlights its efficacy in optimizing channel estimation.It can effectively predict channel coefficients and contribute to enhancing the overall efficiency of radio mobile systems.Through extensive experimentation and evaluation,we demonstrate that SGCE improved performance in channel estimation,surpassing previous techniques.Accordingly,SGCE’s capabilities have significant implications for optimizing channel estimation in modern communication systems.展开更多
In this work the influence of the density of the molten metal on the emergence of the raining phenomenon in the horizontal centrifugal casting process is numerically studied. Transient 2D numerical simulations were ca...In this work the influence of the density of the molten metal on the emergence of the raining phenomenon in the horizontal centrifugal casting process is numerically studied. Transient 2D numerical simulations were carried out using Computational Fluid Dynamics software. Three molten metals with different density, namely aluminum, iron and lead, and three angular frequencies, namely 50, 66 and 77 rad/s were considered. It is found that the density of the molten metal significantly affects the emergence, transient or permanent, of the rain phenomenon. However, the magnitude and duration of the rain phenomenon depend on the angular frequency of the rotating mold. Likewise, since gravitational forces affect the metal according to its density, the value of the critical rotation speed of the mold is also affected.展开更多
In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussiv...In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.展开更多
基金supported by NIH Grants R01NS092651 and R21NS111275-01the Department of Veterans Affairs,BX001148 and BX005899(to PHK)。
文摘Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.
文摘We work within a Winterberg framework where space, i.e., the vacuum, consists of a two component superfluid/super-solid made up of a vast assembly (sea) of positive and negative mass Planck particles, called planckions. These material particles interact indirectly, and have very strong restoring forces keeping them a finite distance apart from each other within their respective species. Because of their mass compensating effect, the vacuum appears massless, charge-less, without pressure, net energy density or entropy. In addition, we consider two varying G models, where G, is Newton’s constant, and G<sup>-1</sup>, increases with an increase in cosmological time. We argue that there are at least two competing models for the quantum vacuum within such a framework. The first follows a strict extension of Winterberg’s model. This leads to nonsensible results, if G increases, going back in cosmological time, as the length scale inherent in such a model will not scale properly. The second model introduces a different length scale, which does scale properly, but keeps the mass of the Planck particle as, ± the Planck mass. Moreover we establish a connection between ordinary matter, dark matter, and dark energy, where all three mass densities within the Friedman equation must be interpreted as residual vacuum energies, which only surface, once aggregate matter has formed, at relatively low CMB temperatures. The symmetry of the vacuum will be shown to be broken, because of the different scaling laws, beginning with the formation of elementary particles. Much like waves on an ocean where positive and negative planckion mass densities effectively cancel each other out and form a zero vacuum energy density/zero vacuum pressure surface, these positive mass densities are very small perturbations (anomalies) about the mean. This greatly alleviates, i.e., minimizes the cosmological constant problem, a long standing problem associated with the vacuum.
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
文摘Satellite communications, pivotal for global connectivity, are increasingly converging with cutting-edge mobile networks, notably 5G, B5G, and 6G. This amalgamation heralds the promise of universal, high-velocity communication, yet it is not without its challenges. Paramount concerns encompass spectrum allocation, the harmonization of network architectures, and inherent latency issues in satellite transmissions. Potential mitigations, such as dynamic spectrum sharing and the deployment of edge computing, are explored as viable solutions. Looking ahead, the advent of quantum communications within satellite frameworks and the integration of AI spotlight promising research trajectories. These advancements aim to foster a seamless and synergistic coexistence between satellite communications and next-gen mobile networks.
基金funded by the National Natural Science Foundation of China(32271776,32171616)the Special Sichuan Postdoctoral Research Projectsthe National Natural Science Foundation of Sichuan Province,China(2024NSFSC0309,2022NSFSC1769,2022NSFSC0110).
文摘Perennial grass-legume mixtures have been extensively used to restore degraded grasslands,increasing grassland productivity and forage quality.Tillage is crucial for seedbed preparation and sustainable weed management for the establishment of grass-legume mixtures.However,a common concern is that intensive tillage may alter soil characteristics,leading to losses in soil organic carbon(SOC).We investigated the plant community composition,SOC,soil microbial biomass carbon(MBC),soil enzyme activities,and soil properties in long-term perennial grass-legume mixtures under two different tillage intensities(once and twice)as well as in a fenced grassland(FG).The establishment of grass-legume mixtures increased plant species diversity and plant community coverage,compared with FG.Compared with once tilled grassland(OTG),twice tilled grassland(TTG)enhanced the coverage of high-quality leguminous forage species by 380.3%.Grass-legume mixtures with historical tillage decreased SOC and dissolved organic carbon(DOC)concentrations,whereas soil MBC concentrations in OTG and TTG increased by 16.0%and 16.4%,respectively,compared with FG.TTG significantly decreased the activity of N-acetyl-β-D-glucosaminidase(NAG)by 72.3%,whereas soil enzymeβ-glucosidase(βG)in OTG and TTG increased by 55.9%and 27.3%,respectively,compared with FG.Correlation analysis indicated a close association of the increase in MBC andβG activities with the rapid decline in SOC.This result suggested that MBC was a key driving factor in soil carbon storage dynamics,potentially accelerating soil carbon cycling and facilitating biogeochemical cycling.The establishment of grass-legume mixtures effectively improves forage quality and boosts plant diversity,thereby facilitating the restoration of degraded grasslands.Although tillage assists in establishing legume-grass mixtures by controlling weeds,it accelerates microbial activity and organic carbon decomposition.Our findings provide a foundation for understanding the process and effectiveness of restoration management in degraded grasslands.
基金supported by the Ministerio de Economía,Industria y Competitividad(Agencia Estatal de Investigación,AEI,to CGF and MP)Fondo Europeo de Desarrollo Regional(MINECO-FEDER)(PID2022-139016OA-I00,PDC2022-133441-I00,to CGF and MP),Generalitat de Catalunya(2021 SGR 00357+3 种基金to CGF and MP)co-financed by Secretaria d’Universitats i Recerca del Departament d’Empresai Coneixement de la Generalitat de Catalunya 2021(Llavor 00086,to CGF)the recipient of an Alzheimer’s Association Research Fellowship(AARF-21-848511)the Agència de Gestiód’Ajuts Universitaris i de Recerca(AGAUR)for her FI-SDUR fellowship(2021FISDU 00182).
文摘Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.
基金Supported by the Key Specialty Construction Project of Shanghai Pudong New Area Health Commission,No.PWZzk2022-17Shanghai East Hospital Clinical Research Project,No.DFLC2022019and the Featured Clinical Discipline Project of Shanghai Pudong District,No.PWYts2021-06.
文摘BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes play a significant role in the development of diverse tumors.AIM To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus.The study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and PLA2G12B.Gene Set Enrichment Analysis was utilized to pinpoint associated pathways.Moreover,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was evaluated.RESULTS PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals.Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients.Additionally,the study delineated pathways and miRNAs associated with these genes.CONCLUSION Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA.The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.
基金supported in part by the National Natural Science Foundation of China(NSFC)under Grant 92267202in part by the Municipal Government of Quzhou under Grant 2023D027+2 种基金in part by the National Natural Science Foundation of China(NSFC)under Grant 62321001in part by the National Key Research and Development Program of China under Grant 2020YFA0711303in part by the Beijing Natural Science Foundation under Grant Z220004.
文摘Communicating on millimeter wave(mmWave)bands is ushering in a new epoch of mobile communication which provides the availability of 10 Gbps high data rate transmission.However,mmWave links are easily prone to short transmission range communication because of the serious free space path loss and the blockage by obstacles.To overcome these challenges,highly directional beams are exploited to achieve robust links by hybrid beamforming.Accurately aligning the transmitter and receiver beams,i.e.beam training,is vitally important to high data rate transmission.However,it may cause huge overhead which has negative effects on initial access,handover,and tracking.Besides,the mobility patterns of users are complicated and dynamic,which may cause tracking error and large tracking latency.An efficient beam tracking method has a positive effect on sustaining robust links.This article provides an overview of the beam training and tracking technologies on mmWave bands and reveals the insights for future research in the 6th Generation(6G)mobile network.Especially,some open research problems are proposed to realize fast,accurate,and robust beam training and tracking.We hope that this survey provides guidelines for the researchers in the area of mmWave communications.
基金Natural Science Foundation of Sichuan(2023NSFSC0683)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D202209).
文摘G protein-coupled receptors(GPCRs)are crucial players in various physiological processes,making them attractive candidates for drug discovery.However,traditional approaches to GPCR ligand discovery are time-consuming and resource-intensive.The emergence of artificial intelligence(AI)methods has revolutionized the field of GPCR ligand discovery and has provided valuable tools for accelerating the identification and optimization of GPCR ligands.In this study,we provide guidelines for effectively utilizing AI methods for GPCR ligand discovery,including data collation and representation,model selection,and specific applications.First,the online resources that are instrumental in GPCR ligand discovery were summarized,including databases and repositories that contain valuable GPCR-related information and ligand data.Next,GPCR and ligand representation schemes that can convert data into computer-readable formats were introduced.Subsequently,the key applications of AI methods in the different stages of GPCR drug discovery were discussed,ranging from GPCR function prediction to ligand design and agonist identification.Furthermore,an AI-driven multi-omics integration strategy for GPCR ligand discovery that combines information from various omics disciplines was proposed.Finally,the challenges and future directions of the application of AI in GPCR research were deliberated.In conclusion,continued advancements in AI techniques coupled with interdisciplina ry collaborations will offer great potential for improving the efficiency of GPCR ligand discovery.
文摘Significant technological trends are impacting health care,from consumerisation,datafication,circular economy,and platformization of services.Web 3.0,or the Internet of Value,enables direct peer-to-peer value exchange,opening up new business models that will impact health care.Among the many technologies that will also be part of the healthcare transformation is artificial intelligence,which shocked the world with the debut of ChatGPT in 2022.This opinion piece will explore how AI underpins the health transformation and,far from being an enemy of health,is the critical friend health care has been waiting for.
基金financially supported by the National Key R&D Program of China(No.2022YFB3705300)the National Natural Science Foundation of China(Nos.U1960204 and 51974199)the Postdoctoral Fellowship Program of CPSF(No.GZB20230515)。
文摘The infamous type Ⅳ failure within the fine-grained heat-affected zone (FGHAZ) in G115 steel weldments seriously threatens the safe operation of ultra-supercritical (USC) power plants.In this work,the traditional thermo-mechanical treatment was modified via the replacement of hot-rolling with cold rolling,i.e.,normalizing,cold rolling,and tempering (NCT),which was developed to improve the creep strength of the FGHAZ in G115 steel weldments.The NCT treatment effectively promoted the dissolution of preformed M_(23)C_(6)particles and relieved the boundary segregation of C and Cr during welding thermal cycling,which accelerated the dispersed reprecipitation of M_(23)C_(6) particles within the fresh reaustenitized grains during post-weld heat treatment.In addition,the precipitation of Cu-rich phases and MX particles was promoted evidently due to the deformation-induced dislocations.As a result,the interacting actions between precipitates,dislocations,and boundaries during creep were reinforced considerably.Following this strategy,the creep rupture life of the FGHAZ in G115 steel weldments can be prolonged by 18.6%,which can further push the application of G115 steel in USC power plants.
基金supported by the Key Research and Development Program of China(No.2022YFC3005401)Key Research and Development Program of China,Yunnan Province(No.202203AA080009,202202AF080003)Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX21_0482).
文摘In Beyond the Fifth Generation(B5G)heterogeneous edge networks,numerous users are multiplexed on a channel or served on the same frequency resource block,in which case the transmitter applies coding and the receiver uses interference cancellation.Unfortunately,uncoordinated radio resource allocation can reduce system throughput and lead to user inequity,for this reason,in this paper,channel allocation and power allocation problems are formulated to maximize the system sum rate and minimum user achievable rate.Since the construction model is non-convex and the response variables are high-dimensional,a distributed Deep Reinforcement Learning(DRL)framework called distributed Proximal Policy Optimization(PPO)is proposed to allocate or assign resources.Specifically,several simulated agents are trained in a heterogeneous environment to find robust behaviors that perform well in channel assignment and power allocation.Moreover,agents in the collection stage slow down,which hinders the learning of other agents.Therefore,a preemption strategy is further proposed in this paper to optimize the distributed PPO,form DP-PPO and successfully mitigate the straggler problem.The experimental results show that our mechanism named DP-PPO improves the performance over other DRL methods.
基金This research project was funded by the Deanship of Scientific Research,Princess Nourah bint Abdulrahman University,through the Program of Research Project Funding After Publication,grant No(43-PRFA-P-58).
文摘This study presents a layered generalization ensemble model for next generation radio mobiles,focusing on supervised channel estimation approaches.Channel estimation typically involves the insertion of pilot symbols with a well-balanced rhythm and suitable layout.The model,called Stacked Generalization for Channel Estimation(SGCE),aims to enhance channel estimation performance by eliminating pilot insertion and improving throughput.The SGCE model incorporates six machine learning methods:random forest(RF),gradient boosting machine(GB),light gradient boosting machine(LGBM),support vector regression(SVR),extremely randomized tree(ERT),and extreme gradient boosting(XGB).By generating meta-data from five models(RF,GB,LGBM,SVR,and ERT),we ensure accurate channel coefficient predictions using the XGB model.To validate themodeling performance,we employ the leave-one-out cross-validation(LOOCV)approach,where each observation serves as the validation set while the remaining observations act as the training set.SGCE performances’results demonstrate higher mean andmedian accuracy compared to the separatedmodel.SGCE achieves an average accuracy of 98.4%,precision of 98.1%,and the highest F1-score of 98.5%,accurately predicting channel coefficients.Furthermore,our proposedmethod outperforms prior traditional and intelligent techniques in terms of throughput and bit error rate.SGCE’s superior performance highlights its efficacy in optimizing channel estimation.It can effectively predict channel coefficients and contribute to enhancing the overall efficiency of radio mobile systems.Through extensive experimentation and evaluation,we demonstrate that SGCE improved performance in channel estimation,surpassing previous techniques.Accordingly,SGCE’s capabilities have significant implications for optimizing channel estimation in modern communication systems.
文摘In this work the influence of the density of the molten metal on the emergence of the raining phenomenon in the horizontal centrifugal casting process is numerically studied. Transient 2D numerical simulations were carried out using Computational Fluid Dynamics software. Three molten metals with different density, namely aluminum, iron and lead, and three angular frequencies, namely 50, 66 and 77 rad/s were considered. It is found that the density of the molten metal significantly affects the emergence, transient or permanent, of the rain phenomenon. However, the magnitude and duration of the rain phenomenon depend on the angular frequency of the rotating mold. Likewise, since gravitational forces affect the metal according to its density, the value of the critical rotation speed of the mold is also affected.
基金the National Natural Science Foundation(81773982,82003937)Youth Academic leaders of the Qinglan Project in Jiangsu province for financial support。
文摘In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.