Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for ...Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.展开更多
lonic-conductive solid-state polymer electrolytes are promising for the development of advanced lithium batteries yet a deeper understanding of their underlying ion-transfer mechanism is needed to improve performance....lonic-conductive solid-state polymer electrolytes are promising for the development of advanced lithium batteries yet a deeper understanding of their underlying ion-transfer mechanism is needed to improve performance.Here we demonstrate the low-enthalpy and high-entropy(LEHE)electrolytes can intrinsically generate remarkably free ions and high mobility,enabling them to efficiently drive lithium-ion storage.The LEHE electrolytes are constructed on the basis of introducing CsPbl_(3)perovskite quantum dots(PQDs)to strengthen PEO@LiTFSI complexes.An extremely stable cycling>1000 h at 0.3 mA cm^(-2)can be delivered by LEHE electrolytes.Also,the as-developed Li|LEHE|LiFePO_(4)cell retains 92.3%of the initial capacity(160.7 mAh g^(-1))after 200 cycles.This cycling stability is ascribed to the suppressed charge concentration gradient leading to free lithium dendrites.It is realized by a dramatic increment in lithium-ion transference number(0.57 vs 0.19)and a significant decline in ion-transfer activation energy(0.14 eV vs 0.22 eV)for LEHE electrolytes comparing with PEO@LiTFSI counterpart.The CsPbl_(3)PQDs promote highly structural disorder by inhibiting crystallization and hence endow polymer electrolytes with low melting enthalpy and high structural entropy,which in turn facilitate long-term cycling stability and excellent rate-capability of lithium-metal batteries.展开更多
Background:Soybean has long been utilized in the realm of traditional Chinese medicine.One of its extracts,soybean glycolipids,serves as a vital by-product of soybean oil refining,but its chemical composition and phar...Background:Soybean has long been utilized in the realm of traditional Chinese medicine.One of its extracts,soybean glycolipids,serves as a vital by-product of soybean oil refining,but its chemical composition and pharmacological potential have yet to be fully elucidated.Methods:In this study,the chemical components were isolated,and the inhibitory effects of these isolates were explored in different zebrafish inflammatory models by survival rate,Histological examination assay and quantitative Real-time PCR assay.The cytotoxicity of daidzin in RAW264.7 cells was evaluated by cell viability assay,and the effect of daidzin on the release of inflammatory cytokines in RAW264.7 cells was detected by enzyme linked immunosorbent assay(ELISA).Western blotting,immunofluorescence assay and alpha7 nicotinic acetylcholine receptors siRNA transfection assay were used to further explore the anti-inflammatory mechanism of daidzin.Results:Four compounds(verticilloside,soya-cerebroside I,soya-cerebroside II and daidzin)were firstly isolated from the soybean glycolipids,among which verticilloside and daidzin inhibited the lipopolysaccharide,CuSO4-and tail cut-stimulated zebrafish inflammation.Noticeably,daidzin exhibited anti-inflammatory activities by increasing the survival rate,alleviating the inflammatory cells infiltration,and down-regulating the expression of pro-inflammatory cytokines and nuclear factor kappa-B,NF-kappa-B inhibitor alpha,and signal transducer and activator of transcription3 in zebrafish.Moreover,daidzin decreased the secretion of IL-6 and TNF-α,inhibited the nuclear translocations of nuclear factor kappa-B p65 and p-signal transducer and activator of transcription3 as well as the NF-kappa-B inhibitor alpha phosphorylation at Ser32 in RAW 264.7 cells.More importantly,it elevated the expression level of alpha7 nicotinic acetylcholine receptors in both zebrafish and RAW 264.7 cells,and the inhibitory effect of daidzin was attenuated after the addition of alpha7 nicotinic acetylcholine receptors siRNA.Conclusion:Our study revealed that daidzin inhibited inflammation by activating the cholinergic anti-inflammatory pathway and further inhibiting the nuclear factor kappa-B and signal transducer and activator of transcription3 signaling.At the same time,it also promotes the recycling of crude soybean glycolipids and supports the potential use of daidzin as a functional food or natural dietary anti-inflammatory agent.展开更多
Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD ...Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD is an important risk factor for cardiovascular and cerebrovascular diseases,including coronary heart disease,stroke,and tumors,with no specific therapeutic drugs currently available.The ethanol extract of cassia seed(CSEE)has shown promise in lowering blood lipids and improving hepatic steatosis,but its mechanism in treating MASLD remains underexplored.This study aims to investigate the therapeutic effects and mechanisms of CSEE.Methods:MASLD models were established in male Wistar rats and golden hamsters using a high fat diet(HFD).CSEE(10,50,250 mg/kg)was administered via gavage for six weeks.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),as well as liver TC and TG,were measured using biochemical kits.Histopathological changes in the liver were evaluated using Oil Red O staining,Hematoxylin-eosin(H&E)staining,and transmission electron microscopy(TEM).HepG2 cell viability was assessed using the cell counting kit-8(CCK8)and Calcein-AM/PI staining.Network pharmacology was used to analyze drug-disease targets,and western blotting was used to confirm these predictions.Results:CSEE treatment significantly reduced serum levels of TC,TG,LDL-C,ALT,and AST,and improved liver weight,liver index,and hepatic lipid deposition in rats and golden hamsters.In addition,CSEE alleviated free fatty acid(FFA)-induced lipid deposition in HepG2 cells.Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK,p-ACC,PPARα,CPT1A,PI3K P110 and p-AKT,while decreasing the protein levels of SREBP1,FASN,C/EBPα,and PPARγ,thus improving hepatic lipid metabolism and reducing lipid deposition.The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro.Conclusion:CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK,PPARα,and PI3K/AKT signaling pathways.展开更多
Background and objective:Immediate breast reconstruction not only reduces the number of surgeries for patients after mastectomy but also decreases psychological and physical trauma,making it increasingly popular.Howev...Background and objective:Immediate breast reconstruction not only reduces the number of surgeries for patients after mastectomy but also decreases psychological and physical trauma,making it increasingly popular.However,there is currently no consensus on the integration of post-mastectomy radiotherapy(PMRT)with reconstruction techniques.This review evaluates the impact of PMRT on complications following immediate breast reconstruction,providing guidance for clinical treatment decisions.Methods:PubMed,Web of Science,Embase,and other databases were searched for studies published in the past 15 years on outcomes of implant-based breast reconstruction in the context of radiotherapy to identify articles for analysis.RevMan 5.4 software was used to analyze the risks of seroma,infection,wound dehiscence,flap necrosis,implant exposure,capsule contracture,and reconstruction failure.Results:A total of 1l relevant studies were included,comprising 6323 cases of immediate breast reconstruction.It was found that breasts receiving postoperative irradiation had a significantly increased risk of complications,with statistically significant differences in seroma(P=0.004),infection(P<0.00001),wound dehiscence(P=0.04),implant exposure(P<0.00001),capsule contracture(P<0.00001),and reconstruction failure(P<0.00001).There was no statistically significant difference in flap necrosis(P=0.88).Conclusion:The results indicate that postoperative radiotherapy significantly increases the risk of complications for patients undergoing immediate implant-based reconstruction.Preventive measures may be taken in advance with the assistance of healthcare providers if necessary.展开更多
Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatme...Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatments may help treat Parkinson's disease.To further investigate the mechanisms of action of these two compounds,we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor linagliptin.We found that both exendin-4 and linagliptin reversed motor dysfunction,glial activation,and dopaminergic neuronal death in this model.In addition,both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion.Moreover,in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain-and leucine-rich-repeat-and pyrin-domaincontaining 3/caspase-1/interleukin-1βpathway and subsequent pyroptosis by decreasing the production of reactive oxygen species.These findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotidebinding oligomerization domain-and leucine-rich-repeat-and pyrin-domain-containing 3/caspase-1/interleukin-1βpathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Therefore,these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.展开更多
In the present study,the effects of cooked rice(CR)with added fructo-oligosaccharide(FOS)on faecal flora were studied by a simulated in vitro digestion and fermentation method.The total carbohydrate content,p H,and s ...In the present study,the effects of cooked rice(CR)with added fructo-oligosaccharide(FOS)on faecal flora were studied by a simulated in vitro digestion and fermentation method.The total carbohydrate content,p H,and s hort-chain fatty acids(SCFAs)were determined during in vitro digestion and fermentation.The change in the bacterial phase distribution after the fermentation was also analysed.The results showed that t he total carbohydrate content of the CR with added FOS(FCR)significantly decreased during the simulated digestion.Meanwhile,the p H of the FCR decreased and the SCFAs concentration increased significantly compared to those of the CR during the simulated fermentation.In addition,the FCR showed the advantage of promoting beneficial bacteria,such as Bifidobacterium and Lactobacillus,and inhibiting harmful bacteria,such as Bacteroides and Klebsiella compared to the CR.Therefore,the FOS as a prebiotic could be recommended to produce the high-quality healthy rice food.展开更多
Objective Liraglutide is a commonly used hypoglycemic agent in clinical practice,and has been demonstrated to have protective effects against the development of cardiovascular disease.However,its potential role in myo...Objective Liraglutide is a commonly used hypoglycemic agent in clinical practice,and has been demonstrated to have protective effects against the development of cardiovascular disease.However,its potential role in myocardial fibrosis remains unexplored.The present study aims to assess the impact of liraglutide on the activation of cardiac fibroblasts.Methods Primary rat adult fibroblasts were isolated,cultured,and randomly allocated into 4 groups:control group,transforming growth factor beta1(TGFβ1)stimulation group,liraglutide group,and TGFβ1+liraglutide group.Fibroblast activation was induced by TGFβ1.Cell proliferation activity was assessed using the CKK-8 kit,and cellular activity was determined using the MTT kit.Reverse transcrition-quantitative polymerase chain reaction(RT-qPCR)was utilized to quantify the level of collagen transcription,immunofluorescence staining was performed to detect the expression level of type III collagen andα-smooth muscle protein(α-SMA),and immunoblotting was conducted to monitor alterations in signal pathways.Results The addition of 10,25,50 and 100 nmol/L of liraglutide did not induce any significant impact on the viability of fibroblasts(P>0.05).The rate of cellular proliferation was significantly higher in the TGFβl stimulation group than in the control group.However,the treatment with 50 and 100 nmol/L of liraglutide resulted in the reduction of TGFβl-induced cell proliferation(P<0.05).The RT-qPCR results revealed that the transcription levels of type I collagen,type III collagen,andα-SMA were significantly upregulated in the TGFβl stimulation group,when compared to the control group(P<0.05).However,the expression levels of these aforementioned factors significantly decreased in the TGFβl+liraglutide group(P<0.05).The immunofluorescence staining results revealed a significant increase in the expression levels of type III collagen andα-SMA in the TGFβl stimulation group,when compared to the control group(P<0.05).However,these expression levels significantly decreased in the TGFβl+liraglutide group,when compared to the TGFβl stimulation group(P<0.05).The Western blotting results revealed that the expression levels of phosphorylated smad2 and smad3 significantly increased in the TGFβl stimulation group,when compared to the control group(P<0.05),while these decreased in the TGFβl+liraglutide group(P<0.05).Conclusion Liraglutide inhibits myocardial fibrosis development by suppressing the smad signaling pathway,reducing the activation and secretion of cardiac fibroblasts.展开更多
Probabilistic time series forecasting aims at estimating future probabilistic distributions based on given time series observations.It is a widespread challenge in various tasks,such as risk management and decision ma...Probabilistic time series forecasting aims at estimating future probabilistic distributions based on given time series observations.It is a widespread challenge in various tasks,such as risk management and decision making.To investigate temporal patterns in time series data and predict subsequent probabilities,the state space model(SSM)provides a general framework.Variants of SSM achieve considerable success in many fields,such as engineering and statistics.However,since underlying processes in real-world scenarios are usually unknown and complicated,actual time series observations are always irregular and noisy.Therefore,it is very difficult to determinate an SSM for classical statistical approaches.In this paper,a general time series forecasting framework,called Deep Nonlinear State Space Model(DNLSSM),is proposed to predict the probabilistic distribution based on estimated underlying unknown processes from historical time series data.We fuse deep neural networks and statistical methods to iteratively estimate states and network parameters and thus exploit intricate temporal patterns of time series data.In particular,the unscented Kalman filter(UKF)is adopted to calculate marginal likelihoods and update distributions recursively for non-linear functions.After that,a non-linear Joseph form covariance update is developed to ensure that calculated covariance matrices in UKF updates are symmetric and positive definitive.Therefore,the authors enhance the tolerance of UKF to round-off errors and manage to combine UKF and deep neural networks.In this manner,the DNLSSM effectively models non-linear correlations between observed time series data and underlying dynamic processes.Experiments in both synthetic and real-world datasets demonstrate that the DNLSSM consistently improves the accuracy of probability forecasts compared to the baseline methods.展开更多
AIM:To observe the effect of low oxygen concentration on the neural retina in human induced pluripotent stem cell(hiPSC)-derived retinal organoids(ROs).METHODS:The hiPSC and a three-dimensional culture method were use...AIM:To observe the effect of low oxygen concentration on the neural retina in human induced pluripotent stem cell(hiPSC)-derived retinal organoids(ROs).METHODS:The hiPSC and a three-dimensional culture method were used for the experiments.Generated embryoid bodies(EBs)were randomly and equally divided into hypoxic and normoxic groups.Photographs of the EBs were taken on days 38,45,and 52,and the corresponding volume of EBs was calculated.Simultaneously,samples were collected at these three timepoints,followed by fixation,sectioning,and immunofluorescence.RESULTS:The proportion of Ki67-positive proliferating cells increased steadily on day 38;this proliferationpromoting effect tended to increase tissue density rather than tissue volume.On days 45 and 52,the two groups had relatively similar ratios of Ki67-positive cells.Further immunofluorescence analysis showed that the ratio of SOX2-positive cells significantly increased within the neural retina on day 52(P<0.05).In contrast,the percentage of PAX6-and CHX10-positive cells significantly decreased following hypoxia treatment at all three timepoints(P<0.01),except for CHX10 at day 45(P>0.05).Moreover,the proportion of PAX6-/TUJ1+cells within the neural retinas increased considerably(P<0.01,<0.05,<0.05 respectively).CONCLUSION:Low oxygen promotes stemness and proliferation of neural retinas,suggesting that hypoxic conditions can enlarge the retinal progenitor cell pool in hiPSC-derived ROs.展开更多
[Objectives]The paper was to clone and analyze bioinformatics of vscN gene from Vibrio alginolyticus.[Methods]A pair of specific primers was designed based on the vscN gene sequence of V.alginolyticus HY9901.The full ...[Objectives]The paper was to clone and analyze bioinformatics of vscN gene from Vibrio alginolyticus.[Methods]A pair of specific primers was designed based on the vscN gene sequence of V.alginolyticus HY9901.The full length of vscN gene was amplified by PCR and bioinformatics analysis was performed.[Results]The vscN gene was 1323 bp in total,encoding 440 amino acids,with the theoretical molecular weight of 47.86 kD and the theoretical pI value of 5.89.The online prediction showed that there was no signal peptide and no transmembrane region in VscN.The amino acid sequence had 10 N-myristoylation sites,8 phosphorylation sites(2 protein kinase C phosphorylation sites,6 casein kinase II phosphorylation sites),1 amidation site,11 microbody C-terminal target signal sites,1 ATP/GTP binding site motif A(P ring),and 1 ATPaseαandβsubunit specific site.Homology analysis showed that the VscN protein of V.alginolyticus had high homology with that of V.antiquarius,with a similarity of 95.14%.Phylogenetic tree analysis showed that the VscN of V.alginolyticus was clustered into the same subgroup as that of V.diabolicus and V.antiquarius.Functional domain analysis of VscN protein showed that it had Pfam and AAA domains,and involved in the regulation of bacterial virulence.The three-dimensional structure model of VscN simulated by SWISS-MODEL software was similar to the structure of flagellate-specific ATPase FliH-FliI complex.[Conclusions]The results lay a foundation for further study on the regulatory mechanism of VscN protein on bacterial virulence.展开更多
Background:Chinese herbal medicines have been proven to be effective in clinical treatment and disease prevention.Jinlingzi San is a herbal medicine used for the treatment of endometriosis.However,a comprehensive netw...Background:Chinese herbal medicines have been proven to be effective in clinical treatment and disease prevention.Jinlingzi San is a herbal medicine used for the treatment of endometriosis.However,a comprehensive network pharmacology approach has not been used to understand the active ingredients and therapeutic mechanisms behind Jinlingzi San in the treatment of endometriosis.Methods:A network pharmacology approach and a molecular docking approach were used to predict the active ingredients and potential targets of Jinlingzi San in the treatment of endometriosis.Results:The integrated network pharmacology approach successfully identified 60 active ingredients and 540 key targets of action in Jinlingzi San dispersion.Among them,STAT3,TP53,MAPK3,RELA,MAPK1,JUN and other key genes were mainly regulated through pathways in cancer,lipid and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,pancreatic cancer,prostate cancer,PI3K-Akt signaling pathway,Th17 cell differentiation,and other signaling pathways in the cell body,receptor complexes,cytoplasm,nucleoplasm,and plasma membrane.Conclusion:Based on a systems network pharmacology approach,our work successfully predicts the active components and potential targets of Jinlingzi San for the treatment of endometriosis and helps to illustrate the mechanism of action at an integrative level.This demonstrates that Jinlingzi San for the treatment of endometriosis is regulated through a multi-component,multi-target,multi-system co-regulation.This study identifies key genes and pathways associated with endometriosis and pathogenesis from new insights,and also provides a viable approach to the chemical basis and pharmacological studies of Jinlingzi San.展开更多
基金supported by the National Natural Science Foundation of China,No.31970906(to WLei)the Natural Science Foundation of Guangdong Province,No.2020A1515011079(to WLei)+4 种基金Key Technologies R&D Program of Guangdong Province,No.2018B030332001(to GC)Science and Technology Projects of Guangzhou,No.202206060002(to GC)the Youth Science Program of the National Natural Science Foundation of China,No.32100793(to ZX)the Pearl River Innovation and Entrepreneurship Team,No.2021ZT09 Y552Yi-Liang Liu Endowment Fund from Jinan University Education Development Foundation。
文摘Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.
基金the National Natural Science Foundation of China(Nos.51977185,51972277)the financial supported from Southwest Jiaotong University Science and Technology Rising Star Program(No.2682021CG021)
文摘lonic-conductive solid-state polymer electrolytes are promising for the development of advanced lithium batteries yet a deeper understanding of their underlying ion-transfer mechanism is needed to improve performance.Here we demonstrate the low-enthalpy and high-entropy(LEHE)electrolytes can intrinsically generate remarkably free ions and high mobility,enabling them to efficiently drive lithium-ion storage.The LEHE electrolytes are constructed on the basis of introducing CsPbl_(3)perovskite quantum dots(PQDs)to strengthen PEO@LiTFSI complexes.An extremely stable cycling>1000 h at 0.3 mA cm^(-2)can be delivered by LEHE electrolytes.Also,the as-developed Li|LEHE|LiFePO_(4)cell retains 92.3%of the initial capacity(160.7 mAh g^(-1))after 200 cycles.This cycling stability is ascribed to the suppressed charge concentration gradient leading to free lithium dendrites.It is realized by a dramatic increment in lithium-ion transference number(0.57 vs 0.19)and a significant decline in ion-transfer activation energy(0.14 eV vs 0.22 eV)for LEHE electrolytes comparing with PEO@LiTFSI counterpart.The CsPbl_(3)PQDs promote highly structural disorder by inhibiting crystallization and hence endow polymer electrolytes with low melting enthalpy and high structural entropy,which in turn facilitate long-term cycling stability and excellent rate-capability of lithium-metal batteries.
基金funded by the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(grant number GDHVPS2018)the Young Elite Scientists Sponsorship Program by CACM(grant number 2019-QNRC2-C14)+1 种基金National Natural Science Foundation of China(grant number 31920103012,31901603)the Guangzhou education bureau university scientific research project(201831845).
文摘Background:Soybean has long been utilized in the realm of traditional Chinese medicine.One of its extracts,soybean glycolipids,serves as a vital by-product of soybean oil refining,but its chemical composition and pharmacological potential have yet to be fully elucidated.Methods:In this study,the chemical components were isolated,and the inhibitory effects of these isolates were explored in different zebrafish inflammatory models by survival rate,Histological examination assay and quantitative Real-time PCR assay.The cytotoxicity of daidzin in RAW264.7 cells was evaluated by cell viability assay,and the effect of daidzin on the release of inflammatory cytokines in RAW264.7 cells was detected by enzyme linked immunosorbent assay(ELISA).Western blotting,immunofluorescence assay and alpha7 nicotinic acetylcholine receptors siRNA transfection assay were used to further explore the anti-inflammatory mechanism of daidzin.Results:Four compounds(verticilloside,soya-cerebroside I,soya-cerebroside II and daidzin)were firstly isolated from the soybean glycolipids,among which verticilloside and daidzin inhibited the lipopolysaccharide,CuSO4-and tail cut-stimulated zebrafish inflammation.Noticeably,daidzin exhibited anti-inflammatory activities by increasing the survival rate,alleviating the inflammatory cells infiltration,and down-regulating the expression of pro-inflammatory cytokines and nuclear factor kappa-B,NF-kappa-B inhibitor alpha,and signal transducer and activator of transcription3 in zebrafish.Moreover,daidzin decreased the secretion of IL-6 and TNF-α,inhibited the nuclear translocations of nuclear factor kappa-B p65 and p-signal transducer and activator of transcription3 as well as the NF-kappa-B inhibitor alpha phosphorylation at Ser32 in RAW 264.7 cells.More importantly,it elevated the expression level of alpha7 nicotinic acetylcholine receptors in both zebrafish and RAW 264.7 cells,and the inhibitory effect of daidzin was attenuated after the addition of alpha7 nicotinic acetylcholine receptors siRNA.Conclusion:Our study revealed that daidzin inhibited inflammation by activating the cholinergic anti-inflammatory pathway and further inhibiting the nuclear factor kappa-B and signal transducer and activator of transcription3 signaling.At the same time,it also promotes the recycling of crude soybean glycolipids and supports the potential use of daidzin as a functional food or natural dietary anti-inflammatory agent.
基金The animal protocols were approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University(SYDW2019-258).
文摘Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD is an important risk factor for cardiovascular and cerebrovascular diseases,including coronary heart disease,stroke,and tumors,with no specific therapeutic drugs currently available.The ethanol extract of cassia seed(CSEE)has shown promise in lowering blood lipids and improving hepatic steatosis,but its mechanism in treating MASLD remains underexplored.This study aims to investigate the therapeutic effects and mechanisms of CSEE.Methods:MASLD models were established in male Wistar rats and golden hamsters using a high fat diet(HFD).CSEE(10,50,250 mg/kg)was administered via gavage for six weeks.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),as well as liver TC and TG,were measured using biochemical kits.Histopathological changes in the liver were evaluated using Oil Red O staining,Hematoxylin-eosin(H&E)staining,and transmission electron microscopy(TEM).HepG2 cell viability was assessed using the cell counting kit-8(CCK8)and Calcein-AM/PI staining.Network pharmacology was used to analyze drug-disease targets,and western blotting was used to confirm these predictions.Results:CSEE treatment significantly reduced serum levels of TC,TG,LDL-C,ALT,and AST,and improved liver weight,liver index,and hepatic lipid deposition in rats and golden hamsters.In addition,CSEE alleviated free fatty acid(FFA)-induced lipid deposition in HepG2 cells.Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK,p-ACC,PPARα,CPT1A,PI3K P110 and p-AKT,while decreasing the protein levels of SREBP1,FASN,C/EBPα,and PPARγ,thus improving hepatic lipid metabolism and reducing lipid deposition.The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro.Conclusion:CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK,PPARα,and PI3K/AKT signaling pathways.
文摘Background and objective:Immediate breast reconstruction not only reduces the number of surgeries for patients after mastectomy but also decreases psychological and physical trauma,making it increasingly popular.However,there is currently no consensus on the integration of post-mastectomy radiotherapy(PMRT)with reconstruction techniques.This review evaluates the impact of PMRT on complications following immediate breast reconstruction,providing guidance for clinical treatment decisions.Methods:PubMed,Web of Science,Embase,and other databases were searched for studies published in the past 15 years on outcomes of implant-based breast reconstruction in the context of radiotherapy to identify articles for analysis.RevMan 5.4 software was used to analyze the risks of seroma,infection,wound dehiscence,flap necrosis,implant exposure,capsule contracture,and reconstruction failure.Results:A total of 1l relevant studies were included,comprising 6323 cases of immediate breast reconstruction.It was found that breasts receiving postoperative irradiation had a significantly increased risk of complications,with statistically significant differences in seroma(P=0.004),infection(P<0.00001),wound dehiscence(P=0.04),implant exposure(P<0.00001),capsule contracture(P<0.00001),and reconstruction failure(P<0.00001).There was no statistically significant difference in flap necrosis(P=0.88).Conclusion:The results indicate that postoperative radiotherapy significantly increases the risk of complications for patients undergoing immediate implant-based reconstruction.Preventive measures may be taken in advance with the assistance of healthcare providers if necessary.
基金supported by the National Natural Science Foundation of China,Nos.81771271(to JF),31800898(to WL),81430025(to JYL),and U1801681(to JYL)Key Research and Development Program of Liaoning Province,No.2020JH2/10300047(to JF)+1 种基金the Key Field Research Development Program of Guangdong Province,No.2018B030337001(to JYL)the Outstanding Scientific Fund of Shengjing Hospital,No.M0475(to JF)。
文摘Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatments may help treat Parkinson's disease.To further investigate the mechanisms of action of these two compounds,we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor linagliptin.We found that both exendin-4 and linagliptin reversed motor dysfunction,glial activation,and dopaminergic neuronal death in this model.In addition,both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion.Moreover,in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain-and leucine-rich-repeat-and pyrin-domaincontaining 3/caspase-1/interleukin-1βpathway and subsequent pyroptosis by decreasing the production of reactive oxygen species.These findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotidebinding oligomerization domain-and leucine-rich-repeat-and pyrin-domain-containing 3/caspase-1/interleukin-1βpathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Therefore,these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.
基金financial support from the National Key R&D Program of China(2018YFD0400500)the Key Research and Development Program of Jiangsu Province(BE2018323)Qing Lan Project of Jiangsu Province and the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘In the present study,the effects of cooked rice(CR)with added fructo-oligosaccharide(FOS)on faecal flora were studied by a simulated in vitro digestion and fermentation method.The total carbohydrate content,p H,and s hort-chain fatty acids(SCFAs)were determined during in vitro digestion and fermentation.The change in the bacterial phase distribution after the fermentation was also analysed.The results showed that t he total carbohydrate content of the CR with added FOS(FCR)significantly decreased during the simulated digestion.Meanwhile,the p H of the FCR decreased and the SCFAs concentration increased significantly compared to those of the CR during the simulated fermentation.In addition,the FCR showed the advantage of promoting beneficial bacteria,such as Bifidobacterium and Lactobacillus,and inhibiting harmful bacteria,such as Bacteroides and Klebsiella compared to the CR.Therefore,the FOS as a prebiotic could be recommended to produce the high-quality healthy rice food.
基金supported by grants from the Natural Science Foundation of Hubei Province(No.2022CFB671)Health Research Project of Hubei Province(No.WJ2023F020)Hubei Province Key Laboratory Open Project(No.2021KFY023).
文摘Objective Liraglutide is a commonly used hypoglycemic agent in clinical practice,and has been demonstrated to have protective effects against the development of cardiovascular disease.However,its potential role in myocardial fibrosis remains unexplored.The present study aims to assess the impact of liraglutide on the activation of cardiac fibroblasts.Methods Primary rat adult fibroblasts were isolated,cultured,and randomly allocated into 4 groups:control group,transforming growth factor beta1(TGFβ1)stimulation group,liraglutide group,and TGFβ1+liraglutide group.Fibroblast activation was induced by TGFβ1.Cell proliferation activity was assessed using the CKK-8 kit,and cellular activity was determined using the MTT kit.Reverse transcrition-quantitative polymerase chain reaction(RT-qPCR)was utilized to quantify the level of collagen transcription,immunofluorescence staining was performed to detect the expression level of type III collagen andα-smooth muscle protein(α-SMA),and immunoblotting was conducted to monitor alterations in signal pathways.Results The addition of 10,25,50 and 100 nmol/L of liraglutide did not induce any significant impact on the viability of fibroblasts(P>0.05).The rate of cellular proliferation was significantly higher in the TGFβl stimulation group than in the control group.However,the treatment with 50 and 100 nmol/L of liraglutide resulted in the reduction of TGFβl-induced cell proliferation(P<0.05).The RT-qPCR results revealed that the transcription levels of type I collagen,type III collagen,andα-SMA were significantly upregulated in the TGFβl stimulation group,when compared to the control group(P<0.05).However,the expression levels of these aforementioned factors significantly decreased in the TGFβl+liraglutide group(P<0.05).The immunofluorescence staining results revealed a significant increase in the expression levels of type III collagen andα-SMA in the TGFβl stimulation group,when compared to the control group(P<0.05).However,these expression levels significantly decreased in the TGFβl+liraglutide group,when compared to the TGFβl stimulation group(P<0.05).The Western blotting results revealed that the expression levels of phosphorylated smad2 and smad3 significantly increased in the TGFβl stimulation group,when compared to the control group(P<0.05),while these decreased in the TGFβl+liraglutide group(P<0.05).Conclusion Liraglutide inhibits myocardial fibrosis development by suppressing the smad signaling pathway,reducing the activation and secretion of cardiac fibroblasts.
基金National Natural Science Foundation of China,Grant/Award Number:12171310。
文摘Probabilistic time series forecasting aims at estimating future probabilistic distributions based on given time series observations.It is a widespread challenge in various tasks,such as risk management and decision making.To investigate temporal patterns in time series data and predict subsequent probabilities,the state space model(SSM)provides a general framework.Variants of SSM achieve considerable success in many fields,such as engineering and statistics.However,since underlying processes in real-world scenarios are usually unknown and complicated,actual time series observations are always irregular and noisy.Therefore,it is very difficult to determinate an SSM for classical statistical approaches.In this paper,a general time series forecasting framework,called Deep Nonlinear State Space Model(DNLSSM),is proposed to predict the probabilistic distribution based on estimated underlying unknown processes from historical time series data.We fuse deep neural networks and statistical methods to iteratively estimate states and network parameters and thus exploit intricate temporal patterns of time series data.In particular,the unscented Kalman filter(UKF)is adopted to calculate marginal likelihoods and update distributions recursively for non-linear functions.After that,a non-linear Joseph form covariance update is developed to ensure that calculated covariance matrices in UKF updates are symmetric and positive definitive.Therefore,the authors enhance the tolerance of UKF to round-off errors and manage to combine UKF and deep neural networks.In this manner,the DNLSSM effectively models non-linear correlations between observed time series data and underlying dynamic processes.Experiments in both synthetic and real-world datasets demonstrate that the DNLSSM consistently improves the accuracy of probability forecasts compared to the baseline methods.
基金Supported by the National Nature Science Foundation of China(No.82070937,No.81870640,No.82000923).
文摘AIM:To observe the effect of low oxygen concentration on the neural retina in human induced pluripotent stem cell(hiPSC)-derived retinal organoids(ROs).METHODS:The hiPSC and a three-dimensional culture method were used for the experiments.Generated embryoid bodies(EBs)were randomly and equally divided into hypoxic and normoxic groups.Photographs of the EBs were taken on days 38,45,and 52,and the corresponding volume of EBs was calculated.Simultaneously,samples were collected at these three timepoints,followed by fixation,sectioning,and immunofluorescence.RESULTS:The proportion of Ki67-positive proliferating cells increased steadily on day 38;this proliferationpromoting effect tended to increase tissue density rather than tissue volume.On days 45 and 52,the two groups had relatively similar ratios of Ki67-positive cells.Further immunofluorescence analysis showed that the ratio of SOX2-positive cells significantly increased within the neural retina on day 52(P<0.05).In contrast,the percentage of PAX6-and CHX10-positive cells significantly decreased following hypoxia treatment at all three timepoints(P<0.01),except for CHX10 at day 45(P>0.05).Moreover,the proportion of PAX6-/TUJ1+cells within the neural retinas increased considerably(P<0.01,<0.05,<0.05 respectively).CONCLUSION:Low oxygen promotes stemness and proliferation of neural retinas,suggesting that hypoxic conditions can enlarge the retinal progenitor cell pool in hiPSC-derived ROs.
基金Supported by Outstanding Graduate Entering Laboratory Project of College of FisheriesGuangdong Ocean University+3 种基金National Natural Science Foundation of China (32073015)Natural Science Foundation of Guangdong Province(2021A1515011078)Undergraduate Innovation and Entrepreneurship Training Program of Guangdong Ocean University (CXXL2022005)Undergraduate Innovation Team of Guangdong Ocean University (CCTD201802)
文摘[Objectives]The paper was to clone and analyze bioinformatics of vscN gene from Vibrio alginolyticus.[Methods]A pair of specific primers was designed based on the vscN gene sequence of V.alginolyticus HY9901.The full length of vscN gene was amplified by PCR and bioinformatics analysis was performed.[Results]The vscN gene was 1323 bp in total,encoding 440 amino acids,with the theoretical molecular weight of 47.86 kD and the theoretical pI value of 5.89.The online prediction showed that there was no signal peptide and no transmembrane region in VscN.The amino acid sequence had 10 N-myristoylation sites,8 phosphorylation sites(2 protein kinase C phosphorylation sites,6 casein kinase II phosphorylation sites),1 amidation site,11 microbody C-terminal target signal sites,1 ATP/GTP binding site motif A(P ring),and 1 ATPaseαandβsubunit specific site.Homology analysis showed that the VscN protein of V.alginolyticus had high homology with that of V.antiquarius,with a similarity of 95.14%.Phylogenetic tree analysis showed that the VscN of V.alginolyticus was clustered into the same subgroup as that of V.diabolicus and V.antiquarius.Functional domain analysis of VscN protein showed that it had Pfam and AAA domains,and involved in the regulation of bacterial virulence.The three-dimensional structure model of VscN simulated by SWISS-MODEL software was similar to the structure of flagellate-specific ATPase FliH-FliI complex.[Conclusions]The results lay a foundation for further study on the regulatory mechanism of VscN protein on bacterial virulence.
基金supported by grants from the Heilongjiang Provincial Traditional Chinese Medicine Research Project:Mechanism study of Zhuyu Ning in treating endometriosis based on the Wnt/β-catenin signaling pathway (ZHY2022-130)the National Traditional Chinese Medicine Clinical Research Base Business Construction Scientific Research Special Project (JDZX2015057)of the State Administration of Traditional Chinese Medicine:Clinical observation of the therapeutic effect of acupuncture on dysmenorrhea in endometriosis based on the VEGF/VEGFR pathway.
文摘Background:Chinese herbal medicines have been proven to be effective in clinical treatment and disease prevention.Jinlingzi San is a herbal medicine used for the treatment of endometriosis.However,a comprehensive network pharmacology approach has not been used to understand the active ingredients and therapeutic mechanisms behind Jinlingzi San in the treatment of endometriosis.Methods:A network pharmacology approach and a molecular docking approach were used to predict the active ingredients and potential targets of Jinlingzi San in the treatment of endometriosis.Results:The integrated network pharmacology approach successfully identified 60 active ingredients and 540 key targets of action in Jinlingzi San dispersion.Among them,STAT3,TP53,MAPK3,RELA,MAPK1,JUN and other key genes were mainly regulated through pathways in cancer,lipid and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,pancreatic cancer,prostate cancer,PI3K-Akt signaling pathway,Th17 cell differentiation,and other signaling pathways in the cell body,receptor complexes,cytoplasm,nucleoplasm,and plasma membrane.Conclusion:Based on a systems network pharmacology approach,our work successfully predicts the active components and potential targets of Jinlingzi San for the treatment of endometriosis and helps to illustrate the mechanism of action at an integrative level.This demonstrates that Jinlingzi San for the treatment of endometriosis is regulated through a multi-component,multi-target,multi-system co-regulation.This study identifies key genes and pathways associated with endometriosis and pathogenesis from new insights,and also provides a viable approach to the chemical basis and pharmacological studies of Jinlingzi San.