Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to p...Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.展开更多
After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact...After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.展开更多
Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may de...Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.展开更多
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.展开更多
In order to improve the efficiency of cloud-based web services,an improved plant growth simulation algorithm scheduling model.This model first used mathematical methods to describe the relationships between cloud-base...In order to improve the efficiency of cloud-based web services,an improved plant growth simulation algorithm scheduling model.This model first used mathematical methods to describe the relationships between cloud-based web services and the constraints of system resources.Then,a light-induced plant growth simulation algorithm was established.The performance of the algorithm was compared through several plant types,and the best plant model was selected as the setting for the system.Experimental results show that when the number of test cloud-based web services reaches 2048,the model being 2.14 times faster than PSO,2.8 times faster than the ant colony algorithm,2.9 times faster than the bee colony algorithm,and a remarkable 8.38 times faster than the genetic algorithm.展开更多
Florfenicol(FLO)is a chemically synthesized broad-spectrum antimicrobial agent of amide alcohols for animals,which is one of the most widely used antimicrobials in livestock,poultry,and aquaculture.With the use of FLo...Florfenicol(FLO)is a chemically synthesized broad-spectrum antimicrobial agent of amide alcohols for animals,which is one of the most widely used antimicrobials in livestock,poultry,and aquaculture.With the use of FLo,more and more attention has been paid to its hematopoietic toxicity,immunotoxicity,genotoxicity,and embryotoxicity.In this study,SPF chicks.at the age of 3 d began to drink water with the FLO at a dose of 100 mg L^(-1)for 6 consecutive days,and the growth performance of chicks was monitored,the effect of FLO on immune organs was detected by pathological examination and TdT-mediated dUTP nick-end labeling(TUNEL)apoptosis staining.In order to evaluate the level of organism immunity,the level of Newcastle disease virus antibody in serum was detected by hemagglutination inhibition test,the content of cytokines(IL-1,IL-2,IL-6,TNF-α,IFN-γ)in serum was detected by enzyme linked immunosorbent assay(ELISA),and the transcription of interferon-related genes(IRF-7,2′-5′OAS,Mx1)and cytokine genes(IL-6,TNF-α,IFN-γ)in immune organs were detected by real time fluorescence quantitative PCR.The results showed that the early application of FLO could inhibit the growth and development of chicks,and the body weight and immune organ index of the treatment group were lower than those of the control group.Histopathological examination showed that there was a decrease in the number of lymphocytes in the bursa of Fabricius in the treatment group in the early stage of drug withdrawal,and the results of TUNEL apoptosis staining in the bursa of Fabricius showed that obvious lymphocyte apoptosis occurred in the FLO treatment group.Compared with the control group,the transcription levels of interferon-related genes IRF-7,2′-5′OAS,and cytokine genes IL-6,TNF-αand IFN-γin FLO treatment group decreased to a certain extent,while the transcription level of Mx1 gene had no significant difference at all time points.The level of serum Newcastle disease virus(NDV)antibody and the contents of cytokines IL-1,IL-2 and IFN-γin the FLO treatment group were significantly lower than those in the control group in the early stage of drug withdrawal,but recovered gradually in the later stage.This study showed that FLO has a certain degree of effect on the immune function of chicks,and the results of the study laid the foundation for further research on the mechanism of FLO-induced immunotoxicity.展开更多
Rapid growth is an innovative trait of woody bamboos that has been widely studied.However,the genetic basis and evolution of this trait are poorly understood.Taking advantage of genomic resources of 11 representative ...Rapid growth is an innovative trait of woody bamboos that has been widely studied.However,the genetic basis and evolution of this trait are poorly understood.Taking advantage of genomic resources of 11 representative bamboos at different ploidal levels,we integrated morphological,physiological,and transcriptomic datasets to investigate rapid growth.In particular,these bamboos include two large-sized and a small-sized woody species,compared with a diploid herbaceous species.Our results showed that gibberellin A1 was important for the rapid shoot growth of the world's largest bamboo,Dendrocalamus sinicus,and indicated that two gibberellins(GAs)-related genes,KAO and SLRL1,were key to the rapid shoot growth and culm size in woody bamboos.The expression of GAs-related genes exhibited significant subgenome asymmetry with subgenomes A and C demonstrating expression dominance in the large-sized woody bamboos while the generally submissive subgenomes B and D dominating in the small-sized species.The subgenome asymmetry was found to be correlated with the subgenome-specific gene structure,particularly UTRs and core promoters.Our study provides novel insights into the molecular mechanism and evolution of rapid shoot growth following allopolyploidization in woody bamboos,particularly via subgenome asymmetry.These findings are helpful for understanding of how polyploidization in general and subgenome asymmetry in particular contributed to the origin of innovative traits in plants.展开更多
Influenced by complex external factors,the displacement-time curve of reservoir landslides demonstrates both short-term and long-term diversity and dynamic complexity.It is difficult for existing methods,including Reg...Influenced by complex external factors,the displacement-time curve of reservoir landslides demonstrates both short-term and long-term diversity and dynamic complexity.It is difficult for existing methods,including Regression models and Neural network models,to perform multi-characteristic coupled displacement prediction because they fail to consider landslide creep characteristics.This paper integrates the creep characteristics of landslides with non-linear intelligent algorithms and proposes a dynamic intelligent landslide displacement prediction method based on a combination of the Biological Growth model(BG),Convolutional Neural Network(CNN),and Long ShortTerm Memory Network(LSTM).This prediction approach improves three different biological growth models,thereby effectively extracting landslide creep characteristic parameters.Simultaneously,it integrates external factors(rainfall and reservoir water level)to construct an internal and external comprehensive dataset for data augmentation,which is input into the improved CNN-LSTM model.Thereafter,harnessing the robust feature extraction capabilities and spatial translation invariance of CNN,the model autonomously captures short-term local fluctuation characteristics of landslide displacement,and combines LSTM's efficient handling of long-term nonlinear temporal data to improve prediction performance.An evaluation of the Liangshuijing landslide in the Three Gorges Reservoir Area indicates that BG-CNN-LSTM exhibits high prediction accuracy,excellent generalization capabilities when dealing with various types of landslides.The research provides an innovative approach to achieving the whole-process,realtime,high-precision displacement predictions for multicharacteristic coupled landslides.展开更多
Biological soil crusts(BSCs)play crucial roles in improving soil fertility and promoting plants settlement and reproduction in arid areas.However,the specific effects of BSCs on growth status and nutrient accumulation...Biological soil crusts(BSCs)play crucial roles in improving soil fertility and promoting plants settlement and reproduction in arid areas.However,the specific effects of BSCs on growth status and nutrient accumulation of plants are still unclear in different arid areas.This study analyzed the effects of three different BSCs treatments(without crust(WC),intact crust(IC),and broken crust(BC))on the growth,inorganic nutrient absorption,and organic solute synthesis of three typical desert plants(Grubovia dasyphylla(Fisch.&C.A.Mey.)Freitag&G.Kadereit,Nitraria tangutorum Bobrov,and Caragana koraiensis Kom.)in the Minqin desert-oasis ecotone of Northwest China.Results showed that the effects of three BSCs treatments on seed emergence and survival of three plants varied with seed types.The IC treatment significantly hindered the emergence and survival of seeds,while the BC treatment was more conducive to seed emergence and survival of plants.BSCs significantly promoted the growth of three plants,but their effects on plant growth varied at different stages of the growth.Briefly,the growth of G.dasyphylla was affected by BSCs in early stage,but the effects on the growth of G.dasyphylla significantly weakened in the middle and late stages.However,the growth of N.tangutorum and C.koraiensis only showed differences at the middle and late stages,with a significant enhancement in growth.Analysis of variance showed that BSCs,plant species,growth period,and their interactions had significant effects on the biomass and root:shoot ratio of three plants.BSC significantly affected the nutrients absorption and organic solute synthesis in plants.Specifically,BSCs significantly promoted nitrogen(N)absorption in plants and increased plant adaptability in N poor desert ecosystems,but had no significant effects on phosphorus(P)absorption.The effects of BSCs on inorganic nutrient absorption and organic solute synthesis in plants varied significantly among different plant species.The results suggest that BSCs have significant effects on the growth and nutrient accumulation of desert plants,which will provide theoretical basis for exploring the effects of BSCs on desert plant diversity,biodiversity conservation,and ecosystem management measures in arid and semi-arid areas.展开更多
The exopolysaccharide matrix of diazotrophic cyanobacteria was used to integrate phosphorus(P)and potassium(K)solubilizing bacteria,enhancing the survival of plant growth-promoting rhizobacteria,and ultimately the sur...The exopolysaccharide matrix of diazotrophic cyanobacteria was used to integrate phosphorus(P)and potassium(K)solubilizing bacteria,enhancing the survival of plant growth-promoting rhizobacteria,and ultimately the survival of bacteria in the rhizosphere for better plant growth.A new biofilm-based formulation comprising the diazotrophic cyanobacteria Anabaena AMP2,P-solubilizing Bacillus megaterium var.phosphaticum PB1,and K-solubilizing Rhizobium pusense KRBKKM1 was tested for efficacy in rice.The growth medium with half-strength BG-11 medium supplemented with 3%glucose showed best for biofilm formation under in vitro conditions.Analysis of the methanolic extract of the cyanobacterial-bacterial biofilm(CBB)showed the activity of antioxidants,such as 2-methoxy phenol and pentadecane,which are proven to improve plant-microbe interactions and plant growth,respectively.Treatment of rice seeds with CBB extract at 100 mL/kg or 200 mL/kg showed significant enhancement in germination rate and seedling length.Therefore,a pot culture experiment with the CBB formulations was carried out,and different growth and yield parameters were recorded.Principal component analysis showed that plant growth,yield,soil dehydrogenase activity,and soil chlorophyll content were positively correlated with rice plants amended with vermiculite-based CBB at 2 kg/hm^(2) followed by a spray with aqueous CBB formulation at 5 mL/L at 15 and 30 d after rice transplanting grown with a 25%reduced level of nitrogen/phosphorus/potassium chemical fertilizers than the recommended dose.Further,Pearson correlation analysis showed that yield was positively correlated with soil dehydrogenase(r=0.92**)and soil chlorophyll content(r=0.96**).We concluded that CBB could be used as a novel biofilm-based bio-inoculant to increase rice productivity and crop fitness as a component in integrated nutrient management and sustainable organic farming strategies with reduced chemical fertilizers.展开更多
The high Ba-Sr rocks can provide significant clues about the evolution of the continent lithosphere,but their petrogenesis remains controversial.Identifying the Late Cretaceous high Ba–Sr granodiorites in the SE Lhas...The high Ba-Sr rocks can provide significant clues about the evolution of the continent lithosphere,but their petrogenesis remains controversial.Identifying the Late Cretaceous high Ba–Sr granodiorites in the SE Lhasa Block could potentially provide valuable insights into the continent evolution of the Qinghai-Tibet Plateau.Zircon U–Pb ages suggest that the granodiorites were emplaced at 87.32±0.43 Ma.Geochemically,the high Ba–Sr granodiorites are characterized by elevated K_(2)O+Na_(2)O contents(8.18-8.73 wt%)and K_(2)O/Na_(2)O ratios(0.99-1.25,mostly>1),and belong to high-K calc-alkaline to shoshonitic series.The Yonglaga granodiorites show notably high Sr(653-783 ppm)and Ba(1346-1531 ppm)contents,plus high Sr/Y(30.92-38.18)and(La/Yb)_(N)(27.7-34.7)ratios,but low Y(20.0-22.8 ppm)and Yb(1.92-2.19 ppm)contents with absence of negative Eu anomalies(δEu=0.83-0.88),all similar to typical high Ba–Sr granitoids.The variable zirconεHf(t)values of-4.58 to+12.97,elevated initial^(87)Sr/^(86)Sr isotopic ratios of 0.707254 to 0.707322 and lowεNd(t)values of-2.8 to-3.6 with decoupling from the Hf system suggest that a metasomatized mantle source included significant recycled ancient materials.The occurrence of such high Ba–Sr intrusions indicates previous contributions of metasomatized mantle-derived juvenile material to the continents,which imply the growth of continental crust during the Late Cretaceous in the SE Lhasa.Together with regional data,we infer that the underplated mafic magma provides a significant amount of heat,which leads to partial melting of the juvenile crust.The melting of the metasomatized mantle could produce a juvenile mafic lower crust,from which the high Ba–Sr granitoids were derived from reworking of previous mafic crust during the Late Cretaceous(ca.100-80 Ma)in the SE Lhasa.展开更多
The epidermal growth factor receptor(EGFR)is a transmembrane glycoprotein that plays a crucial role in signal transduction and cellular responses.This review explores the function of EGFR in kidney physiology and its ...The epidermal growth factor receptor(EGFR)is a transmembrane glycoprotein that plays a crucial role in signal transduction and cellular responses.This review explores the function of EGFR in kidney physiology and its implications for various kidney diseases.EGFR signaling is essential for kidney function and repair mechanisms,and its dysregulation significantly impacts both acute and chronic kidney conditions.The review discusses the normal distribution of EGFR in kidney tubular segments,the mechanism of its activation and inhibition,and the therapeutic potential of EGFR-targeting antagonists and ligands.Additionally,it explores the pathophysiological characteristics observed in rodent models of kidney diseases through pharmacological and genetic inhibition of EGFR,highlighting therapeutic challenges and limitations such as species differences,variability in disease models,and potential adverse effects.Overall,the findings underscore the multifaceted role of EGFR in kidney diseases,influencing inflammation,fibrosis,and tissue injury.This complex involvement suggests that targeting EGFR may be a beneficial therapeutic strategy for managing these conditions,potentially mitigating inflammation and fibrosis while promoting tissue repair.展开更多
BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metasta...BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.展开更多
In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growt...In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.展开更多
Ice storms can cause substantial damage to tree crowns and lead to growth reduction.However,in uneven-aged stands,the growth of an individual tree may also increase due to crown release caused by the damage or mortali...Ice storms can cause substantial damage to tree crowns and lead to growth reduction.However,in uneven-aged stands,the growth of an individual tree may also increase due to crown release caused by the damage or mortality of neighboring trees.Three years after the devastating ice storm in 2014 in mixed uneven-aged Dinaric forests(Croatia),we cored 156 European beech(Fagus sylvatica)and 85 silver fir(Abies alba)trees across 20 permanent sample plots to study the post-storm growth response as a function of tree,stand,site,spatial arrangement and local competition factors.The ice storm damaged over 84% of trees on the sampled plots.Among the cored trees,52.7% exhibited growth reduction,which on average amounted to3.1%relative to the pre-disturbance average.Trees with less than 40% crown damage maintained their pre-disturbance growth rates or experienced only minor growth suppression.While 60% of beech trees suffered a growth reduction at an average rate of 7.2%,the average radial increment of fir after the storm was 14.0% higher compared to the pre-storm rate.A linear mixedeffects model suggests that the growth response can largely be explained by the focal and neighboring tree species identity,tree competition pressure,focal and neighboring tree damage,crown size,slenderness index and stoniness.Growth release was positively associated with fir,inverse distance-weighted crown damage of the nearest neighbor,shorter crowns,slenderness,less stony sites and less damaged trees.The analysis suggests that at the same level of local competition load,trees with a broadleaved and damaged nearest neighbor are more likely to experience growth release than those with a coniferous or undamaged nearest neighbor.This implies that unevenaged stands with a substantial presence and mingling of both conifers and broadleaves are expected to be more resilient to ice storms and are less likely to suffer growth reduction.展开更多
There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In part ...There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In part I, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part Ⅱ will detail the effects of glucagon-like peptide (GLP)-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids.展开更多
AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing rec...AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF(165) complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated. RESULTS: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF(165) antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein (immunofluorescence intensity, 8.9%) (P【0.05). Conversely, stable integration of VEGF(165) in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P【0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tumor volume: 345.40 +/- 136.31 mm3)(P【0.05 vs control SGC-7901 group: 1534.40 +/- 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tumor volume: 2350.50 +/- 637.70 mm3) (P【0.05 vs control SGC-7901 group). CONCLUSION: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.展开更多
Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, ...Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.展开更多
Site conditions and species identity have a combined effect on fine root growth of trees in pure and mixed stands.However,mechanisms that may contribute to this effect are rarely studied,even though they are essential...Site conditions and species identity have a combined effect on fine root growth of trees in pure and mixed stands.However,mechanisms that may contribute to this effect are rarely studied,even though they are essential to assess the potential of species to cope with climate change.This study examined fine root overlap and the linkage between fine root and stem growth of European beech(Fagus sylvatica)growing in pure and mixed stands with Douglas fir(Pseudotsuga menziesii)or Norway spruce(Picea abies)at two different study sites in northwestern Germany.The study sites represented substantially different soil and climate conditions.At each site,three stands,and at each stand,three pairs of trees were studied.In the pure beech stand,the pairs consisted of two beech trees,while in the mixed stands each pair was composed of a beech tree and a conifer.Between each pair,three evenly spaced soil cores were taken monthly throughout the growing season.In the pure beech stands,microsatellite markers were used to assign the fine roots to individual trees.Changes in stem diameter of beech were quantified and then upscaled to aboveground wood productivity with automatic high-resolution circumference dendrometers.We found that fine root overlap between neighboring trees varied independently of the distance between the paired trees or the stand types(pure versus mixed stands),indicating that there was no territorial competition.Aboveground wood productivity(wood NPP)and fine root productivity(root NPP)showed similar unimodal seasonal patterns,peaking in June.However,this pattern was more distinct for root NPP,and root NPP started earlier and lasted longer than wood NPP.The influence of site conditions on the variation in wood and root NPP of beech was stronger than that of stand type.Wood NPP was,as expected,higher at the richer site than at the poorer site.In contrast,root NPP was higher at the poorer than at the richer site.We concluded that beech can respond to limited resources not only above-but also belowground and that the negative relationship between above-and belowground growth across the study sites suggests an‘optimal partitioning’of growth under stress.展开更多
Zinc(Zn)-air batteries are widely used in secondary battery research owing to their high theoretical energy density,good electrochemical reversibility,stable discharge performance,and low cost of the anode active mate...Zinc(Zn)-air batteries are widely used in secondary battery research owing to their high theoretical energy density,good electrochemical reversibility,stable discharge performance,and low cost of the anode active material Zn.However,the Zn anode also leads to many challenges,including dendrite growth,deformation,and hydrogen precipitation self-corrosion.In this context,Zn dendrite growth has a greater impact on the cycle lives.In this dissertation,a dendrite growth model for a Zn-air battery was established based on electrochemical phase field theory,and the effects of the charging time,anisotropy strength,and electrolyte temperature on the morphology and growth height of Zn dendrites were studied.A series of experiments was designed with different gradient influencing factors in subsequent experiments to verify the theoretical simulations,including elevated electrolyte temperatures,flowing electrolytes,and pulsed charging.The simulation results show that the growth of Zn dendrites is controlled mainly by diffusion and mass transfer processes,whereas the electrolyte temperature,flow rate,and interfacial energy anisotropy intensity are the main factors.The experimental results show that an optimal electrolyte temperature of 343.15 K,an optimal electrolyte flow rate of 40 ml·min^(-1),and an effective pulse charging mode.展开更多
基金supported by the Natio`nal Natural Science Foundation of China,No. 81801241a grant from Sichuan Science and Technology Program,No. 2023NSFSC1578Scientific Research Projects of Southwest Medical University,No. 2022ZD002 (all to JX)。
文摘Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.
基金supported by European Regional Development Funds RE0022527 ZEBRATOX(EU-Région Réunion-French State national counterpart,to Nicolas Diotel and Jean-Loup Bascands).
文摘After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.
基金supported by the Natural Science Foundation of Guangdong Province,Nos.2019A1515010649(to WC),2022A1515012044(to JS)the China Postdoctoral Science Foundation,No.2018M633091(to JS).
文摘Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
基金Shanxi Province Higher Education Science and Technology Innovation Fund Project(2022-676)Shanxi Soft Science Program Research Fund Project(2016041008-6)。
文摘In order to improve the efficiency of cloud-based web services,an improved plant growth simulation algorithm scheduling model.This model first used mathematical methods to describe the relationships between cloud-based web services and the constraints of system resources.Then,a light-induced plant growth simulation algorithm was established.The performance of the algorithm was compared through several plant types,and the best plant model was selected as the setting for the system.Experimental results show that when the number of test cloud-based web services reaches 2048,the model being 2.14 times faster than PSO,2.8 times faster than the ant colony algorithm,2.9 times faster than the bee colony algorithm,and a remarkable 8.38 times faster than the genetic algorithm.
文摘Florfenicol(FLO)is a chemically synthesized broad-spectrum antimicrobial agent of amide alcohols for animals,which is one of the most widely used antimicrobials in livestock,poultry,and aquaculture.With the use of FLo,more and more attention has been paid to its hematopoietic toxicity,immunotoxicity,genotoxicity,and embryotoxicity.In this study,SPF chicks.at the age of 3 d began to drink water with the FLO at a dose of 100 mg L^(-1)for 6 consecutive days,and the growth performance of chicks was monitored,the effect of FLO on immune organs was detected by pathological examination and TdT-mediated dUTP nick-end labeling(TUNEL)apoptosis staining.In order to evaluate the level of organism immunity,the level of Newcastle disease virus antibody in serum was detected by hemagglutination inhibition test,the content of cytokines(IL-1,IL-2,IL-6,TNF-α,IFN-γ)in serum was detected by enzyme linked immunosorbent assay(ELISA),and the transcription of interferon-related genes(IRF-7,2′-5′OAS,Mx1)and cytokine genes(IL-6,TNF-α,IFN-γ)in immune organs were detected by real time fluorescence quantitative PCR.The results showed that the early application of FLO could inhibit the growth and development of chicks,and the body weight and immune organ index of the treatment group were lower than those of the control group.Histopathological examination showed that there was a decrease in the number of lymphocytes in the bursa of Fabricius in the treatment group in the early stage of drug withdrawal,and the results of TUNEL apoptosis staining in the bursa of Fabricius showed that obvious lymphocyte apoptosis occurred in the FLO treatment group.Compared with the control group,the transcription levels of interferon-related genes IRF-7,2′-5′OAS,and cytokine genes IL-6,TNF-αand IFN-γin FLO treatment group decreased to a certain extent,while the transcription level of Mx1 gene had no significant difference at all time points.The level of serum Newcastle disease virus(NDV)antibody and the contents of cytokines IL-1,IL-2 and IFN-γin the FLO treatment group were significantly lower than those in the control group in the early stage of drug withdrawal,but recovered gradually in the later stage.This study showed that FLO has a certain degree of effect on the immune function of chicks,and the results of the study laid the foundation for further research on the mechanism of FLO-induced immunotoxicity.
基金supported by the Key Project of Natural Science Foundation of Yunnan Province(202401AS070082)the National Natural Science Foundation of China(grants 32120103003 and 31970355)facilitated by the Germplasm Bank of Wild Species.
文摘Rapid growth is an innovative trait of woody bamboos that has been widely studied.However,the genetic basis and evolution of this trait are poorly understood.Taking advantage of genomic resources of 11 representative bamboos at different ploidal levels,we integrated morphological,physiological,and transcriptomic datasets to investigate rapid growth.In particular,these bamboos include two large-sized and a small-sized woody species,compared with a diploid herbaceous species.Our results showed that gibberellin A1 was important for the rapid shoot growth of the world's largest bamboo,Dendrocalamus sinicus,and indicated that two gibberellins(GAs)-related genes,KAO and SLRL1,were key to the rapid shoot growth and culm size in woody bamboos.The expression of GAs-related genes exhibited significant subgenome asymmetry with subgenomes A and C demonstrating expression dominance in the large-sized woody bamboos while the generally submissive subgenomes B and D dominating in the small-sized species.The subgenome asymmetry was found to be correlated with the subgenome-specific gene structure,particularly UTRs and core promoters.Our study provides novel insights into the molecular mechanism and evolution of rapid shoot growth following allopolyploidization in woody bamboos,particularly via subgenome asymmetry.These findings are helpful for understanding of how polyploidization in general and subgenome asymmetry in particular contributed to the origin of innovative traits in plants.
基金the funding support from the National Natural Science Foundation of China(Grant No.52308340)Chongqing Talent Innovation and Entrepreneurship Demonstration Team Project(Grant No.cstc2024ycjh-bgzxm0012)the Science and Technology Projects supported by China Coal Technology and Engineering Chongqing Design and Research Institute(Group)Co.,Ltd..(Grant No.H20230317)。
文摘Influenced by complex external factors,the displacement-time curve of reservoir landslides demonstrates both short-term and long-term diversity and dynamic complexity.It is difficult for existing methods,including Regression models and Neural network models,to perform multi-characteristic coupled displacement prediction because they fail to consider landslide creep characteristics.This paper integrates the creep characteristics of landslides with non-linear intelligent algorithms and proposes a dynamic intelligent landslide displacement prediction method based on a combination of the Biological Growth model(BG),Convolutional Neural Network(CNN),and Long ShortTerm Memory Network(LSTM).This prediction approach improves three different biological growth models,thereby effectively extracting landslide creep characteristic parameters.Simultaneously,it integrates external factors(rainfall and reservoir water level)to construct an internal and external comprehensive dataset for data augmentation,which is input into the improved CNN-LSTM model.Thereafter,harnessing the robust feature extraction capabilities and spatial translation invariance of CNN,the model autonomously captures short-term local fluctuation characteristics of landslide displacement,and combines LSTM's efficient handling of long-term nonlinear temporal data to improve prediction performance.An evaluation of the Liangshuijing landslide in the Three Gorges Reservoir Area indicates that BG-CNN-LSTM exhibits high prediction accuracy,excellent generalization capabilities when dealing with various types of landslides.The research provides an innovative approach to achieving the whole-process,realtime,high-precision displacement predictions for multicharacteristic coupled landslides.
基金supported by the Natural Science Foundation of Gansu Province,China(24JRRA733,23JRRA589)the National Natural Science Foundation of China(42377470,42207539)the Light of Western Light Program of Talent Cultivation of Chinese Academy of Sciences(22JR9KA028).
文摘Biological soil crusts(BSCs)play crucial roles in improving soil fertility and promoting plants settlement and reproduction in arid areas.However,the specific effects of BSCs on growth status and nutrient accumulation of plants are still unclear in different arid areas.This study analyzed the effects of three different BSCs treatments(without crust(WC),intact crust(IC),and broken crust(BC))on the growth,inorganic nutrient absorption,and organic solute synthesis of three typical desert plants(Grubovia dasyphylla(Fisch.&C.A.Mey.)Freitag&G.Kadereit,Nitraria tangutorum Bobrov,and Caragana koraiensis Kom.)in the Minqin desert-oasis ecotone of Northwest China.Results showed that the effects of three BSCs treatments on seed emergence and survival of three plants varied with seed types.The IC treatment significantly hindered the emergence and survival of seeds,while the BC treatment was more conducive to seed emergence and survival of plants.BSCs significantly promoted the growth of three plants,but their effects on plant growth varied at different stages of the growth.Briefly,the growth of G.dasyphylla was affected by BSCs in early stage,but the effects on the growth of G.dasyphylla significantly weakened in the middle and late stages.However,the growth of N.tangutorum and C.koraiensis only showed differences at the middle and late stages,with a significant enhancement in growth.Analysis of variance showed that BSCs,plant species,growth period,and their interactions had significant effects on the biomass and root:shoot ratio of three plants.BSC significantly affected the nutrients absorption and organic solute synthesis in plants.Specifically,BSCs significantly promoted nitrogen(N)absorption in plants and increased plant adaptability in N poor desert ecosystems,but had no significant effects on phosphorus(P)absorption.The effects of BSCs on inorganic nutrient absorption and organic solute synthesis in plants varied significantly among different plant species.The results suggest that BSCs have significant effects on the growth and nutrient accumulation of desert plants,which will provide theoretical basis for exploring the effects of BSCs on desert plant diversity,biodiversity conservation,and ecosystem management measures in arid and semi-arid areas.
基金supported by the Researchers Supporting Project of King Saud University,Riyadh,Saudi Arabia(Grant No.RSP2025R358)Tamil Nadu Agricultural University,Coimbatore,India(Grant No.NRM-MDU-AGM-14-006).
文摘The exopolysaccharide matrix of diazotrophic cyanobacteria was used to integrate phosphorus(P)and potassium(K)solubilizing bacteria,enhancing the survival of plant growth-promoting rhizobacteria,and ultimately the survival of bacteria in the rhizosphere for better plant growth.A new biofilm-based formulation comprising the diazotrophic cyanobacteria Anabaena AMP2,P-solubilizing Bacillus megaterium var.phosphaticum PB1,and K-solubilizing Rhizobium pusense KRBKKM1 was tested for efficacy in rice.The growth medium with half-strength BG-11 medium supplemented with 3%glucose showed best for biofilm formation under in vitro conditions.Analysis of the methanolic extract of the cyanobacterial-bacterial biofilm(CBB)showed the activity of antioxidants,such as 2-methoxy phenol and pentadecane,which are proven to improve plant-microbe interactions and plant growth,respectively.Treatment of rice seeds with CBB extract at 100 mL/kg or 200 mL/kg showed significant enhancement in germination rate and seedling length.Therefore,a pot culture experiment with the CBB formulations was carried out,and different growth and yield parameters were recorded.Principal component analysis showed that plant growth,yield,soil dehydrogenase activity,and soil chlorophyll content were positively correlated with rice plants amended with vermiculite-based CBB at 2 kg/hm^(2) followed by a spray with aqueous CBB formulation at 5 mL/L at 15 and 30 d after rice transplanting grown with a 25%reduced level of nitrogen/phosphorus/potassium chemical fertilizers than the recommended dose.Further,Pearson correlation analysis showed that yield was positively correlated with soil dehydrogenase(r=0.92**)and soil chlorophyll content(r=0.96**).We concluded that CBB could be used as a novel biofilm-based bio-inoculant to increase rice productivity and crop fitness as a component in integrated nutrient management and sustainable organic farming strategies with reduced chemical fertilizers.
基金supported by the National Natural Science Foundation of China[Grants.41802054]supported by a Royal Society SinoBritish Fellowship Trust International Exchanges Award[Grant No.IESR3213093]。
文摘The high Ba-Sr rocks can provide significant clues about the evolution of the continent lithosphere,but their petrogenesis remains controversial.Identifying the Late Cretaceous high Ba–Sr granodiorites in the SE Lhasa Block could potentially provide valuable insights into the continent evolution of the Qinghai-Tibet Plateau.Zircon U–Pb ages suggest that the granodiorites were emplaced at 87.32±0.43 Ma.Geochemically,the high Ba–Sr granodiorites are characterized by elevated K_(2)O+Na_(2)O contents(8.18-8.73 wt%)and K_(2)O/Na_(2)O ratios(0.99-1.25,mostly>1),and belong to high-K calc-alkaline to shoshonitic series.The Yonglaga granodiorites show notably high Sr(653-783 ppm)and Ba(1346-1531 ppm)contents,plus high Sr/Y(30.92-38.18)and(La/Yb)_(N)(27.7-34.7)ratios,but low Y(20.0-22.8 ppm)and Yb(1.92-2.19 ppm)contents with absence of negative Eu anomalies(δEu=0.83-0.88),all similar to typical high Ba–Sr granitoids.The variable zirconεHf(t)values of-4.58 to+12.97,elevated initial^(87)Sr/^(86)Sr isotopic ratios of 0.707254 to 0.707322 and lowεNd(t)values of-2.8 to-3.6 with decoupling from the Hf system suggest that a metasomatized mantle source included significant recycled ancient materials.The occurrence of such high Ba–Sr intrusions indicates previous contributions of metasomatized mantle-derived juvenile material to the continents,which imply the growth of continental crust during the Late Cretaceous in the SE Lhasa.Together with regional data,we infer that the underplated mafic magma provides a significant amount of heat,which leads to partial melting of the juvenile crust.The melting of the metasomatized mantle could produce a juvenile mafic lower crust,from which the high Ba–Sr granitoids were derived from reworking of previous mafic crust during the Late Cretaceous(ca.100-80 Ma)in the SE Lhasa.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)and funded by the Ministry of Education(2021R1I1A3056002,to Jinu Kim,RS-2023-00274853,to Daeun MOON).
文摘The epidermal growth factor receptor(EGFR)is a transmembrane glycoprotein that plays a crucial role in signal transduction and cellular responses.This review explores the function of EGFR in kidney physiology and its implications for various kidney diseases.EGFR signaling is essential for kidney function and repair mechanisms,and its dysregulation significantly impacts both acute and chronic kidney conditions.The review discusses the normal distribution of EGFR in kidney tubular segments,the mechanism of its activation and inhibition,and the therapeutic potential of EGFR-targeting antagonists and ligands.Additionally,it explores the pathophysiological characteristics observed in rodent models of kidney diseases through pharmacological and genetic inhibition of EGFR,highlighting therapeutic challenges and limitations such as species differences,variability in disease models,and potential adverse effects.Overall,the findings underscore the multifaceted role of EGFR in kidney diseases,influencing inflammation,fibrosis,and tissue injury.This complex involvement suggests that targeting EGFR may be a beneficial therapeutic strategy for managing these conditions,potentially mitigating inflammation and fibrosis while promoting tissue repair.
文摘BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.
基金This work was supported by the Special Project of Performance Incentive and Guidance for Scientific Research Institutions of Chongqing,China (jxyn2022-5)。
文摘In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.
基金supported by the Croatian Science Foundation(project number IP-2018-01-8820)the Slovenian Research Agency core funding(grant number P4-0059).
文摘Ice storms can cause substantial damage to tree crowns and lead to growth reduction.However,in uneven-aged stands,the growth of an individual tree may also increase due to crown release caused by the damage or mortality of neighboring trees.Three years after the devastating ice storm in 2014 in mixed uneven-aged Dinaric forests(Croatia),we cored 156 European beech(Fagus sylvatica)and 85 silver fir(Abies alba)trees across 20 permanent sample plots to study the post-storm growth response as a function of tree,stand,site,spatial arrangement and local competition factors.The ice storm damaged over 84% of trees on the sampled plots.Among the cored trees,52.7% exhibited growth reduction,which on average amounted to3.1%relative to the pre-disturbance average.Trees with less than 40% crown damage maintained their pre-disturbance growth rates or experienced only minor growth suppression.While 60% of beech trees suffered a growth reduction at an average rate of 7.2%,the average radial increment of fir after the storm was 14.0% higher compared to the pre-storm rate.A linear mixedeffects model suggests that the growth response can largely be explained by the focal and neighboring tree species identity,tree competition pressure,focal and neighboring tree damage,crown size,slenderness index and stoniness.Growth release was positively associated with fir,inverse distance-weighted crown damage of the nearest neighbor,shorter crowns,slenderness,less stony sites and less damaged trees.The analysis suggests that at the same level of local competition load,trees with a broadleaved and damaged nearest neighbor are more likely to experience growth release than those with a coniferous or undamaged nearest neighbor.This implies that unevenaged stands with a substantial presence and mingling of both conifers and broadleaves are expected to be more resilient to ice storms and are less likely to suffer growth reduction.
文摘There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In part I, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part Ⅱ will detail the effects of glucagon-like peptide (GLP)-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids.
文摘AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF(165) complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated. RESULTS: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF(165) antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein (immunofluorescence intensity, 8.9%) (P【0.05). Conversely, stable integration of VEGF(165) in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P【0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tumor volume: 345.40 +/- 136.31 mm3)(P【0.05 vs control SGC-7901 group: 1534.40 +/- 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tumor volume: 2350.50 +/- 637.70 mm3) (P【0.05 vs control SGC-7901 group). CONCLUSION: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,Nos.2021A1515011371 (to JP),2021A1515110290 (to YO),2020A1515110564 (to XW)2023A 1 515010150 (to MZ)+2 种基金Science and Technology Planning Project of Guangzhou,No.202102020977 (to ZF)the National Natural Science Foundation of China,Nos.82201516 (to YO) and 81900709 (to ZF)President Foundation of Nanfang Hospital,Southern Medical University,Nos.2019C001 (to MZ),2019C016 (to XW), 2021C045 (to YO)。
文摘Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.
基金part of the Research Training Group 2300,funded by the German research funding organization (Deutsche Forschungsgemeinschaft-DFG) Grand id:316045089
文摘Site conditions and species identity have a combined effect on fine root growth of trees in pure and mixed stands.However,mechanisms that may contribute to this effect are rarely studied,even though they are essential to assess the potential of species to cope with climate change.This study examined fine root overlap and the linkage between fine root and stem growth of European beech(Fagus sylvatica)growing in pure and mixed stands with Douglas fir(Pseudotsuga menziesii)or Norway spruce(Picea abies)at two different study sites in northwestern Germany.The study sites represented substantially different soil and climate conditions.At each site,three stands,and at each stand,three pairs of trees were studied.In the pure beech stand,the pairs consisted of two beech trees,while in the mixed stands each pair was composed of a beech tree and a conifer.Between each pair,three evenly spaced soil cores were taken monthly throughout the growing season.In the pure beech stands,microsatellite markers were used to assign the fine roots to individual trees.Changes in stem diameter of beech were quantified and then upscaled to aboveground wood productivity with automatic high-resolution circumference dendrometers.We found that fine root overlap between neighboring trees varied independently of the distance between the paired trees or the stand types(pure versus mixed stands),indicating that there was no territorial competition.Aboveground wood productivity(wood NPP)and fine root productivity(root NPP)showed similar unimodal seasonal patterns,peaking in June.However,this pattern was more distinct for root NPP,and root NPP started earlier and lasted longer than wood NPP.The influence of site conditions on the variation in wood and root NPP of beech was stronger than that of stand type.Wood NPP was,as expected,higher at the richer site than at the poorer site.In contrast,root NPP was higher at the poorer than at the richer site.We concluded that beech can respond to limited resources not only above-but also belowground and that the negative relationship between above-and belowground growth across the study sites suggests an‘optimal partitioning’of growth under stress.
基金financially supported by the National Natural Science Foundation of China(22168019 and 52074141)the Major Science and Technology Projects in Yunnan Province(202202AB080014)+1 种基金The authors are grateful to the National Natural Science Foundation of Chinathe Major Science and Technology Projects in Yunnan Province for their support.
文摘Zinc(Zn)-air batteries are widely used in secondary battery research owing to their high theoretical energy density,good electrochemical reversibility,stable discharge performance,and low cost of the anode active material Zn.However,the Zn anode also leads to many challenges,including dendrite growth,deformation,and hydrogen precipitation self-corrosion.In this context,Zn dendrite growth has a greater impact on the cycle lives.In this dissertation,a dendrite growth model for a Zn-air battery was established based on electrochemical phase field theory,and the effects of the charging time,anisotropy strength,and electrolyte temperature on the morphology and growth height of Zn dendrites were studied.A series of experiments was designed with different gradient influencing factors in subsequent experiments to verify the theoretical simulations,including elevated electrolyte temperatures,flowing electrolytes,and pulsed charging.The simulation results show that the growth of Zn dendrites is controlled mainly by diffusion and mass transfer processes,whereas the electrolyte temperature,flow rate,and interfacial energy anisotropy intensity are the main factors.The experimental results show that an optimal electrolyte temperature of 343.15 K,an optimal electrolyte flow rate of 40 ml·min^(-1),and an effective pulse charging mode.