In traditional Chinese medicine(TCM),ophthalmic syndrome differentiation is an ophthalmology-specific method for identifying syndromes based on the“Five Orbiculi”theory.It was devised by Professor Qing-Hua PENG thro...In traditional Chinese medicine(TCM),ophthalmic syndrome differentiation is an ophthalmology-specific method for identifying syndromes based on the“Five Orbiculi”theory.It was devised by Professor Qing-Hua PENG through an unprecedented combination of syndrome element differentiation and ophthalmic clinical practices,based on the Clinical Terminology of Chinese Medical Diagnosis and Treatment-Syndromes of the National Standards of the People's Republic of China.This approach integrates an ophthalmic syndrome differentiation system with digital Chinese medicine(DCM),and proposes the extraction of syndrome elements of ophthalmic diseases from research on DCM.These elements are then quantified and organized to form a model of digital diagnosis and treatment specific to ophthalmology,which should help to achieve synergistic development of the ophthalmic syndrome differentiation system and DCM.展开更多
It is well known that Traditional Chinese Medicine(TCM)has two outstanding academic characteristics:the holistic concept comes from Huang Di Nei Jing,and the syndrome differentiation and treatment comes from Shang Han...It is well known that Traditional Chinese Medicine(TCM)has two outstanding academic characteristics:the holistic concept comes from Huang Di Nei Jing,and the syndrome differentiation and treatment comes from Shang Han Lun.These two characteristics denote the two major academic systems of TCM:one is the medical system of Huang Di Nei Jing,also named syndrome differentiation and treatment system of Zang-Fu organs and meridians,focuses on theoretical exploration,which highlights functional connection and emphasizes philosophical thinking.The treatment in this system is based on physiological functions by taking Zang-Fu organs as the main body,Qi,blood,essence,and body fluid as the auxiliary body,and the meridians and collaterals as the connection channels.The other is the syndrome differentiation and treatment system of the six meridians,which emphasizes clinical practice.It encompasses the idea that the six meridians govern various diseases,emphasizes the disease sites and divisional treatment,and pays attention to the precision and appropriateness of prescription-syndrome differentiation.These two academic systems,with mutual influences and relations,are both the essence and pearl of TCM,nevertheless,there are obvious differences between the two in clinical application,so they should be distinguished.This paper will elaborate on the connection and difference between them,and how to organically combine the two systems for better application in clinical practice of TCM.展开更多
At the start of the new year,Cao Xiucheng,Chairman of Henan No.2 Textile Machinery Co.,Ltd.,was on his way to visit clients when he kept receiving urgent calls from the Xinyang production base regarding order scheduli...At the start of the new year,Cao Xiucheng,Chairman of Henan No.2 Textile Machinery Co.,Ltd.,was on his way to visit clients when he kept receiving urgent calls from the Xinyang production base regarding order scheduling.It turned out that since the end of 2025,the company had successively secured bulk spindle orders from overseas clients in Bangladesh and other countries,coupled with continuous urgent requests for orders from domestic manufacturers.Faced with such a production peak right at the beginning of the year,Mr.Cao Xiucheng admitted,“It was truly unexpected.”展开更多
[Objectives]To characterize the expression pattern of Fibroblast growth factor 10(FGF10)during the differentiation of rat L6 myoblasts and to identify potential key transcription factors(TFs)regulating its expression ...[Objectives]To characterize the expression pattern of Fibroblast growth factor 10(FGF10)during the differentiation of rat L6 myoblasts and to identify potential key transcription factors(TFs)regulating its expression through bioinformatics approaches.[Methods]Rat L6 myoblasts were induced to differentiate by culturing them in DMEM supplemented with 2%donor horse serum(DHS).Morphological changes were observed using an inverted microscope.Cell samples were collected prior to induction(day 0)and on days 1,3,5,and 7 post-induction.The relative expression levels of FGF10 mRNA and protein at each time point were quantified using RT-qPCR and Western blot analysis,respectively.Furthermore,a 2000 bp sequence upstream of the transcription start site of the rat Fgf10 gene was extracted as the promoter region.Putative TF binding sites were predicted using four databases(TRANSFAC,JASPAR,HOCOMOCO,and CISBP),and high-confidence candidates were screened to construct a regulatory network.[Results]Morphological observations confirmed successful differentiation,as evidenced by the appearance of binucleated myotubes on day 3 and the formation of numerous thick,multinucleated myotubes by day 7.Both RT-qPCR and Western blot analysis demonstrated a significant dynamic expression pattern of FGF10.Expression levels were markedly upregulated during the early phase(days 1-3),reaching a peak on day 3(P<0.01),followed by a decline to basal levels during the late phase(days 5-7).Cross-validation across multiple databases identified 48 high-confidence TFs,among which Elf5,Tcf3,Nkx3-2,Zic2,Tcf7,and Egr1 were consistently predicted by all four databases.[Conclusions]FGF10 exhibits high expression levels during the early stage of differentiation,indicating its crucial role in the initiation of myogenesis.The six identified TFs serve as core candidate regulators of Fgf10 expression,offering novel insights into the molecular mechanisms underlying muscle development.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,w...Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,we examined the role of Pou4f3,an important transcription factor,in vestibular HC differentiation using Pou4f3^(DTR/DTR)(deficient)and Pou4f3CreER/CreER(knockout)mouse models.In Pou4f3-deficient mice,the HC number decreased,and immature HCs failed to develop type I characteristics,indicating a developmental arrest.While type II HCs differentiated normally,Pou4f3 deficiency disrupted HC bundle formation and cell polarity.Findings from knockout models further confirmed the essential role of Pou4f3 in vestibular HC subtype specification.This study underscores the critical role of Pou4f3 in determining vestibular HC subtypes and offers insights into potential strategies for restoring vestibular function through HC regeneration.展开更多
The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a d...The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a distinct NKD1^(+) subpopulation exhibiting secretory odontoblast characteristics,which was specifically induced in dental pulp stem cells(DPSCs) by Wnt3a,but not by Wnt5a or Wnt10a through single-cell transcriptomic profiling.We then found that the NKD1^(+) subpopulation was functional conservation,which were consistently identified in the odontoblast layers of developing tooth germs in both murine and miniature pig models,as well as within the apical open area in human molars.This conserved spatial distribution and co-localization with DSPP strongly indicates that NKD1^(+) cells were active dentin-secreting odontoblasts.Analysis of gene regulatory networks using SCENIC identified MSX1 as a key transcription factor regulating the specification of NKD1^(+) lineage.Mechanistically,Wnt3a orchestrates a tripartite cascade:upregulating NKD1/MSX1 expression,triggering NKD1 membrane detachment,and facilitating direct NKD1-MSX1interaction to promote MSX1 nuclear translocation.CUT&Tag analysis demonstrated MSX1 occupancy at promoters of odontogenic regulato rs,esta blishing its necessity for odontogenic gene activation.Murine pulp exposure models validated that Wnt3a-activated NKD1-MSX1 signaling significantly enhances reparative dentin formation.This study delineates an evolutionarily conserved Wnt3aNKD1-MSX1 axis that resolves stem cell heterogeneity into functional odontoblast commitment,providing both mechanistic insights into dentin-pulp regeneration and a foundation for targeted regenerative therapies.展开更多
Objective To address the dual challenges of long-tail distribution and feature sparsity in traditional Chinese medicine(TCM)syndrome differentiation within real clinical settings,we propose a data-efficient learning f...Objective To address the dual challenges of long-tail distribution and feature sparsity in traditional Chinese medicine(TCM)syndrome differentiation within real clinical settings,we propose a data-efficient learning framework enhanced by knowledge graphs.Methods We developed Agent-GNN,a three-stage decoupled learning framework,and validated it on the Traditional Chinese Medicine Syndrome Diagnosis(TCM-SD)dataset containing 54152 clinical records across 148 syndrome categories.First,we constructed a comprehensive medical knowledge graph encoding the complete TCM reasoning system.Second,we proposed a Functional Patient Profiling(FPP)method that utilizes large language models(LLMs)combined with Graph Retrieval-Augmented Generation(RAG)to extract structured symptom-etiology-pathogenesis subgraphs from medical records.Third,we employed heterogeneous graph neural networks to learn structured combination patterns explicitly.We compared our method against multiple baselines including BERT,ZY-BERT,ZY-BERT+Know,GAT,and GPT-4 Few-shot,using macro-F1 score as the primary evaluation metric.Additionally,ablation experiments were conducted to validate the contribution of each key component to model performance.Results Agent-GNN achieved an overall macro-F1 score of 72.4%,representing an 8.7 percentage points improvement over ZY-BERT+Know(63.7%),the strongest baseline among traditional methods.For long-tail syndromes with fewer than 10 samples,Agent-GNN reached a macro-F1 score of 58.6%,compared with 39.3%for ZY-BERT+Know and 41.2%for GPT-4 Few-shot,representing relative improvements of 49.2%and 42.2%,respectively.Ablation experiments confirmed that the explicit modeling of etiology-pathogenesis nodes contributed 12.4 percentage points to this enhanced long-tail syndrome performance.Conclusion This study proposes Agent-GNN,a knowledge graph-enhanced framework that effectively addresses the long-tail distribution challenge in TCM syndrome differentiation.By explicitly modeling manifestation-mechanism-essence patterns through structured knowledge graphs,our approach achieves superior performance in data-scarce scenarios while providing interpretable reasoning paths for TCM intelligent diagnosis.展开更多
Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain ...Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.展开更多
Information collaboration is crucial for optimizing resource allocation and improving diagnostic efficiency across hospital tiers through enhanced information technology capacity.To characterize the dynamic decision-m...Information collaboration is crucial for optimizing resource allocation and improving diagnostic efficiency across hospital tiers through enhanced information technology capacity.To characterize the dynamic decision-making mechanism between general hospitals(GHs)and primary healthcare centers(PHCs),a two-player differential game model was constructed to analyze the relationship between optimal investment levels and corresponding payoffs and explore how GHs can incentivize collaboration by adjusting their investment intensity and sharing PHCs’costs.The results indicate that information collaboration is a win-win strategy.Its dynamic equilibrium shows that GHs make intensive efforts in the early stage of digital construction.However,such investment decreases over time as patient information accessibility becomes limited.Under the collaboration mode,although GHs’digital investment is lower than that in the independent operation,the total system payoff significantly increases.This improvement arises because PHCs,with their locational and informational advantages,undertake major digitalization tasks,allowing GHs to focus resources on disease treatment.The introduction of collaboration incentives strengthens this performance improvement.展开更多
This paper studies an indefinite mean-field game with Markov jump parameters,where all agents'diffusion terms depend on control variables and both state and control average terms(x.^((N)),u.^((N)))are considered.O...This paper studies an indefinite mean-field game with Markov jump parameters,where all agents'diffusion terms depend on control variables and both state and control average terms(x.^((N)),u.^((N)))are considered.One notable aspect is the relaxation of the assumption regarding the positivity or non-negativity of weight matrices within costs,allowing for zero or even negative values.By virtue of mean-field methods and decomposition techniques,we have derived decentralized strategies presented by Hamiltonian systems and a new type of consistency condition system.These systems consist of fully coupled regime-switching forward-backward stochastic differential equations that do not conform to the Monotonicity condition.The well-posedness of these strategies is established by employing a relaxed compensator method with an easily verifiable Condition(RC)and the decomposition technique.Furthermore,we demonstrate that the resulting decentralized strategies achieve anϵ-Nash equilibrium in the indefinite case without any assumptions on admissible control sets using novel estimates of the disturbed state and cost function.Finally,our theoretical results are applied to resolve a class of mean-variance portfolio selection problems.We provide corresponding numerical simulation results and economic explanations.展开更多
Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we use...Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we used a single-cell RNA sequencing dataset to create a comprehensive profile of the diverse cell types in the dorsal root ganglia and spinal cord of a mid-thoracic contusion injury model in cynomolgus monkeys.Cell communication analysis indicated that specific signaling events among various dorsal root ganglia cell types occur in response to spinal cord injury.Single-cell analysis using dimensionality reduction clustering identified distinct molecular signatures for nine cell types,including macrophage subpopulations,and differential gene expression profiles between dorsal root ganglia cells and spinal cord cells following spinal cord injury.The macrophage subpopulations were categorized into 11 clusters(MC0-MC10)based on differentially expressed genes,with the top 10 genes being ABCA6,RBMS3,EBF1,LAMA4,ANTXR2,LAMA2,SOX5,FOXP2,GHR,and APOD.MC0,MC1,and MC2 constituted the predominant macrophage populations.MC4,MC6,and MC9 were nearly absent in the spinal cord,but exhibited significant increases in the dorsal root ganglia post-spinal cord injury.Notably,these subpopulations possess a strong capacity for regulating axonal regeneration.The developmental progression of dorsal root ganglia macrophages after spinal cord injury was elucidated using cell trajectory and pseudo-time analyses.Genes such as EBF1(MC6 and MC9 marker),RBMS3(MC6 and MC9 marker),and ABCA6(MC6 marker)showed high expression levels in the critical pathways of macrophage function.Through ligand-receptor pair analysis,we determined that the effects of macrophages on microglia are predominantly mediated through interaction pairs(e.g.,SPP1-CD44,LAMC1-CD44,and FN1-CD44),potentially facilitating specific cellular communications within the immune microenvironment.The single-cell RNA sequencing dataset used in this study represents the first comprehensive transcriptional analysis of the dorsal root ganglia after spinal cord injury in cynomolgus monkeys,encompassing nearly all cell types within the dorsal root ganglia region.Using this dataset,we evaluated diverse subtypes of macrophages in the post-spinal cord injury dorsal root ganglia area and examined the signaling pathways that facilitate interactions among immune response-related macrophages in the dorsal root ganglia.Findings from this study provide a theoretical basis for understanding how the immune microenvironment influences the regenerative capacity of dorsal root ganglia neurons after spinal cord injury and offer novel insights into the complex processes underlying the pathobiology of spinal cord injury.展开更多
Addressing the limitations of inadequate stochastic disturbance characterization during wind turbine degradation processes that result in constrained modeling accuracy,replacement-based maintenance practices that devi...Addressing the limitations of inadequate stochastic disturbance characterization during wind turbine degradation processes that result in constrained modeling accuracy,replacement-based maintenance practices that deviate from actual operational conditions,and static maintenance strategies that fail to adapt to accelerated deterioration trends leading to suboptimal remaining useful life utilization,this study proposes a Time-Based Incomplete Maintenance(TBIM)strategy incorporating reliability constraints through stochastic differential equations(SDE).By quantifying stochastic interference via Brownian motion terms and characterizing nonlinear degradation features through state influence rate functions,a high-precision SDE degradation model is constructed,achieving 16%residual reduction compared to conventional ordinary differential equation(ODE)methods.The introduction of age reduction factors and failure rate growth factors establishes an incomplete maintenance mechanism that transcends traditional“as-good-as-new”assumptions,with the TBIM model demonstrating an additional 8.5%residual reduction relative to baseline SDE approaches.A dynamic maintenance interval optimization model driven by dual parameters—preventive maintenance threshold R_(p) and replacement threshold R_(r)—is designed to achieve synergistic optimization of equipment reliability and maintenance economics.Experimental validation demonstrates that the optimized TBIM extends equipment lifespan by 4.4%and reducesmaintenance costs by 4.16%at R_(p)=0.80,while achieving 17.2%lifespan enhancement and 14.6%cost reduction at R_(p)=0.90.This methodology provides a solution for wind turbine preventive maintenance that integrates condition sensitivity with strategic foresight.展开更多
Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus...Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.展开更多
AIM： To investigate the association between the configurational and compositional changes of nuclear matrix and the differentiation of carcinoma cells. METHODS： Cells cultured with or without 5 × 10^-3 mmol/L o...AIM： To investigate the association between the configurational and compositional changes of nuclear matrix and the differentiation of carcinoma cells. METHODS： Cells cultured with or without 5 × 10^-3 mmol/L of hexamethylene bisacetamide （HMBA） on Nickel grids were treated by selective extraction and prepared for whole mount observation under electron microscopy. The samples were examined under transmission electron microscope. Nuclear matrix proteins were selectively extracted and subjected to subcellular proteomics study. The protein expression patterns were analyzed by PDQuest software. Spots of differentially expressed nuclear matrix proteins were excised and subjected to in situ digestion with trypsin. The peptides were analyzed by matrix-assisted laser- desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS）. Data were submitted for database searching using Mascot tool （www.matrixscience.com）. RESULTS： The nuclear matrix （NM） and intermediate filament （IF） in SMMC-7721 hepatocarcinoma cells were found relatively sparse and arranged irregularly. The nuclear lamina was non-uniform, and two kinds of filaments were not tightly connected. After induction for differentiation by HMBA, the NM-IF filaments were concentrated and distributed uniformly. The heterogeneous population of filaments, including highly branched utrathin filaments could also be seen in the regular meshwork. The connection between the two kinds of filaments and the relatively thin, condensed and sharply demarcated lamina composed of intermediate- sized filaments was relatively fastened. Meanwhile, 21 NM proteins changed remarkably during SMMC-7721 cell differentiation. Four proteins, i.e. mutant Pystl, hypothetical protein, nucleophosminl, and LBP were downregulated, whereas four other proteins, eIF6, p44 subunit, 13-tubulin, and SIN3B were upregulated with the last one, SR2/ASF found only in the differentiated SMMC-7721 cells. CONCLUSION： The induced differentiation of SMMC-7721 cells by HMBA is accompanied by the configurational changes of nuclear matrix-intermediate filament （NM-IF） system and the compositional changes of nuclear matrix protein expression. These changes may be important morphological or functional indications of the cancer cell reversion.展开更多
The relationship between paleogeographic pattern and sedimentary differentiation of evaporite-carbonate symbiotic system is examined based on logging,core and thin section data,by taking the sixth sub-member of fifth ...The relationship between paleogeographic pattern and sedimentary differentiation of evaporite-carbonate symbiotic system is examined based on logging,core and thin section data,by taking the sixth sub-member of fifth member of Ordovician Majiagou Formation(M56)in the central-eastern Ordos Basin as an example.(1)Seven sub-geomorphic units(Taolimiao west low,Taolimiao underwater high,Taolimiao east low,Hengshan high,East salt low,North slope and Southwest slope)developed in the study area.(2)The“three lows”from west to east developed dolomitic restricted lagoon,evaporite evaporative lagoon and salt evaporative lagoon sedimentary facies respectively,the"two highs"developed high-energy grain beach and microbial mound,and the north and south slopes developed dolomitic flats around land.(3)The paleogeographic pattern caused natural differentiation of replenishment seawater from the northwest Qilian sea,leading to the eccentric sedimentary differentiation of dolomite,evaporite and salt rock symbiotic system from west to east,which is different from the classic“bull's eye”and“tear drop”distribution patterns.(4)As the Middle Qilian block subducted and collided into the North China Plate,the far-end compression stress transferred,giving rise to the alternate highland and lowland in near north to south direction during the sedimentary period of M56 sub-member.(5)Taolimiao underwater high and Hengshan high developed favorable zones of microbial mounds and grain shoals in south to north strike in M56 sub-member,making them favorable exploration areas with great exploration potential in the future.展开更多
The role played by cytokines, other than interferon （IFN）-a, in the differentiation and function of dendritic cells （DCs） in systemic lupus erythematosus （SLE）, remains unclear. Serum interleukin-10 （IL-10） le...The role played by cytokines, other than interferon （IFN）-a, in the differentiation and function of dendritic cells （DCs） in systemic lupus erythematosus （SLE）, remains unclear. Serum interleukin-10 （IL-10） levels are generally elevated in SLE patients, which might modulate the differentiation of DCs. In this study, DCs were induced from monocytes either by transendothelial trafficking or by culture with granulocyte-macrophage colony-stimulating factor （GM-CSF） ＋ IL-4 ＋ tumor necrosis factor （TNF）-a. Both systems were used to investigate the effects of elevated serum IL-10 level on DC differentiation in SLE patients. The results showed that monocyte-derived DCs induced by either SLE serum or exogenous IL-10 reduced the expression of human leukocyte antigen （HLA）-DR and CD80, decreased IL-12p40 level, and increased IL-10 level, and exhibited an impaired capacity to stimulate allogenic T-cell proliferation. These results indicate that serum IL-10 may be involved in the pathogenesis of SLE by modulating the differentiation and function of DCs.展开更多
BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is i...BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.展开更多
BACKGROUND Mesenchymal stem cells are pluripotent cells that have the ability to generate cells from a cell line or in other cell types from different tissues but from the same origin.Although those cells have more li...BACKGROUND Mesenchymal stem cells are pluripotent cells that have the ability to generate cells from a cell line or in other cell types from different tissues but from the same origin.Although those cells have more limited differentiation capacity than embryonic stem cells,they are easily obtained from somatic tissue and can be grown in large quantities.This characteristic of undifferentiated stem cells differentiating into different cell lines arouses strategies in regenerative medicine for the treatment of different diseases such as neurodegenerative diseases.AIM To evaluate the cell differentiation capacity of human breastmilk stem cells for the three germ layers by a systematic review.METHODS The searched databases were PubMed,EMBASE,OVID,and COCHRANE LIBRARY,published between 2007 and 2018 in the English language.All were in vitro studies for analysis of the"cell differentiation potential"in the literature using the keywords“human breastmilk,”“stem cells,”and keywords combined with the Boolean operator“NOT”were used to exclude those articles that had the word“CANCER”and their respective synonyms,which were previously consulted according to medical subject heading terms.PRISMA 2009 guidelines were followed in this study.RESULTS A total of 315 titles and abstracts of articles were examined.From these,21 were in common with more than one database,leaving 294 articles for analysis.Of that total,five publications met the inclusion criteria.When analyzing the publications,it was demonstrated that human breastmilk stem cells have a high cellular plasticity,exhibiting the ability to generate cells of all three germ layers,endoderm,mesoderm,and ectoderm,demonstrating their stemness.Those cells expressed the genes,TRA-1-60/81,octamer-binding transcription factor 4,and NANOG,of which NANOG,a critical regulator for self-renewal and maintenance,was the most highly expressed.Those cells have the ability to differentiate in vitro into adipocytes,chondrocytes,osteocytes,oligodendrocytes,astrocytes,and neurons as well hepatocytes,β-pancreatic cells,and cardiomyocytes.CONCLUSION Although the literature has been scarce,the pluripotentiality of these cells represents great potential for tissue engineering and cellular therapy.Further studies for safe clinical translation are needed.展开更多
On the basis of the study on areal differentiation of the natural environment of oasis agriculture ecosystems in the Shiyang River Basin, this paper comparatively analyzes the natural productivities, water economic be...On the basis of the study on areal differentiation of the natural environment of oasis agriculture ecosystems in the Shiyang River Basin, this paper comparatively analyzes the natural productivities, water economic benefits, production efficiency, ecological stabilities and developmental conditions of the Wuwei Oasis agricultural ecosystem in the middle reaches of the river basin and the Minqin Oasis agricultural ecosystem in the lower reaches. Under a same management level and investment of . material and energy, primary productiveness and economic benefits of the former are higher than those of the latter. Construction directions of Wuwei and Minqin oases should be different in order to alleviate the water- use contradiction between the middle and lower reaches. The construction objective of Wuwei Oasis should be efficient irrigated farming production system and Minqin Oasis should become a mixed forestry-pastoral-farming ecosystem taking ecological protection as its major function.展开更多
文摘In traditional Chinese medicine(TCM),ophthalmic syndrome differentiation is an ophthalmology-specific method for identifying syndromes based on the“Five Orbiculi”theory.It was devised by Professor Qing-Hua PENG through an unprecedented combination of syndrome element differentiation and ophthalmic clinical practices,based on the Clinical Terminology of Chinese Medical Diagnosis and Treatment-Syndromes of the National Standards of the People's Republic of China.This approach integrates an ophthalmic syndrome differentiation system with digital Chinese medicine(DCM),and proposes the extraction of syndrome elements of ophthalmic diseases from research on DCM.These elements are then quantified and organized to form a model of digital diagnosis and treatment specific to ophthalmology,which should help to achieve synergistic development of the ophthalmic syndrome differentiation system and DCM.
基金Supported by Central Government Major Budget Adjustment Program(the Research on the Medicinal Properties of Brazilian Ginseng,Tonico,and Guarana,No.2060302)。
文摘It is well known that Traditional Chinese Medicine(TCM)has two outstanding academic characteristics:the holistic concept comes from Huang Di Nei Jing,and the syndrome differentiation and treatment comes from Shang Han Lun.These two characteristics denote the two major academic systems of TCM:one is the medical system of Huang Di Nei Jing,also named syndrome differentiation and treatment system of Zang-Fu organs and meridians,focuses on theoretical exploration,which highlights functional connection and emphasizes philosophical thinking.The treatment in this system is based on physiological functions by taking Zang-Fu organs as the main body,Qi,blood,essence,and body fluid as the auxiliary body,and the meridians and collaterals as the connection channels.The other is the syndrome differentiation and treatment system of the six meridians,which emphasizes clinical practice.It encompasses the idea that the six meridians govern various diseases,emphasizes the disease sites and divisional treatment,and pays attention to the precision and appropriateness of prescription-syndrome differentiation.These two academic systems,with mutual influences and relations,are both the essence and pearl of TCM,nevertheless,there are obvious differences between the two in clinical application,so they should be distinguished.This paper will elaborate on the connection and difference between them,and how to organically combine the two systems for better application in clinical practice of TCM.
文摘At the start of the new year,Cao Xiucheng,Chairman of Henan No.2 Textile Machinery Co.,Ltd.,was on his way to visit clients when he kept receiving urgent calls from the Xinyang production base regarding order scheduling.It turned out that since the end of 2025,the company had successively secured bulk spindle orders from overseas clients in Bangladesh and other countries,coupled with continuous urgent requests for orders from domestic manufacturers.Faced with such a production peak right at the beginning of the year,Mr.Cao Xiucheng admitted,“It was truly unexpected.”
基金Supported by Guangdong Basic and Applied Basic Research Foundation(2023A1515110973)Guangdong Provincial Young Innovative Talents Project of General Colleges and Universities(2023KQNCX089)+6 种基金Key Field Special Project of Guangdong Provincial Colleges and Universities(2025ZDZX2077)the Rural Science and Technology Commissioner Program of Guangdong Province(KTP20240673)Undergraduate Higher Education Teaching Quality and Reform Projects of Guangdong Province(Yuejiao Gao Han[2024]No.9Yuejiao Gao Han[2024]No.30)Zhaoqing Science and Technology Innovation Guidance Project(Zhaoke[2025]No.4)Scientific Research Foundation of Zhaoqing University(QN202436)College Student Innovation Training Program Project(S202510580042).
文摘[Objectives]To characterize the expression pattern of Fibroblast growth factor 10(FGF10)during the differentiation of rat L6 myoblasts and to identify potential key transcription factors(TFs)regulating its expression through bioinformatics approaches.[Methods]Rat L6 myoblasts were induced to differentiate by culturing them in DMEM supplemented with 2%donor horse serum(DHS).Morphological changes were observed using an inverted microscope.Cell samples were collected prior to induction(day 0)and on days 1,3,5,and 7 post-induction.The relative expression levels of FGF10 mRNA and protein at each time point were quantified using RT-qPCR and Western blot analysis,respectively.Furthermore,a 2000 bp sequence upstream of the transcription start site of the rat Fgf10 gene was extracted as the promoter region.Putative TF binding sites were predicted using four databases(TRANSFAC,JASPAR,HOCOMOCO,and CISBP),and high-confidence candidates were screened to construct a regulatory network.[Results]Morphological observations confirmed successful differentiation,as evidenced by the appearance of binucleated myotubes on day 3 and the formation of numerous thick,multinucleated myotubes by day 7.Both RT-qPCR and Western blot analysis demonstrated a significant dynamic expression pattern of FGF10.Expression levels were markedly upregulated during the early phase(days 1-3),reaching a peak on day 3(P<0.01),followed by a decline to basal levels during the late phase(days 5-7).Cross-validation across multiple databases identified 48 high-confidence TFs,among which Elf5,Tcf3,Nkx3-2,Zic2,Tcf7,and Egr1 were consistently predicted by all four databases.[Conclusions]FGF10 exhibits high expression levels during the early stage of differentiation,indicating its crucial role in the initiation of myogenesis.The six identified TFs serve as core candidate regulators of Fgf10 expression,offering novel insights into the molecular mechanisms underlying muscle development.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
基金supported by the National Natural Science Foundation of China(82271159,82071049,82425018,and 82101219)the STI2030-Major Projects(2022ZD0205400).
文摘Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,we examined the role of Pou4f3,an important transcription factor,in vestibular HC differentiation using Pou4f3^(DTR/DTR)(deficient)and Pou4f3CreER/CreER(knockout)mouse models.In Pou4f3-deficient mice,the HC number decreased,and immature HCs failed to develop type I characteristics,indicating a developmental arrest.While type II HCs differentiated normally,Pou4f3 deficiency disrupted HC bundle formation and cell polarity.Findings from knockout models further confirmed the essential role of Pou4f3 in vestibular HC subtype specification.This study underscores the critical role of Pou4f3 in determining vestibular HC subtypes and offers insights into potential strategies for restoring vestibular function through HC regeneration.
基金supported by the National Natural Science Foundation of China(82170951,82470961)the Beijing Natural Science Foundation (7222079)+4 种基金the Beijing Hospital Authority"Dengfeng"Talent Training Plan (DFL 20221301)the Beijing Stomatological HospitalCapital Medical University Young Scientist Program (No.YSP202401)the Laboratory for Clinical Medicine and the Central Laboratory of Capital Medical University for their technical support and fundingthe Japan China Sasakawa Medical Fellowship for their generous support and funding。
文摘The functional regeneration of the dentin-pulp complex is pivotal for tooth preservation,yet the molecular mechanisms governing odontoblast differentiation remain poorly understood.In the current study,we revealed a distinct NKD1^(+) subpopulation exhibiting secretory odontoblast characteristics,which was specifically induced in dental pulp stem cells(DPSCs) by Wnt3a,but not by Wnt5a or Wnt10a through single-cell transcriptomic profiling.We then found that the NKD1^(+) subpopulation was functional conservation,which were consistently identified in the odontoblast layers of developing tooth germs in both murine and miniature pig models,as well as within the apical open area in human molars.This conserved spatial distribution and co-localization with DSPP strongly indicates that NKD1^(+) cells were active dentin-secreting odontoblasts.Analysis of gene regulatory networks using SCENIC identified MSX1 as a key transcription factor regulating the specification of NKD1^(+) lineage.Mechanistically,Wnt3a orchestrates a tripartite cascade:upregulating NKD1/MSX1 expression,triggering NKD1 membrane detachment,and facilitating direct NKD1-MSX1interaction to promote MSX1 nuclear translocation.CUT&Tag analysis demonstrated MSX1 occupancy at promoters of odontogenic regulato rs,esta blishing its necessity for odontogenic gene activation.Murine pulp exposure models validated that Wnt3a-activated NKD1-MSX1 signaling significantly enhances reparative dentin formation.This study delineates an evolutionarily conserved Wnt3aNKD1-MSX1 axis that resolves stem cell heterogeneity into functional odontoblast commitment,providing both mechanistic insights into dentin-pulp regeneration and a foundation for targeted regenerative therapies.
基金Sichuan TCM Culture Coordinated Development Research Center Project(2023XT131)National Key Science and Technology Project of China(2023ZD0509405)National Natural Science Foundation of China(82174236).
文摘Objective To address the dual challenges of long-tail distribution and feature sparsity in traditional Chinese medicine(TCM)syndrome differentiation within real clinical settings,we propose a data-efficient learning framework enhanced by knowledge graphs.Methods We developed Agent-GNN,a three-stage decoupled learning framework,and validated it on the Traditional Chinese Medicine Syndrome Diagnosis(TCM-SD)dataset containing 54152 clinical records across 148 syndrome categories.First,we constructed a comprehensive medical knowledge graph encoding the complete TCM reasoning system.Second,we proposed a Functional Patient Profiling(FPP)method that utilizes large language models(LLMs)combined with Graph Retrieval-Augmented Generation(RAG)to extract structured symptom-etiology-pathogenesis subgraphs from medical records.Third,we employed heterogeneous graph neural networks to learn structured combination patterns explicitly.We compared our method against multiple baselines including BERT,ZY-BERT,ZY-BERT+Know,GAT,and GPT-4 Few-shot,using macro-F1 score as the primary evaluation metric.Additionally,ablation experiments were conducted to validate the contribution of each key component to model performance.Results Agent-GNN achieved an overall macro-F1 score of 72.4%,representing an 8.7 percentage points improvement over ZY-BERT+Know(63.7%),the strongest baseline among traditional methods.For long-tail syndromes with fewer than 10 samples,Agent-GNN reached a macro-F1 score of 58.6%,compared with 39.3%for ZY-BERT+Know and 41.2%for GPT-4 Few-shot,representing relative improvements of 49.2%and 42.2%,respectively.Ablation experiments confirmed that the explicit modeling of etiology-pathogenesis nodes contributed 12.4 percentage points to this enhanced long-tail syndrome performance.Conclusion This study proposes Agent-GNN,a knowledge graph-enhanced framework that effectively addresses the long-tail distribution challenge in TCM syndrome differentiation.By explicitly modeling manifestation-mechanism-essence patterns through structured knowledge graphs,our approach achieves superior performance in data-scarce scenarios while providing interpretable reasoning paths for TCM intelligent diagnosis.
文摘Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.
基金The National Natural Science Foundation of China(No.72071042).
文摘Information collaboration is crucial for optimizing resource allocation and improving diagnostic efficiency across hospital tiers through enhanced information technology capacity.To characterize the dynamic decision-making mechanism between general hospitals(GHs)and primary healthcare centers(PHCs),a two-player differential game model was constructed to analyze the relationship between optimal investment levels and corresponding payoffs and explore how GHs can incentivize collaboration by adjusting their investment intensity and sharing PHCs’costs.The results indicate that information collaboration is a win-win strategy.Its dynamic equilibrium shows that GHs make intensive efforts in the early stage of digital construction.However,such investment decreases over time as patient information accessibility becomes limited.Under the collaboration mode,although GHs’digital investment is lower than that in the independent operation,the total system payoff significantly increases.This improvement arises because PHCs,with their locational and informational advantages,undertake major digitalization tasks,allowing GHs to focus resources on disease treatment.The introduction of collaboration incentives strengthens this performance improvement.
基金supported by the National Key Research and Development Program of China(2023YFA1009200)the National Natural Science Foundation of China(12401583,12571482,12521001)+2 种基金the Taishan Scholars Climbing Program of Shandong(TSPD20210302)the Basic Research Program of Jiangsu(BK20240416)the General Program of Philosophy and Social Science Research(PSSR)of Shandong Higher Education Institutions(2024ZSMS007)。
文摘This paper studies an indefinite mean-field game with Markov jump parameters,where all agents'diffusion terms depend on control variables and both state and control average terms(x.^((N)),u.^((N)))are considered.One notable aspect is the relaxation of the assumption regarding the positivity or non-negativity of weight matrices within costs,allowing for zero or even negative values.By virtue of mean-field methods and decomposition techniques,we have derived decentralized strategies presented by Hamiltonian systems and a new type of consistency condition system.These systems consist of fully coupled regime-switching forward-backward stochastic differential equations that do not conform to the Monotonicity condition.The well-posedness of these strategies is established by employing a relaxed compensator method with an easily verifiable Condition(RC)and the decomposition technique.Furthermore,we demonstrate that the resulting decentralized strategies achieve anϵ-Nash equilibrium in the indefinite case without any assumptions on admissible control sets using novel estimates of the disturbed state and cost function.Finally,our theoretical results are applied to resolve a class of mean-variance portfolio selection problems.We provide corresponding numerical simulation results and economic explanations.
基金supported by the Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)the National Key Research andDevelopment Project of Stem Cell and Transformation Research,No.2019YFA0112100(to SF)+2 种基金Tianjin Natural Science Foundation’s Youth Project for DiverseInvestments,No.21JCQNJC01300(to BF)the National Natural Science Foundation of China(Youth Program),No.82102563(to BF)Tianjin Major Science andTechnology Special Projects and Engineering Projects,No.21ZXJBSY00080(to YR).
文摘Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we used a single-cell RNA sequencing dataset to create a comprehensive profile of the diverse cell types in the dorsal root ganglia and spinal cord of a mid-thoracic contusion injury model in cynomolgus monkeys.Cell communication analysis indicated that specific signaling events among various dorsal root ganglia cell types occur in response to spinal cord injury.Single-cell analysis using dimensionality reduction clustering identified distinct molecular signatures for nine cell types,including macrophage subpopulations,and differential gene expression profiles between dorsal root ganglia cells and spinal cord cells following spinal cord injury.The macrophage subpopulations were categorized into 11 clusters(MC0-MC10)based on differentially expressed genes,with the top 10 genes being ABCA6,RBMS3,EBF1,LAMA4,ANTXR2,LAMA2,SOX5,FOXP2,GHR,and APOD.MC0,MC1,and MC2 constituted the predominant macrophage populations.MC4,MC6,and MC9 were nearly absent in the spinal cord,but exhibited significant increases in the dorsal root ganglia post-spinal cord injury.Notably,these subpopulations possess a strong capacity for regulating axonal regeneration.The developmental progression of dorsal root ganglia macrophages after spinal cord injury was elucidated using cell trajectory and pseudo-time analyses.Genes such as EBF1(MC6 and MC9 marker),RBMS3(MC6 and MC9 marker),and ABCA6(MC6 marker)showed high expression levels in the critical pathways of macrophage function.Through ligand-receptor pair analysis,we determined that the effects of macrophages on microglia are predominantly mediated through interaction pairs(e.g.,SPP1-CD44,LAMC1-CD44,and FN1-CD44),potentially facilitating specific cellular communications within the immune microenvironment.The single-cell RNA sequencing dataset used in this study represents the first comprehensive transcriptional analysis of the dorsal root ganglia after spinal cord injury in cynomolgus monkeys,encompassing nearly all cell types within the dorsal root ganglia region.Using this dataset,we evaluated diverse subtypes of macrophages in the post-spinal cord injury dorsal root ganglia area and examined the signaling pathways that facilitate interactions among immune response-related macrophages in the dorsal root ganglia.Findings from this study provide a theoretical basis for understanding how the immune microenvironment influences the regenerative capacity of dorsal root ganglia neurons after spinal cord injury and offer novel insights into the complex processes underlying the pathobiology of spinal cord injury.
基金supported in part by the National Natural Science Foundation of China(No.52467008)Gansu Provincial Depatment of Education Youth Doctoral Suppo Project(2024QB-051).
文摘Addressing the limitations of inadequate stochastic disturbance characterization during wind turbine degradation processes that result in constrained modeling accuracy,replacement-based maintenance practices that deviate from actual operational conditions,and static maintenance strategies that fail to adapt to accelerated deterioration trends leading to suboptimal remaining useful life utilization,this study proposes a Time-Based Incomplete Maintenance(TBIM)strategy incorporating reliability constraints through stochastic differential equations(SDE).By quantifying stochastic interference via Brownian motion terms and characterizing nonlinear degradation features through state influence rate functions,a high-precision SDE degradation model is constructed,achieving 16%residual reduction compared to conventional ordinary differential equation(ODE)methods.The introduction of age reduction factors and failure rate growth factors establishes an incomplete maintenance mechanism that transcends traditional“as-good-as-new”assumptions,with the TBIM model demonstrating an additional 8.5%residual reduction relative to baseline SDE approaches.A dynamic maintenance interval optimization model driven by dual parameters—preventive maintenance threshold R_(p) and replacement threshold R_(r)—is designed to achieve synergistic optimization of equipment reliability and maintenance economics.Experimental validation demonstrates that the optimized TBIM extends equipment lifespan by 4.4%and reducesmaintenance costs by 4.16%at R_(p)=0.80,while achieving 17.2%lifespan enhancement and 14.6%cost reduction at R_(p)=0.90.This methodology provides a solution for wind turbine preventive maintenance that integrates condition sensitivity with strategic foresight.
基金supported by the Natural Science Foundation of Hubei Province of China(Grant No.2023AFB671)the National Natural Science Foundation of China(Grant Nos.82360177 and 82560182)+1 种基金the Key Project of Jiangxi Provincial Natural Science Foundation(Grant No.20224ACB206011)“Xuncheng Talents”Project in Jiujiang City,Jiangxi Province(Grant No.JJXC2023071).
文摘Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.
基金Supported by the National Natural Science Foundation of China, No. 30470877
文摘AIM： To investigate the association between the configurational and compositional changes of nuclear matrix and the differentiation of carcinoma cells. METHODS： Cells cultured with or without 5 × 10^-3 mmol/L of hexamethylene bisacetamide （HMBA） on Nickel grids were treated by selective extraction and prepared for whole mount observation under electron microscopy. The samples were examined under transmission electron microscope. Nuclear matrix proteins were selectively extracted and subjected to subcellular proteomics study. The protein expression patterns were analyzed by PDQuest software. Spots of differentially expressed nuclear matrix proteins were excised and subjected to in situ digestion with trypsin. The peptides were analyzed by matrix-assisted laser- desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS）. Data were submitted for database searching using Mascot tool （www.matrixscience.com）. RESULTS： The nuclear matrix （NM） and intermediate filament （IF） in SMMC-7721 hepatocarcinoma cells were found relatively sparse and arranged irregularly. The nuclear lamina was non-uniform, and two kinds of filaments were not tightly connected. After induction for differentiation by HMBA, the NM-IF filaments were concentrated and distributed uniformly. The heterogeneous population of filaments, including highly branched utrathin filaments could also be seen in the regular meshwork. The connection between the two kinds of filaments and the relatively thin, condensed and sharply demarcated lamina composed of intermediate- sized filaments was relatively fastened. Meanwhile, 21 NM proteins changed remarkably during SMMC-7721 cell differentiation. Four proteins, i.e. mutant Pystl, hypothetical protein, nucleophosminl, and LBP were downregulated, whereas four other proteins, eIF6, p44 subunit, 13-tubulin, and SIN3B were upregulated with the last one, SR2/ASF found only in the differentiated SMMC-7721 cells. CONCLUSION： The induced differentiation of SMMC-7721 cells by HMBA is accompanied by the configurational changes of nuclear matrix-intermediate filament （NM-IF） system and the compositional changes of nuclear matrix protein expression. These changes may be important morphological or functional indications of the cancer cell reversion.
基金Supported by the Fundamental Project of China National Petroleum Corporation(2021DJ0501).
文摘The relationship between paleogeographic pattern and sedimentary differentiation of evaporite-carbonate symbiotic system is examined based on logging,core and thin section data,by taking the sixth sub-member of fifth member of Ordovician Majiagou Formation(M56)in the central-eastern Ordos Basin as an example.(1)Seven sub-geomorphic units(Taolimiao west low,Taolimiao underwater high,Taolimiao east low,Hengshan high,East salt low,North slope and Southwest slope)developed in the study area.(2)The“three lows”from west to east developed dolomitic restricted lagoon,evaporite evaporative lagoon and salt evaporative lagoon sedimentary facies respectively,the"two highs"developed high-energy grain beach and microbial mound,and the north and south slopes developed dolomitic flats around land.(3)The paleogeographic pattern caused natural differentiation of replenishment seawater from the northwest Qilian sea,leading to the eccentric sedimentary differentiation of dolomite,evaporite and salt rock symbiotic system from west to east,which is different from the classic“bull's eye”and“tear drop”distribution patterns.(4)As the Middle Qilian block subducted and collided into the North China Plate,the far-end compression stress transferred,giving rise to the alternate highland and lowland in near north to south direction during the sedimentary period of M56 sub-member.(5)Taolimiao underwater high and Hengshan high developed favorable zones of microbial mounds and grain shoals in south to north strike in M56 sub-member,making them favorable exploration areas with great exploration potential in the future.
基金supported by grants from Science Research Foundation of Ministry of Education of China (No. 205057)Foundation of Jiangsu Province Natural Science (No. 2004148)
文摘The role played by cytokines, other than interferon （IFN）-a, in the differentiation and function of dendritic cells （DCs） in systemic lupus erythematosus （SLE）, remains unclear. Serum interleukin-10 （IL-10） levels are generally elevated in SLE patients, which might modulate the differentiation of DCs. In this study, DCs were induced from monocytes either by transendothelial trafficking or by culture with granulocyte-macrophage colony-stimulating factor （GM-CSF） ＋ IL-4 ＋ tumor necrosis factor （TNF）-a. Both systems were used to investigate the effects of elevated serum IL-10 level on DC differentiation in SLE patients. The results showed that monocyte-derived DCs induced by either SLE serum or exogenous IL-10 reduced the expression of human leukocyte antigen （HLA）-DR and CD80, decreased IL-12p40 level, and increased IL-10 level, and exhibited an impaired capacity to stimulate allogenic T-cell proliferation. These results indicate that serum IL-10 may be involved in the pathogenesis of SLE by modulating the differentiation and function of DCs.
基金Supported by National Natural Science Foundation of China,No.81771373Key Research and Development Plan of Zibo City,No.2019ZC010169 and No.2019ZC010166.
文摘BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.
基金Supported by Araucária Foundation(ParanáState-Brazil)the Coordination for the Improvement of Higher Education Personnel-Brazil(Capes),Financial code 001
文摘BACKGROUND Mesenchymal stem cells are pluripotent cells that have the ability to generate cells from a cell line or in other cell types from different tissues but from the same origin.Although those cells have more limited differentiation capacity than embryonic stem cells,they are easily obtained from somatic tissue and can be grown in large quantities.This characteristic of undifferentiated stem cells differentiating into different cell lines arouses strategies in regenerative medicine for the treatment of different diseases such as neurodegenerative diseases.AIM To evaluate the cell differentiation capacity of human breastmilk stem cells for the three germ layers by a systematic review.METHODS The searched databases were PubMed,EMBASE,OVID,and COCHRANE LIBRARY,published between 2007 and 2018 in the English language.All were in vitro studies for analysis of the"cell differentiation potential"in the literature using the keywords“human breastmilk,”“stem cells,”and keywords combined with the Boolean operator“NOT”were used to exclude those articles that had the word“CANCER”and their respective synonyms,which were previously consulted according to medical subject heading terms.PRISMA 2009 guidelines were followed in this study.RESULTS A total of 315 titles and abstracts of articles were examined.From these,21 were in common with more than one database,leaving 294 articles for analysis.Of that total,five publications met the inclusion criteria.When analyzing the publications,it was demonstrated that human breastmilk stem cells have a high cellular plasticity,exhibiting the ability to generate cells of all three germ layers,endoderm,mesoderm,and ectoderm,demonstrating their stemness.Those cells expressed the genes,TRA-1-60/81,octamer-binding transcription factor 4,and NANOG,of which NANOG,a critical regulator for self-renewal and maintenance,was the most highly expressed.Those cells have the ability to differentiate in vitro into adipocytes,chondrocytes,osteocytes,oligodendrocytes,astrocytes,and neurons as well hepatocytes,β-pancreatic cells,and cardiomyocytes.CONCLUSION Although the literature has been scarce,the pluripotentiality of these cells represents great potential for tissue engineering and cellular therapy.Further studies for safe clinical translation are needed.
文摘On the basis of the study on areal differentiation of the natural environment of oasis agriculture ecosystems in the Shiyang River Basin, this paper comparatively analyzes the natural productivities, water economic benefits, production efficiency, ecological stabilities and developmental conditions of the Wuwei Oasis agricultural ecosystem in the middle reaches of the river basin and the Minqin Oasis agricultural ecosystem in the lower reaches. Under a same management level and investment of . material and energy, primary productiveness and economic benefits of the former are higher than those of the latter. Construction directions of Wuwei and Minqin oases should be different in order to alleviate the water- use contradiction between the middle and lower reaches. The construction objective of Wuwei Oasis should be efficient irrigated farming production system and Minqin Oasis should become a mixed forestry-pastoral-farming ecosystem taking ecological protection as its major function.
