In the relentless quest for digital sovereignty, organizations face an unprecedented challenge in safeguarding sensitive information, protecting against cyber threats, and maintaining regulatory compliance. This manus...In the relentless quest for digital sovereignty, organizations face an unprecedented challenge in safeguarding sensitive information, protecting against cyber threats, and maintaining regulatory compliance. This manuscript unveils a revolutionary blueprint for cyber resilience, empowering organizations to transcend the limitations of traditional cybersecurity paradigms and forge ahead into uncharted territories of data security excellence and frictionless secrets management experience. Enter a new era of cybersecurity innovation and continued excellence. By seamlessly integrating secrets based on logical environments and applications (assets), dynamic secrets management orchestrates and automates the secrets lifecycle management with other platform cohesive integrations. Enterprises can enhance security, streamline operations, fasten development practices, avoid secrets sprawl, and improve overall compliance and DevSecOps practice. This enables the enterprises to enhance security, streamline operations, fasten development & deployment practices, avoid secrets spawls, and improve overall volume in shipping software with paved-road DevSecOps Practices, and improve developers’ productivity. By seamlessly integrating secrets based on logical environments and applications (assets), dynamic secrets management orchestrates and automates the application secrets lifecycle with other platform cohesive integrations. Organizations can enhance security, streamline operations, fasten development & deployment practices, avoid secrets sprawl, and improve overall volume in shipping software with paved-road DevSecOps practices. Most importantly, increases developer productivity.展开更多
Alice Munro,the first short story writer in Canada to receive the Nobel Prize laureate in 2013,applies the unconscious to the portrayal of characters and the construction of engrossing stories.Based on the unconscious...Alice Munro,the first short story writer in Canada to receive the Nobel Prize laureate in 2013,applies the unconscious to the portrayal of characters and the construction of engrossing stories.Based on the unconscious theory of Sigmund Freud’s psychoanalysis,this article focuses on one of Alice Munro’s short stories,Open Secrets,by analyzing the unconscious of representative characters,to explore their power conversion through the conflicts triggered by their unconscious mind.Via uncovering their unique personalities and values,as well as displaying their power against each other through conflict,this article reveals that the relationship between characters is sophisticated and changeable,and their power against each other has been a state of change in continuous conflicts.Behind the unconscious displays a thoroughly different comparison of forces:the strong who behaves violently and arrogantly actually shows weakness;in turn,the obedience and endurance of the weak strongly manifest a tenacious resistance.展开更多
Visual secret sharing has received more and more attention over the past years due to the fact that neither complex computation nor cryptographic knowledge is required to decrypt the secret image directly according to...Visual secret sharing has received more and more attention over the past years due to the fact that neither complex computation nor cryptographic knowledge is required to decrypt the secret image directly according to the characteristics of the human vision system. Considering the issue of sharing the secret image at multiple image resolutions with the meaningful shadows, in this paper, we present a friendly progressive visual secret sharing scheme without expanding the image size in the shadows and the reconstructed secret image based on applying a 2x2-sized block-wise operation to generate the shadows block by block. The proposed method can achieve these benefits： 1） the generated shadows are meaningful, and their sizes are not expanded, and 2） the secret image can be recovered at different resolutions by stacking different quantities of shadows together. The experimental results also show that the proposed method is superior to other compared schemes.展开更多
IT is a common notion that Cantonese seldom make noodles because the climate of southern China’s Guangdong Province is unsuitable for growing highquality wheat.But along with the exchanges and integration between nor...IT is a common notion that Cantonese seldom make noodles because the climate of southern China’s Guangdong Province is unsuitable for growing highquality wheat.But along with the exchanges and integration between northern and southern food in China,Cantonese have mastered their own way of making jook-sing noodles,or bamboo pressed noodles,ingredients for a variety of local specialties like wonton noodles,shrimp noodles,longevity noodles and Teochew-style sweet and sour fried noodles.展开更多
Living to a ripe old age in China is on the increase - and a healthy lifestyle emerges as the key by Tang Yuankai SHE moves about with ease and sees and hears without any trouble.And on most days she climbs a mountain...Living to a ripe old age in China is on the increase - and a healthy lifestyle emerges as the key by Tang Yuankai SHE moves about with ease and sees and hears without any trouble.And on most days she climbs a mountain to work on展开更多
History shows that once a nation declines, chances of revival are slim, especially for very small nations. They are either assimilated by other strong nations or shut up deep in the mountains, living a slash and burn ...History shows that once a nation declines, chances of revival are slim, especially for very small nations. They are either assimilated by other strong nations or shut up deep in the mountains, living a slash and burn way of living. Even if there are some ancient nations that have survived and made some progress, they did so with great difficulty. Mesopotamia, Egypt, India, Greece and Persia all are proud of their glorious past and are ambitious for national revival. But the path is not smooth. The Jewish nation, however, is an exception. What is the secret of its survival and seemingly sudden revival？展开更多
一年一度的莱卡风尚大典,每次都是明星的聚会,时尚的 SHOW 场。从星光大道的红地毯到华丽大气的颁奖现场再到与记者面对面的采访大厅,他们时时刻刻都在展示着自己的绰约丰姿。当天的盛况你可能已经从其他媒体领略了一二,但你一定没有看...一年一度的莱卡风尚大典,每次都是明星的聚会,时尚的 SHOW 场。从星光大道的红地毯到华丽大气的颁奖现场再到与记者面对面的采访大厅,他们时时刻刻都在展示着自己的绰约丰姿。当天的盛况你可能已经从其他媒体领略了一二,但你一定没有看过 Easy 要Show 你的聚光灯背后的点点滴滴。不信?Let's Go.展开更多
We consider the reconstruction of shared secrets in communication networks, which are modelled by graphs whose components are subject to possible failure. The reconstruction probability can be approximated using minim...We consider the reconstruction of shared secrets in communication networks, which are modelled by graphs whose components are subject to possible failure. The reconstruction probability can be approximated using minimal cuts, if the failure probabilities of vertices and edges are close to zero. As the main contribution of this paper, node separators are used to design a heuristic for the near-optimal placement of secrets sets on the vertices of the graph.展开更多
Dr Emily Thompson decided it was time to set sail on her first major maritime research expedition.She had always been fascinated by the mysteries of the ocean and wanted to uncover the secrets hidden beneath the waves...Dr Emily Thompson decided it was time to set sail on her first major maritime research expedition.She had always been fascinated by the mysteries of the ocean and wanted to uncover the secrets hidden beneath the waves.Her team boarded the research vessel early in the morning,excited at the adventure that awaited them.展开更多
Lysobacter enzymogenes is less-studied, but emerging as a powerful biocontrol bacterium producing multiple antimicrobial weapons including lytic enzymes, toxins, secondary metabolites and protein secretion systems.The...Lysobacter enzymogenes is less-studied, but emerging as a powerful biocontrol bacterium producing multiple antimicrobial weapons including lytic enzymes, toxins, secondary metabolites and protein secretion systems.The loss of surface-attached flagellum, production of heat-stable antifungal factor(HSAF, also named as Ningrongmycin) as a novel antifungal antibiotic, and the use of the type Ⅳ secretion system(T4SS) rather than the common type Ⅵ secretion system(T6SS) to kill competitor bacteria make this species unique. These distinct features set L. enzymogenes apart from well-studied plant beneficial biocontrol agents, such as Bacillus and Pseudomonas. This review describes what takes L. enzymogenes to be a unique biocontrol warrior by focusing to illustrate how the lack of flagellum governs morphological and functional co-adaptability, what adapted signaling transduction pathways are adopted to coordinate the biosynthesis of HSAF, and how to ecologically adapt plant rhizosphere by cell-to-cell interacting with microbiome members via the bacterial-killing T4SS.展开更多
Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was dimini...Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.展开更多
Autophagy is well-known for delivering cargo materials to lysosomes for proteolytic digestion.Recently,autophagy has emerged as a key mechanism in unconventional protein secretion(UPS).This perspective introduces unco...Autophagy is well-known for delivering cargo materials to lysosomes for proteolytic digestion.Recently,autophagy has emerged as a key mechanism in unconventional protein secretion(UPS).This perspective introduces unconventional secretion pathways,focusing on secretory autophagy and its role in secreting protein aggregates associated with neurodegenerative disorders.We also explore additional neuronal functions of secretory autophagy beyond the release of protein aggregates.We propose autophagosomes as transport organelles that deliver cargo material directly from the endoplasmatic reticulum(ER)to the plasma membrane rather than solely to lysosomes.展开更多
An increasing number of studies have characterized the bone as an endocrine organ,and that bone secreted factors may not only regulate local bone remodeling,but also other tissues and whole-body metabolic functions.Th...An increasing number of studies have characterized the bone as an endocrine organ,and that bone secreted factors may not only regulate local bone remodeling,but also other tissues and whole-body metabolic functions.The precise nature of these regulatory factors and their roles at bridging the bone,bone marrow adipose tissue,extramedullary body fat and whole-body energy homeostasis are being explored.In this study,we report that KIAA1199,a secreted factor produced from bone and bone marrow,previously described as an inhibitor of bone formation,also plays a role at promoting adipogenesis.KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue,subcutaneous and visceral fat tissue mass,blood cholesterol,triglycerides,free fatty acids and glycerol,as well as improved insulin sensitivity in skeletal muscle,liver and fat.Moreover,these mice are protected from the detrimental effects of high-fat diet feeding,with decreased obesity,lower blood glucose and glucose tolerance,as well as decreased adipose tissue inflammation,insulin resistance and hepatic steatosis.In human studies,plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol,triglycerides,free fatty acids,glycerol,fasting glucose and HOMA-IR.Mechanistically,KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT/ERK signaling.These findings provide evidence for the role of bone secreted factors on coupling bone,fat and whole-body energy homeostasis.展开更多
In many people's eyes,denim is a basic part of their clothes,but for Ian Berry,an artist from London,it's a way to make art.Over the past 20 years,Berry has used the dark blue fabric to make detailed artworks,...In many people's eyes,denim is a basic part of their clothes,but for Ian Berry,an artist from London,it's a way to make art.Over the past 20 years,Berry has used the dark blue fabric to make detailed artworks,and even lifelike pictures of places like California.His newest piece shows even more cool and surprising ways to use denim.Called Secret Garden,it's now at the Garden Museum in London.This artwork shows a peaceful scene with a fish pond,flowers,and vines—all made from old denim jeans.展开更多
The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components....The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components.The transmembrane protein-39(TMEM-39)mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles.TMEM-39 primarily co-localizes with the coat protein II complex(COPII)in large vesicles rather than small COPII vesicles.These TMEM-39-associated large vesicles(TMEM-39-LVs)form robustly during the molting period and co-localize with various extracellular matrix components,including BLI-1 collagen,BLI-3 dual oxidase,and carboxypeptidases.Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells,we identify TMEM39A-associated proteins,including TMEM131.Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C.elegans and human sarcoma cells,indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles.Given the conservation of TMEM39A and its associated proteins between C.elegans and humans,TMEM39A-LVs may represent a fundamental machinery for rapid and extensive secretion across metazoans.展开更多
BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicat...BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicated by diabetes is highly pre-valent in clinical settings.AIM To analyze the results of nasal secretion cultures in diabetic patients with CRS and identify the factors influencing postoperative recurrence.METHODS A retrospective analysis was conducted on the clinical data of 203 diabetic pa-tients with CRS with nasal polyps who underwent the Messerklinger technique at Qingdao Hiser Hospital Affiliated of Qingdao University between January 2021 and January 2023.Preoperative nasal secretions were cultured to determine the types and distribution of pathogenic bacteria and assess antimicrobial suscept-ibility.Based on a one-year follow-up,patients were categorized into recurrence and nonrecurrence groups to analyze differences in their clinical data.Univariate and multivariate analyses were used to identify factors influencing postoperative recurrence.RESULTS Pathogens were detected in 153 of the 203 nasal secretion specimens collected from diabetic patients with CRS.A total of 134 pathogenic bacteria strains were isolated and identified,including 81 strains(60.4%)of gram-positive bacteria and 53 strains(39.6%)of gram-negative bacteria.Gram-positive bacteria exhibited relatively high resistance to penicillin G and erythromycin,while remaining highly sensitive to vancomycin,gentamicin,and rifampicin.Gram-negative bacteria demonstrated relatively high resistance to cefazolin and gentamicin,but showed high sensitivity to imipenem,meropenem,cefepime,and ceftazidime.Univariate analysis revealed statistically significant differences between the recurrence and nonrecurrence groups in fasting blood glucose levels,smoking history,Lund-Mackay scores,visual analog scale(VAS)scores,nasal septum deviation,allergic rhinitis,bronchial asthma,postoperative infection,long-term use of nasal decongestants,and adherence to medical prescriptions.Multivariate regression analysis identified fasting blood glucose levels and VAS-measured nasal symptom severity scores as independent factors influencing postoperative recurrence.CONCLUSION In CRS patients with nasal polyps(CRSwNP),the detection rate of nasal pathogens is relatively high,and most of the isolated bacteria exhibit antimicrobial resistance.Additionally,the blood glucose level of patients with CRS combined with CRSwNP is a risk factor for postoperative recurrence.展开更多
The soil-resident pathogen, Plasmodiophora brassicae, infects cruciferous crops, causing obligate parasitic clubroot disease and posing a significant threat to the Brassica vegetable industry in China. To learn more a...The soil-resident pathogen, Plasmodiophora brassicae, infects cruciferous crops, causing obligate parasitic clubroot disease and posing a significant threat to the Brassica vegetable industry in China. To learn more about its pathogenesis, we reported a Nanopore sequencing-derived25.3 Mb high-quality genome sequence of P. brassicae pathotype 4 strain(P.b 4). Comparing the P.b 4 genome with that of the published P.brassicae e3 genome(P.b e3) identified single nucleotide polymorphisms, structural variations, and small insertions and deletions. We then carried out RNA-sequencing of root samples from a clubroot-susceptible line at 5, 14, and 28 days after inoculation(DAI), and classified genes into five categories based on their expression patterns. Interestingly, 158 genes were highly expressed at 14 DAI, which were enriched in budding cell isotropic bud growth, ascospore wall assembly, spore wall assembly, spore wall biogenesis, and ascospore wall biogenesis.Subsequently, we bioinformatically predicted 555 secreted effector candidates, among which only 125 were expressed during infection and had amino acid lengths less than 400. The putative effector Pb010018, which was highly expressed at 14 DAI, was validated to have a signal peptide using a yeast secretion system. Luciferase activity and co-immunoprecipitation assays demonstrated that Pb010018 interacts with serine hydroxymethyltransferase BrSHMT1, and expression analysis showed that SHMT1 was upregulated in both Arabidopsis and B. rapa during infection. Furthermore, after infection, the Arabidopsis shmt1 mutant(atshmt1) showed reduced severity of clubroot disease, together with downregulated expression of Pb010018. Our results offer new insights into plant-pathogen interaction mechanisms, and provide the possibility for improving Brassica resistance to clubroot disease.展开更多
文摘In the relentless quest for digital sovereignty, organizations face an unprecedented challenge in safeguarding sensitive information, protecting against cyber threats, and maintaining regulatory compliance. This manuscript unveils a revolutionary blueprint for cyber resilience, empowering organizations to transcend the limitations of traditional cybersecurity paradigms and forge ahead into uncharted territories of data security excellence and frictionless secrets management experience. Enter a new era of cybersecurity innovation and continued excellence. By seamlessly integrating secrets based on logical environments and applications (assets), dynamic secrets management orchestrates and automates the secrets lifecycle management with other platform cohesive integrations. Enterprises can enhance security, streamline operations, fasten development practices, avoid secrets sprawl, and improve overall compliance and DevSecOps practice. This enables the enterprises to enhance security, streamline operations, fasten development & deployment practices, avoid secrets spawls, and improve overall volume in shipping software with paved-road DevSecOps Practices, and improve developers’ productivity. By seamlessly integrating secrets based on logical environments and applications (assets), dynamic secrets management orchestrates and automates the application secrets lifecycle with other platform cohesive integrations. Organizations can enhance security, streamline operations, fasten development & deployment practices, avoid secrets sprawl, and improve overall volume in shipping software with paved-road DevSecOps practices. Most importantly, increases developer productivity.
文摘Alice Munro,the first short story writer in Canada to receive the Nobel Prize laureate in 2013,applies the unconscious to the portrayal of characters and the construction of engrossing stories.Based on the unconscious theory of Sigmund Freud’s psychoanalysis,this article focuses on one of Alice Munro’s short stories,Open Secrets,by analyzing the unconscious of representative characters,to explore their power conversion through the conflicts triggered by their unconscious mind.Via uncovering their unique personalities and values,as well as displaying their power against each other through conflict,this article reveals that the relationship between characters is sophisticated and changeable,and their power against each other has been a state of change in continuous conflicts.Behind the unconscious displays a thoroughly different comparison of forces:the strong who behaves violently and arrogantly actually shows weakness;in turn,the obedience and endurance of the weak strongly manifest a tenacious resistance.
文摘Visual secret sharing has received more and more attention over the past years due to the fact that neither complex computation nor cryptographic knowledge is required to decrypt the secret image directly according to the characteristics of the human vision system. Considering the issue of sharing the secret image at multiple image resolutions with the meaningful shadows, in this paper, we present a friendly progressive visual secret sharing scheme without expanding the image size in the shadows and the reconstructed secret image based on applying a 2x2-sized block-wise operation to generate the shadows block by block. The proposed method can achieve these benefits： 1） the generated shadows are meaningful, and their sizes are not expanded, and 2） the secret image can be recovered at different resolutions by stacking different quantities of shadows together. The experimental results also show that the proposed method is superior to other compared schemes.
文摘IT is a common notion that Cantonese seldom make noodles because the climate of southern China’s Guangdong Province is unsuitable for growing highquality wheat.But along with the exchanges and integration between northern and southern food in China,Cantonese have mastered their own way of making jook-sing noodles,or bamboo pressed noodles,ingredients for a variety of local specialties like wonton noodles,shrimp noodles,longevity noodles and Teochew-style sweet and sour fried noodles.
文摘Living to a ripe old age in China is on the increase - and a healthy lifestyle emerges as the key by Tang Yuankai SHE moves about with ease and sees and hears without any trouble.And on most days she climbs a mountain to work on
文摘History shows that once a nation declines, chances of revival are slim, especially for very small nations. They are either assimilated by other strong nations or shut up deep in the mountains, living a slash and burn way of living. Even if there are some ancient nations that have survived and made some progress, they did so with great difficulty. Mesopotamia, Egypt, India, Greece and Persia all are proud of their glorious past and are ambitious for national revival. But the path is not smooth. The Jewish nation, however, is an exception. What is the secret of its survival and seemingly sudden revival？
文摘We consider the reconstruction of shared secrets in communication networks, which are modelled by graphs whose components are subject to possible failure. The reconstruction probability can be approximated using minimal cuts, if the failure probabilities of vertices and edges are close to zero. As the main contribution of this paper, node separators are used to design a heuristic for the near-optimal placement of secrets sets on the vertices of the graph.
文摘Dr Emily Thompson decided it was time to set sail on her first major maritime research expedition.She had always been fascinated by the mysteries of the ocean and wanted to uncover the secrets hidden beneath the waves.Her team boarded the research vessel early in the morning,excited at the adventure that awaited them.
基金funded by the the Fundamental Research Funds for the Central Universities, China (RENCAI2024002 and KJJQ2024014)the Natural Key Research and Development Program of China (2022YFD1400200)the National Natural Science Foundation of China (U22A20486, 32072470, 32001955 and 32470112)
文摘Lysobacter enzymogenes is less-studied, but emerging as a powerful biocontrol bacterium producing multiple antimicrobial weapons including lytic enzymes, toxins, secondary metabolites and protein secretion systems.The loss of surface-attached flagellum, production of heat-stable antifungal factor(HSAF, also named as Ningrongmycin) as a novel antifungal antibiotic, and the use of the type Ⅳ secretion system(T4SS) rather than the common type Ⅵ secretion system(T6SS) to kill competitor bacteria make this species unique. These distinct features set L. enzymogenes apart from well-studied plant beneficial biocontrol agents, such as Bacillus and Pseudomonas. This review describes what takes L. enzymogenes to be a unique biocontrol warrior by focusing to illustrate how the lack of flagellum governs morphological and functional co-adaptability, what adapted signaling transduction pathways are adopted to coordinate the biosynthesis of HSAF, and how to ecologically adapt plant rhizosphere by cell-to-cell interacting with microbiome members via the bacterial-killing T4SS.
基金supported by grants from National Natural Science Foundation of China(82272444,81972031,81972033)China Postdoctoral Science Foundation(2022M722382)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-032A)。
文摘Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.
基金supported by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)grant LU 2347/3-1(to PL).
文摘Autophagy is well-known for delivering cargo materials to lysosomes for proteolytic digestion.Recently,autophagy has emerged as a key mechanism in unconventional protein secretion(UPS).This perspective introduces unconventional secretion pathways,focusing on secretory autophagy and its role in secreting protein aggregates associated with neurodegenerative disorders.We also explore additional neuronal functions of secretory autophagy beyond the release of protein aggregates.We propose autophagosomes as transport organelles that deliver cargo material directly from the endoplasmatic reticulum(ER)to the plasma membrane rather than solely to lysosomes.
基金supports from Odense University Hospital PhD fellowship(2014)the NovoNordisk Foundations(NNF15OC0016284,NNF19OC0057449)+2 种基金the Innovation Foundation of Denmark(5166-00002B)National Natural Science Foundation of China(No.32060155,82260284)Guangxi Medical and Health Key Discipline Construction Project.
文摘An increasing number of studies have characterized the bone as an endocrine organ,and that bone secreted factors may not only regulate local bone remodeling,but also other tissues and whole-body metabolic functions.The precise nature of these regulatory factors and their roles at bridging the bone,bone marrow adipose tissue,extramedullary body fat and whole-body energy homeostasis are being explored.In this study,we report that KIAA1199,a secreted factor produced from bone and bone marrow,previously described as an inhibitor of bone formation,also plays a role at promoting adipogenesis.KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue,subcutaneous and visceral fat tissue mass,blood cholesterol,triglycerides,free fatty acids and glycerol,as well as improved insulin sensitivity in skeletal muscle,liver and fat.Moreover,these mice are protected from the detrimental effects of high-fat diet feeding,with decreased obesity,lower blood glucose and glucose tolerance,as well as decreased adipose tissue inflammation,insulin resistance and hepatic steatosis.In human studies,plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol,triglycerides,free fatty acids,glycerol,fasting glucose and HOMA-IR.Mechanistically,KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT/ERK signaling.These findings provide evidence for the role of bone secreted factors on coupling bone,fat and whole-body energy homeostasis.
文摘In many people's eyes,denim is a basic part of their clothes,but for Ian Berry,an artist from London,it's a way to make art.Over the past 20 years,Berry has used the dark blue fabric to make detailed artworks,and even lifelike pictures of places like California.His newest piece shows even more cool and surprising ways to use denim.Called Secret Garden,it's now at the Garden Museum in London.This artwork shows a peaceful scene with a fish pond,flowers,and vines—all made from old denim jeans.
基金supported by the National Institutes of Health-Office of Research Infrastructure Programs(P40 OD010440)supported in part by grants from the National Cancer Center of Korea(NCC-2110160,NCC-2110263,and NCC-2310750)supported by the Basic Science Research Program of the National Research Foundation of Korea,funded by the Ministry of Science,ICT,and Future Planning(NRF-2015R1C1A1A01053611).
文摘The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components.The transmembrane protein-39(TMEM-39)mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles.TMEM-39 primarily co-localizes with the coat protein II complex(COPII)in large vesicles rather than small COPII vesicles.These TMEM-39-associated large vesicles(TMEM-39-LVs)form robustly during the molting period and co-localize with various extracellular matrix components,including BLI-1 collagen,BLI-3 dual oxidase,and carboxypeptidases.Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells,we identify TMEM39A-associated proteins,including TMEM131.Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C.elegans and human sarcoma cells,indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles.Given the conservation of TMEM39A and its associated proteins between C.elegans and humans,TMEM39A-LVs may represent a fundamental machinery for rapid and extensive secretion across metazoans.
文摘BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicated by diabetes is highly pre-valent in clinical settings.AIM To analyze the results of nasal secretion cultures in diabetic patients with CRS and identify the factors influencing postoperative recurrence.METHODS A retrospective analysis was conducted on the clinical data of 203 diabetic pa-tients with CRS with nasal polyps who underwent the Messerklinger technique at Qingdao Hiser Hospital Affiliated of Qingdao University between January 2021 and January 2023.Preoperative nasal secretions were cultured to determine the types and distribution of pathogenic bacteria and assess antimicrobial suscept-ibility.Based on a one-year follow-up,patients were categorized into recurrence and nonrecurrence groups to analyze differences in their clinical data.Univariate and multivariate analyses were used to identify factors influencing postoperative recurrence.RESULTS Pathogens were detected in 153 of the 203 nasal secretion specimens collected from diabetic patients with CRS.A total of 134 pathogenic bacteria strains were isolated and identified,including 81 strains(60.4%)of gram-positive bacteria and 53 strains(39.6%)of gram-negative bacteria.Gram-positive bacteria exhibited relatively high resistance to penicillin G and erythromycin,while remaining highly sensitive to vancomycin,gentamicin,and rifampicin.Gram-negative bacteria demonstrated relatively high resistance to cefazolin and gentamicin,but showed high sensitivity to imipenem,meropenem,cefepime,and ceftazidime.Univariate analysis revealed statistically significant differences between the recurrence and nonrecurrence groups in fasting blood glucose levels,smoking history,Lund-Mackay scores,visual analog scale(VAS)scores,nasal septum deviation,allergic rhinitis,bronchial asthma,postoperative infection,long-term use of nasal decongestants,and adherence to medical prescriptions.Multivariate regression analysis identified fasting blood glucose levels and VAS-measured nasal symptom severity scores as independent factors influencing postoperative recurrence.CONCLUSION In CRS patients with nasal polyps(CRSwNP),the detection rate of nasal pathogens is relatively high,and most of the isolated bacteria exhibit antimicrobial resistance.Additionally,the blood glucose level of patients with CRS combined with CRSwNP is a risk factor for postoperative recurrence.
基金supported by the Youth Foundation of Beijing Academy of Agriculture and Forestry Sciences[Grant No.QNJJ202242]the Excellent Young Scholars of Beijing Academy of Agriculture and Forestry Sciences[Grant No.YXQN202205]+3 种基金the Beijing Nova Program[Grant No.20220484052]the National Natural Science Foundation of China[Grant No.31801852]the Collaborative Innovation Center of Beijing Academy of Agriculture and Forestry Sciences[Grant No.KJCX201907-2]the Earmarked Fund for China Agriculture Research System[Grant No.CARS-23-A-05].
文摘The soil-resident pathogen, Plasmodiophora brassicae, infects cruciferous crops, causing obligate parasitic clubroot disease and posing a significant threat to the Brassica vegetable industry in China. To learn more about its pathogenesis, we reported a Nanopore sequencing-derived25.3 Mb high-quality genome sequence of P. brassicae pathotype 4 strain(P.b 4). Comparing the P.b 4 genome with that of the published P.brassicae e3 genome(P.b e3) identified single nucleotide polymorphisms, structural variations, and small insertions and deletions. We then carried out RNA-sequencing of root samples from a clubroot-susceptible line at 5, 14, and 28 days after inoculation(DAI), and classified genes into five categories based on their expression patterns. Interestingly, 158 genes were highly expressed at 14 DAI, which were enriched in budding cell isotropic bud growth, ascospore wall assembly, spore wall assembly, spore wall biogenesis, and ascospore wall biogenesis.Subsequently, we bioinformatically predicted 555 secreted effector candidates, among which only 125 were expressed during infection and had amino acid lengths less than 400. The putative effector Pb010018, which was highly expressed at 14 DAI, was validated to have a signal peptide using a yeast secretion system. Luciferase activity and co-immunoprecipitation assays demonstrated that Pb010018 interacts with serine hydroxymethyltransferase BrSHMT1, and expression analysis showed that SHMT1 was upregulated in both Arabidopsis and B. rapa during infection. Furthermore, after infection, the Arabidopsis shmt1 mutant(atshmt1) showed reduced severity of clubroot disease, together with downregulated expression of Pb010018. Our results offer new insights into plant-pathogen interaction mechanisms, and provide the possibility for improving Brassica resistance to clubroot disease.
