BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling p...BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.展开更多
Toxoplasma gondii(T.gondii)is an obligate intracellular parasite with a wide range of hosts,including humans and many warm-blooded animals.The parasite exists in two interconvertible forms,namely tachyzoites and brady...Toxoplasma gondii(T.gondii)is an obligate intracellular parasite with a wide range of hosts,including humans and many warm-blooded animals.The parasite exists in two interconvertible forms,namely tachyzoites and bradyzoites in intermediate hosts that are responsible for acute and chronic infections respectively.Mature bradyzoites accumulate large amounts of amylopectin granules but their roles have not been fully characterized.In this study,the predicted key enzymes involved in amylopectin synthesis(UDP-sugar pyrophospharylase,USP)and degradation(alpha-glucan water dikinase,GWD)of ME49 strain were individually knocked out,and then bradyzoite-related phenotyping experiments in vitro and in vivo were performed to dissect their roles during parasite growth and development.Deletion of the usp or gwd gene in the type II strain ME49 reduced the replication rates of tachyzoites in vitro and parasite virulence in vivo,suggesting that amylopectin metabolism is important for optimal tachyzoite growth.Interestingly,the Δusp mutant grew slightly faster than the parental strain under stress conditions that induced bradyzoite transition,which was likely due to the decreased efficiency of bradyzoite formation of theΔusp mutant.Although theΔgwd mutant could convert to bradyzoite robustly in vitro,it was significantly impaired in establishing chronic infection in vivo.Both the Δusp and Δgwd mutants showed a dramatic reduction in the reactivation of chronic infection in an in vitro model.Together,these results suggest that USP and GWD,which are involved in amylopectin synthesis and degradation have important roles in tachyzoite growth,as well as in the formation and reactivation of bradyzoites in T.gondii.展开更多
Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitor...Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitors have emerged as a key strategy in cancer treatment.However,anti-programmed cell death 1/programmed death ligand 1 therapies,one of the main immunotherapeutic approaches,only elicit a response in only approximately 20%of advanced HCC.This suggests that there may be other immune checkpoints playing important roles in HCC immunotherapy.Recent studies have highlighted Signal regulatory protein alpha(SIRPα)is a phagocytic checkpoint in macrophages and other immune cells,as a promising novel therapeutic target in tumor immunotherapy.This review summarizes current progress on SIRPαin HCC and identifies key challenges for future related research.展开更多
In nuclear power engineering,the quality requirements for concrete are extremely stringent.Concrete structures must exhibit high durability to withstand the effects of nuclear radiation,chemical corrosion,and environm...In nuclear power engineering,the quality requirements for concrete are extremely stringent.Concrete structures must exhibit high durability to withstand the effects of nuclear radiation,chemical corrosion,and environmental changes.In particular,nuclear power projects impose higher design standards and safety requirements regarding concrete density.Traditional manual vibration and visual inspection methods are difficult to ensure the required level of concrete compaction.This paper presents an intelligent vibration technology for concrete in nuclear power engineering to enhance construction quality and efficiency.By integrating intelligent sensors,control systems,and data processing algorithms,the technology enables real-time monitoring and evaluation of the vibration process.Results show that intelligent vibration technology effectively ensures the density and uniformity of concrete in nuclear power engineering,thereby improving structural safety and reliability.展开更多
Segmentation tasks require multiple annotation work which is time-consuming and labour-intensive.How to make full use of unlabelled data to assist in training deep learning models has been a research hotspot in recent...Segmentation tasks require multiple annotation work which is time-consuming and labour-intensive.How to make full use of unlabelled data to assist in training deep learning models has been a research hotspot in recent years.This paper takes instrument segmentation in endoscopic surgery as the background to explore how to use unlabelled data for semi-supervised learning more reasonably and effectively.An adaptive gradient correction method based on the degree of perturbation is proposed to improve segmentation accuracy.This paper integrates the recently popular segment anything model(SAM)with semi-supervised learning,taking full advantage of the large model to enhance the zero-shot ability of the model.Experimental results demonstrate the superior performance of the proposed segmentation strategy compared to traditional semi-supervised segmentation methods,achieving a 2.56% improvement in mean intersection over union(mIoU).The visual segmentation results show that incorporation of SAM significantly enhances our method,resulting in more accurate segmentation boundaries.展开更多
文摘BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.
基金supported by the Fundamental Research Funds for the Central Universities in China(Grant no.2662022DKPY003)the HZAU-AGIS Cooperation Fund(Grant no.SZYJY2022015).
文摘Toxoplasma gondii(T.gondii)is an obligate intracellular parasite with a wide range of hosts,including humans and many warm-blooded animals.The parasite exists in two interconvertible forms,namely tachyzoites and bradyzoites in intermediate hosts that are responsible for acute and chronic infections respectively.Mature bradyzoites accumulate large amounts of amylopectin granules but their roles have not been fully characterized.In this study,the predicted key enzymes involved in amylopectin synthesis(UDP-sugar pyrophospharylase,USP)and degradation(alpha-glucan water dikinase,GWD)of ME49 strain were individually knocked out,and then bradyzoite-related phenotyping experiments in vitro and in vivo were performed to dissect their roles during parasite growth and development.Deletion of the usp or gwd gene in the type II strain ME49 reduced the replication rates of tachyzoites in vitro and parasite virulence in vivo,suggesting that amylopectin metabolism is important for optimal tachyzoite growth.Interestingly,the Δusp mutant grew slightly faster than the parental strain under stress conditions that induced bradyzoite transition,which was likely due to the decreased efficiency of bradyzoite formation of theΔusp mutant.Although theΔgwd mutant could convert to bradyzoite robustly in vitro,it was significantly impaired in establishing chronic infection in vivo.Both the Δusp and Δgwd mutants showed a dramatic reduction in the reactivation of chronic infection in an in vitro model.Together,these results suggest that USP and GWD,which are involved in amylopectin synthesis and degradation have important roles in tachyzoite growth,as well as in the formation and reactivation of bradyzoites in T.gondii.
基金Supported by the National Key Sci-Tech Special Project of China,No.2018ZX10302207the Beijing Natural Science Foundation,No.7222191+3 种基金the Beijing Natural Science Foundation,No.7244426the Fundamental Research Funds for the Central Universities,Peking University,No.PKU2024XGK005the Peking University Medicine Seed Fund for Interdisciplinary Research,No.BMU2021MX007 and No.BMU2022MX001Fundamental Research Funds for the Central Universities,Peking University People’s Hospital Scientific Research Development Funds,No.RDY2020-06 and No.RDJ2022-14.
文摘Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitors have emerged as a key strategy in cancer treatment.However,anti-programmed cell death 1/programmed death ligand 1 therapies,one of the main immunotherapeutic approaches,only elicit a response in only approximately 20%of advanced HCC.This suggests that there may be other immune checkpoints playing important roles in HCC immunotherapy.Recent studies have highlighted Signal regulatory protein alpha(SIRPα)is a phagocytic checkpoint in macrophages and other immune cells,as a promising novel therapeutic target in tumor immunotherapy.This review summarizes current progress on SIRPαin HCC and identifies key challenges for future related research.
基金The Advanced Civil Design and Construction Technology Joint LAB of Nuclear Engineering(Project No.:KY23015).
文摘In nuclear power engineering,the quality requirements for concrete are extremely stringent.Concrete structures must exhibit high durability to withstand the effects of nuclear radiation,chemical corrosion,and environmental changes.In particular,nuclear power projects impose higher design standards and safety requirements regarding concrete density.Traditional manual vibration and visual inspection methods are difficult to ensure the required level of concrete compaction.This paper presents an intelligent vibration technology for concrete in nuclear power engineering to enhance construction quality and efficiency.By integrating intelligent sensors,control systems,and data processing algorithms,the technology enables real-time monitoring and evaluation of the vibration process.Results show that intelligent vibration technology effectively ensures the density and uniformity of concrete in nuclear power engineering,thereby improving structural safety and reliability.
基金supported by the National Key R and D Program of China(Grant No.2023YFB4706300).
文摘Segmentation tasks require multiple annotation work which is time-consuming and labour-intensive.How to make full use of unlabelled data to assist in training deep learning models has been a research hotspot in recent years.This paper takes instrument segmentation in endoscopic surgery as the background to explore how to use unlabelled data for semi-supervised learning more reasonably and effectively.An adaptive gradient correction method based on the degree of perturbation is proposed to improve segmentation accuracy.This paper integrates the recently popular segment anything model(SAM)with semi-supervised learning,taking full advantage of the large model to enhance the zero-shot ability of the model.Experimental results demonstrate the superior performance of the proposed segmentation strategy compared to traditional semi-supervised segmentation methods,achieving a 2.56% improvement in mean intersection over union(mIoU).The visual segmentation results show that incorporation of SAM significantly enhances our method,resulting in more accurate segmentation boundaries.
