Thermal behavior and physical properties of castables during curing and drying-out are associated with their binding system. In this work, five alumina based （ Al2O3 〉 87% ） castables with different combinations of...Thermal behavior and physical properties of castables during curing and drying-out are associated with their binding system. In this work, five alumina based （ Al2O3 〉 87% ） castables with different combinations of binding materials, i. e. , （ 1 ） CA cement （CA） ＋ Reactive alumina （ RA ） ＋ H2O ; （ 2 ） high level addi- tion of CA ＋ Microsilica （MS） ＋ H2O ; （ 3 ） low level addition of CA ＋ MS ＋ H2O ; （4） MS ＋ Hydratable alumina ＋ H20 and （ 5 ） MS ＋ Magnesia ＋ H2O, respectively, have been investigated on the flowability and thermal behavior during curing at room temperature, drying at 110% and heating from 200℃ to 1000℃ at an interval of 100℃ , in terms of water addition, vibration flow value, porosity, dehydration, explosion resistance, cold and hot bending strengths. Differences in dehydrating behavior and the mentioned properties have been revealed and correlated to the binding system.展开更多
Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, le...Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, leukemia, and lymphomas. Quantitative characterization of the interactions between CDK2 and its inhibitors at atomic level may provide a deep understanding of protein-inhibitor interactions and clues for more effective drug discovery. In this study, we have used the computational alanine scanning approach in combination with an efficient interaction entropy method to study the microscopic mechanism of binding between CDK2 and its 13 inhibitors. The total binding free energy from the method shows a correlation of 0.76?0.83 with the experimental values. The free energy component reveals two binding mode in the 13 complexes, namely van der Waals dominant, and electrostatic dominant. Decomposition of the total energy to per-residue contribution allows us to identify five hydrophobic residues as hot spots during the binding. Residues that are responsible for determining the strength of the binding were also analyzed.展开更多
Age-related macular degeneration(AMD)is the leading cause of irreversible vision loss in older adults,with early-stage features including subretinal lipid deposits and progressing to retinal geographic atrophy and cho...Age-related macular degeneration(AMD)is the leading cause of irreversible vision loss in older adults,with early-stage features including subretinal lipid deposits and progressing to retinal geographic atrophy and choroidal neovascularization in advanced stages.The dysregulation of ocular lipid metabolism,oxidative stress,and inflammation are critical risk factors for AMD pathogenesis.7-ketocholesterol(7-KC),a hallmark of ocular lipid metabolism disorders,is a significant component of subretinal lipid deposits in AMD patients,exhibiting toxicity to retinal cells and exacerbating lipotoxic aging.This review elaborates on the biosynthesis and metabolism of 7-KC in the retina,investigates its detoxification mechanisms by examining its binding proteins,and summarizes recent progress on kinase signaling pathways induced by 7-KC through inflammatory cytokines and intracellular effectors.The aim is to pinpoint potential pharmacological targets,nutritional compounds,and synthetic molecules to explore the potential of targeting 7-KC for AMD treatment.展开更多
Polyolefins with intrinsic antimicrobial properties have attracted significant attention.In this study,various ion-functionalized polyolefins were successfully constructed by incorporating iodine-containing comonomers...Polyolefins with intrinsic antimicrobial properties have attracted significant attention.In this study,various ion-functionalized polyolefins were successfully constructed by incorporating iodine-containing comonomers into a polypropylene backbone,followed by post-functionalization strategies that utilized the conversion reactions of pre-introduced iodine groups.The introduction of ionic groups induced notable changes in both the thermal properties and the melt rheological behavior of the material.The dual crosslinking mechanism based on ionic interactions and polypropylene crystallization significantly enhanced the mechanical strength of the material.In addition,imidazolium-based ionomers exhibit highly effective antimicrobial properties against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus.Specifically,the P5-CCl_(3)CO_(2)^(−)sample achieved a sterilization rate of 99.99%against both bacteria and maintained a high bactericidal efficacy of above 90%,even after continuous supplementation with fresh bacterial solutions for 15 days.Consequently,this polypropylene-based ionomer,which combines excellent mechanical strength with outstanding antimicrobial performance,demonstrates substantial application potential in children’s toys,food packaging,and medicine.展开更多
RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progre...RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progression of numerous diseases,making RBPs potential therapeutic targets.However,the limited tissue penetration of 254 nm UV irradiation makes it difficult to efficiently crosslink weak and dynamic RNA-protein interactions in mammal tissues.Additionally,RNA degradation in metal catalyzed click reaction further hinders the enrichment of RNA-protein complexes(RPCs).Due to these inherent limitations,globally profiling the RNA binding proteome in mammal organs has long been a challenge.Herein,we proposed a novel method,which utilized a dual crosslinking with formaldehyde and 254 nm UV irradiation,metabolic labeling and metal-free thiol-yne click reaction to enable large-scale enrichment and identification of RBPs in mouse liver,called FTYc_UV.In this method,formaldehyde is first used to crosslink the crude RNA-protein complexes(cRPCs) in situ to address the problem of poor tissue penetration of 254 nm UV irradiation.Furthermore,this method integrates metabolic labeling with a metal-free thiol-yne click reaction to achieve non-destructive RNA tagging.After specifically RNA-RBPs crosslinking by 254 nm UV irradiation in tissue lysates,formaldehyde decrosslinking is employed to remove non-specific proteins,leading to effective enrichment of RPCs from mouse liver and thereby overcoming the poor specificity of formaldehyde crosslinking.Application of FTYc_UV in mouse liver successfully identified over 1600 RBPs covering approximately 75 % of previously reported RBPs.Furthermore,420 candidate RBPs,including 151metabolic enzymes,were also obtained,demonstrating the sensitivity of FTYc_UV and the potential of this method for in-depth exploration of RNA-protein interactions in biological and clinical research.展开更多
Seed vigor is critical for uniform germination and emergence,directly influencing subsequent seedling development.This is especially important under both normal and stress conditions that may arise post-sowing.Chillin...Seed vigor is critical for uniform germination and emergence,directly influencing subsequent seedling development.This is especially important under both normal and stress conditions that may arise post-sowing.Chilling stress during emergence and early growth poses significant challenges for tomato seedlings,potentially leading to uneven emergence,abnormal growth,and higher seedling mortality.This study evaluated the effectiveness of combining drum-priming with melatonin to alleviate chilling stress during these two critical stages.Tomato seeds were primed with melatonin at various concentrations and compared to untreated controls under chilling stress conditions.Higher concentrations of melatonin significantly accelerated emergence and improved early growth under stress.These stress-mitigating effects were evidenced by reductions in oxidative stress markers,such as malondialdehyde and hydrogen peroxide,along with increased total polyphenol and flavonoid contents.Furthermore,melatonin priming preserved photosynthetic efficiency,typically reduced by chilling stress,and enhanced the activities of antioxidant enzymes,including catalase and peroxidase.These biochemical changes reduced oxidative damage and promoted stress resilience.Melatonin also accelerated the expression of genes within the C-repeat binding factor pathway,which is crucial for cold acclimation.This suggests that melatonin priming enabled quicker adaptation to chilling stress following sowing and bolstered seedling resilience during subsequent growth stages.Overall,our results demonstrate that melatonin priming not only enhances germination but also significantly supports seedling growth under adverse conditions.The findings highlight melatonin as a promising tool in crop management strategies to improve resilience against sudden chilling stress.展开更多
Lithium-sulfur batteries(LSBs)represent a next-generation energy storage technology,but widespread applications are restricted by the shuttle of lithium polysulfides(LiPSs).The rational design of separators has been d...Lithium-sulfur batteries(LSBs)represent a next-generation energy storage technology,but widespread applications are restricted by the shuttle of lithium polysulfides(LiPSs).The rational design of separators has been demonstrated to be one of the most efficient and cost-effective strategies to curb the shuttle effect,and tremendous research progress has been achieved.The efficiency of a separator depends on its interaction with LiPSs,which is governed by the surface energy and binding strength.Despite several review works that have been reported to advance the separators,most of them primarily focus on active material innovation and construction.The most crucial issues of surface binding energy have not been systematically reviewed,limiting the precise design of efficient separators.In this review,fundamentals related to surface energy and binding interactions with LiPSs are comprehensively analyzed and discussed.With surface binding and energy main lines,the advancements in separator engineering strategies are elaborately summarized and discussed.Moreover,techniques for evaluating affinity to LiPSs are thoroughly analyzed to avoid any ambiguities in measurement.Based on the research context,valuable research directions are suggested to construct efficient separators.This work provides guidelines to regulate the surface binding and energy of separators for high-performance LSBs.展开更多
Kinesin-8 motors can move with a high processivity on microtubule lattices toward the plus end.After reaching the plus end,the kinesin-8 motors can pause for a long time and promote the microtubule depolymerization.He...Kinesin-8 motors can move with a high processivity on microtubule lattices toward the plus end.After reaching the plus end,the kinesin-8 motors can pause for a long time and promote the microtubule depolymerization.Here,using atomistic molecular dynamics simulations we studied the structural changes of the kinesin-8 head in different nucleotide states bound to the straight and curved tubulins and the corresponding interactions between them.We found that the kinesin-8 head in ATP and/or ADP–Pi state has the similar strong affinity while in ADP state has the similar weak affinity to both the straight and curved tubulins,which is strongly implicated in the mechanism of the long but very different residence times of the kinesin-8 motor on the microtubule lattice and at the end.Moreover,we found that loop-2 of the kinesin-8 head bound strongly to the curved tubulin in the stable state has a large interference with its neck linker pulled in the minusended orientation.This is contrary to the case of the head bound strongly to the straight tubulin,where loop-2 has little interference with its neck linker pulled in the minus-ended orientation.The large interference can induce a larger internal force between the two heads and thus can induce the two curved tubulins bound strongly by the two heads to be more curved relative to each other.This is strongly implicated in the mechanism of the depolymerase activity of the kinesin-8motors and explains the origin of loop-2 playing a facilitating role in the depolymerase activity.展开更多
Oviposition behavior in insects has received considerable attention,but studies have mainly focused on the antennae,neglecting the role of the ovipositor.In this study,we investigated the functional characteristics of...Oviposition behavior in insects has received considerable attention,but studies have mainly focused on the antennae,neglecting the role of the ovipositor.In this study,we investigated the functional characteristics of the ovipositor in oviposition site selection by the fall armyworm(FAW)Spodoptera frugiperda,a destructive invasive pest of maize and other cereals.In oviposition choice assays females exhibited significant repellency to isothiocyanate(ITC),volatiles specific to non-preferred cruciferous plants.Females retained repellency to ITC or attraction to maize volatiles even after antennae removal.Scanning electron microscopy indicated the presence of olfactory-associated sensilla on the ovipositor.Comparative transcriptome analysis and in vitro functional studies showed that S.frugiperda odorant binding protein 30(SfruOBP30),exclusively expressed in the ovipositor,displayed a broad sensitivity toward 18 maize volatiles and 10 ITC compounds.Site-directed mutant assay revealed that Ser71 and Ser85 were the key binding sites for SfruOBP30 interacting with ITCs and key maize volatiles,respectively.Silencing the expression of SfruOBP30 resulted in the loss of bias in oviposition of FAW,significantly inhibiting their ability to avoid ITCs and locate the maize substrate.Overall,we propose that the ovipositor does not just seek out advantageous conditions for immature stages but more importantly,avoids potential risks during the oviposition process.Apparently,the involvement of SfruOBP30 plays a critical role in detecting both beneficial and harmful substances during this intricate process.展开更多
As a key low-carbon energy source,nuclear power plays a vital role in the global transition toward sustainable energy.Photocatalytic uranium extraction from seawater(UES)offers a promising solution to ensure long-term...As a key low-carbon energy source,nuclear power plays a vital role in the global transition toward sustainable energy.Photocatalytic uranium extraction from seawater(UES)offers a promising solution to ensure long-term uranium supply but is challenged by ultra-low uranium concentrations and ion interference.To overcome these issues,we design three diketopyrrolopyrrole-based covalent organic frameworks(COFs)via a synergisticπ-extended lock and carboxyl-functionalized anchor molecular engineering strategy.Among them,TPy-DPP-COF features a covalently lockedπ-conjugated structure that enhances planarity,optimizes energy alignment,and minimizes exciton binding energy,thereby promoting charge transfer and suppressing recombination.Concurrently,carboxyl groups enable uranyl-specific coordination and create local electric fields to facilitate charge separation.These features contribute to the outstanding performance of TPy-DPP-COF,which achieves a high uranium adsorption capacity of 16.33 mg g−1 in natural seawater under irradiation,with only 29.3%capacity loss after 10 cycles,surpassing industrial benchmarks.Density functional theory(DFT)calculations and experimental studies reveal a synergistic photocatalysis-adsorption pathway,with DPP units acting as active sites for uranium reduction.This work highlights a molecular design strategy for developing efficient COF-based photocatalysts for practical marine uranium recovery.展开更多
To address the issues of frequent identity switches(IDs)and degraded identification accuracy in multi object tracking(MOT)under complex occlusion scenarios,this study proposes an occlusion-robust tracking framework ba...To address the issues of frequent identity switches(IDs)and degraded identification accuracy in multi object tracking(MOT)under complex occlusion scenarios,this study proposes an occlusion-robust tracking framework based on face-pedestrian joint feature modeling.By constructing a joint tracking model centered on“intra-class independent tracking+cross-category dynamic binding”,designing a multi-modal matching metric with spatio-temporal and appearance constraints,and innovatively introducing a cross-category feature mutual verification mechanism and a dual matching strategy,this work effectively resolves performance degradation in traditional single-category tracking methods caused by short-term occlusion,cross-camera tracking,and crowded environments.Experiments on the Chokepoint_Face_Pedestrian_Track test set demonstrate that in complex scenes,the proposed method improves Face-Pedestrian Matching F1 area under the curve(F1 AUC)by approximately 4 to 43 percentage points compared to several traditional methods.The joint tracking model achieves overall performance metrics of IDF1:85.1825%and MOTA:86.5956%,representing improvements of 0.91 and 0.06 percentage points,respectively,over the baseline model.Ablation studies confirm the effectiveness of key modules such as the Intersection over Area(IoA)/Intersection over Union(IoU)joint metric and dynamic threshold adjustment,validating the significant role of the cross-category identity matching mechanism in enhancing tracking stability.Our_model shows a 16.7%frame per second(FPS)drop vs.fairness of detection and re-identification in multiple object tracking(FairMOT),with its cross-category binding module adding aboute 10%overhead,yet maintains near-real-time performance for essential face-pedestrian tracking at small resolutions.展开更多
Background Ruminants and monogastric animals exhibit significant differences in gluconeogenic efficiency.In dairy cows,hepatic gluconeogenesis serves as the primary source of glucose.Metabolites modulate gluconeogenes...Background Ruminants and monogastric animals exhibit significant differences in gluconeogenic efficiency.In dairy cows,hepatic gluconeogenesis serves as the primary source of glucose.Metabolites modulate gluconeogenesis efficiency through allosteric regulation,redox state,and signal transduction pathways.However,the liver-enriched metabolites that regulate hepatic gluconeogenesis in dairy cows and their specific regulatory mechanisms remain incompletely characterized.Results Six Holstein dairy cows and six Duroc×(Landrace×Yorkshire)(DLY)crossbred pigs served as research subjects.Employing non-targeted and targeted metabolomics,we discovered that three bile acids—taurodeoxycholic acid(TDCA),taurocholic acid(TCA),and glycocholic acid(GCA)—were highly enriched in Holstein dairy cows'livers.In bovine hepatocytes,individual or combined stimulation of these bile acids significantly upregulated the expression of gluconeogenesis genes(FBP1,PCK1 and G6PC)and enhanced glucose production.In fasting mice with induced gluconeogenesis,TDCA,TCA,and GCA increased fasting blood glucose levels,and pyruvate tolerance tests further revealed their capacity to enhance hepatic gluconeogenesis,enabling more efficient glucose synthesis from pyruvate.Mechanistically,these bile acids activated Takeda G protein-coupled receptor 5(TGR5),elevated intracellular cAMP levels,and ultimately enhanced gluconeogenesis via the transcription factor cAMP-response element binding protein(CREB).Notably,a TGR5 inhibitor abrogated the stimulatory effects of TDCA,TCA,and GCA on hepatic gluconeogenesis in fasting mice.Conclusion TDCA,TCA,and GCA are key metabolites promoting hepatic gluconeogenesis in dairy cows,with TGR5 as the pivotal receptor and the cAMP/PKA/CREB pathway as the critical downstream mechanism.展开更多
Nuclear receptor subfamily 2 group F member 1(NR2F1,also called COUP-TF1)is a transcription factor and part of the steroid/thyroid hormone receptor superfamily(Gay et al.,2002).NR2F1 is an orphan receptor that dimeriz...Nuclear receptor subfamily 2 group F member 1(NR2F1,also called COUP-TF1)is a transcription factor and part of the steroid/thyroid hormone receptor superfamily(Gay et al.,2002).NR2F1 is an orphan receptor that dimerizes to bind DNA and acts as a repressor as well as an activator of the target genes(Gay et al.,2002;Bertacchi et al.,2019;Bonzano et al.,2023).展开更多
Tumors are defined by uncontrolled cell proliferation(Hariharan and Bilder,2006).Benign tumors are typically slow-growing and localized,while malignant ones are invasive and aggressive.The nuclear receptor Eip75B(E75)...Tumors are defined by uncontrolled cell proliferation(Hariharan and Bilder,2006).Benign tumors are typically slow-growing and localized,while malignant ones are invasive and aggressive.The nuclear receptor Eip75B(E75),a heme-binding protein responsive to ecdysone signaling,encodes three major isoforms,E75A,E75B,and E75C(Bialecki et al.,2002),among them,only E75A and E75C contain zinc finger domains that enable DNA binding.展开更多
Superoxide dismutase 1(SOD1)is a thermodynamically stable,zinc and copper binding homodimeric enzyme responsible for breaking down superoxide radicals.More than 200,mostly missense,mutations spread throughout the SOD1...Superoxide dismutase 1(SOD1)is a thermodynamically stable,zinc and copper binding homodimeric enzyme responsible for breaking down superoxide radicals.More than 200,mostly missense,mutations spread throughout the SOD1 gene are associated with the fatal neurodegenerative disease,amyotrophic lateral sclerosis(ALS).A unifying feature of ALS-associated SOD1 mutations is the destabilization of the SOD1 protein structure,increasing the propensity for misfolding and subsequent pathological aggregation.Post-mortem analysis of SOD1-associated ALS tissue shows the accumulation of misfolded SOD1 protein and ubiquitinated SOD1 inclusions within motor neurons.Misfolded SOD1 accumulation and aggregates are implicated in cellular dysfunction via a number of disparate but critical processes,including endoplasmic reticulum stress,oxidative damage,proteasome dysfunction,axonal transport abnormalities and synaptic dysfunction;culminating in motor neuron degeneration associated with ALS.展开更多
Ufmylation is an ubiquitin-like post-translational modification characterized by the covalent binding of mature UFM1 to target proteins.Although the consequences of ufmylation on target proteins are not fully understo...Ufmylation is an ubiquitin-like post-translational modification characterized by the covalent binding of mature UFM1 to target proteins.Although the consequences of ufmylation on target proteins are not fully understood,its importance is evident from the disorders resulting from its dysfunction.Numerous case reports have established a link between biallelic loss-of-function and/or hypomorphic variants in ufmylation-related genes and a spectrum of pediatric neurodevelopmental disorders.展开更多
Human induced pluripotent stem cell-derived neural stem/progenitor cells are used in cell-replacement and regenerative therapeutic strategies after traumatic central nervous system injury.Traumatic injury alters the h...Human induced pluripotent stem cell-derived neural stem/progenitor cells are used in cell-replacement and regenerative therapeutic strategies after traumatic central nervous system injury.Traumatic injury alters the host microenvironment,which in turn affects the functionality of transplanted human neural stem/progenitor cells and potentially limits their benefits for neurorepair.However,the underlying mechanisms through which the host environment alters the fate and functionality of transplanted human neural stem/progenitor cells remain poorly understood.Here,we showed that massive deposition of blood-derived fibrinogen in a mouse model of spinal cord injury contributed to an altered lesion environment.Fibrinogen promoted human neural stem/progenitor cell differentiation into reactive astrocytes by activating the BMP receptor signaling pathway and inducing of the transcriptional regulator inhibitor of DNA binding 3.ID3-depleted human neural stem/progenitor cells,generated by CRISPR/Cas9-mediated genome editing,reduced astrocyte formation in response to astrogenic stimuli.Instead,ID3-depleted human neural stem/progenitor cells had a bipolar,immature glial progenitor cell phenotype.These modified cells secreted extracellular vesicles with a distinct miRNA profile that enhanced neurite outgrowth.We conclude that targeting inhibitor of DNA binding 3 in human neural stem/progenitor cells can beneficially modulate their functionality and cell fate in the injured central nervous system toward glial progenitor cells,potentially enhancing their capacity to promote central nervous system repair.展开更多
Currently, some commercial software applications support users to work in an integrated environment. However, this is limited to the suite of models provided by the software vendor and consequently it forces all the p...Currently, some commercial software applications support users to work in an integrated environment. However, this is limited to the suite of models provided by the software vendor and consequently it forces all the parties to use the same software. In contrast, the research described in this paper investigates ways of using standard software applications, which may be specialized for different professional domains. These are linked for effective transfer of information and a binding mechanism is provided to support consistency. The proposed solution was implemented using a CAD application and an independent finite element application in order to verify the theoretical aspects of this work.展开更多
Background:To investigate SCL/TAL 1 interrupting locus(STIL)’s role and prognostic significance in lung adenocarcinoma(LUAD)progression,we examined STIL and E2 promoter binding factor 1(E2F1)expression and their impa...Background:To investigate SCL/TAL 1 interrupting locus(STIL)’s role and prognostic significance in lung adenocarcinoma(LUAD)progression,we examined STIL and E2 promoter binding factor 1(E2F1)expression and their impacts on LUAD prognosis using Gene Expression Profiling Interactive Analysis(GEPIA).Methods:Functional assays including CCK-8,wound-healing,5-ethynyl-2-deoxyuridine(EdU),Transwell assays,and flow cytometry,elucidated STIL and E2F1’s effects on cell viability,proliferation,apoptosis,and migration.Gene set enrichment analysis(GSEA)identified potential pathways,while metabolic assays assessed glucose metabolism.Results:Our findings reveal that STIL and E2F1 are overexpressed in LUAD,correlating with adverse outcomes.It enhances cell proliferation,migration,and invasion,and suppresses apoptosis,activating downstream of E2F1.Silencing E2F1 reversed the promotion effect of the STIL overexpression on cell viability and invasiveness.Importantly,STIL modulates glycolysis,influencing glucose consumption,lactate production,and energy balance in LUAD cells.Conclusion:Our model,incorporating STIL,age,and disease stage,robustly predicts patient prognosis,underscored STIL’s pivotal role in LUAD pathogenesis through metabolic reprogramming.This comprehensive approach not only confirms STIL’s prognostic value but also highlights its potential as a therapeutic target in LUAD.展开更多
文摘Thermal behavior and physical properties of castables during curing and drying-out are associated with their binding system. In this work, five alumina based （ Al2O3 〉 87% ） castables with different combinations of binding materials, i. e. , （ 1 ） CA cement （CA） ＋ Reactive alumina （ RA ） ＋ H2O ; （ 2 ） high level addi- tion of CA ＋ Microsilica （MS） ＋ H2O ; （ 3 ） low level addition of CA ＋ MS ＋ H2O ; （4） MS ＋ Hydratable alumina ＋ H20 and （ 5 ） MS ＋ Magnesia ＋ H2O, respectively, have been investigated on the flowability and thermal behavior during curing at room temperature, drying at 110% and heating from 200℃ to 1000℃ at an interval of 100℃ , in terms of water addition, vibration flow value, porosity, dehydration, explosion resistance, cold and hot bending strengths. Differences in dehydrating behavior and the mentioned properties have been revealed and correlated to the binding system.
基金supported by National Key R&D Program of China (No.2016YFA0501700)National Natural Science Foundation of China (No.21433004, No.31700646, No.91753103)+1 种基金Innovation Program of Shanghai Municipal Education Commission (201701070005E00020)NYU Global Seed Grant
文摘Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, leukemia, and lymphomas. Quantitative characterization of the interactions between CDK2 and its inhibitors at atomic level may provide a deep understanding of protein-inhibitor interactions and clues for more effective drug discovery. In this study, we have used the computational alanine scanning approach in combination with an efficient interaction entropy method to study the microscopic mechanism of binding between CDK2 and its 13 inhibitors. The total binding free energy from the method shows a correlation of 0.76?0.83 with the experimental values. The free energy component reveals two binding mode in the 13 complexes, namely van der Waals dominant, and electrostatic dominant. Decomposition of the total energy to per-residue contribution allows us to identify five hydrophobic residues as hot spots during the binding. Residues that are responsible for determining the strength of the binding were also analyzed.
文摘Age-related macular degeneration(AMD)is the leading cause of irreversible vision loss in older adults,with early-stage features including subretinal lipid deposits and progressing to retinal geographic atrophy and choroidal neovascularization in advanced stages.The dysregulation of ocular lipid metabolism,oxidative stress,and inflammation are critical risk factors for AMD pathogenesis.7-ketocholesterol(7-KC),a hallmark of ocular lipid metabolism disorders,is a significant component of subretinal lipid deposits in AMD patients,exhibiting toxicity to retinal cells and exacerbating lipotoxic aging.This review elaborates on the biosynthesis and metabolism of 7-KC in the retina,investigates its detoxification mechanisms by examining its binding proteins,and summarizes recent progress on kinase signaling pathways induced by 7-KC through inflammatory cytokines and intracellular effectors.The aim is to pinpoint potential pharmacological targets,nutritional compounds,and synthetic molecules to explore the potential of targeting 7-KC for AMD treatment.
基金financially supported by the National Natural Science Foundation of China(Nos.52130307 and 52121002).
文摘Polyolefins with intrinsic antimicrobial properties have attracted significant attention.In this study,various ion-functionalized polyolefins were successfully constructed by incorporating iodine-containing comonomers into a polypropylene backbone,followed by post-functionalization strategies that utilized the conversion reactions of pre-introduced iodine groups.The introduction of ionic groups induced notable changes in both the thermal properties and the melt rheological behavior of the material.The dual crosslinking mechanism based on ionic interactions and polypropylene crystallization significantly enhanced the mechanical strength of the material.In addition,imidazolium-based ionomers exhibit highly effective antimicrobial properties against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus.Specifically,the P5-CCl_(3)CO_(2)^(−)sample achieved a sterilization rate of 99.99%against both bacteria and maintained a high bactericidal efficacy of above 90%,even after continuous supplementation with fresh bacterial solutions for 15 days.Consequently,this polypropylene-based ionomer,which combines excellent mechanical strength with outstanding antimicrobial performance,demonstrates substantial application potential in children’s toys,food packaging,and medicine.
基金financial support from the National Key R&D Program of China (No.2021YFA1302604)Scientific and technological innovation project of China Academy of Chinese Medical Sciences (No.CI2021B017)China Postdoctoral Science Foundation (No.2023T160727)。
文摘RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progression of numerous diseases,making RBPs potential therapeutic targets.However,the limited tissue penetration of 254 nm UV irradiation makes it difficult to efficiently crosslink weak and dynamic RNA-protein interactions in mammal tissues.Additionally,RNA degradation in metal catalyzed click reaction further hinders the enrichment of RNA-protein complexes(RPCs).Due to these inherent limitations,globally profiling the RNA binding proteome in mammal organs has long been a challenge.Herein,we proposed a novel method,which utilized a dual crosslinking with formaldehyde and 254 nm UV irradiation,metabolic labeling and metal-free thiol-yne click reaction to enable large-scale enrichment and identification of RBPs in mouse liver,called FTYc_UV.In this method,formaldehyde is first used to crosslink the crude RNA-protein complexes(cRPCs) in situ to address the problem of poor tissue penetration of 254 nm UV irradiation.Furthermore,this method integrates metabolic labeling with a metal-free thiol-yne click reaction to achieve non-destructive RNA tagging.After specifically RNA-RBPs crosslinking by 254 nm UV irradiation in tissue lysates,formaldehyde decrosslinking is employed to remove non-specific proteins,leading to effective enrichment of RPCs from mouse liver and thereby overcoming the poor specificity of formaldehyde crosslinking.Application of FTYc_UV in mouse liver successfully identified over 1600 RBPs covering approximately 75 % of previously reported RBPs.Furthermore,420 candidate RBPs,including 151metabolic enzymes,were also obtained,demonstrating the sensitivity of FTYc_UV and the potential of this method for in-depth exploration of RNA-protein interactions in biological and clinical research.
文摘Seed vigor is critical for uniform germination and emergence,directly influencing subsequent seedling development.This is especially important under both normal and stress conditions that may arise post-sowing.Chilling stress during emergence and early growth poses significant challenges for tomato seedlings,potentially leading to uneven emergence,abnormal growth,and higher seedling mortality.This study evaluated the effectiveness of combining drum-priming with melatonin to alleviate chilling stress during these two critical stages.Tomato seeds were primed with melatonin at various concentrations and compared to untreated controls under chilling stress conditions.Higher concentrations of melatonin significantly accelerated emergence and improved early growth under stress.These stress-mitigating effects were evidenced by reductions in oxidative stress markers,such as malondialdehyde and hydrogen peroxide,along with increased total polyphenol and flavonoid contents.Furthermore,melatonin priming preserved photosynthetic efficiency,typically reduced by chilling stress,and enhanced the activities of antioxidant enzymes,including catalase and peroxidase.These biochemical changes reduced oxidative damage and promoted stress resilience.Melatonin also accelerated the expression of genes within the C-repeat binding factor pathway,which is crucial for cold acclimation.This suggests that melatonin priming enabled quicker adaptation to chilling stress following sowing and bolstered seedling resilience during subsequent growth stages.Overall,our results demonstrate that melatonin priming not only enhances germination but also significantly supports seedling growth under adverse conditions.The findings highlight melatonin as a promising tool in crop management strategies to improve resilience against sudden chilling stress.
基金supported by the National Natural Science Foundation of China (52172228)the Natural Science Foundation of Fujian Province (2024J01475 and 2023J05127)
文摘Lithium-sulfur batteries(LSBs)represent a next-generation energy storage technology,but widespread applications are restricted by the shuttle of lithium polysulfides(LiPSs).The rational design of separators has been demonstrated to be one of the most efficient and cost-effective strategies to curb the shuttle effect,and tremendous research progress has been achieved.The efficiency of a separator depends on its interaction with LiPSs,which is governed by the surface energy and binding strength.Despite several review works that have been reported to advance the separators,most of them primarily focus on active material innovation and construction.The most crucial issues of surface binding energy have not been systematically reviewed,limiting the precise design of efficient separators.In this review,fundamentals related to surface energy and binding interactions with LiPSs are comprehensively analyzed and discussed.With surface binding and energy main lines,the advancements in separator engineering strategies are elaborately summarized and discussed.Moreover,techniques for evaluating affinity to LiPSs are thoroughly analyzed to avoid any ambiguities in measurement.Based on the research context,valuable research directions are suggested to construct efficient separators.This work provides guidelines to regulate the surface binding and energy of separators for high-performance LSBs.
基金Project supported by the Science and Technology Research Program of Chongqing Municipal Education Commission(Grant No.KJQN202504529)the General Program of Chongqing Natural Science Foundation(Grant No.CSTB2025NSCQ-GPX0833)。
文摘Kinesin-8 motors can move with a high processivity on microtubule lattices toward the plus end.After reaching the plus end,the kinesin-8 motors can pause for a long time and promote the microtubule depolymerization.Here,using atomistic molecular dynamics simulations we studied the structural changes of the kinesin-8 head in different nucleotide states bound to the straight and curved tubulins and the corresponding interactions between them.We found that the kinesin-8 head in ATP and/or ADP–Pi state has the similar strong affinity while in ADP state has the similar weak affinity to both the straight and curved tubulins,which is strongly implicated in the mechanism of the long but very different residence times of the kinesin-8 motor on the microtubule lattice and at the end.Moreover,we found that loop-2 of the kinesin-8 head bound strongly to the curved tubulin in the stable state has a large interference with its neck linker pulled in the minusended orientation.This is contrary to the case of the head bound strongly to the straight tubulin,where loop-2 has little interference with its neck linker pulled in the minus-ended orientation.The large interference can induce a larger internal force between the two heads and thus can induce the two curved tubulins bound strongly by the two heads to be more curved relative to each other.This is strongly implicated in the mechanism of the depolymerase activity of the kinesin-8motors and explains the origin of loop-2 playing a facilitating role in the depolymerase activity.
基金funded by National Key R&D Program of China(2021YFD1400703)Young Talent Support Project of Guangzhou Association for Science and Technology(QT2024-020).
文摘Oviposition behavior in insects has received considerable attention,but studies have mainly focused on the antennae,neglecting the role of the ovipositor.In this study,we investigated the functional characteristics of the ovipositor in oviposition site selection by the fall armyworm(FAW)Spodoptera frugiperda,a destructive invasive pest of maize and other cereals.In oviposition choice assays females exhibited significant repellency to isothiocyanate(ITC),volatiles specific to non-preferred cruciferous plants.Females retained repellency to ITC or attraction to maize volatiles even after antennae removal.Scanning electron microscopy indicated the presence of olfactory-associated sensilla on the ovipositor.Comparative transcriptome analysis and in vitro functional studies showed that S.frugiperda odorant binding protein 30(SfruOBP30),exclusively expressed in the ovipositor,displayed a broad sensitivity toward 18 maize volatiles and 10 ITC compounds.Site-directed mutant assay revealed that Ser71 and Ser85 were the key binding sites for SfruOBP30 interacting with ITCs and key maize volatiles,respectively.Silencing the expression of SfruOBP30 resulted in the loss of bias in oviposition of FAW,significantly inhibiting their ability to avoid ITCs and locate the maize substrate.Overall,we propose that the ovipositor does not just seek out advantageous conditions for immature stages but more importantly,avoids potential risks during the oviposition process.Apparently,the involvement of SfruOBP30 plays a critical role in detecting both beneficial and harmful substances during this intricate process.
基金the Young Elite Scientists Sponsorship Program by JXAST(2024QT11)the National Natural Science Foundation of China(22465001,22309003)the Jiangxi Provincial Natural Science Foundation(20232BAB203042,20242BAB22002).
文摘As a key low-carbon energy source,nuclear power plays a vital role in the global transition toward sustainable energy.Photocatalytic uranium extraction from seawater(UES)offers a promising solution to ensure long-term uranium supply but is challenged by ultra-low uranium concentrations and ion interference.To overcome these issues,we design three diketopyrrolopyrrole-based covalent organic frameworks(COFs)via a synergisticπ-extended lock and carboxyl-functionalized anchor molecular engineering strategy.Among them,TPy-DPP-COF features a covalently lockedπ-conjugated structure that enhances planarity,optimizes energy alignment,and minimizes exciton binding energy,thereby promoting charge transfer and suppressing recombination.Concurrently,carboxyl groups enable uranyl-specific coordination and create local electric fields to facilitate charge separation.These features contribute to the outstanding performance of TPy-DPP-COF,which achieves a high uranium adsorption capacity of 16.33 mg g−1 in natural seawater under irradiation,with only 29.3%capacity loss after 10 cycles,surpassing industrial benchmarks.Density functional theory(DFT)calculations and experimental studies reveal a synergistic photocatalysis-adsorption pathway,with DPP units acting as active sites for uranium reduction.This work highlights a molecular design strategy for developing efficient COF-based photocatalysts for practical marine uranium recovery.
基金supported by the confidential research grant No.a8317。
文摘To address the issues of frequent identity switches(IDs)and degraded identification accuracy in multi object tracking(MOT)under complex occlusion scenarios,this study proposes an occlusion-robust tracking framework based on face-pedestrian joint feature modeling.By constructing a joint tracking model centered on“intra-class independent tracking+cross-category dynamic binding”,designing a multi-modal matching metric with spatio-temporal and appearance constraints,and innovatively introducing a cross-category feature mutual verification mechanism and a dual matching strategy,this work effectively resolves performance degradation in traditional single-category tracking methods caused by short-term occlusion,cross-camera tracking,and crowded environments.Experiments on the Chokepoint_Face_Pedestrian_Track test set demonstrate that in complex scenes,the proposed method improves Face-Pedestrian Matching F1 area under the curve(F1 AUC)by approximately 4 to 43 percentage points compared to several traditional methods.The joint tracking model achieves overall performance metrics of IDF1:85.1825%and MOTA:86.5956%,representing improvements of 0.91 and 0.06 percentage points,respectively,over the baseline model.Ablation studies confirm the effectiveness of key modules such as the Intersection over Area(IoA)/Intersection over Union(IoU)joint metric and dynamic threshold adjustment,validating the significant role of the cross-category identity matching mechanism in enhancing tracking stability.Our_model shows a 16.7%frame per second(FPS)drop vs.fairness of detection and re-identification in multiple object tracking(FairMOT),with its cross-category binding module adding aboute 10%overhead,yet maintains near-real-time performance for essential face-pedestrian tracking at small resolutions.
基金supported by the National Science Fund for Excellent Young Scholars(grant number 32422082)the Natural Science Basic Research Plan in Shaanxi Province(grant number 2025JC-QYXQ-009)。
文摘Background Ruminants and monogastric animals exhibit significant differences in gluconeogenic efficiency.In dairy cows,hepatic gluconeogenesis serves as the primary source of glucose.Metabolites modulate gluconeogenesis efficiency through allosteric regulation,redox state,and signal transduction pathways.However,the liver-enriched metabolites that regulate hepatic gluconeogenesis in dairy cows and their specific regulatory mechanisms remain incompletely characterized.Results Six Holstein dairy cows and six Duroc×(Landrace×Yorkshire)(DLY)crossbred pigs served as research subjects.Employing non-targeted and targeted metabolomics,we discovered that three bile acids—taurodeoxycholic acid(TDCA),taurocholic acid(TCA),and glycocholic acid(GCA)—were highly enriched in Holstein dairy cows'livers.In bovine hepatocytes,individual or combined stimulation of these bile acids significantly upregulated the expression of gluconeogenesis genes(FBP1,PCK1 and G6PC)and enhanced glucose production.In fasting mice with induced gluconeogenesis,TDCA,TCA,and GCA increased fasting blood glucose levels,and pyruvate tolerance tests further revealed their capacity to enhance hepatic gluconeogenesis,enabling more efficient glucose synthesis from pyruvate.Mechanistically,these bile acids activated Takeda G protein-coupled receptor 5(TGR5),elevated intracellular cAMP levels,and ultimately enhanced gluconeogenesis via the transcription factor cAMP-response element binding protein(CREB).Notably,a TGR5 inhibitor abrogated the stimulatory effects of TDCA,TCA,and GCA on hepatic gluconeogenesis in fasting mice.Conclusion TDCA,TCA,and GCA are key metabolites promoting hepatic gluconeogenesis in dairy cows,with TGR5 as the pivotal receptor and the cAMP/PKA/CREB pathway as the critical downstream mechanism.
文摘Nuclear receptor subfamily 2 group F member 1(NR2F1,also called COUP-TF1)is a transcription factor and part of the steroid/thyroid hormone receptor superfamily(Gay et al.,2002).NR2F1 is an orphan receptor that dimerizes to bind DNA and acts as a repressor as well as an activator of the target genes(Gay et al.,2002;Bertacchi et al.,2019;Bonzano et al.,2023).
基金supported by the National Natural Science Foundation of China(32170824 and 32322027 to X.M.)HRHI program of Westlake Laboratory of Life Sciences and Biomedicine(1011103360222B1 to X.M.)+1 种基金"Pioneer"and"Leading Goose"R&D Program of Zhejiang(2024SSYS0034)State Key Laboratory of Gene Expression.
文摘Tumors are defined by uncontrolled cell proliferation(Hariharan and Bilder,2006).Benign tumors are typically slow-growing and localized,while malignant ones are invasive and aggressive.The nuclear receptor Eip75B(E75),a heme-binding protein responsive to ecdysone signaling,encodes three major isoforms,E75A,E75B,and E75C(Bialecki et al.,2002),among them,only E75A and E75C contain zinc finger domains that enable DNA binding.
基金Motor Neuron Disease Research Australia in the form of a Bill Gole Postdoctoral Fellowship(PDF2307)FightMND in the form of Drug Development Grants(DDG-159 and DDG137 to JSL)。
文摘Superoxide dismutase 1(SOD1)is a thermodynamically stable,zinc and copper binding homodimeric enzyme responsible for breaking down superoxide radicals.More than 200,mostly missense,mutations spread throughout the SOD1 gene are associated with the fatal neurodegenerative disease,amyotrophic lateral sclerosis(ALS).A unifying feature of ALS-associated SOD1 mutations is the destabilization of the SOD1 protein structure,increasing the propensity for misfolding and subsequent pathological aggregation.Post-mortem analysis of SOD1-associated ALS tissue shows the accumulation of misfolded SOD1 protein and ubiquitinated SOD1 inclusions within motor neurons.Misfolded SOD1 accumulation and aggregates are implicated in cellular dysfunction via a number of disparate but critical processes,including endoplasmic reticulum stress,oxidative damage,proteasome dysfunction,axonal transport abnormalities and synaptic dysfunction;culminating in motor neuron degeneration associated with ALS.
文摘Ufmylation is an ubiquitin-like post-translational modification characterized by the covalent binding of mature UFM1 to target proteins.Although the consequences of ufmylation on target proteins are not fully understood,its importance is evident from the disorders resulting from its dysfunction.Numerous case reports have established a link between biallelic loss-of-function and/or hypomorphic variants in ufmylation-related genes and a spectrum of pediatric neurodevelopmental disorders.
基金supported by a Fill in the Gap fellowship(Medical Faculty Freiburg)(to JDL)a Fritz Thyssen Stiftung grant,a European Stroke Research Foundation(ESRF)grant,a Wings for Life foundation grantthe DFG grants SCHA 1442/8-1,SCHA 1442/8-3,and SCHA 1442/9-1(to CS).
文摘Human induced pluripotent stem cell-derived neural stem/progenitor cells are used in cell-replacement and regenerative therapeutic strategies after traumatic central nervous system injury.Traumatic injury alters the host microenvironment,which in turn affects the functionality of transplanted human neural stem/progenitor cells and potentially limits their benefits for neurorepair.However,the underlying mechanisms through which the host environment alters the fate and functionality of transplanted human neural stem/progenitor cells remain poorly understood.Here,we showed that massive deposition of blood-derived fibrinogen in a mouse model of spinal cord injury contributed to an altered lesion environment.Fibrinogen promoted human neural stem/progenitor cell differentiation into reactive astrocytes by activating the BMP receptor signaling pathway and inducing of the transcriptional regulator inhibitor of DNA binding 3.ID3-depleted human neural stem/progenitor cells,generated by CRISPR/Cas9-mediated genome editing,reduced astrocyte formation in response to astrogenic stimuli.Instead,ID3-depleted human neural stem/progenitor cells had a bipolar,immature glial progenitor cell phenotype.These modified cells secreted extracellular vesicles with a distinct miRNA profile that enhanced neurite outgrowth.We conclude that targeting inhibitor of DNA binding 3 in human neural stem/progenitor cells can beneficially modulate their functionality and cell fate in the injured central nervous system toward glial progenitor cells,potentially enhancing their capacity to promote central nervous system repair.
文摘Currently, some commercial software applications support users to work in an integrated environment. However, this is limited to the suite of models provided by the software vendor and consequently it forces all the parties to use the same software. In contrast, the research described in this paper investigates ways of using standard software applications, which may be specialized for different professional domains. These are linked for effective transfer of information and a binding mechanism is provided to support consistency. The proposed solution was implemented using a CAD application and an independent finite element application in order to verify the theoretical aspects of this work.
文摘Background:To investigate SCL/TAL 1 interrupting locus(STIL)’s role and prognostic significance in lung adenocarcinoma(LUAD)progression,we examined STIL and E2 promoter binding factor 1(E2F1)expression and their impacts on LUAD prognosis using Gene Expression Profiling Interactive Analysis(GEPIA).Methods:Functional assays including CCK-8,wound-healing,5-ethynyl-2-deoxyuridine(EdU),Transwell assays,and flow cytometry,elucidated STIL and E2F1’s effects on cell viability,proliferation,apoptosis,and migration.Gene set enrichment analysis(GSEA)identified potential pathways,while metabolic assays assessed glucose metabolism.Results:Our findings reveal that STIL and E2F1 are overexpressed in LUAD,correlating with adverse outcomes.It enhances cell proliferation,migration,and invasion,and suppresses apoptosis,activating downstream of E2F1.Silencing E2F1 reversed the promotion effect of the STIL overexpression on cell viability and invasiveness.Importantly,STIL modulates glycolysis,influencing glucose consumption,lactate production,and energy balance in LUAD cells.Conclusion:Our model,incorporating STIL,age,and disease stage,robustly predicts patient prognosis,underscored STIL’s pivotal role in LUAD pathogenesis through metabolic reprogramming.This comprehensive approach not only confirms STIL’s prognostic value but also highlights its potential as a therapeutic target in LUAD.
