Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure.Although folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often...Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure.Although folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain unpreventable.The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains unclear.Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate.To determine the role of SHROOM3 in early developmental morphogenesis,we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase.Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei.These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins,namely fibrous actin(F-actin),myosin II,and phospho-myosin light chain(PMLC),to the apical side of the neuroepithelial cells.Notably,these defects were not rescued by folate supplementation.RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis.In summary,we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.展开更多
Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2...Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.展开更多
Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic ...Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.展开更多
Objective:To investigate the underlying mechanism of anti-inflammatory action of coumarin and eugenol in lipopolysaccharide(LPS)-stimulated RAW 264.7 cells.Methods:RAW 264.7 cells were treated with 2.5μg/mL of LPS,50...Objective:To investigate the underlying mechanism of anti-inflammatory action of coumarin and eugenol in lipopolysaccharide(LPS)-stimulated RAW 264.7 cells.Methods:RAW 264.7 cells were treated with 2.5μg/mL of LPS,50μM of coumarin,and 50μM eugenol for 24 h.The viability of the cells was assessed using MTT assay.The production of nitric oxide was determined using Griess reagent and DCFH-DA was used to measure the production of reactive oxygen species.The protein expression of NLRP3,IL-1β,NF-κB,and cyclooxygenase 2 was assessed using Western blot analysis.Results:Coumarin and eugenol showed anti-inflammatory effects against LPS-induced inflammatory response by ameliorating the expression of NLRP3 inflammasome and NF-κB,which further led to a subsequent reduction in IL-1β,nitric oxide,and reactive oxygen species.Conclusions:Coumarin and eugenol exert their anti-inflammatory activities by modulating the NLRP3 inflammasome pathway and NF-κB.These compounds may have promising therapeutic applications for the treatment of various inflammatory diseases.展开更多
Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with ...Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.展开更多
Surface-supported isolated atoms in single-atom catalysts(SACs)grant maximum utilization of metals in heterogeneous catalysis.Herein,we report a feasible pyrolysis strategy to synthesize Pd single atoms by thermally m...Surface-supported isolated atoms in single-atom catalysts(SACs)grant maximum utilization of metals in heterogeneous catalysis.Herein,we report a feasible pyrolysis strategy to synthesize Pd single atoms by thermally melting Pd nanoparticles on an oxygen-vacancy-rich tungsten-oxide matrix at reduction atmosphere.Near ambient pressure X-ray photoelectron spectroscopy was used to monitor the formation of zero-valence Pd single atoms and the increased metallic feature of WO_(3-x)substrate.Accordingly,the as-obtained zero-valence Pd single-atom catalyst exhibits a markedly boosted HER activity with a low overpotential(η_(10)=70 mV)at the current density of 10 mA/cm2and a small Tafel slope(b=68 mV/dec),nearly 150 mV and a 3,0-fold enhancement than those of Pd nanoparticles(η_(10)=220 mV,b=133 mV/dec)under the same conditions.In addition,quasi in situ XPS results suggest the hydrogen spillover effect is more likely to occur on Pd single atoms during the electrochemical process.Our work may pave an interesting route for the rational design of highly-efficient single-atom catalysts,and the elucidation of corresponding enhanced reaction mechanisms by the utilization of advanced characterization techniques.展开更多
BiVO_(4)(BVO)is a promising material as the photoanode for use in photoelectrochemical applications.However,the high charge recombination and slow charge transfer of the BVO have been obstacles to achieving satisfacto...BiVO_(4)(BVO)is a promising material as the photoanode for use in photoelectrochemical applications.However,the high charge recombination and slow charge transfer of the BVO have been obstacles to achieving satisfactory photoelectrochemical performance.To address this,various modifications have been attempted,including the use of ferroelectric materials.Ferroelectric materials can form a permanent polarization within the layer,enhancing the separation and transport of photo-excited electron-hole pairs.In this study,we propose a novel approach by depositing an epitaxial BiFeO_(3)(BFO)thin film underneath the BVO thin film(BVO/BFO)to harness the ferroelectric property of BFO.The self-polarization of the inserted BFO thin film simultaneously functions as a buffer layer to enhance charge transport and a hole-blocking layer to reduce charge recombination.As a result,the BVO/BFO photoanodes showed more than 3.5 times higher photocurrent density(0.65 mA cm^(-2))at 1.23 V_(RHE)under the illumination compared to the bare BVO photoanodes(0.18 m A cm^(-2)),which is consistent with the increase of the applied bias photon-to-current conversion efficiencies(ABPE)and the result of electrochemical impedance spectroscopy(EIS)analysis.These results can be attributed to the self-polarization exhibited by the inserted BFO thin film,which promoted the charge separation and transfer efficiency of the BVO photoanodes.展开更多
A mixed nitrate (NO_(3)^(–)) and ammonium (NH_(4)^(+)) supply can promote root growth in maize (Zea mays),however,the changes in root morphology and the related physiological mechanism under different N forms are sti...A mixed nitrate (NO_(3)^(–)) and ammonium (NH_(4)^(+)) supply can promote root growth in maize (Zea mays),however,the changes in root morphology and the related physiological mechanism under different N forms are still unclear.Here,maize seedlings were grown hydroponically with three N supplied in three different forms (NO_(3)^(–)only,75/25 NO_(3)^(–)/NH_(4)^(+)and NH_(4)^(+)only).Compared with sole NO_(3)^(–)or NH_(4)^(+),the mixed N supply increased the total root length of maize but did not affect the number of axial roots.The main reason was the increased total lateral root length,while the average lateral root (LR) length in each axle was only slightly increased.In addition,the average LR density of 2nd whorl crown root under mixed N was also increased.Compared with sole nitrate,mixed N could improve the N metabolism of roots (such as the N influx rate,nitrate reductase (NR) and glutamine synthase (GS)enzyme activities and total amino content of the roots).Experiments with exogenously added NR and GS inhibitors suggested that the increase in the average LR length under mixed N was related to the process of N assimilation,and whether the NR mediated NO synthesis participates in this process needs further exploration.Meanwhile,an investigation of the changes in root-shoot ratio and carbon (C) concentration showed that C transportation from shoots to roots may not be the key factor in mediating lateral root elongation,and the changes in the sugar concentration in roots further proved this conclusion.Furthermore,the synthesis and transportation of auxin in axial roots may play a key role in lateral root elongation,in which the expression of ZmPIN1B and ZmPIN9 may be involved in this pathway.This study preliminarily clarified the changes in root morphology and explored the possible physiological mechanism under a mixed N supply in maize,which may provide some theoretical basis for the cultivation of crop varieties with high N efficiency.展开更多
Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect...Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo.Cell free extracts of high dose L.rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1%to 14.9%by inhibiting NLRP3 recruitment,which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder.In purine dietary induced hyperuricemia(PDIH)mice model,liver oedema and pyroptosis were ameliorated after L.rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3,caspase-1 and gasdermin-D from 1.61 to 0.86,3.15 to 1.01 and 5.63 to 2.02,respectively.L.rhamnosus Fmb14 administration restored mitochondrial inner membrane protein(MPV17)and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice,indicating that dysbiosis of mitochondrial membrane potential was restored in liver.Intriguingly,PDIH pyroptosis stimulates the process of apoptosis,which leads to severe leakage of hepatocytes,and both of pyroptosis and apoptosis were decreased after L.rhamnosus Fmb14 treatment.Therefore,L.rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.展开更多
BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancre...BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.展开更多
Monocular 3D object detection is challenging due to the lack of accurate depth information.Some methods estimate the pixel-wise depth maps from off-the-shelf depth estimators and then use them as an additional input t...Monocular 3D object detection is challenging due to the lack of accurate depth information.Some methods estimate the pixel-wise depth maps from off-the-shelf depth estimators and then use them as an additional input to augment the RGB images.Depth-based methods attempt to convert estimated depth maps to pseudo-LiDAR and then use LiDAR-based object detectors or focus on the perspective of image and depth fusion learning.However,they demonstrate limited performance and efficiency as a result of depth inaccuracy and complex fusion mode with convolutions.Different from these approaches,our proposed depth-guided vision transformer with a normalizing flows(NF-DVT)network uses normalizing flows to build priors in depth maps to achieve more accurate depth information.Then we develop a novel Swin-Transformer-based backbone with a fusion module to process RGB image patches and depth map patches with two separate branches and fuse them using cross-attention to exchange information with each other.Furthermore,with the help of pixel-wise relative depth values in depth maps,we develop new relative position embeddings in the cross-attention mechanism to capture more accurate sequence ordering of input tokens.Our method is the first Swin-Transformer-based backbone architecture for monocular 3D object detection.The experimental results on the KITTI and the challenging Waymo Open datasets show the effectiveness of our proposed method and superior performance over previous counterparts.展开更多
BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value...BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.展开更多
Objective:To investigate the effect of honokiol on microglia polarization and the underlying mechanism.Methods:Inflammatory factors were detected using ELISA to determine the optimal concentration of cobalt chloride t...Objective:To investigate the effect of honokiol on microglia polarization and the underlying mechanism.Methods:Inflammatory factors were detected using ELISA to determine the optimal concentration of cobalt chloride to induce,and that of honokiol to treat chronic hypoxia(48 h)in microglia cell line BV2 cells.BV2 cells were divided into four groups:control,chronic hypoxia,chronic hypoxia+honokiol,chronic hypoxia+honokiol+3-TYP(SIRT3 inhibitor).ELISA was used to measure the concentration of supernatant TNFαand IL-1βproteins,qPCR was used to detect the expression of cellular M1 and M2 polarization markers,and biochemical assays were used to detect the level of reactive oxygen species in each group.Western Blot was used to detect protein levels of SIRT3 and upstream inflammatory molecules NLRP3 and caspase1.Results:Chronic cobalt chloride stimulation of BV2 cells at an optimal concentration of 100μmol/L significantly increased the release of inflammatory fac-tors TNFαand IL-1βafter stimulation compared with the control group(P<0.05);compared with the control group,cells in the chronic hypoxia group had down-regulation of SIRT3 protein expression,whereas the ROS levels,NLRP3 and caspase1 protein levels,the M1 polarization marker CD86,iNOS mRNA levels and CD16/32 ratio were upregulated.and honokiol(10μmol/L)significantly up-regulated the SIRT3 protein and mRNA levels of M2 markers Arg-1 and CD206 in chronic hypoxic cells(P<0.05)and down-regulated levels of ROS,NLRP3/caspase1 protein,and mRNA levels of M1 markers(P<0.05),and this anti-oxidative and anti-inflammatory effect was able to be reversed by SIRT3 inhibitor.Conclusion:Honokiol inhibits chronic hypoxia-induced microglia M1 polarization and inflammatory pathway activation,and its anti-inflammatory effects are SIRT3-de-pendent.展开更多
MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to...MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.展开更多
Background:Hepatocellular carcinoma(HCC),the most common type of primary liver cancer,is the fourth leading cause of cancer-related deaths worldwide.Previous evidence shows that the expression of circulating RNA ZFR(c...Background:Hepatocellular carcinoma(HCC),the most common type of primary liver cancer,is the fourth leading cause of cancer-related deaths worldwide.Previous evidence shows that the expression of circulating RNA ZFR(circZFR)is upregulated in HCC tissues.However,the molecular mechanism of circZFR in HCC is unclear.Methods:Quantitative reverse transcriptase polymerase chain reaction(qRT-PCR)was employed to detect the expression of circZFR,microRNA-624-3p(miR-624-3p)and WEE1 in HCC tissues and cells.RNase R assay and actinomycin D treatment assay were used to analyze the characteristics of circZFR.For functional analysis,the capacities of colony formation,cell proliferation,cell apoptosis,migration and invasion were assessed by colony formation assay,5-ethynyl-2-deoxyuridine(EdU)assay,flow cytometry assay and transwell assay.Western blot was used to examine the protein levels of WEE1 and epithelial-mesenchymal transition(EMT)-related proteins.The interactions between miR-624-3p and circZFR or WEE1 were validated by dual-luciferase reporter assay and RNA immunoprecipitation(RIP)assay.Xenograft models were established to determine the role of circZFR in vivo.Results:circZFR and WEE1 were upregulated,while miR-624-3p expression was reduced in HCC tissues and cells.circZFR could sponge miR-624-3p,and WEE1 was a downstream gene of miR-624-3p.Knockdown of circZFR significantly reduced the malignant behaviors of HCC and that co-transfection with miR624-3p inhibitor restored this change.Overexpression of WEE1 abolished the inhibitory effect of miR624-3p mimic on HCC cells.Mechanistically,circZFR acted as a competitive endogenous RNA(ceRNA)to regulate WEE1 expression by targeting miR-624-3p.Furthermore,in vivo studies have illustrated that circZFR knockdown inhibited tumor growth.Conclusions:circZFR knockdown reduced HCC cell proliferation,migration and invasion and promoted apoptosis by regulating the miR-624-3p/WEE1 axis,suggesting that the circZFR/miR-624-3p/WEE1 axis might be a potential target for HCC treatment.展开更多
A novel three-dimensional-fiber reinforced soft pneumatic actuator(3D-FRSPA)inspired by crab claw and human hand structure that can bend and deform independently in each segment is proposed.It has an omni-directional ...A novel three-dimensional-fiber reinforced soft pneumatic actuator(3D-FRSPA)inspired by crab claw and human hand structure that can bend and deform independently in each segment is proposed.It has an omni-directional bending configuration,and the fibers twined symmetrically on both sides to improve the bending performance of FRSPA.In this paper,the static and kinematic analysis of 3D-FRSPA are carried out in detail.The effects of fiber,pneumatic chamber and segment length,and circular air chamber radius of 3D-FRSPA on the mechanical performance of the actuator are discussed,respectively.The soft mobile robot composed of 3D-FRSPA has the ability to crawl.Finally,the crawling processes of the soft mobile robot on different road conditions are studied,respectively,and the motion mechanism of the mobile actuator is shown.The numerical results show that the soft mobile robots have a good comprehensive performance,which verifies the correctness of the proposedmodel.This work shows that the proposed structures have great potential in complex road conditions,unknown space detection and other operations.展开更多
Background:Oxidative stress is one of the key elements in the progression of non-alcoholic fatty liver disease(NAFLD),and Yiqi Tongluo capsule(YTC)have a variety of physiological activities which include antioxidant.T...Background:Oxidative stress is one of the key elements in the progression of non-alcoholic fatty liver disease(NAFLD),and Yiqi Tongluo capsule(YTC)have a variety of physiological activities which include antioxidant.The purpose of this investigation was to discover the potential mechanisms of YTC ameliorates NAFLD.Methods:In this investigation,a high-fat diet(HFD)was adopted to establish a NAFLD mouse model.Liver samples were stained for oil red O and hematoxylin and eosin staining.The levels of total cholesterol(TC),triglyceride(TG),malondialdehyde(MDA),and superoxide dismutase(SOD)in the tissues were also detected.Network pharmacology was analyzed to filter out the key ingredients and targets of effect of YTC for the therapy of NAFLD.Subsequently,free fatty acids(FFA)was applied to induce Aml12 cells for in vitro experiments,and the cell samples were stained with oil red O and assayed for TC,TG,MDA,and SOD contents.At last,the Western blot technique was used to illuminate the pathway by which YTC plays a protective role against NAFLD.Results:Histopathological results demonstrated that YTC ameliorated tissue damage in the HFD-induced mouse model.At the same time,it also reduced the contents of TC,TG,MDA and increased the expression of SOD in the liver tissue of NAFLD mouse model.All of these findings demonstrate that YTC can play a role in the treatment of NAFLD by ameliorating oxidative stress.Network analysis of YTC ameliorates NAFLD mainly by modulating the PI3K-Akt signaling pathway.Follow-up in vitro experiments revealed that FFA caused lipid accumulation in Aml12 cells,which was dramatically reduced by YTC.Meanwhile,YTC could remarkably reduce the FFA-induced elevation of TC,TG,and MDA contents,and reverse the FFA-induced reduction of SOD contents.Western blot was verified for the PI3K-Akt signaling pathway.It was found that FFA could remarkably decrease the expression of p-PI3K,p-Akt,and p-GSK-3βproteins,which could be significantly increased after YTC treatment.Conclusions:The combination of network analysis prediction and experimental verification was used to identify the therapeutic effect of YTC on NAFLD.The protective effect was achieved by YTC through upregulation of PI3K-Akt-GSK-3βpathway.展开更多
Genetic manipulation(either restraint or enhancement)of the biosynthesis pathway ofα-linolenic acid(ALA)in seed oil is an important goal in Brassica napus breeding.B.napus is a tetraploid plant whose genome often har...Genetic manipulation(either restraint or enhancement)of the biosynthesis pathway ofα-linolenic acid(ALA)in seed oil is an important goal in Brassica napus breeding.B.napus is a tetraploid plant whose genome often har-bors four and six homologous copies,respectively,of the two fatty acid desaturases FAD2 and FAD3,which con-trol the last two steps of ALA biosynthesis during seed oil accumulation.In this study,we compared their promoters,coding sequences,and expression levels in three high-ALA inbred lines 2006L,R8Q10,and YH25005,a low-ALA line A28,a low-ALA/high-oleic-acid accession SW,and the wildtype ZS11.The expression levels of most FAD2 and FAD3 homologs in the three high-ALA accessions were higher than those in ZS11 and much higher than those in A28 and SW.The three high-ALA accessions shared similar sequences with the pro-moters and CDSs of BnFAD3.C4 and BnFAD3.A3.In A28 and SW,substitution of three amino acid residues in BnFAD2.A5 and BnFAD2.C5,an absence of BnFAD2.C1 locus,and a 549 bp long deletion on the BnFAD3.A3 promoter were detected.The profile of BnFAD2 mutation in the two low-ALA accessions A28 and SW is different from that reported in previous studies.The mutations in BnFAD3 in the high-ALA accessions are reported for thefirst time.In identifying the sites of these mutations,we provide detailed information to aid the design of mole-cular markers for accelerated breeding schemes.展开更多
BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to asce...BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic activity.METHODS Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and MC5R.Colonic sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal mucosa.CONCLUSION MC3R and MC5R are expressed in the colon of IBD patients.Furthermore,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.展开更多
基金supported by the National Natural Science Foundation of China (81930121,82125008 to Y.C.C.)National Key Research and Development Program of China (2018YFA0107902 to Y.C.C.and 2018YFA0801403 to Z.B.W.)+1 种基金Major Basic Research Project of Science and Technology of Yunnan (202001BC070001 to Y.C.C.)Natural Science Foundation of Yunnan Province (202102AA100053 to Y.C.C.)。
文摘Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure.Although folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain unpreventable.The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains unclear.Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate.To determine the role of SHROOM3 in early developmental morphogenesis,we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase.Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei.These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins,namely fibrous actin(F-actin),myosin II,and phospho-myosin light chain(PMLC),to the apical side of the neuroepithelial cells.Notably,these defects were not rescued by folate supplementation.RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis.In summary,we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.
基金funded by the National Key Research and Development Program of China(2020YFD0900902)Zhejiang Province Public Welfare Technology Application Research Project(LGJ21C20001)Zhejiang Provincial Key Research and Development Project of China(2019C02076 and 2019C02075)。
文摘Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.
基金supported by the National Natural Science Foundation of China,No.81971246 (to TM)Opening Foundation of Jiangsu Key Laboratory of Neurodegeneration,Nanjing Medical University,No.KF202204 (to LZ and SF)。
文摘Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.
基金supported by the Defence Institute of Physiology and Allied Sciences.
文摘Objective:To investigate the underlying mechanism of anti-inflammatory action of coumarin and eugenol in lipopolysaccharide(LPS)-stimulated RAW 264.7 cells.Methods:RAW 264.7 cells were treated with 2.5μg/mL of LPS,50μM of coumarin,and 50μM eugenol for 24 h.The viability of the cells was assessed using MTT assay.The production of nitric oxide was determined using Griess reagent and DCFH-DA was used to measure the production of reactive oxygen species.The protein expression of NLRP3,IL-1β,NF-κB,and cyclooxygenase 2 was assessed using Western blot analysis.Results:Coumarin and eugenol showed anti-inflammatory effects against LPS-induced inflammatory response by ameliorating the expression of NLRP3 inflammasome and NF-κB,which further led to a subsequent reduction in IL-1β,nitric oxide,and reactive oxygen species.Conclusions:Coumarin and eugenol exert their anti-inflammatory activities by modulating the NLRP3 inflammasome pathway and NF-κB.These compounds may have promising therapeutic applications for the treatment of various inflammatory diseases.
基金supported by grants from the Spanish Ministry of Health-PNSD(2019-I039 and 2023-I024)(to MP)FEDER/Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación PID2021-1243590B-I100(to VMM)+2 种基金GVA(CIAICO/2021/203)(to MP)the Primary Addiction Care Research Network(RD21/0009/0005)(to MP)and a predoctoral fellowship from the Generalitat Valenciana(ACIF/2021/338)(to CPC).
文摘Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.
基金the support from the National Key R&D Program of China(No.2022YFA1503801)the National Natural Science Foundation of China(No.22172190,No.22202232 and No.22109171)。
文摘Surface-supported isolated atoms in single-atom catalysts(SACs)grant maximum utilization of metals in heterogeneous catalysis.Herein,we report a feasible pyrolysis strategy to synthesize Pd single atoms by thermally melting Pd nanoparticles on an oxygen-vacancy-rich tungsten-oxide matrix at reduction atmosphere.Near ambient pressure X-ray photoelectron spectroscopy was used to monitor the formation of zero-valence Pd single atoms and the increased metallic feature of WO_(3-x)substrate.Accordingly,the as-obtained zero-valence Pd single-atom catalyst exhibits a markedly boosted HER activity with a low overpotential(η_(10)=70 mV)at the current density of 10 mA/cm2and a small Tafel slope(b=68 mV/dec),nearly 150 mV and a 3,0-fold enhancement than those of Pd nanoparticles(η_(10)=220 mV,b=133 mV/dec)under the same conditions.In addition,quasi in situ XPS results suggest the hydrogen spillover effect is more likely to occur on Pd single atoms during the electrochemical process.Our work may pave an interesting route for the rational design of highly-efficient single-atom catalysts,and the elucidation of corresponding enhanced reaction mechanisms by the utilization of advanced characterization techniques.
基金supported by the program of Future Hydrogen Original Technology Development(2021M3I3A1084747),through the National Research Foundation of Korea(NRF)funded by the Korean government(Ministry of Science and ICT(MSIT))by the NRF grant funded by the Korea government(MSIT)(No.2020R1A2C1005590)。
文摘BiVO_(4)(BVO)is a promising material as the photoanode for use in photoelectrochemical applications.However,the high charge recombination and slow charge transfer of the BVO have been obstacles to achieving satisfactory photoelectrochemical performance.To address this,various modifications have been attempted,including the use of ferroelectric materials.Ferroelectric materials can form a permanent polarization within the layer,enhancing the separation and transport of photo-excited electron-hole pairs.In this study,we propose a novel approach by depositing an epitaxial BiFeO_(3)(BFO)thin film underneath the BVO thin film(BVO/BFO)to harness the ferroelectric property of BFO.The self-polarization of the inserted BFO thin film simultaneously functions as a buffer layer to enhance charge transport and a hole-blocking layer to reduce charge recombination.As a result,the BVO/BFO photoanodes showed more than 3.5 times higher photocurrent density(0.65 mA cm^(-2))at 1.23 V_(RHE)under the illumination compared to the bare BVO photoanodes(0.18 m A cm^(-2)),which is consistent with the increase of the applied bias photon-to-current conversion efficiencies(ABPE)and the result of electrochemical impedance spectroscopy(EIS)analysis.These results can be attributed to the self-polarization exhibited by the inserted BFO thin film,which promoted the charge separation and transfer efficiency of the BVO photoanodes.
基金supported by the National Natural Science Foundation of China(31421092)the Central Publicinterest Scientific Institution Basal Research Fund,China(1610232023023)。
文摘A mixed nitrate (NO_(3)^(–)) and ammonium (NH_(4)^(+)) supply can promote root growth in maize (Zea mays),however,the changes in root morphology and the related physiological mechanism under different N forms are still unclear.Here,maize seedlings were grown hydroponically with three N supplied in three different forms (NO_(3)^(–)only,75/25 NO_(3)^(–)/NH_(4)^(+)and NH_(4)^(+)only).Compared with sole NO_(3)^(–)or NH_(4)^(+),the mixed N supply increased the total root length of maize but did not affect the number of axial roots.The main reason was the increased total lateral root length,while the average lateral root (LR) length in each axle was only slightly increased.In addition,the average LR density of 2nd whorl crown root under mixed N was also increased.Compared with sole nitrate,mixed N could improve the N metabolism of roots (such as the N influx rate,nitrate reductase (NR) and glutamine synthase (GS)enzyme activities and total amino content of the roots).Experiments with exogenously added NR and GS inhibitors suggested that the increase in the average LR length under mixed N was related to the process of N assimilation,and whether the NR mediated NO synthesis participates in this process needs further exploration.Meanwhile,an investigation of the changes in root-shoot ratio and carbon (C) concentration showed that C transportation from shoots to roots may not be the key factor in mediating lateral root elongation,and the changes in the sugar concentration in roots further proved this conclusion.Furthermore,the synthesis and transportation of auxin in axial roots may play a key role in lateral root elongation,in which the expression of ZmPIN1B and ZmPIN9 may be involved in this pathway.This study preliminarily clarified the changes in root morphology and explored the possible physiological mechanism under a mixed N supply in maize,which may provide some theoretical basis for the cultivation of crop varieties with high N efficiency.
基金Grant support was received from the National Natural Science Foundation of China(32072182).
文摘Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo.Cell free extracts of high dose L.rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1%to 14.9%by inhibiting NLRP3 recruitment,which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder.In purine dietary induced hyperuricemia(PDIH)mice model,liver oedema and pyroptosis were ameliorated after L.rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3,caspase-1 and gasdermin-D from 1.61 to 0.86,3.15 to 1.01 and 5.63 to 2.02,respectively.L.rhamnosus Fmb14 administration restored mitochondrial inner membrane protein(MPV17)and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice,indicating that dysbiosis of mitochondrial membrane potential was restored in liver.Intriguingly,PDIH pyroptosis stimulates the process of apoptosis,which leads to severe leakage of hepatocytes,and both of pyroptosis and apoptosis were decreased after L.rhamnosus Fmb14 treatment.Therefore,L.rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.
基金Supported by National Natural Science Foundation of China,No.81802450and Natural Science Foundation of Hunan Province,No.2020JJ4133 and No.2021JJ31135.
文摘BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.
基金supported in part by the Major Project for New Generation of AI (2018AAA0100400)the National Natural Science Foundation of China (61836014,U21B2042,62072457,62006231)the InnoHK Program。
文摘Monocular 3D object detection is challenging due to the lack of accurate depth information.Some methods estimate the pixel-wise depth maps from off-the-shelf depth estimators and then use them as an additional input to augment the RGB images.Depth-based methods attempt to convert estimated depth maps to pseudo-LiDAR and then use LiDAR-based object detectors or focus on the perspective of image and depth fusion learning.However,they demonstrate limited performance and efficiency as a result of depth inaccuracy and complex fusion mode with convolutions.Different from these approaches,our proposed depth-guided vision transformer with a normalizing flows(NF-DVT)network uses normalizing flows to build priors in depth maps to achieve more accurate depth information.Then we develop a novel Swin-Transformer-based backbone with a fusion module to process RGB image patches and depth map patches with two separate branches and fuse them using cross-attention to exchange information with each other.Furthermore,with the help of pixel-wise relative depth values in depth maps,we develop new relative position embeddings in the cross-attention mechanism to capture more accurate sequence ordering of input tokens.Our method is the first Swin-Transformer-based backbone architecture for monocular 3D object detection.The experimental results on the KITTI and the challenging Waymo Open datasets show the effectiveness of our proposed method and superior performance over previous counterparts.
基金Supported by National Nature Science Foundation of China,No.82060450,No.82360517,No.81460374,and No.31460304Nature Science Foundation of Jiangxi Province of China,No.20232BAB206086,No.20192BAB205072,No.20203BBGL73206,No.2017BCB23086,No.2017BAB205062,and No.20181BAB205050.
文摘BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.
基金National Natural Science Foundation of China(No.82101280)。
文摘Objective:To investigate the effect of honokiol on microglia polarization and the underlying mechanism.Methods:Inflammatory factors were detected using ELISA to determine the optimal concentration of cobalt chloride to induce,and that of honokiol to treat chronic hypoxia(48 h)in microglia cell line BV2 cells.BV2 cells were divided into four groups:control,chronic hypoxia,chronic hypoxia+honokiol,chronic hypoxia+honokiol+3-TYP(SIRT3 inhibitor).ELISA was used to measure the concentration of supernatant TNFαand IL-1βproteins,qPCR was used to detect the expression of cellular M1 and M2 polarization markers,and biochemical assays were used to detect the level of reactive oxygen species in each group.Western Blot was used to detect protein levels of SIRT3 and upstream inflammatory molecules NLRP3 and caspase1.Results:Chronic cobalt chloride stimulation of BV2 cells at an optimal concentration of 100μmol/L significantly increased the release of inflammatory fac-tors TNFαand IL-1βafter stimulation compared with the control group(P<0.05);compared with the control group,cells in the chronic hypoxia group had down-regulation of SIRT3 protein expression,whereas the ROS levels,NLRP3 and caspase1 protein levels,the M1 polarization marker CD86,iNOS mRNA levels and CD16/32 ratio were upregulated.and honokiol(10μmol/L)significantly up-regulated the SIRT3 protein and mRNA levels of M2 markers Arg-1 and CD206 in chronic hypoxic cells(P<0.05)and down-regulated levels of ROS,NLRP3/caspase1 protein,and mRNA levels of M1 markers(P<0.05),and this anti-oxidative and anti-inflammatory effect was able to be reversed by SIRT3 inhibitor.Conclusion:Honokiol inhibits chronic hypoxia-induced microglia M1 polarization and inflammatory pathway activation,and its anti-inflammatory effects are SIRT3-de-pendent.
基金supported by Correlation between RECK and GH-type pituitary adenomas(No.21JR11RE027).
文摘MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.
文摘Background:Hepatocellular carcinoma(HCC),the most common type of primary liver cancer,is the fourth leading cause of cancer-related deaths worldwide.Previous evidence shows that the expression of circulating RNA ZFR(circZFR)is upregulated in HCC tissues.However,the molecular mechanism of circZFR in HCC is unclear.Methods:Quantitative reverse transcriptase polymerase chain reaction(qRT-PCR)was employed to detect the expression of circZFR,microRNA-624-3p(miR-624-3p)and WEE1 in HCC tissues and cells.RNase R assay and actinomycin D treatment assay were used to analyze the characteristics of circZFR.For functional analysis,the capacities of colony formation,cell proliferation,cell apoptosis,migration and invasion were assessed by colony formation assay,5-ethynyl-2-deoxyuridine(EdU)assay,flow cytometry assay and transwell assay.Western blot was used to examine the protein levels of WEE1 and epithelial-mesenchymal transition(EMT)-related proteins.The interactions between miR-624-3p and circZFR or WEE1 were validated by dual-luciferase reporter assay and RNA immunoprecipitation(RIP)assay.Xenograft models were established to determine the role of circZFR in vivo.Results:circZFR and WEE1 were upregulated,while miR-624-3p expression was reduced in HCC tissues and cells.circZFR could sponge miR-624-3p,and WEE1 was a downstream gene of miR-624-3p.Knockdown of circZFR significantly reduced the malignant behaviors of HCC and that co-transfection with miR624-3p inhibitor restored this change.Overexpression of WEE1 abolished the inhibitory effect of miR624-3p mimic on HCC cells.Mechanistically,circZFR acted as a competitive endogenous RNA(ceRNA)to regulate WEE1 expression by targeting miR-624-3p.Furthermore,in vivo studies have illustrated that circZFR knockdown inhibited tumor growth.Conclusions:circZFR knockdown reduced HCC cell proliferation,migration and invasion and promoted apoptosis by regulating the miR-624-3p/WEE1 axis,suggesting that the circZFR/miR-624-3p/WEE1 axis might be a potential target for HCC treatment.
基金work is supported by the Fundamental Research Funds for the Central Universities(Grant No.B230205021)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(GrantNo.KYCX22_0592).The financial supports are gratefully acknowl-edged.
文摘A novel three-dimensional-fiber reinforced soft pneumatic actuator(3D-FRSPA)inspired by crab claw and human hand structure that can bend and deform independently in each segment is proposed.It has an omni-directional bending configuration,and the fibers twined symmetrically on both sides to improve the bending performance of FRSPA.In this paper,the static and kinematic analysis of 3D-FRSPA are carried out in detail.The effects of fiber,pneumatic chamber and segment length,and circular air chamber radius of 3D-FRSPA on the mechanical performance of the actuator are discussed,respectively.The soft mobile robot composed of 3D-FRSPA has the ability to crawl.Finally,the crawling processes of the soft mobile robot on different road conditions are studied,respectively,and the motion mechanism of the mobile actuator is shown.The numerical results show that the soft mobile robots have a good comprehensive performance,which verifies the correctness of the proposedmodel.This work shows that the proposed structures have great potential in complex road conditions,unknown space detection and other operations.
基金This work was supported by Science and Technology Program of Guangyuan city(grant number:23ZDYF0018)Sichuan Science and Technology Program(grant number:2020YFS0523)。
文摘Background:Oxidative stress is one of the key elements in the progression of non-alcoholic fatty liver disease(NAFLD),and Yiqi Tongluo capsule(YTC)have a variety of physiological activities which include antioxidant.The purpose of this investigation was to discover the potential mechanisms of YTC ameliorates NAFLD.Methods:In this investigation,a high-fat diet(HFD)was adopted to establish a NAFLD mouse model.Liver samples were stained for oil red O and hematoxylin and eosin staining.The levels of total cholesterol(TC),triglyceride(TG),malondialdehyde(MDA),and superoxide dismutase(SOD)in the tissues were also detected.Network pharmacology was analyzed to filter out the key ingredients and targets of effect of YTC for the therapy of NAFLD.Subsequently,free fatty acids(FFA)was applied to induce Aml12 cells for in vitro experiments,and the cell samples were stained with oil red O and assayed for TC,TG,MDA,and SOD contents.At last,the Western blot technique was used to illuminate the pathway by which YTC plays a protective role against NAFLD.Results:Histopathological results demonstrated that YTC ameliorated tissue damage in the HFD-induced mouse model.At the same time,it also reduced the contents of TC,TG,MDA and increased the expression of SOD in the liver tissue of NAFLD mouse model.All of these findings demonstrate that YTC can play a role in the treatment of NAFLD by ameliorating oxidative stress.Network analysis of YTC ameliorates NAFLD mainly by modulating the PI3K-Akt signaling pathway.Follow-up in vitro experiments revealed that FFA caused lipid accumulation in Aml12 cells,which was dramatically reduced by YTC.Meanwhile,YTC could remarkably reduce the FFA-induced elevation of TC,TG,and MDA contents,and reverse the FFA-induced reduction of SOD contents.Western blot was verified for the PI3K-Akt signaling pathway.It was found that FFA could remarkably decrease the expression of p-PI3K,p-Akt,and p-GSK-3βproteins,which could be significantly increased after YTC treatment.Conclusions:The combination of network analysis prediction and experimental verification was used to identify the therapeutic effect of YTC on NAFLD.The protective effect was achieved by YTC through upregulation of PI3K-Akt-GSK-3βpathway.
基金The study was financially supported by Projects from Shaanxi Province(2021LLRH-07-03-01 and 2023-ZDLNY-07)Yangling Seed Industry Innovation(YLzy-yc2021-01).The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Genetic manipulation(either restraint or enhancement)of the biosynthesis pathway ofα-linolenic acid(ALA)in seed oil is an important goal in Brassica napus breeding.B.napus is a tetraploid plant whose genome often har-bors four and six homologous copies,respectively,of the two fatty acid desaturases FAD2 and FAD3,which con-trol the last two steps of ALA biosynthesis during seed oil accumulation.In this study,we compared their promoters,coding sequences,and expression levels in three high-ALA inbred lines 2006L,R8Q10,and YH25005,a low-ALA line A28,a low-ALA/high-oleic-acid accession SW,and the wildtype ZS11.The expression levels of most FAD2 and FAD3 homologs in the three high-ALA accessions were higher than those in ZS11 and much higher than those in A28 and SW.The three high-ALA accessions shared similar sequences with the pro-moters and CDSs of BnFAD3.C4 and BnFAD3.A3.In A28 and SW,substitution of three amino acid residues in BnFAD2.A5 and BnFAD2.C5,an absence of BnFAD2.C1 locus,and a 549 bp long deletion on the BnFAD3.A3 promoter were detected.The profile of BnFAD2 mutation in the two low-ALA accessions A28 and SW is different from that reported in previous studies.The mutations in BnFAD3 in the high-ALA accessions are reported for thefirst time.In identifying the sites of these mutations,we provide detailed information to aid the design of mole-cular markers for accelerated breeding schemes.
基金The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of University of Campania Luigi Vanvitelli(Protocol code 795 on December 23,2019).
文摘BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic activity.METHODS Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and MC5R.Colonic sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal mucosa.CONCLUSION MC3R and MC5R are expressed in the colon of IBD patients.Furthermore,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.