Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
This paper studies cooperative robust parallel operation of multiple actuators over an undirected communication graph.The plant is modeled as an uncertain linear system,and the actuators are linear and identical.Based...This paper studies cooperative robust parallel operation of multiple actuators over an undirected communication graph.The plant is modeled as an uncertain linear system,and the actuators are linear and identical.Based on the internal model principle,a distributed dynamic output feedback control law is proposed to achieve both robust output regulation of the closed-loop system and plant input sharing among the actuators.A practical example of five motors cooperatively driving an uncertain shaft under an external load torque is presented to show the effectiveness of the proposed control law.展开更多
Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more ...Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more effective and safer treatments.In the present study,we administered Lycium barbarum glycopeptide to a mouse model of experimental autoimmune encephalomyelitis-an animal model of multiple sclerosis-and evaluated its effects on pathogenic CD4^(+)T cell activation both in vivo and in vitro.Lycium barbarum glycopeptide significantly mitigated the clinical severity of experimental autoimmune encephalomyelitis,as demonstrated by reduced demyelination and neuroinflammation.Moreover,Lycium barbarum glycopeptide treatment decreased the infiltration of peripheral leukocytes into the central nervous system and suppressed pro-inflammatory cytokine expression.Lycium barbarum glycopeptide also modulated pathogenic CD4^(+)T cell activation by inhibiting T helper 1/T helper 17 cell differentiation while promoting regulatory T cell expansion.Notably,no side effects were observed,suggesting the long-term safety and tolerability of Lycium barbarum glycopeptide.Furthermore,RNA sequencing data indicated that Lycium barbarum glycopeptide inhibits activator protein-1,an essential regulator of T cell activation and differentiation.This finding was supported by the reversal of T helper/T helper 17 cell response suppression upon AP-1 blockade.Collectively,these results highlight the potential of Lycium barbarum glycopeptide as an innovative therapeutic agent for CD4^(+)T cell-associated autoimmune or inflammatory diseases,such as multiple sclerosis.展开更多
To conduct marine surveys,multiple unmanned surface vessels(Multi-USV)with different capabilities perform collaborative mapping in multiple designated areas.This paper proposes a task allocation algorithm based on int...To conduct marine surveys,multiple unmanned surface vessels(Multi-USV)with different capabilities perform collaborative mapping in multiple designated areas.This paper proposes a task allocation algorithm based on integer linear programming(ILP)with flow balance constraints,ensuring the fair and efficient distribution of sub-areas among USVs and maintaining strong connectivity of assigned regions.In the established gridmap,a search-based path planning algorithm is performed on the sub-areas according to the allocation scheme.It uses the greedy algorithm and the A*algorithm to achieve complete coverage of the barrier-free area and obtain an efficient trajectory of each USV.The greedy algorithm enables fast local traversal of unvisited grids,while the A*algorithm ensures navigation to escape from deadlock areas and maintains global path continuity.The comparison of task allocation results proves that the task allocation algorithm based on ILP improves the mapping efficiency and task distribution fairness.The proposed allocation method and result analysis provide a certain reference for the practical application ofMulti-USV to perform survey tasks collaboratively.展开更多
Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory v...Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.展开更多
The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were develop...The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were developed to effectively combat drug-resistant bacteria by synergistically integrating the triple strategies of oxidative damage,cuproptosis-like death and disruption of cell wall synthesis.Density functional theory revealed that each Cu center coordinated with three sulfur ligands,enhancing the adsorption of H_(2)O_(2),which reduced the activation energy of the key step by 17%,thereby improving peroxidase-like(PODlike)activity.The generation of reactive oxygen species in combination with CuSAs/MoS_(2) glutathione peroxidase-like(GSH-Px-like)for glutathione scavenging resulted in an imbalance in redox homeostasis within bacteria.CuSAs/MoS_(2),which act as nanopioneers,drive oxidative stress to initiate the process of cuproptosis-like death,leading to abnormal aggregation of lipoylated proteins and inactivation of iron-sulfur cluster proteins.Moreover,CuSAs/MoS_(2) inhibited the biosynthesis of the peptidoglycan synthesis precursors D-glutamate and m-diaminopimelic acid and disrupted the peptidoglycan cross-linking process mediated by penicillin-binding proteins,effectively blocking the compensatory cell wall remodeling pathway ofβ-lactam-resistant bacteria.Overall,CuSAs/MoS_(2) with multiple functions can not only efficiently kill bacteria but also decelerate the development of bacterial resistance to combat drug-resistant bacterial infections.展开更多
Formation control of multiple spacecraft has attracted extensive research attention.However,achieving reliable performance under sensor failures remains a significant challenge.This paper develops an integrated framew...Formation control of multiple spacecraft has attracted extensive research attention.However,achieving reliable performance under sensor failures remains a significant challenge.This paper develops an integrated framework that jointly designs distributed observers and local controllers to ensure robust formation control in the presence of external disturbances and sensor malfunctions.Treating the spacecraft formation as a single interconnected system,each spacecraft constructs a distributed observer that estimates the overall system state by incorporating both its own measurements and the predicted control information shared among the spacecraft.Based on the observer estimates,a local control law is synthesized to maintain the desired formation.Rigorous theoretical analysis and numerical simulations demonstrate that the proposed integrated approach effectively guarantees formation stability and resilience against sensor failures and disturbances.展开更多
Governance debates gained strong momentum in Africa in early December 2025 as the China-Kenya Readers Forum on Xi Jinping:The Governance of China convened in Nairobi on 1 December 2025,followed by a promotional event ...Governance debates gained strong momentum in Africa in early December 2025 as the China-Kenya Readers Forum on Xi Jinping:The Governance of China convened in Nairobi on 1 December 2025,followed by a promotional event for the English edition of the book’s fifth volume on 3 December 2025 in Johannesburg,South Africa.展开更多
Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains uncle...Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.展开更多
Educational cooperation,as the cornerstone and vanguard of people-to-people exchanges and practical cooperation between China and Africa,holds irreplaceable strategic significance for enhancing the quality of Africa&#...Educational cooperation,as the cornerstone and vanguard of people-to-people exchanges and practical cooperation between China and Africa,holds irreplaceable strategic significance for enhancing the quality of Africa's human capital and accelerating its structural transformation and modernization process.This paper employs“demand–supply–adaptation”as its core analytical framework and aims to systematically explore how the educational cooperation between China and Africa can serve Africa's goal of modernization more precisely and effectively.First,through reviewing and analyzing the domestic and international research literature,this paper clarifies the focus,paradigms,and shortcomings of existing research,identifying the knowledge contribution of this study.Second,utilizing detailed macro-level data,case studies,and comparative research methods,it comprehensively presents the multidimensional status,structural characteristics,and development trends of China–Africa educational cooperation in areas such as student exchanges,cooperative education,vocational and technical training,language and cultural exchange,and emerging digital education.This paper also deeply analyzes the pressing and specific demands placed on the education system by Africa's modernization development across key dimensions like economic diversification,industrialization,agricultural modernization,social governance upgrading,and digital transformation.Third,based on the cooperative principle of“Africa's needs and China's strengths,”this paper innovatively proposes systematic countermeasures and suggestions for constructing new,multi-level,high-quality,sustainable,and future-oriented pathways for China–Africa educational cooperation:(a)promoting the strategic focus of cooperation to extend from“hard infrastructure”support to empowering“soft infrastructure”;(b)deepening the integration of industry and education and school–enterprise collaboration to precisely align with Africa's industrial development needs;vigorously developing digital education and jointly building a smart education ecosystem to help Africa bridge the digital divide;(c)improving an evidence-based,third-party evaluation system for cooperative effectiveness and a full-process quality assurance system;and(d)promoting the collaborative participation of multiple actors including governments,schools,enterprises,think tanks,and social organizations to build a new cooperative pattern of coconstruction,co-governance,and shared benefits.展开更多
BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning ofte...BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.展开更多
AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patie...AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.展开更多
This narrative review examines recent advances in salivary biomarkers for oral squamous cell carcinoma(OSCC),a major subtype of oral cancer with persistently low five-year survival rates due to delayed diagnosis.Saliv...This narrative review examines recent advances in salivary biomarkers for oral squamous cell carcinoma(OSCC),a major subtype of oral cancer with persistently low five-year survival rates due to delayed diagnosis.Saliva has emerged as a noninvasive diagnostic medium capable of reflecting both local tumor activity and systemic physiological changes.Various salivary biomarkers,including microRNAs,cytokines,proteins,metabolites,and exosomes,have been linked to oncogenic signaling pathways involved in tumor progression,immune modulation,and therapeutic resistance.Advances in quantitative polymerase chain reaction,mass spectrometry,and next-generation sequencing have enabled comprehensive biomarker profiling,while point-of-care detection systems and saliva-based omics platforms are accelerating clinical translation.Remaining challenges include variability in salivary composition,lack of standardized collection protocols,and insufficient validation across large patient cohorts.This review highlights the mechanistic relevance,diagnostic potential,and translational challenges of salivary biomarkers in OSCC.展开更多
From lecture halls in Beijing to villages in the mountains of southwest China,a group of young rural innovators from Global South countries recently embarked on a journey that connected policy thinking,technological p...From lecture halls in Beijing to villages in the mountains of southwest China,a group of young rural innovators from Global South countries recently embarked on a journey that connected policy thinking,technological practice and lived rural experience.展开更多
Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in m...Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in mitigating intrahepatic cholestasis,the precise mechanisms underlying its therapeutic effects remain inadequately understood.This study aims to comprehensively investigate the pharmacological mechanisms underlying the therapeutic effects of ZZBPD in cholestatic liver injury(CLI).Methods:Firstly,we evaluated the hepatoprotective effects of ZZBPD on mice with CLI induced byα-naphthylisothiocyanate(ANIT),by measuring biochemical markers,inflammatory factors,and bile acid levels.Subsequently,we employed network pharmacology and single-cell RNA sequencing(scRNA-seq)to identify key targets and potential signaling pathways for the prevention and treatment of CLI.Finally,we further validated the mechanism of action of ZZBPD on these key targets through molecular docking,western blotting,and immunofluorescence techniques.Results:ZZBPD notably improved serum liver function,reduced hepatic inflammation,and restored bile acid balance.Through network pharmacology and scRNA-seq analysis,48 core targets were identified,including TNF,IL-6,and NFKB1,all of which are linked to the IL-17 and NF-κB signaling pathways,as shown by KEGG enrichment analysis.Molecular docking further confirmed stable interactions between ZZBPD’s key active components and molecules such as IL-6,IL-17,and NF-κB.Additionally,western blotting and immunofluorescence validated the downregulation of IL-17 and NF-κB protein expression in liver tissue.Conclusion:ZZBPD effectively treats CLI by activating pathways related to the bile acid receptor FXR,while also modulating the IL-17/NF-κB signaling pathway.This dual action enhances bile secretion and alleviates liver inflammation.These findings offer important insights into the pharmacological mechanisms of ZZBPD and underscore its potential as a promising therapeutic for CLI.展开更多
Carbon dioxide(CO_(2))is the main greenhouse gas(GHG)released by human activities.The substitution of fossil resources by biomass as a bio-renewable resource,has significant potential to reduce GHG emissions.The appro...Carbon dioxide(CO_(2))is the main greenhouse gas(GHG)released by human activities.The substitution of fossil resources by biomass as a bio-renewable resource,has significant potential to reduce GHG emissions.The approach to biomass,as the only true full-scale alternative to fossil resources,is progressing rapidly.Converting biomass into furanic compounds,as versatile platform chemicals for synthesizing a wide range of bio-based products is the cornerstone of sustainable technologies.The extensive body of this review combines the biomass valorization to furanic compounds by CO_(2)utilization and furanic compounds conversion by CO_(2)fixation.These processes can be strategically applied through both‘thermochemical’and‘electrochemical’pathways,by utilizing CO_(2)from the atmosphere or industrial emission point and returning it to the natural carbon cycle.In the thermochemical pathway CO_(2)acts as a carbon source(carboxylation and polymerization)or active reaction assistant in the biomass conversion(CO_(2)-assisted conversion),without altering its oxidation state,facilitating the synthesis of valuable products and polymers.Conversely,in the electrochemical pathway,CO_(2)can be used as a carbon source(electrocarboxylation)to give the corresponding carboxylic acid,or it can undergo reduction,yielding methanol,carbon monoxide(CO),formic acid,and analogous compounds,while on the other side,furanic compounds undergo oxidation yielding high-value-added chemicals.Finally,potential future research directions are suggested to promote CO_(2)utilization and fixation in the valorization of biomass-derived furanic compounds,and challenges facing further research are highlighted.展开更多
To explore the effect of multiple pathway intervention in acute cerebral ischemia injury, we prepared a medicine formula （formula 2） consisting of ginsenosides, pueraria flavonoids, ophiopogonis and borneol as a too...To explore the effect of multiple pathway intervention in acute cerebral ischemia injury, we prepared a medicine formula （formula 2） consisting of ginsenosides, pueraria flavonoids, ophiopogonis and borneol as a tool medicine. The effects of formula 2 and its components on PC12 cell viability and potential pathway were investigated, and the influence of this formula on venous thrombosis and platelet aggregation was also assessed, then the effect of formula 2 on middle cerebral artery occlusion （MCAO） reperfusion was observed in rats. Formula 2 markedly enhanced the cell viability, which was stronger than that of each individual component. Formula 2 significantly inhibited the NO production in PC12 cells induced by H202, and this effect was also stronger than that of each individual component. Moreover, formula 2 enhanced the SOD activity, and the effect was stronger than that of ginsenosides. In addition, formula 2 reduced the MDA content, and this effect was stronger than that of ophiopogonins. In vivo, formula 2 showed potent inhibitory effects on platelet aggregation and venous thrombosis. Furthermore, formula 2 （single dose, s.c.） significantly reduced the infarct volume and neurobehavioral scores in MCAO reperfusion rats. Take together, our results suggests that formula 2 has powerful ability of inhibiting the ischemia/reperfusion injury, and this effect might be attributed to its simultaneous intervention in the cascade reaction of neuronal injury via multiple pathways contributed by multiple components during cerebral ischemia/reperfusion.展开更多
BACKGROUND In traditional Chinese medicine(TCM),frankincense and myrrh are the main components of the antitumor drug Xihuang Pill.These compounds show anticancer activity in other biological systems.However,whether fr...BACKGROUND In traditional Chinese medicine(TCM),frankincense and myrrh are the main components of the antitumor drug Xihuang Pill.These compounds show anticancer activity in other biological systems.However,whether frankincense and/or myrrh can inhibit the occurrence of hepatocellular carcinoma(HCC)is unknown,and the potential molecular mechanism(s)has not yet been determined.AIM To predict and determine latent anti-HCC therapeutic targets and molecular mechanisms of frankincense and myrrh in vivo.METHODS In the present study,which was based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(http://tcmspw.com/tcmsp.php),Universal Protein database(http://www.uniprot.org),GeneCards:The Human Gene Database(http://www.genecards.org/)and Comparative Toxicogenomics Database(http://www.ctdbase.org/),the efficacy of and mechanism by which frankincense and myrrh act as anti-HCC compounds were predicted.The core prediction targets were screened by molecular docking.In vivo,SMMC-7721 human liver cancer cells were transplanted as xenografts into nude mice to establish a subcutaneous tumor model,and two doses of frankincense plus myrrh or one dose of an EGFR inhibitor was administered to these mice continuously for 14 d.The tumors were collected and evaluated:the tumor volume and growth rate were gauged to evaluate tumor growth;hematoxylineosin staining was performed to estimate histopathological changes;immunofluorescence(IF)was performed to detect the expression of CD31,α-SMA and collagen IV;transmission electron microscopy(TEM)was conducted to observe the morphological structure of vascular cells;enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of secreted HIF-1αand TNF-α;reverse transcription-polymerase chain reaction(RT-qPCR)was performed to measure the mRNA expression of HIF-1α,TNF-α,VEGF and MMP-9;and Western blot(WB)was performed to determine the levels of proteins expressed in the EGFR-mediated PI3K/Akt and MAPK signaling pathways.RESULTS The results of the network pharmacology analysis showed that there were 35 active components in the frankincense and myrrh extracts targeting 151 key targets.The molecular docking analysis showed that both boswellic acid and stigmasterol showed strong affinity for the targets,with the greatest affinity for EGFR.Frankincense and myrrh treatment may play a role in the treatment of HCC by regulating hypoxia responses and vascular system-related pathological processes,such as cytokine-receptor binding,and pathways,such as those involving serine/threonine protein kinase complexes and MAPK,HIF-1 and ErbB signaling cascades.The animal experiment results were verified.First,we found that,through frankincense and/or myrrh treatment,the volume of subcutaneously transplanted HCC tumors was significantly reduced,and the pathological morphology was attenuated.Then,IF and TEM showed that frankincense and/or myrrh treatment reduced CD31 and collagen IV expression,increased the coverage of perivascular cells,tightened the connection between cells,and improved the shape of blood vessels.In addition,ELISA,RT-qPCR and WB analyses showed that frankincense and/or myrrh treatment inhibited the levels of hypoxia-inducible factors,inflammatory factors and angiogenesis-related factors,namely,HIF-1α,TNF-α,VEGF and MMP-9.Furthermore,mechanistic experiments illustrated that the effect of frankincense plus myrrh treatment was similar to that of an EGFR inhibitor with regard to controlling EGFR activation,thereby inhibiting the phosphorylation activity of its downstream targets:the PI3K/Akt and MAPK(ERK,p38 and JNK)pathways.CONCLUSION In summary,frankincense and myrrh treatment targets tumor blood vessels to exert anti-HCC effects via EGFR-activated PI3K/Akt and MAPK signaling pathways,highlighting the potential of this dual TCM compound as an anti-HCC candidate.展开更多
Metformin,an inexpensive and well-tolerated oral agent commonly used in the first-line treatment of type 2 diabetes,has become the focus of intense research as a candidate anticancer agent.Here,we discuss the potentia...Metformin,an inexpensive and well-tolerated oral agent commonly used in the first-line treatment of type 2 diabetes,has become the focus of intense research as a candidate anticancer agent.Here,we discuss the potential of metformin in cancer therapeutics,particularly its functions in multiple signaling pathways,including AMP-activated protein kinase,mammalian target of rapamycin,insulin-like growth factor,c-Jun N-terminal kinase/mitogen-activated protein kinase(p38 MARK),human epidermal growth factor receptor-2,and nuclear factor kappaB pathways.In addition,cutting-edge targeting of cancer stem cells by metformin is summarized.展开更多
Considering the great potential of natural products as anticancer agents, the present study was designed to explore the molecular mechanisms responsible for anticancer activities of Mesua ferrea stem bark extract agai...Considering the great potential of natural products as anticancer agents, the present study was designed to explore the molecular mechanisms responsible for anticancer activities of Mesua ferrea stem bark extract against human colorectal carcinoma. Based on MTT assay results, bioactive sub-fraction(SF-3) was selected for further studies using HCT 116 cells. Repeated column chromatography resulted in isolation of less active α-amyrin from SF-3, which was identified and characterized by GC-MS and HPLC methods. α-amyrin and betulinic acid contents of SF-3 were measured by HPLC methods. Fluorescent assays revealed characteristic apoptotic features, including cell shrinkage, nuclear condensation, and marked decrease in mitochondrial membrane potential in SF-3 treated cells. In addition, increased levels of caspases-9 and-3/7 levels were also observed in SF-3 treated cells. SF-3 showed promising antimetastatic properties in multiple in vitro assays. Multi-pathway analysis revealed significant down-regulation of WNT, HIF-1α, and EGFR with simultaneous up-regulation of p53, Myc/Max, and TGF-β signalling pathways in SF-3 treated cells. In addition, promising growth inhibitory effects were observed in SF-3 treated HCT 116 tumour spheroids, which give a hint about in vivo antitumor efficacy of SF-3 phytoconstituents. In conclusion, these results demonstrated that anticancer effects of SF-3 towards colon cancer are through modulation of multiple molecular pathways.展开更多
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
基金Supported by the Shenzhen Key Laboratory of Control Theory and Intelligent Systems (ZDSYS20220330161800001)the National Natural Science Foundation of China (62303207)the Guangdong Basic and Applied Basic Research Foundation (2024A1515010725)。
文摘This paper studies cooperative robust parallel operation of multiple actuators over an undirected communication graph.The plant is modeled as an uncertain linear system,and the actuators are linear and identical.Based on the internal model principle,a distributed dynamic output feedback control law is proposed to achieve both robust output regulation of the closed-loop system and plant input sharing among the actuators.A practical example of five motors cooperatively driving an uncertain shaft under an external load torque is presented to show the effectiveness of the proposed control law.
基金supported by the National Natural Science Foundational of China,Nos.U24A20692(to CJZ),82371355(to CJZ),and 82101414(to MH)National NaturalScience Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)+5 种基金Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovationand Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’sHospital,No.30420230005Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(toCJZ)Sichuan Science and Technology Support Project,No.2023YFS0212(to BH)Project of Sichuan Provincial Health Commission,No.19PJ265(to LD).
文摘Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more effective and safer treatments.In the present study,we administered Lycium barbarum glycopeptide to a mouse model of experimental autoimmune encephalomyelitis-an animal model of multiple sclerosis-and evaluated its effects on pathogenic CD4^(+)T cell activation both in vivo and in vitro.Lycium barbarum glycopeptide significantly mitigated the clinical severity of experimental autoimmune encephalomyelitis,as demonstrated by reduced demyelination and neuroinflammation.Moreover,Lycium barbarum glycopeptide treatment decreased the infiltration of peripheral leukocytes into the central nervous system and suppressed pro-inflammatory cytokine expression.Lycium barbarum glycopeptide also modulated pathogenic CD4^(+)T cell activation by inhibiting T helper 1/T helper 17 cell differentiation while promoting regulatory T cell expansion.Notably,no side effects were observed,suggesting the long-term safety and tolerability of Lycium barbarum glycopeptide.Furthermore,RNA sequencing data indicated that Lycium barbarum glycopeptide inhibits activator protein-1,an essential regulator of T cell activation and differentiation.This finding was supported by the reversal of T helper/T helper 17 cell response suppression upon AP-1 blockade.Collectively,these results highlight the potential of Lycium barbarum glycopeptide as an innovative therapeutic agent for CD4^(+)T cell-associated autoimmune or inflammatory diseases,such as multiple sclerosis.
基金supported in part by the International Science and Technology Project of Guangzhou Development District under Grant 2023GH08the Science and Technology Development Fund,MSAR,under Grants 0029/2022/AGJ and 0029/2023/RIA1the Program of Guangdong under Grant 2023A0505020003.
文摘To conduct marine surveys,multiple unmanned surface vessels(Multi-USV)with different capabilities perform collaborative mapping in multiple designated areas.This paper proposes a task allocation algorithm based on integer linear programming(ILP)with flow balance constraints,ensuring the fair and efficient distribution of sub-areas among USVs and maintaining strong connectivity of assigned regions.In the established gridmap,a search-based path planning algorithm is performed on the sub-areas according to the allocation scheme.It uses the greedy algorithm and the A*algorithm to achieve complete coverage of the barrier-free area and obtain an efficient trajectory of each USV.The greedy algorithm enables fast local traversal of unvisited grids,while the A*algorithm ensures navigation to escape from deadlock areas and maintains global path continuity.The comparison of task allocation results proves that the task allocation algorithm based on ILP improves the mapping efficiency and task distribution fairness.The proposed allocation method and result analysis provide a certain reference for the practical application ofMulti-USV to perform survey tasks collaboratively.
文摘Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.
基金supported by the National Natural Science Foundation of China(82372552)the Excellent Youth of Natural Science Research Projects in Anhui Province Universities(2023AH030060)+1 种基金Anhui Provincial Natural Science Foundation(2408085Y016)Anhui Province Excellent Research and Innovation Team Project(2024AH010013)。
文摘The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were developed to effectively combat drug-resistant bacteria by synergistically integrating the triple strategies of oxidative damage,cuproptosis-like death and disruption of cell wall synthesis.Density functional theory revealed that each Cu center coordinated with three sulfur ligands,enhancing the adsorption of H_(2)O_(2),which reduced the activation energy of the key step by 17%,thereby improving peroxidase-like(PODlike)activity.The generation of reactive oxygen species in combination with CuSAs/MoS_(2) glutathione peroxidase-like(GSH-Px-like)for glutathione scavenging resulted in an imbalance in redox homeostasis within bacteria.CuSAs/MoS_(2),which act as nanopioneers,drive oxidative stress to initiate the process of cuproptosis-like death,leading to abnormal aggregation of lipoylated proteins and inactivation of iron-sulfur cluster proteins.Moreover,CuSAs/MoS_(2) inhibited the biosynthesis of the peptidoglycan synthesis precursors D-glutamate and m-diaminopimelic acid and disrupted the peptidoglycan cross-linking process mediated by penicillin-binding proteins,effectively blocking the compensatory cell wall remodeling pathway ofβ-lactam-resistant bacteria.Overall,CuSAs/MoS_(2) with multiple functions can not only efficiently kill bacteria but also decelerate the development of bacterial resistance to combat drug-resistant bacterial infections.
基金supported by the National Natural Science Foundation of China(62088101,62522307,62273045,U2341213)Beijing Nova Program(20230484481)。
文摘Formation control of multiple spacecraft has attracted extensive research attention.However,achieving reliable performance under sensor failures remains a significant challenge.This paper develops an integrated framework that jointly designs distributed observers and local controllers to ensure robust formation control in the presence of external disturbances and sensor malfunctions.Treating the spacecraft formation as a single interconnected system,each spacecraft constructs a distributed observer that estimates the overall system state by incorporating both its own measurements and the predicted control information shared among the spacecraft.Based on the observer estimates,a local control law is synthesized to maintain the desired formation.Rigorous theoretical analysis and numerical simulations demonstrate that the proposed integrated approach effectively guarantees formation stability and resilience against sensor failures and disturbances.
文摘Governance debates gained strong momentum in Africa in early December 2025 as the China-Kenya Readers Forum on Xi Jinping:The Governance of China convened in Nairobi on 1 December 2025,followed by a promotional event for the English edition of the book’s fifth volume on 3 December 2025 in Johannesburg,South Africa.
基金supported by the National Natural Science Foundation of China (32072936 and 32273080)。
文摘Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.
文摘Educational cooperation,as the cornerstone and vanguard of people-to-people exchanges and practical cooperation between China and Africa,holds irreplaceable strategic significance for enhancing the quality of Africa's human capital and accelerating its structural transformation and modernization process.This paper employs“demand–supply–adaptation”as its core analytical framework and aims to systematically explore how the educational cooperation between China and Africa can serve Africa's goal of modernization more precisely and effectively.First,through reviewing and analyzing the domestic and international research literature,this paper clarifies the focus,paradigms,and shortcomings of existing research,identifying the knowledge contribution of this study.Second,utilizing detailed macro-level data,case studies,and comparative research methods,it comprehensively presents the multidimensional status,structural characteristics,and development trends of China–Africa educational cooperation in areas such as student exchanges,cooperative education,vocational and technical training,language and cultural exchange,and emerging digital education.This paper also deeply analyzes the pressing and specific demands placed on the education system by Africa's modernization development across key dimensions like economic diversification,industrialization,agricultural modernization,social governance upgrading,and digital transformation.Third,based on the cooperative principle of“Africa's needs and China's strengths,”this paper innovatively proposes systematic countermeasures and suggestions for constructing new,multi-level,high-quality,sustainable,and future-oriented pathways for China–Africa educational cooperation:(a)promoting the strategic focus of cooperation to extend from“hard infrastructure”support to empowering“soft infrastructure”;(b)deepening the integration of industry and education and school–enterprise collaboration to precisely align with Africa's industrial development needs;vigorously developing digital education and jointly building a smart education ecosystem to help Africa bridge the digital divide;(c)improving an evidence-based,third-party evaluation system for cooperative effectiveness and a full-process quality assurance system;and(d)promoting the collaborative participation of multiple actors including governments,schools,enterprises,think tanks,and social organizations to build a new cooperative pattern of coconstruction,co-governance,and shared benefits.
基金Supported by Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2023MSXM060.
文摘BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.
文摘AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.
基金supported by the College of Oral Medicine,Taipei Medical University,Taipei,Taiwan(Grant No.TMUCOM202502)supported by Taipei Medical University Hospital,Taipei,Taiwan(Grant No.114TMUH-NE-05).
文摘This narrative review examines recent advances in salivary biomarkers for oral squamous cell carcinoma(OSCC),a major subtype of oral cancer with persistently low five-year survival rates due to delayed diagnosis.Saliva has emerged as a noninvasive diagnostic medium capable of reflecting both local tumor activity and systemic physiological changes.Various salivary biomarkers,including microRNAs,cytokines,proteins,metabolites,and exosomes,have been linked to oncogenic signaling pathways involved in tumor progression,immune modulation,and therapeutic resistance.Advances in quantitative polymerase chain reaction,mass spectrometry,and next-generation sequencing have enabled comprehensive biomarker profiling,while point-of-care detection systems and saliva-based omics platforms are accelerating clinical translation.Remaining challenges include variability in salivary composition,lack of standardized collection protocols,and insufficient validation across large patient cohorts.This review highlights the mechanistic relevance,diagnostic potential,and translational challenges of salivary biomarkers in OSCC.
文摘From lecture halls in Beijing to villages in the mountains of southwest China,a group of young rural innovators from Global South countries recently embarked on a journey that connected policy thinking,technological practice and lived rural experience.
基金supported by the National Science Foundation of China(No.82405004,82474253)the Natural Science Foundation postdoctoral project of Chongqing(CSTB2022NSCQ-BHX0709)+2 种基金Chongqing Wanzhou District doctoral“through train”scientific research project(wzstc-20220124)Natural Science Foundation of Chongqing,China(No.Cstc2021jcyj-msxmX0996)Chongqing Wanzhou District Science and Health Joint Medical Research Project(wzstc-kw2023032)。
文摘Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in mitigating intrahepatic cholestasis,the precise mechanisms underlying its therapeutic effects remain inadequately understood.This study aims to comprehensively investigate the pharmacological mechanisms underlying the therapeutic effects of ZZBPD in cholestatic liver injury(CLI).Methods:Firstly,we evaluated the hepatoprotective effects of ZZBPD on mice with CLI induced byα-naphthylisothiocyanate(ANIT),by measuring biochemical markers,inflammatory factors,and bile acid levels.Subsequently,we employed network pharmacology and single-cell RNA sequencing(scRNA-seq)to identify key targets and potential signaling pathways for the prevention and treatment of CLI.Finally,we further validated the mechanism of action of ZZBPD on these key targets through molecular docking,western blotting,and immunofluorescence techniques.Results:ZZBPD notably improved serum liver function,reduced hepatic inflammation,and restored bile acid balance.Through network pharmacology and scRNA-seq analysis,48 core targets were identified,including TNF,IL-6,and NFKB1,all of which are linked to the IL-17 and NF-κB signaling pathways,as shown by KEGG enrichment analysis.Molecular docking further confirmed stable interactions between ZZBPD’s key active components and molecules such as IL-6,IL-17,and NF-κB.Additionally,western blotting and immunofluorescence validated the downregulation of IL-17 and NF-κB protein expression in liver tissue.Conclusion:ZZBPD effectively treats CLI by activating pathways related to the bile acid receptor FXR,while also modulating the IL-17/NF-κB signaling pathway.This dual action enhances bile secretion and alleviates liver inflammation.These findings offer important insights into the pharmacological mechanisms of ZZBPD and underscore its potential as a promising therapeutic for CLI.
基金the National Key R&D Program of China(No.2021YFC2101604)National Natural Science Foundation of China(Nos.U23A20123,22278339)+1 种基金Fujian Provincial Key Science and Technology Program of China(No.2022YZ037013)Xiamen University for the financial support.
文摘Carbon dioxide(CO_(2))is the main greenhouse gas(GHG)released by human activities.The substitution of fossil resources by biomass as a bio-renewable resource,has significant potential to reduce GHG emissions.The approach to biomass,as the only true full-scale alternative to fossil resources,is progressing rapidly.Converting biomass into furanic compounds,as versatile platform chemicals for synthesizing a wide range of bio-based products is the cornerstone of sustainable technologies.The extensive body of this review combines the biomass valorization to furanic compounds by CO_(2)utilization and furanic compounds conversion by CO_(2)fixation.These processes can be strategically applied through both‘thermochemical’and‘electrochemical’pathways,by utilizing CO_(2)from the atmosphere or industrial emission point and returning it to the natural carbon cycle.In the thermochemical pathway CO_(2)acts as a carbon source(carboxylation and polymerization)or active reaction assistant in the biomass conversion(CO_(2)-assisted conversion),without altering its oxidation state,facilitating the synthesis of valuable products and polymers.Conversely,in the electrochemical pathway,CO_(2)can be used as a carbon source(electrocarboxylation)to give the corresponding carboxylic acid,or it can undergo reduction,yielding methanol,carbon monoxide(CO),formic acid,and analogous compounds,while on the other side,furanic compounds undergo oxidation yielding high-value-added chemicals.Finally,potential future research directions are suggested to promote CO_(2)utilization and fixation in the valorization of biomass-derived furanic compounds,and challenges facing further research are highlighted.
基金National Natural Science Foundation of China(Grant No.81302763)Beijing Natural Science Foundation(Grant No.7144218)
文摘To explore the effect of multiple pathway intervention in acute cerebral ischemia injury, we prepared a medicine formula （formula 2） consisting of ginsenosides, pueraria flavonoids, ophiopogonis and borneol as a tool medicine. The effects of formula 2 and its components on PC12 cell viability and potential pathway were investigated, and the influence of this formula on venous thrombosis and platelet aggregation was also assessed, then the effect of formula 2 on middle cerebral artery occlusion （MCAO） reperfusion was observed in rats. Formula 2 markedly enhanced the cell viability, which was stronger than that of each individual component. Formula 2 significantly inhibited the NO production in PC12 cells induced by H202, and this effect was also stronger than that of each individual component. Moreover, formula 2 enhanced the SOD activity, and the effect was stronger than that of ginsenosides. In addition, formula 2 reduced the MDA content, and this effect was stronger than that of ophiopogonins. In vivo, formula 2 showed potent inhibitory effects on platelet aggregation and venous thrombosis. Furthermore, formula 2 （single dose, s.c.） significantly reduced the infarct volume and neurobehavioral scores in MCAO reperfusion rats. Take together, our results suggests that formula 2 has powerful ability of inhibiting the ischemia/reperfusion injury, and this effect might be attributed to its simultaneous intervention in the cascade reaction of neuronal injury via multiple pathways contributed by multiple components during cerebral ischemia/reperfusion.
基金the National Natural Science Foundation of China,No.U20A20408(Major Program)and No.82074450(General Program)Natural Science Foundation of Hunan Province,No.2020JJ4066+2 种基金Hunan Province Research and innovation projects for Postgraduates,No.CX20190541Hunan Province"domestic firstclass cultivation discipline"Integrated Traditional Chinese and Western medicine open fund project,No.2018ZXYJH03Hunan University Undergraduate Research Learning and Innovative Experiment Project,No.201609030114.
文摘BACKGROUND In traditional Chinese medicine(TCM),frankincense and myrrh are the main components of the antitumor drug Xihuang Pill.These compounds show anticancer activity in other biological systems.However,whether frankincense and/or myrrh can inhibit the occurrence of hepatocellular carcinoma(HCC)is unknown,and the potential molecular mechanism(s)has not yet been determined.AIM To predict and determine latent anti-HCC therapeutic targets and molecular mechanisms of frankincense and myrrh in vivo.METHODS In the present study,which was based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(http://tcmspw.com/tcmsp.php),Universal Protein database(http://www.uniprot.org),GeneCards:The Human Gene Database(http://www.genecards.org/)and Comparative Toxicogenomics Database(http://www.ctdbase.org/),the efficacy of and mechanism by which frankincense and myrrh act as anti-HCC compounds were predicted.The core prediction targets were screened by molecular docking.In vivo,SMMC-7721 human liver cancer cells were transplanted as xenografts into nude mice to establish a subcutaneous tumor model,and two doses of frankincense plus myrrh or one dose of an EGFR inhibitor was administered to these mice continuously for 14 d.The tumors were collected and evaluated:the tumor volume and growth rate were gauged to evaluate tumor growth;hematoxylineosin staining was performed to estimate histopathological changes;immunofluorescence(IF)was performed to detect the expression of CD31,α-SMA and collagen IV;transmission electron microscopy(TEM)was conducted to observe the morphological structure of vascular cells;enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of secreted HIF-1αand TNF-α;reverse transcription-polymerase chain reaction(RT-qPCR)was performed to measure the mRNA expression of HIF-1α,TNF-α,VEGF and MMP-9;and Western blot(WB)was performed to determine the levels of proteins expressed in the EGFR-mediated PI3K/Akt and MAPK signaling pathways.RESULTS The results of the network pharmacology analysis showed that there were 35 active components in the frankincense and myrrh extracts targeting 151 key targets.The molecular docking analysis showed that both boswellic acid and stigmasterol showed strong affinity for the targets,with the greatest affinity for EGFR.Frankincense and myrrh treatment may play a role in the treatment of HCC by regulating hypoxia responses and vascular system-related pathological processes,such as cytokine-receptor binding,and pathways,such as those involving serine/threonine protein kinase complexes and MAPK,HIF-1 and ErbB signaling cascades.The animal experiment results were verified.First,we found that,through frankincense and/or myrrh treatment,the volume of subcutaneously transplanted HCC tumors was significantly reduced,and the pathological morphology was attenuated.Then,IF and TEM showed that frankincense and/or myrrh treatment reduced CD31 and collagen IV expression,increased the coverage of perivascular cells,tightened the connection between cells,and improved the shape of blood vessels.In addition,ELISA,RT-qPCR and WB analyses showed that frankincense and/or myrrh treatment inhibited the levels of hypoxia-inducible factors,inflammatory factors and angiogenesis-related factors,namely,HIF-1α,TNF-α,VEGF and MMP-9.Furthermore,mechanistic experiments illustrated that the effect of frankincense plus myrrh treatment was similar to that of an EGFR inhibitor with regard to controlling EGFR activation,thereby inhibiting the phosphorylation activity of its downstream targets:the PI3K/Akt and MAPK(ERK,p38 and JNK)pathways.CONCLUSION In summary,frankincense and myrrh treatment targets tumor blood vessels to exert anti-HCC effects via EGFR-activated PI3K/Akt and MAPK signaling pathways,highlighting the potential of this dual TCM compound as an anti-HCC candidate.
基金supported by National Natural Science Foundation of China(NSFC) Key Project 81130046(to JZ)NSFC81171993(to YL) and NSFC81272415(to YL)+2 种基金Guangxi Key Projects 2013GXNSFEA053004(to JZ)Guangxi Projects 1355004-5(to JZ) and 2012GXNSFCB053004(to YL)Guangxi Ministry of Education 201202ZD022(to YL) and 201201ZD004(to JZ)
文摘Metformin,an inexpensive and well-tolerated oral agent commonly used in the first-line treatment of type 2 diabetes,has become the focus of intense research as a candidate anticancer agent.Here,we discuss the potential of metformin in cancer therapeutics,particularly its functions in multiple signaling pathways,including AMP-activated protein kinase,mammalian target of rapamycin,insulin-like growth factor,c-Jun N-terminal kinase/mitogen-activated protein kinase(p38 MARK),human epidermal growth factor receptor-2,and nuclear factor kappaB pathways.In addition,cutting-edge targeting of cancer stem cells by metformin is summarized.
基金supported by the fund from Universti Sains Malaysia(RUT 1001/PFARMASI/851001 NRGS 304/PFARMASI/650735/K123)
文摘Considering the great potential of natural products as anticancer agents, the present study was designed to explore the molecular mechanisms responsible for anticancer activities of Mesua ferrea stem bark extract against human colorectal carcinoma. Based on MTT assay results, bioactive sub-fraction(SF-3) was selected for further studies using HCT 116 cells. Repeated column chromatography resulted in isolation of less active α-amyrin from SF-3, which was identified and characterized by GC-MS and HPLC methods. α-amyrin and betulinic acid contents of SF-3 were measured by HPLC methods. Fluorescent assays revealed characteristic apoptotic features, including cell shrinkage, nuclear condensation, and marked decrease in mitochondrial membrane potential in SF-3 treated cells. In addition, increased levels of caspases-9 and-3/7 levels were also observed in SF-3 treated cells. SF-3 showed promising antimetastatic properties in multiple in vitro assays. Multi-pathway analysis revealed significant down-regulation of WNT, HIF-1α, and EGFR with simultaneous up-regulation of p53, Myc/Max, and TGF-β signalling pathways in SF-3 treated cells. In addition, promising growth inhibitory effects were observed in SF-3 treated HCT 116 tumour spheroids, which give a hint about in vivo antitumor efficacy of SF-3 phytoconstituents. In conclusion, these results demonstrated that anticancer effects of SF-3 towards colon cancer are through modulation of multiple molecular pathways.
