Adult-born oligodendrocytes are continuously produced in the brains of rodents.The functional role of these cells has been linked to the motor-related activities of healthy animals and is vital for acquiring new motor...Adult-born oligodendrocytes are continuously produced in the brains of rodents.The functional role of these cells has been linked to the motor-related activities of healthy animals and is vital for acquiring new motor skills.However,the relationship between these cells and the control of motor-related activities has not been investigated in pathological conditions.Therefore,the aim of this study is to investigate the role of oligodendrocytes in depression-related motor deficits and the effects of training.Psychomotor retardation is a key symptom of depression.Consistent with the impairments observed in rodent motor performance,the proliferation and activation of adult-born oligodendrocytes are altered in a corticosterone-induced stress paradigm.Therapeutic rotarod training can alleviate these symptoms by reversing the aforementioned changes.Notably,these alterations are particularly pronounced in layer I of the motor cortex.Thus,this study provides evidence of the potential functional involvement of adult-born oligodendrocytes in the motor impairments observed in the depressed animals.Additionally,it offers preliminary results for further investigation into layer I of the motor cortex in relation to these pathological conditions.展开更多
Magnetic resonance imaging(MRI)is one of the most widely used diagnostic techniques.Iron oxide nanoparticles,as a promising kind of contrast agents,have attracted intense research interest due to their low toxicity an...Magnetic resonance imaging(MRI)is one of the most widely used diagnostic techniques.Iron oxide nanoparticles,as a promising kind of contrast agents,have attracted intense research interest due to their low toxicity and superparamagnetism.However,it is still a great challenge to prepare ideal iron oxide based contrast agents with high uniformity,excellent water solubility and biocompatibility.In this paper,a novel water-soluble polymer ligand pentaerythritol tetrakis 3-mercaptopropionate-poly(N-vinyl-2-pyrrolidone)(PTMP-PVP)was used as a capping reagent to prepare iron oxide nanoparticles MIONs@PTMP-PVP through one-step co-precipitation of iron precursors in aqueous solution at 100℃.The obtained nanoparticles MIONs@PTMP-PVP had a small size and narrow size distribution,and they were found to be biocompatible as determined through CCK-8 assay and histology analysis.In vivo MRI study demonstrated that the obtained MIONs@PTMP-PVP can be potentially used as an effective T_(2)-weighted MRI contrast agent.展开更多
Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been...Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been extensively studied for diagnosing malignancy and stroke.In recent years,the emerging exploration of chemical exchange saturation transfer magnetic resonance imaging for detecting pathological changes in neurodegenerative diseases has opened up new possibilities for early detection and repetitive scans without ionizing radiation.This review serves as an overview of chemical exchange saturation transfer magnetic resonance imaging with detailed information on contrast mechanisms and processing methods and summarizes recent developments in both clinical and preclinical studies of chemical exchange saturation transfer magnetic resonance imaging for Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and Huntington’s disease.A comprehensive literature search was conducted using databases such as PubMed and Google Scholar,focusing on peer-reviewed articles from the past 15 years relevant to clinical and preclinical applications.The findings suggest that chemical exchange saturation transfer magnetic resonance imaging has the potential to detect molecular changes and altered metabolism,which may aid in early diagnosis and assessment of the severity of neurodegenerative diseases.Although promising results have been observed in selected clinical and preclinical trials,further validations are needed to evaluate their clinical value.When combined with other imaging modalities and advanced analytical methods,chemical exchange saturation transfer magnetic resonance imaging shows potential as an in vivo biomarker,enhancing the understanding of neuropathological mechanisms in neurodegenerative diseases.展开更多
Anterior cruciate ligament(ACL)injuries are frequently caused by sports injuries and trauma.In cases involving complete tears,ACL reconstruction(ACLR)surgery is the only way to restore the ligament’s integrity.When s...Anterior cruciate ligament(ACL)injuries are frequently caused by sports injuries and trauma.In cases involving complete tears,ACL reconstruction(ACLR)surgery is the only way to restore the ligament’s integrity.When selecting a graft,both the potential complications and the mechanical properties and healing efficacies should be considered.Artificial ligaments have been widely applied in clinical ACLR,and most have exhibited satisfactory biocompatibility and short-term follow-up results.Compared with autografts and allografts,however,the lack of bioactivity of currently available artificial ligaments is a major disadvantage.In addition,some long-term follow-up results have revealed other drawbacks of artificial ligaments,such as graft failure and other complications.Here,we summarize attempts to enhance the bioactive performance of artificial ligaments,as such modifications may have good potential for clinical translation and could improve the long-term outcomes of existing products.展开更多
Intelligent manufacturing(IM),a driving force behind the fourth industrial revolution,is reshaping the manufacturing sector by enhancing productivity,efficiency,and sustainability.Despite the rapid technological advan...Intelligent manufacturing(IM),a driving force behind the fourth industrial revolution,is reshaping the manufacturing sector by enhancing productivity,efficiency,and sustainability.Despite the rapid technological advancements in IM,comprehensive bibliometric reviews remain limited.This article systematically reviews the latest research in IM,addressing emerging hotspots,key technologies,and their applications across the entire product manufacturing cycle.Bibliometric analysis is employed to identify research trends visualize publication volume,collaboration patterns,research domains,co-citations,and emerging areas of interest.The article then examines key technologies supporting IM,including sensors,the Internet of Things(IoT),big data analytics,cloud computing,artificial intelligence(AI),digital twins,and virtual reality(VR)/augmented reality(AR).Furthermore,it explores the application of these technologies throughout the manufacturing cycle-from intelligent reliability design,material transportation and tracking,to intelligent planning and scheduling,machining and fabrication,monitoring and maintenance,quality inspection and control,warehousing and management,and sustainable green manufacturing—through specific case studies.Lastly,the article discusses future research directions,highlighting the increasing global market and the need for enhanced interdisciplinary collaboration,technological integration,computing power upgrades,and attention to security and privacy in IM.This study provides valuable insights for scholars and serves as a guide for future research and strategic investment decisions,offering a comprehensive view of the IM field.展开更多
In this paper,a double-effect DNN-based Digital Back-Propagation(DBP)scheme is proposed and studied to achieve the Integrated Communication and Sensing(ICS)ability,which can not only realize nonlinear damage mitigatio...In this paper,a double-effect DNN-based Digital Back-Propagation(DBP)scheme is proposed and studied to achieve the Integrated Communication and Sensing(ICS)ability,which can not only realize nonlinear damage mitigation but also monitor the optical power and dispersion profile over multi-span links.The link status information can be extracted by the characteristics of the learned optical fiber parameters without any other measuring instruments.The efficiency and feasibility of this method have been investigated in different fiber link conditions,including various launch power,transmission distance,and the location and the amount of the abnormal losses.A good monitoring performance can be obtained while the launch optical power is 2 dBm which does not affect the normal operation of the optical communication system and the step size of DBP is 20 km which can provide a better distance resolution.This scheme successfully detects the location of single or multiple optical attenuators in long-distance multi-span fiber links,including different abnormal losses of 2 dB,4 dB,and 6 dB in 360 km and serval combinations of abnormal losses of(1 dB,5 dB),(3 dB,3 dB),(5 dB,1 dB)in 360 km and 760 km.Meanwhile,the transfer relationship of the estimated coefficient values with different step sizes is further investigated to reduce the complexity of the fiber nonlinear damage compensation.These results provide an attractive approach for precisely sensing the optical fiber link status information and making correct strategies timely to ensure optical communication system operations.展开更多
Much attention has been paid on studies of astaxanthin accumulation process in H aematococcus pluvialis industry. However, growth of H. pluvialis in motile vegetative stage is still the most important and problematic ...Much attention has been paid on studies of astaxanthin accumulation process in H aematococcus pluvialis industry. However, growth of H. pluvialis in motile vegetative stage is still the most important and problematic part in the whole cultivation process, such as low growth rate and cell yields. Motile vegetative cells are extremely sensitive to various stresses which make it difficult to maintain the cells of this state to grow. Previous reports showed that motile vegetative cells may have higher biomass yields ifapplied monochromatic red light. However, metabolic responses of these cells are not completely understood, which constraints application of this illumination protocol in industry. The aim of this study was to examine how critical biochemical changes of H. pluvialis motile vegetative cells were af fected by red light when compared with white light. Variation of photosynthetic pigments composition and lipids were mainly studied. By comparing growth process of cultures in red light and white light, prominent variation of pigments composition and lipids changes were observed. The results showed that, even though cell proliferation was the same during exponential growth phase, variation of photosynthetic pigment composition and lipids occurred. The final biomass of cell number was higher in red light group than in white light group. The variations were significant different. Increase or decrease of major photosynthetic membrane lipids to some extent did not influence photosynthesis of the vegetative cells during this phase. However, vegetative cells under polychromatic white light other than monochromatic red light need further metabolic process to adjust its pigment composition and lipids, possibly this is energetically and biochemically unfavorable for motile vegetative cells to growth under white light, a light condition normally not considered as a stress.展开更多
Hemoptysis is defined as bleeding originating from the respiratory tract distal to the larynx and is associated with a wide spectrum of underlying conditions,including bronchiectasis,pulmonary malignancies,tuberculosi...Hemoptysis is defined as bleeding originating from the respiratory tract distal to the larynx and is associated with a wide spectrum of underlying conditions,including bronchiectasis,pulmonary malignancies,tuberculosis,aspergillosis,and vascular malformations.^([1-3]) A metaanalysis involving patients with massive hemoptysis reported a mortality rate of 3.5%.^([4])This underscores the critical importance of prompt and eff ective embolization of the responsible artery to improve outcomes,particularly in patients presenting with life-threatening hemoptysis.展开更多
Objective:To explore the significance of continuing care in improving self-care ability and quality of life in patients with chronic obstructive pulmonary disease(COPD).Methods:A total of 60 COPD patients treated in o...Objective:To explore the significance of continuing care in improving self-care ability and quality of life in patients with chronic obstructive pulmonary disease(COPD).Methods:A total of 60 COPD patients treated in our department between June 2023 and June 2024 were randomly divided into control and observation groups.The control group received routine care,while the observation group received additional continuing care.Self-care ability and quality of life were compared between the two groups.Results:After the intervention,the observation group demonstrated higher self-care ability and quality of life scores compared to the control group(P<0.05).Conclusion:Continuing care for COPD patients has a positive impact on enhancing self-care ability and improving quality of life,making it worth recommending.展开更多
Transition metal dichalcogenides(TMDs)have emerged as promising electrocatalysts for various electrocatalytic processes.Molybdenum disulfide has been widely used,but a single electrocatalyst can hardly be applied to a...Transition metal dichalcogenides(TMDs)have emerged as promising electrocatalysts for various electrocatalytic processes.Molybdenum disulfide has been widely used,but a single electrocatalyst can hardly be applied to all reactions,making it essential to understand the electrochemistry of selected TMDs.Tungsten diselenide(WSe_(2))is reactive in gas evolution processes,similar to molybdenum,yet has received limited attention.This work explores how different exfoliation powers affect WSe_(2)structural configurations and their impact on catalytic performance in hydrogen evolution,oxygen evolution,and capacitive behaviour.The study investigates the structural properties of WSe_(2)nanosheets in both liquid(dispersion)and solid(electrode)phases.Low exfoliation power(90.4 W)contributes to well-defined WSe_(2),while higher power(814 W)leads to an increased number of selenium vacancies.These modifications influence key properties such as thickness,band gaps(1.518 to 1.578 eV),exfoliation yield(0.27 to 0.12 mg mL^(-1)),and oxide content(44.3%to 53.9%),resulting in distinct electrochemical behaviours in different electrolytes.WSe_(2)nanosheets exfoliated at higher power exhibit reduced activity in the hydrogen evolution reaction(HER)due to the loss of W–Se bonds and the formation of an amorphous structure,but they show enhanced oxygen evolution reaction(OER)performance,particularly in alkaline media.Additionally,a higher concentration of selenium vacancies improves capacitive performance in acidic conditions due to proton contributions but are less favourable in neutral and basic electrolytes.This study highlights the importance of exfoliation power in tuning the structural properties of WSe_(2)for specific electrochemical applications,advancing the understanding of its synthesis and performance.展开更多
In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the inte...In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.展开更多
In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-...In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.展开更多
Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate ...Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis.Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling,improved body weights,and attenuated pathological changes in joints of rats with adjuvant-induced arthritis.Additionally,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and IL-1β in the serum and ankle joints were reduced.Bioinformatics analysis,along with the spleen index and measurements of IL-17 and IL-10 levels,suggested a potential relationship between AS and Th17 cells under arthritic conditions.In vitro,AS was shown to block Th17 cell differentiation,as evidenced by the reduced percentages of CD4^(+)IL-17A^(+)T cells and decreased expression levels of RORγt,IL-17A,IL-17F,IL-21,and IL-22,without affecting the cell viability and apoptosis.This effect was attributed to the limited glycolysis,as indicated by metabolomics analysis,reduced glucose uptake,and p H measurements.Further investigation revealed that AS might bind to hexokinase2(HK2)to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase(GAPDH)or pyruvate kinase M2(PKM2),and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation.Furthermore,AS impaired the activation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signals in vivo and in vitro,which was abolished by the addition of lactate.In conclusion,AS significantly improved adjuvant-induced arthritis(AIA)in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.展开更多
Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors...Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors and plays an important role in regulating tumor cell proliferation,invasion,and metastasis.The specific actions of LCN2 in tumors may vary depending on the particular type of cancer involved.In this review,we provide an extensive overview of the transcriptional and post-transcriptional regulation of LCN2 in health and disease.Furthermore,we summarize the impact of LCN2 dysregulation in a broad range of tumors.Lastly,we examine the mechanisms of action of LCN2 during tumorigenesis,progression,and metastasis.Understanding the complex relationships between LCN2 and tumor development,progression,and metastasis is vital for advancing our knowledge of cancer biology,developing biomarkers for diagnosis and clinical decision-making,and creating therapeutic strategies to improve the management of patients with cancer.展开更多
This study explores the clinical efficacy of budesonide combined with ambroxol inhalation therapy for neonatal pneumonia.A total of 68 neonatal pneumonia patients treated at Li County Hospital from January 2023 to Dec...This study explores the clinical efficacy of budesonide combined with ambroxol inhalation therapy for neonatal pneumonia.A total of 68 neonatal pneumonia patients treated at Li County Hospital from January 2023 to December 2024 were randomly divided into a monotherapy group and a combination group,with 34 patients in each.The monotherapy group received ambroxol inhalation therapy,while the combination group received budesonide inhalation therapy in addition to ambroxol.The recovery progress,blood gas analysis indicators,inflammatory response improvement,and overall clinical efficacy were compared between the two groups.Results showed that the combination group experienced a significantly shorter time for body temperature normalization(3.36±0.58 days vs.4.59±0.45 days),oxygen inhalation duration(4.89±0.57min vs.6.96±0.79min),disappearance of shortness of breath and cough(4.56±0.29 days vs.6.63±0.75 days),and resolution of lung wet rales(5.62±1.46 days vs.7.92±1.28 days)compared to the monotherapy group(P<0.05).Additionally,the total effective rate was significantly higher in the combination group(97.06%)than in the monotherapy group(73.52%)(P<0.05).Post-treatment,the combination group exhibited significantly better blood gas analysis and inflammatory response indicators(P<0.05).These findings suggest that budesonide combined with ambroxol inhalation therapy can effectively improve blood oxygen saturation,reduce inflammation,promote faster recovery,and enhance overall clinical efficacy,making it a reliable treatment option for neonatal pneumonia.展开更多
BACKGROUND Hepatocellular carcinoma with portal vein tumor thrombus(HCC-PVTT)is a severe condition with poor prognosis.While transarterial chemoembolization(TACE)combined with lenvatinib(TACE-L)shows some promise,surv...BACKGROUND Hepatocellular carcinoma with portal vein tumor thrombus(HCC-PVTT)is a severe condition with poor prognosis.While transarterial chemoembolization(TACE)combined with lenvatinib(TACE-L)shows some promise,survival outcomes remain suboptimal.We hypothesize that TACE-L plus programmed cell death protein-1 inhibitors(TACE-L-P)may offer superior survival benefits compared to TACE-L in this patient population.AIM To compare efficacy and safety of TACE-L-P vs TACE-L in HCC-PVTT and identify prognostic factors.METHODS Data from HCC-PVTT patients treated with TACE-L-P or TTACE-L from January 2018 to December 2023 were collected and retrospectively analyzed.Propensity score matching(PSM)method with optimal matching was used to minimize confounding bias.Overall survival(OS),progression-free survival(PFS),objective response rate(ORR),and treatment-related adverse events(AEs)were compared between the two groups.Independent prognostic factors for OS and PFS were elucidated using the Cox proportional hazards model.RESULTS A total of 100 patients were included,with 42 patients in the TACE-L-P group and 68 patients in the TACE-L group.After PSM performing optimal matching,baseline characteristics were well balanced between the two groups,each comprising 42 patients.The median OS was significantly longer in the TACE-L-P group compared to the TACE-L group(17.2 months vs 12.6 months,P=0.0207),as was the median PFS(10.6 months vs 7.1 months,P=0.012).The ORR and disease control rate were both superior in the TACE-L-P group compared to the TACE-L group(66.7%vs 42.9%,P=0.049;78.6%vs 50.0%,P=0.012).Multivariate analysis revealed that the independent prognostic factors for both OS and PFS were the treatment regimen and extrahepatic metastasis.The incidence of any-grade and grade 3 AEs was comparable between the TACE-L-P and TACE-L groups(84.5%vs 88.1%,P=0.546),with no occurrences of grade 4/5 AEs or treatment-related mortality in either group.CONCLUSION Compared to TACE-L,the TACE-L-P regimen exhibits an acceptable safety profile and shows potential in improving survival outcomes,making it a promising therapeutic option for patients with HCC-PVTT.展开更多
Objective:To explore the clinical efficacy and safety of Naomaili granules in the treatment of acute ischemic stroke.Methods:Eighty-eight patients were randomly divided into a treatment group and a control group,with ...Objective:To explore the clinical efficacy and safety of Naomaili granules in the treatment of acute ischemic stroke.Methods:Eighty-eight patients were randomly divided into a treatment group and a control group,with 44 patients in each group.The control group received conventional Western medicine treatment,while the treatment group was additionally administered Naomaili granules at 10g per time,3 times per day,for 20 days.Neurological function(NIHSS),activities of daily living(BI),inflammatory factors(hs-CRP,IL-6)levels,and adverse reactions were observed before and after treatment.Results:After 20 days of treatment,the NIHSS score of the treatment group decreased from(9.20±2.10)to(5.12±1.30),the BI index increased from(52.30±8.50)to(78.60±9.20),and hs-CRP and IL-6 decreased to(3.12±1.10)mg/L and(18.20±4.20)pg/mL,respectively,all significantly better than the control group(P<0.01).The incidence of adverse reactions in the treatment group was 4.55%,lower than the 15.91%in the control group(P<0.05).Conclusion:Naomaili granules can improve neurological function and living ability,reduce inflammatory response,and have good safety in patients with acute ischemic stroke.展开更多
Objective:To screen and identify the key active molecules,signaling pathways,and therapeutic targets of Shuxuening(SXN)injection for treating liver cirrhosis(LC)and to evaluate its therapeutic potential using a mouse ...Objective:To screen and identify the key active molecules,signaling pathways,and therapeutic targets of Shuxuening(SXN)injection for treating liver cirrhosis(LC)and to evaluate its therapeutic potential using a mouse model.Methods:Target genes of SXN and LC were retrieved from public databases,and enrichment analysis was performed.A proteineprotein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING),and hub genes were identified using Molecular Complex Detection(MCODE).LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride(CCl4)for 12 weeks.Starting at week 7,SXN was administered intraperitoneally to the mice in the treatment group.Serum and liver tissues of the mice were collected for the detection of indicators,pathological staining,and expression analysis of hub targets using quantitative real-time polymerase chain reaction(qRT-PCR).Results:We identified 368 overlapping genes(OLGs)between SXN and LC targets.These OLGs were subsequently used to build a PPI network and to screen for hub genes.Enrichment analysis showed that these genes were associated with cancer-related pathways,including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes,such as responses to chemicals and metabolic regulation.In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition.Furthermore,qRT-PCR demonstrated that SXN regulated the expression of MAPK8,AR and CASP3 in the livers of LC mice.Conclusion:This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods.The observed effect was associated with modulation of hub gene expression,particularly MAPK8,and CASP3.展开更多
Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in...Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.展开更多
基金supported by Hong Kong Health and Medical Research Fund,No.02133206(to KFS).
文摘Adult-born oligodendrocytes are continuously produced in the brains of rodents.The functional role of these cells has been linked to the motor-related activities of healthy animals and is vital for acquiring new motor skills.However,the relationship between these cells and the control of motor-related activities has not been investigated in pathological conditions.Therefore,the aim of this study is to investigate the role of oligodendrocytes in depression-related motor deficits and the effects of training.Psychomotor retardation is a key symptom of depression.Consistent with the impairments observed in rodent motor performance,the proliferation and activation of adult-born oligodendrocytes are altered in a corticosterone-induced stress paradigm.Therapeutic rotarod training can alleviate these symptoms by reversing the aforementioned changes.Notably,these alterations are particularly pronounced in layer I of the motor cortex.Thus,this study provides evidence of the potential functional involvement of adult-born oligodendrocytes in the motor impairments observed in the depressed animals.Additionally,it offers preliminary results for further investigation into layer I of the motor cortex in relation to these pathological conditions.
基金supported by Health and Medical Research Fund(18190481)Research Impact Fund(R4034-23F)+6 种基金Areas of Excellence(AoE/M-402/20)General Research Fund(14120924)Co-funding Mechanism on Joint Laboratories with the CAS(JLFS/M-401/24)the Knowledge Transfer Project Fund(KPF24GWP05)the IdeaBooster Fund(IDBF25MED07)Natural Science Foundation of Guangdong Province(Guangdong 2021A15150112042021A1515011285).
文摘Magnesium(Mg)-based biomaterials transform inherent limitations—rapid degradation and suboptimal strength—into therapeutic advantages for orthopedic regeneration.Contrary to industrial perceptions,the moderate corrosion rate and bone-mimetic stiffness(~30 GPa)of Mg synergistically support tissue repair:degradation products activate multiple pathways to enhance functional bone regeneration.Clinical translation milestones include China’s first NMPA-approved Mg-based 3D-printed scaffold.Future advancement hinges on three pillars:biomimetic structural design,material refinement,and smart implants.By redefining the“shortcomings”of Mg as regenerative assets,this paradigm accelerates functional bone reconstruction across orthopedic scenarios.
基金financially supported by the International Cooperation Program from the Ministry of Science and Technology of Hubei Province(No.2023EHA069)Shenzhen Science and Technology Program(No.JCYJ20230807143702005)National Foreign Experts Program(No.G2022027015L)。
文摘Magnetic resonance imaging(MRI)is one of the most widely used diagnostic techniques.Iron oxide nanoparticles,as a promising kind of contrast agents,have attracted intense research interest due to their low toxicity and superparamagnetism.However,it is still a great challenge to prepare ideal iron oxide based contrast agents with high uniformity,excellent water solubility and biocompatibility.In this paper,a novel water-soluble polymer ligand pentaerythritol tetrakis 3-mercaptopropionate-poly(N-vinyl-2-pyrrolidone)(PTMP-PVP)was used as a capping reagent to prepare iron oxide nanoparticles MIONs@PTMP-PVP through one-step co-precipitation of iron precursors in aqueous solution at 100℃.The obtained nanoparticles MIONs@PTMP-PVP had a small size and narrow size distribution,and they were found to be biocompatible as determined through CCK-8 assay and histology analysis.In vivo MRI study demonstrated that the obtained MIONs@PTMP-PVP can be potentially used as an effective T_(2)-weighted MRI contrast agent.
基金supported by The University of Hong Kong,China(109000487,109001694,204610401,and 204610519)National Natural Science Foundation of China(82402225)(to JH).
文摘Chemical exchange saturation transfer magnetic resonance imaging is an advanced imaging technique that enables the detection of compounds at low concentrations with high sensitivity and spatial resolution and has been extensively studied for diagnosing malignancy and stroke.In recent years,the emerging exploration of chemical exchange saturation transfer magnetic resonance imaging for detecting pathological changes in neurodegenerative diseases has opened up new possibilities for early detection and repetitive scans without ionizing radiation.This review serves as an overview of chemical exchange saturation transfer magnetic resonance imaging with detailed information on contrast mechanisms and processing methods and summarizes recent developments in both clinical and preclinical studies of chemical exchange saturation transfer magnetic resonance imaging for Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and Huntington’s disease.A comprehensive literature search was conducted using databases such as PubMed and Google Scholar,focusing on peer-reviewed articles from the past 15 years relevant to clinical and preclinical applications.The findings suggest that chemical exchange saturation transfer magnetic resonance imaging has the potential to detect molecular changes and altered metabolism,which may aid in early diagnosis and assessment of the severity of neurodegenerative diseases.Although promising results have been observed in selected clinical and preclinical trials,further validations are needed to evaluate their clinical value.When combined with other imaging modalities and advanced analytical methods,chemical exchange saturation transfer magnetic resonance imaging shows potential as an in vivo biomarker,enhancing the understanding of neuropathological mechanisms in neurodegenerative diseases.
基金supported by the Areas of Excellence Scheme(AoE/M402/20)the Knowledge Transfer Project Fund(KPF24GWP05)+2 种基金the IdeaBooster Fund(IDBF24MED12)the HKSTP Ideation Fund(Ideation 23-0698)the ITC Technology Startup Support Scheme for Universities(TSU24MED05).
文摘Anterior cruciate ligament(ACL)injuries are frequently caused by sports injuries and trauma.In cases involving complete tears,ACL reconstruction(ACLR)surgery is the only way to restore the ligament’s integrity.When selecting a graft,both the potential complications and the mechanical properties and healing efficacies should be considered.Artificial ligaments have been widely applied in clinical ACLR,and most have exhibited satisfactory biocompatibility and short-term follow-up results.Compared with autografts and allografts,however,the lack of bioactivity of currently available artificial ligaments is a major disadvantage.In addition,some long-term follow-up results have revealed other drawbacks of artificial ligaments,such as graft failure and other complications.Here,we summarize attempts to enhance the bioactive performance of artificial ligaments,as such modifications may have good potential for clinical translation and could improve the long-term outcomes of existing products.
基金Supported by National Natural Science Foundation of China(Grant Nos.52375447,52305477 and 52105457)the Shandong Provincial Natural Science Foundation of China(Grant Nos.ZR2023QE057,ZR2024QE100 and ZR2024ME255)+2 种基金Qingdao Municipal Science and Technology Planning Park Cultivation Plan(Grant No.23-1-5-yqpy-17-qy)Shandong Provincial Science and Technology SMEs Innovation Capacity Improvement Project(Grant No.2022TSGC1115)the Special Fund of Taishan Scholars Project。
文摘Intelligent manufacturing(IM),a driving force behind the fourth industrial revolution,is reshaping the manufacturing sector by enhancing productivity,efficiency,and sustainability.Despite the rapid technological advancements in IM,comprehensive bibliometric reviews remain limited.This article systematically reviews the latest research in IM,addressing emerging hotspots,key technologies,and their applications across the entire product manufacturing cycle.Bibliometric analysis is employed to identify research trends visualize publication volume,collaboration patterns,research domains,co-citations,and emerging areas of interest.The article then examines key technologies supporting IM,including sensors,the Internet of Things(IoT),big data analytics,cloud computing,artificial intelligence(AI),digital twins,and virtual reality(VR)/augmented reality(AR).Furthermore,it explores the application of these technologies throughout the manufacturing cycle-from intelligent reliability design,material transportation and tracking,to intelligent planning and scheduling,machining and fabrication,monitoring and maintenance,quality inspection and control,warehousing and management,and sustainable green manufacturing—through specific case studies.Lastly,the article discusses future research directions,highlighting the increasing global market and the need for enhanced interdisciplinary collaboration,technological integration,computing power upgrades,and attention to security and privacy in IM.This study provides valuable insights for scholars and serves as a guide for future research and strategic investment decisions,offering a comprehensive view of the IM field.
基金supported by the National Key Research and Development Program of China (2019YFB1803905)the National Natural Science Foundation of China (No.62171022)+2 种基金Beijing Natural Science Foundation (4222009)Guangdong Basic and Applied Basic Research Foundation (2021B1515120057)the Scientific and Technological Innovation Foundation of Shunde Graduate School,USTB (No.BK19AF005)。
文摘In this paper,a double-effect DNN-based Digital Back-Propagation(DBP)scheme is proposed and studied to achieve the Integrated Communication and Sensing(ICS)ability,which can not only realize nonlinear damage mitigation but also monitor the optical power and dispersion profile over multi-span links.The link status information can be extracted by the characteristics of the learned optical fiber parameters without any other measuring instruments.The efficiency and feasibility of this method have been investigated in different fiber link conditions,including various launch power,transmission distance,and the location and the amount of the abnormal losses.A good monitoring performance can be obtained while the launch optical power is 2 dBm which does not affect the normal operation of the optical communication system and the step size of DBP is 20 km which can provide a better distance resolution.This scheme successfully detects the location of single or multiple optical attenuators in long-distance multi-span fiber links,including different abnormal losses of 2 dB,4 dB,and 6 dB in 360 km and serval combinations of abnormal losses of(1 dB,5 dB),(3 dB,3 dB),(5 dB,1 dB)in 360 km and 760 km.Meanwhile,the transfer relationship of the estimated coefficient values with different step sizes is further investigated to reduce the complexity of the fiber nonlinear damage compensation.These results provide an attractive approach for precisely sensing the optical fiber link status information and making correct strategies timely to ensure optical communication system operations.
基金Supported by the National Sparking Plan Project of China(No.2015GA701001)the Earmarked Fund for Modern Agro-industry Technology Research System,China(No.CARS-48)+1 种基金the Ningbo Science and Technology Research Projects,China(No.2017C110003)the K.C.Wong Magna Fund in Ningbo University
文摘Much attention has been paid on studies of astaxanthin accumulation process in H aematococcus pluvialis industry. However, growth of H. pluvialis in motile vegetative stage is still the most important and problematic part in the whole cultivation process, such as low growth rate and cell yields. Motile vegetative cells are extremely sensitive to various stresses which make it difficult to maintain the cells of this state to grow. Previous reports showed that motile vegetative cells may have higher biomass yields ifapplied monochromatic red light. However, metabolic responses of these cells are not completely understood, which constraints application of this illumination protocol in industry. The aim of this study was to examine how critical biochemical changes of H. pluvialis motile vegetative cells were af fected by red light when compared with white light. Variation of photosynthetic pigments composition and lipids were mainly studied. By comparing growth process of cultures in red light and white light, prominent variation of pigments composition and lipids changes were observed. The results showed that, even though cell proliferation was the same during exponential growth phase, variation of photosynthetic pigment composition and lipids occurred. The final biomass of cell number was higher in red light group than in white light group. The variations were significant different. Increase or decrease of major photosynthetic membrane lipids to some extent did not influence photosynthesis of the vegetative cells during this phase. However, vegetative cells under polychromatic white light other than monochromatic red light need further metabolic process to adjust its pigment composition and lipids, possibly this is energetically and biochemically unfavorable for motile vegetative cells to growth under white light, a light condition normally not considered as a stress.
文摘Hemoptysis is defined as bleeding originating from the respiratory tract distal to the larynx and is associated with a wide spectrum of underlying conditions,including bronchiectasis,pulmonary malignancies,tuberculosis,aspergillosis,and vascular malformations.^([1-3]) A metaanalysis involving patients with massive hemoptysis reported a mortality rate of 3.5%.^([4])This underscores the critical importance of prompt and eff ective embolization of the responsible artery to improve outcomes,particularly in patients presenting with life-threatening hemoptysis.
基金Baoding Science and Technology Bureau Project“Study on the Impact of Continuing Care on Self-Care Ability and Quality of Life in COPD Patients”(Project No.2441ZF276)。
文摘Objective:To explore the significance of continuing care in improving self-care ability and quality of life in patients with chronic obstructive pulmonary disease(COPD).Methods:A total of 60 COPD patients treated in our department between June 2023 and June 2024 were randomly divided into control and observation groups.The control group received routine care,while the observation group received additional continuing care.Self-care ability and quality of life were compared between the two groups.Results:After the intervention,the observation group demonstrated higher self-care ability and quality of life scores compared to the control group(P<0.05).Conclusion:Continuing care for COPD patients has a positive impact on enhancing self-care ability and improving quality of life,making it worth recommending.
基金supported by Matching Fund from Thammasat University Research Fund,Thammasat University,under Contract No.MF2/2567the ETS scholarship awarded by Sirindhorn International Institute of Technology,Thammasat University。
文摘Transition metal dichalcogenides(TMDs)have emerged as promising electrocatalysts for various electrocatalytic processes.Molybdenum disulfide has been widely used,but a single electrocatalyst can hardly be applied to all reactions,making it essential to understand the electrochemistry of selected TMDs.Tungsten diselenide(WSe_(2))is reactive in gas evolution processes,similar to molybdenum,yet has received limited attention.This work explores how different exfoliation powers affect WSe_(2)structural configurations and their impact on catalytic performance in hydrogen evolution,oxygen evolution,and capacitive behaviour.The study investigates the structural properties of WSe_(2)nanosheets in both liquid(dispersion)and solid(electrode)phases.Low exfoliation power(90.4 W)contributes to well-defined WSe_(2),while higher power(814 W)leads to an increased number of selenium vacancies.These modifications influence key properties such as thickness,band gaps(1.518 to 1.578 eV),exfoliation yield(0.27 to 0.12 mg mL^(-1)),and oxide content(44.3%to 53.9%),resulting in distinct electrochemical behaviours in different electrolytes.WSe_(2)nanosheets exfoliated at higher power exhibit reduced activity in the hydrogen evolution reaction(HER)due to the loss of W–Se bonds and the formation of an amorphous structure,but they show enhanced oxygen evolution reaction(OER)performance,particularly in alkaline media.Additionally,a higher concentration of selenium vacancies improves capacitive performance in acidic conditions due to proton contributions but are less favourable in neutral and basic electrolytes.This study highlights the importance of exfoliation power in tuning the structural properties of WSe_(2)for specific electrochemical applications,advancing the understanding of its synthesis and performance.
文摘In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.
基金supported by a grant from the National Key Basic Research Program of China,No.2014CB542202 and 2014CB542205the National Natural Science Foundation of China,No.30973095&81371354+2 种基金a grant from Science and Technology Project of Guangzhou,in China,No.12C32121609the Natural Science Foundation of Guangdong Province of China,No.S2013010014697 to Guo JSHong Kong SCI Fund to Wu WT
文摘In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.
基金supported by the project of Central Funds Guiding the Local Science and Technology Development(No.20212ZDD02010)。
文摘Andrographolide sulfonate(AS)is a sulfonated derivative of andrographolide extracted from Andrographis paniculata(Burm.f.)Nees,and has been approved for several decades in China.The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis.Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling,improved body weights,and attenuated pathological changes in joints of rats with adjuvant-induced arthritis.Additionally,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and IL-1β in the serum and ankle joints were reduced.Bioinformatics analysis,along with the spleen index and measurements of IL-17 and IL-10 levels,suggested a potential relationship between AS and Th17 cells under arthritic conditions.In vitro,AS was shown to block Th17 cell differentiation,as evidenced by the reduced percentages of CD4^(+)IL-17A^(+)T cells and decreased expression levels of RORγt,IL-17A,IL-17F,IL-21,and IL-22,without affecting the cell viability and apoptosis.This effect was attributed to the limited glycolysis,as indicated by metabolomics analysis,reduced glucose uptake,and p H measurements.Further investigation revealed that AS might bind to hexokinase2(HK2)to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase(GAPDH)or pyruvate kinase M2(PKM2),and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation.Furthermore,AS impaired the activation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signals in vivo and in vitro,which was abolished by the addition of lactate.In conclusion,AS significantly improved adjuvant-induced arthritis(AIA)in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
基金supported by the Program for Science Technology and Innovation Committee of Shenzhen(2021N062-JCYJ20210324115408023)Guangdong High-Level Hospital Construction Fund,Shenzhen High-Level Hospital Construction Fund。
文摘Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors and plays an important role in regulating tumor cell proliferation,invasion,and metastasis.The specific actions of LCN2 in tumors may vary depending on the particular type of cancer involved.In this review,we provide an extensive overview of the transcriptional and post-transcriptional regulation of LCN2 in health and disease.Furthermore,we summarize the impact of LCN2 dysregulation in a broad range of tumors.Lastly,we examine the mechanisms of action of LCN2 during tumorigenesis,progression,and metastasis.Understanding the complex relationships between LCN2 and tumor development,progression,and metastasis is vital for advancing our knowledge of cancer biology,developing biomarkers for diagnosis and clinical decision-making,and creating therapeutic strategies to improve the management of patients with cancer.
文摘This study explores the clinical efficacy of budesonide combined with ambroxol inhalation therapy for neonatal pneumonia.A total of 68 neonatal pneumonia patients treated at Li County Hospital from January 2023 to December 2024 were randomly divided into a monotherapy group and a combination group,with 34 patients in each.The monotherapy group received ambroxol inhalation therapy,while the combination group received budesonide inhalation therapy in addition to ambroxol.The recovery progress,blood gas analysis indicators,inflammatory response improvement,and overall clinical efficacy were compared between the two groups.Results showed that the combination group experienced a significantly shorter time for body temperature normalization(3.36±0.58 days vs.4.59±0.45 days),oxygen inhalation duration(4.89±0.57min vs.6.96±0.79min),disappearance of shortness of breath and cough(4.56±0.29 days vs.6.63±0.75 days),and resolution of lung wet rales(5.62±1.46 days vs.7.92±1.28 days)compared to the monotherapy group(P<0.05).Additionally,the total effective rate was significantly higher in the combination group(97.06%)than in the monotherapy group(73.52%)(P<0.05).Post-treatment,the combination group exhibited significantly better blood gas analysis and inflammatory response indicators(P<0.05).These findings suggest that budesonide combined with ambroxol inhalation therapy can effectively improve blood oxygen saturation,reduce inflammation,promote faster recovery,and enhance overall clinical efficacy,making it a reliable treatment option for neonatal pneumonia.
基金Supported by Zhejiang Province Medicine and Health Science and Technology Project,No.2023KY239Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project,No.2024ZL949.
文摘BACKGROUND Hepatocellular carcinoma with portal vein tumor thrombus(HCC-PVTT)is a severe condition with poor prognosis.While transarterial chemoembolization(TACE)combined with lenvatinib(TACE-L)shows some promise,survival outcomes remain suboptimal.We hypothesize that TACE-L plus programmed cell death protein-1 inhibitors(TACE-L-P)may offer superior survival benefits compared to TACE-L in this patient population.AIM To compare efficacy and safety of TACE-L-P vs TACE-L in HCC-PVTT and identify prognostic factors.METHODS Data from HCC-PVTT patients treated with TACE-L-P or TTACE-L from January 2018 to December 2023 were collected and retrospectively analyzed.Propensity score matching(PSM)method with optimal matching was used to minimize confounding bias.Overall survival(OS),progression-free survival(PFS),objective response rate(ORR),and treatment-related adverse events(AEs)were compared between the two groups.Independent prognostic factors for OS and PFS were elucidated using the Cox proportional hazards model.RESULTS A total of 100 patients were included,with 42 patients in the TACE-L-P group and 68 patients in the TACE-L group.After PSM performing optimal matching,baseline characteristics were well balanced between the two groups,each comprising 42 patients.The median OS was significantly longer in the TACE-L-P group compared to the TACE-L group(17.2 months vs 12.6 months,P=0.0207),as was the median PFS(10.6 months vs 7.1 months,P=0.012).The ORR and disease control rate were both superior in the TACE-L-P group compared to the TACE-L group(66.7%vs 42.9%,P=0.049;78.6%vs 50.0%,P=0.012).Multivariate analysis revealed that the independent prognostic factors for both OS and PFS were the treatment regimen and extrahepatic metastasis.The incidence of any-grade and grade 3 AEs was comparable between the TACE-L-P and TACE-L groups(84.5%vs 88.1%,P=0.546),with no occurrences of grade 4/5 AEs or treatment-related mortality in either group.CONCLUSION Compared to TACE-L,the TACE-L-P regimen exhibits an acceptable safety profile and shows potential in improving survival outcomes,making it a promising therapeutic option for patients with HCC-PVTT.
文摘Objective:To explore the clinical efficacy and safety of Naomaili granules in the treatment of acute ischemic stroke.Methods:Eighty-eight patients were randomly divided into a treatment group and a control group,with 44 patients in each group.The control group received conventional Western medicine treatment,while the treatment group was additionally administered Naomaili granules at 10g per time,3 times per day,for 20 days.Neurological function(NIHSS),activities of daily living(BI),inflammatory factors(hs-CRP,IL-6)levels,and adverse reactions were observed before and after treatment.Results:After 20 days of treatment,the NIHSS score of the treatment group decreased from(9.20±2.10)to(5.12±1.30),the BI index increased from(52.30±8.50)to(78.60±9.20),and hs-CRP and IL-6 decreased to(3.12±1.10)mg/L and(18.20±4.20)pg/mL,respectively,all significantly better than the control group(P<0.01).The incidence of adverse reactions in the treatment group was 4.55%,lower than the 15.91%in the control group(P<0.05).Conclusion:Naomaili granules can improve neurological function and living ability,reduce inflammatory response,and have good safety in patients with acute ischemic stroke.
基金Our study was funded by the Clinical Research Special Fund of Wu Jieping Medical Foundation(320.6750.2022-25-8)the Fundamental Research Funds for the Cornell University(2024-JYBXJSJJ042 and 2024-JYB-JBZD-058).
文摘Objective:To screen and identify the key active molecules,signaling pathways,and therapeutic targets of Shuxuening(SXN)injection for treating liver cirrhosis(LC)and to evaluate its therapeutic potential using a mouse model.Methods:Target genes of SXN and LC were retrieved from public databases,and enrichment analysis was performed.A proteineprotein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING),and hub genes were identified using Molecular Complex Detection(MCODE).LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride(CCl4)for 12 weeks.Starting at week 7,SXN was administered intraperitoneally to the mice in the treatment group.Serum and liver tissues of the mice were collected for the detection of indicators,pathological staining,and expression analysis of hub targets using quantitative real-time polymerase chain reaction(qRT-PCR).Results:We identified 368 overlapping genes(OLGs)between SXN and LC targets.These OLGs were subsequently used to build a PPI network and to screen for hub genes.Enrichment analysis showed that these genes were associated with cancer-related pathways,including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes,such as responses to chemicals and metabolic regulation.In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition.Furthermore,qRT-PCR demonstrated that SXN regulated the expression of MAPK8,AR and CASP3 in the livers of LC mice.Conclusion:This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods.The observed effect was associated with modulation of hub gene expression,particularly MAPK8,and CASP3.
基金supported by grants from the Wenzhou Science and Technology Bureau Foundation,China(Grant No.:ZY2019014)“Pioneer”and“Leading Goose”R&D Program of Zhejiang,China(Grant No.:2022C03144)National Natural Science Foundation of China(Grant Nos.:82172494,and 82372461).
文摘Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.
