A human lung squamous carcinoma was transplanted and passaged in Swiss-DF nude mice, called LSX-83, for more than five years in our laboratory. The morphological characteristics of the original tumor were maintained i...A human lung squamous carcinoma was transplanted and passaged in Swiss-DF nude mice, called LSX-83, for more than five years in our laboratory. The morphological characteristics of the original tumor were maintained in passages from 4 to 33. But from the 35th generation, an increasing amount of tonofilaments and nuclear segregation with typical features was found with electron microscopy. The C-type virus particles were first detected in extra cellular space after 40 passages. The viruses were observed in different stages of growth, but their distribution and number did not show apparent change up to 54 passages. Such findings suggest that LSX-83 cells probably possess certain barrier of resistance against C-type viruses. The relation between C-type viruses and the morphological changes of LSX-83 cells was discussed.展开更多
Low pathogenic Avian Influenza (AI) virus has the ability to evolve to high pathogenic viruses resulting in significant economic losses in the poultry sector. This study aims at assessing the impact of H9N2 viral pass...Low pathogenic Avian Influenza (AI) virus has the ability to evolve to high pathogenic viruses resulting in significant economic losses in the poultry sector. This study aims at assessing the impact of H9N2 viral passaging in broilers and its relatedness to pathogenicity and amino acid (a.a) sequences of the hemagglutinin (HA) cleavage site and neuraminidase (NA) stalk. The original H9N2 AI virus (P0) was used to challenge ten-21 days old broilers. Individual recovery of H9N2 virus from homogenates of trachea, lungs and airsacs was attempted in 9 days old chicken embryos, as a conclusion of the first passage (P1). Tracheal isolates of H9N2 were passaged for a second (P2) and a third (P3) time in broilers, followed by a similar embryonic recovery procedure. The a.a. sequence of a part of HA1 cleavage site and Neuraminidase stalk were compared among the differently passaged viruses;an assessement of the relatedness of the determined a.a. sequences to the pathogenicity in broilers, based on frequency of mortality, morbidity signs, gross and microscopic lesions at 3 days post challenge with the P1, P2, and P3-H9N2, is concluded. An increase in certain morbidity signs and specific lesions was observed in P2- and P3-H9N2 challenged broilers compared to birds challenged with P1-H9N2. A conserved R-S-S-R amino acid sequence at the HA1 cleavage site was observed in the differently passaged H9N2, associated with a variability in the NA stalk-a.a sequences. The passaging of the low pathogenic H9N2 virus in broilers leads to a trend of increase in pathogenicity, manifested in higher frequency of morbidity signs, and of specific gross and microscopic lesions of the examined organs. This passaging was associated with a conserved a.a. sequence of the hemaglutinin cleavage site and a variability in the sequence of the neuraminidase stalk. A detailed study of the potential of the detected variability in the neuraminidase stalk of H9N2 in induction of a higher pathogenicity in broilers will be the subject of future investigations.展开更多
We have previously reported on both the osteogenic potential of hydroxyapatite (HA) combined with bone marrow-derived mesenchymal stem cells (BMSCs) and a method involving osteogenic matrix cell sheet transplantation ...We have previously reported on both the osteogenic potential of hydroxyapatite (HA) combined with bone marrow-derived mesenchymal stem cells (BMSCs) and a method involving osteogenic matrix cell sheet transplantation of BMSCs. In the present study, we assessed the osteogenic potential of serially-passaged BMSCs, both in vitro and in vivo. We also assessed whether an additional cell-loading technique can regain the osteogenic potential of the constructs combined with serially-passaged BMSCs. The present study revealed that passage (P) 1 cells cultured in osteogenic-induced medium showed strong positive staining for alkaline phosphatase (ALP) and Alizarin Red S, whereas P3 cells showed faint staining for ALP, with no Alizarin Red S staining. Staining of P1, P2 and P3 cells were progressively weaker, indicating that the osteogenic potential of the serially-passaged rat BMSCs is lost after P3 in vitro. The in vivo study showed that little bone formation was observed in the HA constructs seeded with P3 cells, 4 weeks after subcutaneous implantation. However, P3 cell/HA constructs which had increased cell-loading showed abundant bone formation within the pores of the HA construct. ALP and osteocalcin mRNA expression in these constructs was significantly higher than that of constructs with regular cell-seeding. The present study indicates that the osteogenic potential of the constructs with serially-passaged BMSCs is increased by additional cell-loading. This method can be applied to cases requiring hard tissue reconstruction, where BMSCs require serial expansion of cells.展开更多
Alice opened the door and found that it led into a small passage,not much larger than a rat⁃hole:she knelt down and looked along the passage into the loveliest garden you ever saw.How she longed to get out of that dar...Alice opened the door and found that it led into a small passage,not much larger than a rat⁃hole:she knelt down and looked along the passage into the loveliest garden you ever saw.How she longed to get out of that dark hall,and wander about among those beds of bright flowers and those cool fountains,but she could not even get her head through the doorway;“and even if my head would go through,”thought poor Alice,“it would be of very little use without my shoulders.Oh,how I wish I could shut up like a telescope!I think I could,if I only know how to begin.”For,you see,so many out⁃of⁃the⁃way things had happened lately,that Alice had begun to think that very few things indeed were really impossible.展开更多
NEW MATTER MATTERS.Oriental Outlook.17 April.The Shenzhen-Zhongshan Link,a major cross-sea passage in Guangdong Province,stands as a testament to modern engineering.To meet the demands of its harsh marine environment,...NEW MATTER MATTERS.Oriental Outlook.17 April.The Shenzhen-Zhongshan Link,a major cross-sea passage in Guangdong Province,stands as a testament to modern engineering.To meet the demands of its harsh marine environment,Chinese researchers have developed an advanced protective coating.Reinforced with ultrathin materials,this innovative solution is designed to extend the lifespan of steel structures well beyond a century by shielding them from corrosion.展开更多
Oral squamous cell carcinoma(OSCC)constitutes 90%of oral tumors.Advanced cases severely impair patients'life quality of life due to anatomical location and limited therapies.Conventional treatments often induce dr...Oral squamous cell carcinoma(OSCC)constitutes 90%of oral tumors.Advanced cases severely impair patients'life quality of life due to anatomical location and limited therapies.Conventional treatments often induce drug resistance or recurrence.Patientderived xenograft(PDX)models are widely used to simulate tumor progression and drug responses,serving as translational tools for precision medicine.This study aimed to establish drug-resistant OSCC PDX models.Human OSCC tissues were transplanted into immunodeficient mice and passaged(P1–P2).At P2(tumor volume:40–80 mm^(3)),mice received cisplatin(1 mg/kg,three times/week)with cetuximab(1 mg/kg,weekly),GSK690693(10 mg/kg,five times/week),or rapamycin(4 mg/kg,five times/week).PDX tissues from groups with less-therapeutic response(manifested as larger tumor volumes)were serially passaged to assess treatment efficacy.Tumor tissues with diminished drug sensitivity underwent histopathological analysis and identified stability of their tumor characteristics using hematoxylin–eosin(HE)and immunohistochemical staining after one additional passage and retreatment.Results demonstrated that successive passaging accelerates tumor growth.First-generation treatments showed universal sensitivity.At P2,cisplatin–cetuximab and rapamycin groups remained sensitive,whereas GSK690693 efficacy declined.Continued passaging of GSK690693-treated tumors confirmed resistance,as evidenced by exhibiting enhanced malignant characteristics at histological level.The GSK690693-resistant model was established first,whereas resistant models of other treatment groups were established according to similar protocols.These findings suggest that sequential passaging and drug exposure in PDX models recapitulated clinical tumor evolution,enabling the development of drug-resistant OSCC models.This study can offer methodological insights for precision therapy of OSCC.展开更多
Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and ...Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren’s syndrome(SS).Employing a multifaceted approach involving patient biopsies,non-obese diabetic(NOD)mice as a SS model,salivary gland acinar cell-specific tricellulin conditional knockout(TricCKO)mice,and IFN-γ-stimulated salivary gland epithelial cells,we investigated the role of tricellulin in SS-related hyposalivation.Our data revealed diminished levels of tricellulin in salivary glands of SS patients.Similarly,NOD mice displayed a reduction in tricellulin expression from the onset of the disease,concomitant with hyposecretion and an increase in salivary albumin content.Consistent with these findings,TricCKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals.Mechanistically,the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin.Treatment with AT1001,a TJ sealer,ameliorated epithelial barrier dysfunction,restored tricellulin expression,and consequently alleviated hyposalivation in NOD mice.Importantly,treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage.Collectively,we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS.Our findings highlight tricellulin as a potential therapeutic target for hyposecretion,particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)have been extensively studied for therapeutic potential,due to their regenerative and immunomodulatory properties.Serial passage and stress factors may affect the biological char...BACKGROUND Mesenchymal stem cells(MSCs)have been extensively studied for therapeutic potential,due to their regenerative and immunomodulatory properties.Serial passage and stress factors may affect the biological characteristics of MSCs,but the details of these effects have not been recognized yet.AIM To investigate the effects of stress factors(high glucose and severe hypoxia)on the biological characteristics of MSCs at different passages,in order to optimize the therapeutic applications of MSCs.METHODS In this study,we investigated the impact of two stress conditions;severe hypoxia and high glucose on human adipose-tissue derived MSCs(hAD-MSCs)at passages 6(P6),P8,and P10.Proliferation,senescence and apoptosis were evaluated measuring WST-1,senescence-associated beta-galactosidase,and annexin V,respectively.RESULTS Cells at P6 showed decreased proliferation and increased apoptosis under conditions of high glucose and hypoxia compared to control,while the extent of senescence did not change significantly under stress conditions.At P8 hAD-MSCs cultured in stress conditions had a significant decrease in proliferation and apoptosis and a significant increase in senescence compared to counterpart cells at P6.Cells cultured in high glucose at P10 had lower proliferation and higher senescence than their counterparts in the previous passage,while no change in apoptosis was observed.On the other hand,MSCs cultured under hypoxia showed decreased senescence,increased apoptosis and no significant change in proliferation when compared to the same conditions at P8.CONCLUSION These results indicate that stress factors had distinct effects on the biological processes of MSCs at different passages,and suggest that senescence may be a protective mechanism for MSCs to survive under stress conditions at higher passage numbers.展开更多
To study the stratified stability of a water column in the North Passage of the Yangtze River Estuary,a numerical model of the hydrodynamics of this estuary is established using the EFDC model.On the basis of EFDC res...To study the stratified stability of a water column in the North Passage of the Yangtze River Estuary,a numerical model of the hydrodynamics of this estuary is established using the EFDC model.On the basis of EFDC results,this paper derives and pro-vides the discriminative index of water body stability caused by salinity and analyzes the along-range variation in water body strati-fication stability in the North Passage of the Yangtze River Estuary and the periodic variation at a key location(bend area)based on the simulation results of the numerical model.This work shows that the water body in the bend area varies between mixed and strati-fied types,and the vertical average flow velocity has a good negative correlation with the differential velocity between the surface and bottom layers of the water body.The model simulation results validate the formulae for the stratified stability discriminant during spring tides.展开更多
Most phages—viruses infecting prokaryotes—inject their genomes via a tail structure.The central tail tube,composed of tail tube protein(TTP),typically forms conserved hexameric or trimeric rings.In this paper,we rep...Most phages—viruses infecting prokaryotes—inject their genomes via a tail structure.The central tail tube,composed of tail tube protein(TTP),typically forms conserved hexameric or trimeric rings.In this paper,we report a novel pentameric TTP assembly,solved by cryo-electron microscopy(cryo-EM)at 3.5 A and 3.7 A resolution.Structural analysis reveals a highly negatively charged inner surface of this pentameric tube.Key residues in the loop connectingβ3 andβ4 strands are crucial for pentameric ring formation.Mismatches in interactions between stacked layers can induce curvature in the tube.The cryo-EM structure of the TTP polymer at the tube’s end shows thatβ-strands spanning amino acids 27-65 shift toward the central tunnel,potentially obstructing the passage of the phage genome.This study provides new structural insights into a unique TTP assembly,enhancing our understanding of phage assembly processes.展开更多
Objectives Autologous blood outgrowth endothelial cells(BOECs)have been proposed to induce therapeutic angiogenesis for treating cardiovascular diseases(CVDs).The aim of the present study was to investigate the prolif...Objectives Autologous blood outgrowth endothelial cells(BOECs)have been proposed to induce therapeutic angiogenesis for treating cardiovascular diseases(CVDs).The aim of the present study was to investigate the proliferative potential and angiogenic characteristics of BOECs among middle-aged and older adults,the population particularly susceptible to CVDs.Methods BOECs were isolated from 48 peripheral blood samples of subjects aged 56±4 years.The cells were then distinguished based on their proliferative abilities,and their phenotype,tube formation capacity,and migratory activity were compared using immunofluorescence staining,flow cytometry,tube formation assay,and wound healing assay,respectively.Correlations between demographic,clinical,and dietary parameters with the number of BOECs were also assessed.Results A total of 132 BOEC colonies with different proliferative potentials were obtained,including colonies lost proliferative ability before passage 3(named LPA),stopped proliferating during passage 3–8(HPA(3–8)),and proliferated after passage 8(HPA(>8)).LPA cells appeared later and displayed abnormal morphology,while HPA(3–8)cells exhibited alterations in von Willebrand factor morphology and lower KDR expression.HPA(>8)cells obtained higher branching intervals and individual cell migration velocity compared with those of HPA(3–8)cells.Correlation analysis showed that the number of both LPA and HPA colonies were positively associated with several CVD risk factors.Additionally,the number of LPA colonies was positively associated with servings of meats and alternatives,fruits,fruits and vegetables,as well as the protein intake.Conclusions Our findings provide evidence that the middle-aged and older populations possess BOECs with different proliferative and angiogenic potentials,exhibiting distinctions in cell morphology,appearance dates,VWF morphology,and KDR expression.Strikingly,a higher number of BOECs is likely associated with an increased risk of CVDs,while the number of BOECs with low proliferative ability may be regulated by diet.展开更多
To understand the dynamic process of polymer detachment, it is necessary to determine the mean detachment time of a single breakable link, which is modeled as a spring. Normally, this time can be viewed as the escape ...To understand the dynamic process of polymer detachment, it is necessary to determine the mean detachment time of a single breakable link, which is modeled as a spring. Normally, this time can be viewed as the escape of a Brownian particle from the potential well of the spring. However, as the free dangling length of the polymer chain increases, the conformational entropy of the chain is affected by geometric confinement. It means that the wall exerts a repulsive force on the chain, resulting in accelerated link detachment from a macroscopic perspective. In this work, we investigate the effect of entropy on the detachment rate in the case where the substrate is spherical. We demonstrate that spherical confinement accelerates chain detachment both inside and outside the sphere. An analytical expression for the mean detachment time of breakable links is given, which includes an additional pre-factor that is related to the partition function. Additionally, we analyze the expressions for entropic forces inside the sphere, outside the sphere, and on a flat wall, comparing their magnitudes to explain the difference in mean detachment time.展开更多
This paper investigates logical stochastic resonance(LSR)in a cross-bifurcation non-smooth system driven by Gaussian colored noise.In this system,a bifurcation parameter triggers a transition between monostability,bis...This paper investigates logical stochastic resonance(LSR)in a cross-bifurcation non-smooth system driven by Gaussian colored noise.In this system,a bifurcation parameter triggers a transition between monostability,bistability and tristability.By using Novikov's theorem and the unified colored noise approximation method,the approximate Fokker-Planck equation is obtained.Then we derive the generalized potential function and the transition rates to analyze the LSR phenomenon using numerical simulations.We simulate the logic operation of the system in the bistable and tristable regions respectively.We assess the impact of Gaussian colored noise on the LSR and discover that the reliability of the logic response depends on the noise strength and the bifurcation parameter.Furthermore,it is found that the bistable region has a more extensive parameter range to produce reliable logic operation compared with the tristable region,since the tristable region is more sensitive to noise than the bistable one.展开更多
This article discussed a study by Almahasneh et al,which investigated how high glucose and severe hypoxia affected mesenchymal stem cells(MSCs)at different passages.This research provides insights into the resilience ...This article discussed a study by Almahasneh et al,which investigated how high glucose and severe hypoxia affected mesenchymal stem cells(MSCs)at different passages.This research provides insights into the resilience of higher-passage MSCs under stress conditions,challenging the common use of lower passage MSCs in clinical settings.While this study offers valuable perspectives on the adaptability of MSCs,it relies mainly on in vitro results from a single cell line,limiting broader applicability.It highlights the need for more comprehensive in vivo studies to validate these findings and better understand MSC behavior in clinical scenarios.展开更多
Moellerella wisconsensis is proposed for a member of the family Enterobacteriaceae previously designated as Enteric Group 46.In 1984,the majority of the bacterial isolates(6/8,75%)had been identified in Wisconsin,USA(...Moellerella wisconsensis is proposed for a member of the family Enterobacteriaceae previously designated as Enteric Group 46.In 1984,the majority of the bacterial isolates(6/8,75%)had been identified in Wisconsin,USA(Hickman-Brenner et al.2021).Thus,this bacterial was named M.wisconsensis.Despite the passage of nearly four decades since its discovery,limited research has been conducted on this bacterium.This may be attributed to the misidentification of M.wisconsensis as Escherichia coli(Stock et al.2003).Currently,the presence of these microorganisms has been identified in both humans and animals,leading to the development of various clinical symptoms such as diarrhea,urinary tract infections,and bacteremia(Aller et al.2009;Leroy et al.2016).展开更多
Beijing Central Axis is the backbone of the ancient capital,a cultural spine shaped by the passage of time and spatial changes.Its successful inscription as a World Heritage site presents new opportunities for the con...Beijing Central Axis is the backbone of the ancient capital,a cultural spine shaped by the passage of time and spatial changes.Its successful inscription as a World Heritage site presents new opportunities for the conservation of the Central Axis cultural heritage,while also offering a fresh chance to link cultural and tourism sites along the Axis,fostering coordinated development.展开更多
With the development of aero-engines, the turbine inlet temperature continues to rise. In order to ensure the safety and reliability of the turbine blades, cooling structures must be set inside turbine blades to cool ...With the development of aero-engines, the turbine inlet temperature continues to rise. In order to ensure the safety and reliability of the turbine blades, cooling structures must be set inside turbine blades to cool them. Heat transfer coefficient and flow resistance are the key parameters to measure the cooling characteristics of internal cooling structures. In this paper, the characteristics of flow resistance in a rotating ribbed channel is presented numerical simulation under different rib spacings, rib angles, and thermal boundary conditions. The results show that, separation and reattachment of fluid between ribs is the key effect of rib spacing on flow resistance. The flow resistance is small when the rib spacing is small, because it's difficult for the fluid to form reattachment between the ribs. With the increase of rib spacing, the reattachment phenomenon is more obvious and the flow resistance increases accordingly. In general,p: e=10 channel has the maximum flow resistance. Secondary flow caused by the ribs is the key factor affecting the flow resistance characteristics with different rib angles. The secondary flow interacts with the main flow and causes flow loss through mixing, thus affecting the flow resistance of the channel. Under static condition, the flow resistance of 60°ribbed channel is the largest. The flow resistance of channel was affected by the temperature rise ratio also. And with the increase of the Ro, the temperature rise ratio has a more obvious effect on the flow resistance of the ribbed channel.When Ro=0.45, the flow resistance of the channel with a temperature rise ratio of 0.4 is 2.4 times that of the channel without temperature rise, while when Ro=0.3, it is 1.6 times, and when Ro=0.15, it is 1.2 times.展开更多
1Dive into the depths of the Earth and you'll find a world of quiet mystery:caves.Actually,these are not just dark holes.Imagine the Saint-Marcel Cave in France,a place that's been a human hangout for thousand...1Dive into the depths of the Earth and you'll find a world of quiet mystery:caves.Actually,these are not just dark holes.Imagine the Saint-Marcel Cave in France,a place that's been a human hangout for thousands of years,back to the days when our ancestors used tools made of stone.This cave is no simple tunnel;it's a labyrinth (迷宫) of limestone that stretches for miles beneath the surface.It is like a secret passageway to a quiet universe,a place where the hustle and bustle (熙熙攘攘) of our world seems far away.展开更多
Xiamen University,a beacon of education and culture,invites us to witness the fascinating interplay(相互影响)of movement and stillness within its main gate.As we embark on this journey,we discover a realm(领域)where t...Xiamen University,a beacon of education and culture,invites us to witness the fascinating interplay(相互影响)of movement and stillness within its main gate.As we embark on this journey,we discover a realm(领域)where the passage of time and the transformation of space create an attractive dance,while the enduring essence of knowledge and youthful passion remain ever-present.展开更多
Background: Ureteral stones are the most common leading cause of acute flank pain. This study aimed to identify sociodemographic and clinical variables predicting spontaneous ureteral stone passage and determine the o...Background: Ureteral stones are the most common leading cause of acute flank pain. This study aimed to identify sociodemographic and clinical variables predicting spontaneous ureteral stone passage and determine the optimal size cut-off for predicting such passage. Method: We conducted a retrospective evaluation of patients presenting with acute renal colic at a urology outpatient clinic. Patients with ureteral stones ≤ 10 mm and no surgical intervention post-initial diagnosis, who attended follow-up visits, were included. Exclusion criteria comprised stone size > 1 cm, fever due to obstructive pyelonephritis, acute kidney injury, single kidney status, or bilateral ureteral obstruction. Results: Of 124 included patients, the spontaneous stone passage rate was 57.3%, with a mean passage time of 11.1 (SD 6.25) days. Bivariate analysis revealed that factors predicting spontaneous passage were stone size (p Conclusions: Stone size < 7 mm, UVJ or distal ureter location, emerged as key predictors of stone passage in nephrolithiasis, and stone size below 6.85 mm is a reasonable cut off to initiate MET rather than 10 mm.展开更多
文摘A human lung squamous carcinoma was transplanted and passaged in Swiss-DF nude mice, called LSX-83, for more than five years in our laboratory. The morphological characteristics of the original tumor were maintained in passages from 4 to 33. But from the 35th generation, an increasing amount of tonofilaments and nuclear segregation with typical features was found with electron microscopy. The C-type virus particles were first detected in extra cellular space after 40 passages. The viruses were observed in different stages of growth, but their distribution and number did not show apparent change up to 54 passages. Such findings suggest that LSX-83 cells probably possess certain barrier of resistance against C-type viruses. The relation between C-type viruses and the morphological changes of LSX-83 cells was discussed.
文摘Low pathogenic Avian Influenza (AI) virus has the ability to evolve to high pathogenic viruses resulting in significant economic losses in the poultry sector. This study aims at assessing the impact of H9N2 viral passaging in broilers and its relatedness to pathogenicity and amino acid (a.a) sequences of the hemagglutinin (HA) cleavage site and neuraminidase (NA) stalk. The original H9N2 AI virus (P0) was used to challenge ten-21 days old broilers. Individual recovery of H9N2 virus from homogenates of trachea, lungs and airsacs was attempted in 9 days old chicken embryos, as a conclusion of the first passage (P1). Tracheal isolates of H9N2 were passaged for a second (P2) and a third (P3) time in broilers, followed by a similar embryonic recovery procedure. The a.a. sequence of a part of HA1 cleavage site and Neuraminidase stalk were compared among the differently passaged viruses;an assessement of the relatedness of the determined a.a. sequences to the pathogenicity in broilers, based on frequency of mortality, morbidity signs, gross and microscopic lesions at 3 days post challenge with the P1, P2, and P3-H9N2, is concluded. An increase in certain morbidity signs and specific lesions was observed in P2- and P3-H9N2 challenged broilers compared to birds challenged with P1-H9N2. A conserved R-S-S-R amino acid sequence at the HA1 cleavage site was observed in the differently passaged H9N2, associated with a variability in the NA stalk-a.a sequences. The passaging of the low pathogenic H9N2 virus in broilers leads to a trend of increase in pathogenicity, manifested in higher frequency of morbidity signs, and of specific gross and microscopic lesions of the examined organs. This passaging was associated with a conserved a.a. sequence of the hemaglutinin cleavage site and a variability in the sequence of the neuraminidase stalk. A detailed study of the potential of the detected variability in the neuraminidase stalk of H9N2 in induction of a higher pathogenicity in broilers will be the subject of future investigations.
文摘We have previously reported on both the osteogenic potential of hydroxyapatite (HA) combined with bone marrow-derived mesenchymal stem cells (BMSCs) and a method involving osteogenic matrix cell sheet transplantation of BMSCs. In the present study, we assessed the osteogenic potential of serially-passaged BMSCs, both in vitro and in vivo. We also assessed whether an additional cell-loading technique can regain the osteogenic potential of the constructs combined with serially-passaged BMSCs. The present study revealed that passage (P) 1 cells cultured in osteogenic-induced medium showed strong positive staining for alkaline phosphatase (ALP) and Alizarin Red S, whereas P3 cells showed faint staining for ALP, with no Alizarin Red S staining. Staining of P1, P2 and P3 cells were progressively weaker, indicating that the osteogenic potential of the serially-passaged rat BMSCs is lost after P3 in vitro. The in vivo study showed that little bone formation was observed in the HA constructs seeded with P3 cells, 4 weeks after subcutaneous implantation. However, P3 cell/HA constructs which had increased cell-loading showed abundant bone formation within the pores of the HA construct. ALP and osteocalcin mRNA expression in these constructs was significantly higher than that of constructs with regular cell-seeding. The present study indicates that the osteogenic potential of the constructs with serially-passaged BMSCs is increased by additional cell-loading. This method can be applied to cases requiring hard tissue reconstruction, where BMSCs require serial expansion of cells.
文摘Alice opened the door and found that it led into a small passage,not much larger than a rat⁃hole:she knelt down and looked along the passage into the loveliest garden you ever saw.How she longed to get out of that dark hall,and wander about among those beds of bright flowers and those cool fountains,but she could not even get her head through the doorway;“and even if my head would go through,”thought poor Alice,“it would be of very little use without my shoulders.Oh,how I wish I could shut up like a telescope!I think I could,if I only know how to begin.”For,you see,so many out⁃of⁃the⁃way things had happened lately,that Alice had begun to think that very few things indeed were really impossible.
文摘NEW MATTER MATTERS.Oriental Outlook.17 April.The Shenzhen-Zhongshan Link,a major cross-sea passage in Guangdong Province,stands as a testament to modern engineering.To meet the demands of its harsh marine environment,Chinese researchers have developed an advanced protective coating.Reinforced with ultrathin materials,this innovative solution is designed to extend the lifespan of steel structures well beyond a century by shielding them from corrosion.
基金National Natural Science Foundation of China,Grant/Award Number:82173399Young Elite Scientists Sponsorship Program by CAST,Grant/Award Number:2022QNRC001+2 种基金Beijing Natural Science Foundation,Grant/Award Number:7252096Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund Project,Grant/Award Number:L222145CAMS&Comparative Medicine Center,PUMC (IACUC approval number:QC24002)
文摘Oral squamous cell carcinoma(OSCC)constitutes 90%of oral tumors.Advanced cases severely impair patients'life quality of life due to anatomical location and limited therapies.Conventional treatments often induce drug resistance or recurrence.Patientderived xenograft(PDX)models are widely used to simulate tumor progression and drug responses,serving as translational tools for precision medicine.This study aimed to establish drug-resistant OSCC PDX models.Human OSCC tissues were transplanted into immunodeficient mice and passaged(P1–P2).At P2(tumor volume:40–80 mm^(3)),mice received cisplatin(1 mg/kg,three times/week)with cetuximab(1 mg/kg,weekly),GSK690693(10 mg/kg,five times/week),or rapamycin(4 mg/kg,five times/week).PDX tissues from groups with less-therapeutic response(manifested as larger tumor volumes)were serially passaged to assess treatment efficacy.Tumor tissues with diminished drug sensitivity underwent histopathological analysis and identified stability of their tumor characteristics using hematoxylin–eosin(HE)and immunohistochemical staining after one additional passage and retreatment.Results demonstrated that successive passaging accelerates tumor growth.First-generation treatments showed universal sensitivity.At P2,cisplatin–cetuximab and rapamycin groups remained sensitive,whereas GSK690693 efficacy declined.Continued passaging of GSK690693-treated tumors confirmed resistance,as evidenced by exhibiting enhanced malignant characteristics at histological level.The GSK690693-resistant model was established first,whereas resistant models of other treatment groups were established according to similar protocols.These findings suggest that sequential passaging and drug exposure in PDX models recapitulated clinical tumor evolution,enabling the development of drug-resistant OSCC models.This study can offer methodological insights for precision therapy of OSCC.
基金supported by the National Natural Science Foundation of China(grants 31972908,81991500,81991502,and 32030010)Beijing Natural Science Foundation(grant 7202082).
文摘Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren’s syndrome(SS).Employing a multifaceted approach involving patient biopsies,non-obese diabetic(NOD)mice as a SS model,salivary gland acinar cell-specific tricellulin conditional knockout(TricCKO)mice,and IFN-γ-stimulated salivary gland epithelial cells,we investigated the role of tricellulin in SS-related hyposalivation.Our data revealed diminished levels of tricellulin in salivary glands of SS patients.Similarly,NOD mice displayed a reduction in tricellulin expression from the onset of the disease,concomitant with hyposecretion and an increase in salivary albumin content.Consistent with these findings,TricCKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals.Mechanistically,the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin.Treatment with AT1001,a TJ sealer,ameliorated epithelial barrier dysfunction,restored tricellulin expression,and consequently alleviated hyposalivation in NOD mice.Importantly,treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage.Collectively,we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS.Our findings highlight tricellulin as a potential therapeutic target for hyposecretion,particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
基金Supported by the Deanship of Scientific Research,Yarmouk University,Jordan,No.73/2022.
文摘BACKGROUND Mesenchymal stem cells(MSCs)have been extensively studied for therapeutic potential,due to their regenerative and immunomodulatory properties.Serial passage and stress factors may affect the biological characteristics of MSCs,but the details of these effects have not been recognized yet.AIM To investigate the effects of stress factors(high glucose and severe hypoxia)on the biological characteristics of MSCs at different passages,in order to optimize the therapeutic applications of MSCs.METHODS In this study,we investigated the impact of two stress conditions;severe hypoxia and high glucose on human adipose-tissue derived MSCs(hAD-MSCs)at passages 6(P6),P8,and P10.Proliferation,senescence and apoptosis were evaluated measuring WST-1,senescence-associated beta-galactosidase,and annexin V,respectively.RESULTS Cells at P6 showed decreased proliferation and increased apoptosis under conditions of high glucose and hypoxia compared to control,while the extent of senescence did not change significantly under stress conditions.At P8 hAD-MSCs cultured in stress conditions had a significant decrease in proliferation and apoptosis and a significant increase in senescence compared to counterpart cells at P6.Cells cultured in high glucose at P10 had lower proliferation and higher senescence than their counterparts in the previous passage,while no change in apoptosis was observed.On the other hand,MSCs cultured under hypoxia showed decreased senescence,increased apoptosis and no significant change in proliferation when compared to the same conditions at P8.CONCLUSION These results indicate that stress factors had distinct effects on the biological processes of MSCs at different passages,and suggest that senescence may be a protective mechanism for MSCs to survive under stress conditions at higher passage numbers.
基金supported by the National Natural Science Foundation of China(Nos.42176166,41776024).
文摘To study the stratified stability of a water column in the North Passage of the Yangtze River Estuary,a numerical model of the hydrodynamics of this estuary is established using the EFDC model.On the basis of EFDC results,this paper derives and pro-vides the discriminative index of water body stability caused by salinity and analyzes the along-range variation in water body strati-fication stability in the North Passage of the Yangtze River Estuary and the periodic variation at a key location(bend area)based on the simulation results of the numerical model.This work shows that the water body in the bend area varies between mixed and strati-fied types,and the vertical average flow velocity has a good negative correlation with the differential velocity between the surface and bottom layers of the water body.The model simulation results validate the formulae for the stratified stability discriminant during spring tides.
基金supported by the Chinese Academy of Sciences (Grant Nos. E4V4061 and E2VK311)supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (Grant No. 2021-I2M-1-037)supported by the National Natural Science Foundation of China (Grant Nos. 81971985 and 82272308).
文摘Most phages—viruses infecting prokaryotes—inject their genomes via a tail structure.The central tail tube,composed of tail tube protein(TTP),typically forms conserved hexameric or trimeric rings.In this paper,we report a novel pentameric TTP assembly,solved by cryo-electron microscopy(cryo-EM)at 3.5 A and 3.7 A resolution.Structural analysis reveals a highly negatively charged inner surface of this pentameric tube.Key residues in the loop connectingβ3 andβ4 strands are crucial for pentameric ring formation.Mismatches in interactions between stacked layers can induce curvature in the tube.The cryo-EM structure of the TTP polymer at the tube’s end shows thatβ-strands spanning amino acids 27-65 shift toward the central tunnel,potentially obstructing the passage of the phage genome.This study provides new structural insights into a unique TTP assembly,enhancing our understanding of phage assembly processes.
基金sponsored by Shanghai Pujiang Program(23PJ1409600)Intergovernmental International Science and Technology Innovation Cooperation Key Project of Chinese National Key R&D Program(2024YFE0102600)Singapore Ministry of Education Academic Research Fund Tier 1(R160-000-A26–114).
文摘Objectives Autologous blood outgrowth endothelial cells(BOECs)have been proposed to induce therapeutic angiogenesis for treating cardiovascular diseases(CVDs).The aim of the present study was to investigate the proliferative potential and angiogenic characteristics of BOECs among middle-aged and older adults,the population particularly susceptible to CVDs.Methods BOECs were isolated from 48 peripheral blood samples of subjects aged 56±4 years.The cells were then distinguished based on their proliferative abilities,and their phenotype,tube formation capacity,and migratory activity were compared using immunofluorescence staining,flow cytometry,tube formation assay,and wound healing assay,respectively.Correlations between demographic,clinical,and dietary parameters with the number of BOECs were also assessed.Results A total of 132 BOEC colonies with different proliferative potentials were obtained,including colonies lost proliferative ability before passage 3(named LPA),stopped proliferating during passage 3–8(HPA(3–8)),and proliferated after passage 8(HPA(>8)).LPA cells appeared later and displayed abnormal morphology,while HPA(3–8)cells exhibited alterations in von Willebrand factor morphology and lower KDR expression.HPA(>8)cells obtained higher branching intervals and individual cell migration velocity compared with those of HPA(3–8)cells.Correlation analysis showed that the number of both LPA and HPA colonies were positively associated with several CVD risk factors.Additionally,the number of LPA colonies was positively associated with servings of meats and alternatives,fruits,fruits and vegetables,as well as the protein intake.Conclusions Our findings provide evidence that the middle-aged and older populations possess BOECs with different proliferative and angiogenic potentials,exhibiting distinctions in cell morphology,appearance dates,VWF morphology,and KDR expression.Strikingly,a higher number of BOECs is likely associated with an increased risk of CVDs,while the number of BOECs with low proliferative ability may be regulated by diet.
基金financially supported by the National Natural Science Foundation of China (No.51965057)Xinjiang Tianchi Ph D Project (No.TCBS202113)+3 种基金the Natural Science Foundation of Xinjiang (No.2022D01C34)Xinjiang Basic Research Funds for Universities (No.XJEDU2022P017)Robot-Intelligent Equipment Technology Innovation (No.2022D14002)Xinjiang Tianshan Science Technology Innovation Leading Talents Program (No.2022TSYCLJ0044)。
文摘To understand the dynamic process of polymer detachment, it is necessary to determine the mean detachment time of a single breakable link, which is modeled as a spring. Normally, this time can be viewed as the escape of a Brownian particle from the potential well of the spring. However, as the free dangling length of the polymer chain increases, the conformational entropy of the chain is affected by geometric confinement. It means that the wall exerts a repulsive force on the chain, resulting in accelerated link detachment from a macroscopic perspective. In this work, we investigate the effect of entropy on the detachment rate in the case where the substrate is spherical. We demonstrate that spherical confinement accelerates chain detachment both inside and outside the sphere. An analytical expression for the mean detachment time of breakable links is given, which includes an additional pre-factor that is related to the partition function. Additionally, we analyze the expressions for entropic forces inside the sphere, outside the sphere, and on a flat wall, comparing their magnitudes to explain the difference in mean detachment time.
基金Project supported by the National Natural Science Foundation of China(Grant No.12072262)the Shaanxi Computer Society&Xiangteng Company Foundation.
文摘This paper investigates logical stochastic resonance(LSR)in a cross-bifurcation non-smooth system driven by Gaussian colored noise.In this system,a bifurcation parameter triggers a transition between monostability,bistability and tristability.By using Novikov's theorem and the unified colored noise approximation method,the approximate Fokker-Planck equation is obtained.Then we derive the generalized potential function and the transition rates to analyze the LSR phenomenon using numerical simulations.We simulate the logic operation of the system in the bistable and tristable regions respectively.We assess the impact of Gaussian colored noise on the LSR and discover that the reliability of the logic response depends on the noise strength and the bifurcation parameter.Furthermore,it is found that the bistable region has a more extensive parameter range to produce reliable logic operation compared with the tristable region,since the tristable region is more sensitive to noise than the bistable one.
基金Supported by the National Natural Science Foundation of China,No.81500207 to Xiao-Ting Liangand the Pyramid Talent Project,No.YQ677 to Yue Ding.
文摘This article discussed a study by Almahasneh et al,which investigated how high glucose and severe hypoxia affected mesenchymal stem cells(MSCs)at different passages.This research provides insights into the resilience of higher-passage MSCs under stress conditions,challenging the common use of lower passage MSCs in clinical settings.While this study offers valuable perspectives on the adaptability of MSCs,it relies mainly on in vitro results from a single cell line,limiting broader applicability.It highlights the need for more comprehensive in vivo studies to validate these findings and better understand MSC behavior in clinical scenarios.
基金funded by the National Natural Science Foundation of China(32141002)the Postdoctoral Fellowship Program of CPSF under Grant,China(GZC20241939)the China Agriculture Research System of MOF and MARA(CARS-39-14).
文摘Moellerella wisconsensis is proposed for a member of the family Enterobacteriaceae previously designated as Enteric Group 46.In 1984,the majority of the bacterial isolates(6/8,75%)had been identified in Wisconsin,USA(Hickman-Brenner et al.2021).Thus,this bacterial was named M.wisconsensis.Despite the passage of nearly four decades since its discovery,limited research has been conducted on this bacterium.This may be attributed to the misidentification of M.wisconsensis as Escherichia coli(Stock et al.2003).Currently,the presence of these microorganisms has been identified in both humans and animals,leading to the development of various clinical symptoms such as diarrhea,urinary tract infections,and bacteremia(Aller et al.2009;Leroy et al.2016).
文摘Beijing Central Axis is the backbone of the ancient capital,a cultural spine shaped by the passage of time and spatial changes.Its successful inscription as a World Heritage site presents new opportunities for the conservation of the Central Axis cultural heritage,while also offering a fresh chance to link cultural and tourism sites along the Axis,fostering coordinated development.
基金Beijing Nova Program (No. 20220484129)National Natural Science Foundation of China (No.52376042)+1 种基金Advanced Aerodynamic Innovation Workstation (Grant No. HKCX2022-01-07)National Science and Technology Major Project (Grant No. J2019-II-0022-0043)。
文摘With the development of aero-engines, the turbine inlet temperature continues to rise. In order to ensure the safety and reliability of the turbine blades, cooling structures must be set inside turbine blades to cool them. Heat transfer coefficient and flow resistance are the key parameters to measure the cooling characteristics of internal cooling structures. In this paper, the characteristics of flow resistance in a rotating ribbed channel is presented numerical simulation under different rib spacings, rib angles, and thermal boundary conditions. The results show that, separation and reattachment of fluid between ribs is the key effect of rib spacing on flow resistance. The flow resistance is small when the rib spacing is small, because it's difficult for the fluid to form reattachment between the ribs. With the increase of rib spacing, the reattachment phenomenon is more obvious and the flow resistance increases accordingly. In general,p: e=10 channel has the maximum flow resistance. Secondary flow caused by the ribs is the key factor affecting the flow resistance characteristics with different rib angles. The secondary flow interacts with the main flow and causes flow loss through mixing, thus affecting the flow resistance of the channel. Under static condition, the flow resistance of 60°ribbed channel is the largest. The flow resistance of channel was affected by the temperature rise ratio also. And with the increase of the Ro, the temperature rise ratio has a more obvious effect on the flow resistance of the ribbed channel.When Ro=0.45, the flow resistance of the channel with a temperature rise ratio of 0.4 is 2.4 times that of the channel without temperature rise, while when Ro=0.3, it is 1.6 times, and when Ro=0.15, it is 1.2 times.
文摘1Dive into the depths of the Earth and you'll find a world of quiet mystery:caves.Actually,these are not just dark holes.Imagine the Saint-Marcel Cave in France,a place that's been a human hangout for thousands of years,back to the days when our ancestors used tools made of stone.This cave is no simple tunnel;it's a labyrinth (迷宫) of limestone that stretches for miles beneath the surface.It is like a secret passageway to a quiet universe,a place where the hustle and bustle (熙熙攘攘) of our world seems far away.
文摘Xiamen University,a beacon of education and culture,invites us to witness the fascinating interplay(相互影响)of movement and stillness within its main gate.As we embark on this journey,we discover a realm(领域)where the passage of time and the transformation of space create an attractive dance,while the enduring essence of knowledge and youthful passion remain ever-present.
文摘Background: Ureteral stones are the most common leading cause of acute flank pain. This study aimed to identify sociodemographic and clinical variables predicting spontaneous ureteral stone passage and determine the optimal size cut-off for predicting such passage. Method: We conducted a retrospective evaluation of patients presenting with acute renal colic at a urology outpatient clinic. Patients with ureteral stones ≤ 10 mm and no surgical intervention post-initial diagnosis, who attended follow-up visits, were included. Exclusion criteria comprised stone size > 1 cm, fever due to obstructive pyelonephritis, acute kidney injury, single kidney status, or bilateral ureteral obstruction. Results: Of 124 included patients, the spontaneous stone passage rate was 57.3%, with a mean passage time of 11.1 (SD 6.25) days. Bivariate analysis revealed that factors predicting spontaneous passage were stone size (p Conclusions: Stone size < 7 mm, UVJ or distal ureter location, emerged as key predictors of stone passage in nephrolithiasis, and stone size below 6.85 mm is a reasonable cut off to initiate MET rather than 10 mm.