The diffusion trajectory of a Brownian particle passing over the saddle point of a two-dimensional quadratic potential energy surface is tracked in detail according to the deep learning strategies.Generative adversari...The diffusion trajectory of a Brownian particle passing over the saddle point of a two-dimensional quadratic potential energy surface is tracked in detail according to the deep learning strategies.Generative adversarial networks(GANs)emanating in the category of machine learning(ML)frameworks are used to generate and assess the rationality of the data.While their optimization is based on the long short-term memory(LSTM)strategies.In addition to drawing a heat map,the optimal path of two-dimensional(2D)diffusion is simultaneously demonstrated in a stereoscopic space.The results of our simulation are completely consistent with the previous theoretical predictions.展开更多
The Openness based on DEM emphasizes the terrain convexity and concavity. It facilitates the interpretation of detailed landforms on the Earth＇s surface. Compared with the layer stacking of ETM＋ with less three-dime...The Openness based on DEM emphasizes the terrain convexity and concavity. It facilitates the interpretation of detailed landforms on the Earth＇s surface. Compared with the layer stacking of ETM＋ with less three-dimensionality and visualizability and with indefinite details of linear images in the deep cutting or deep covered region, the Openness is used for accurate interpretation of tectonic geomorphic units and linear structures. In this paper, the ETM＋ images（741 RGB） and RRIM based on Openness combined with the field geological investigation are used to trace the escaping structure in SE Asia. The east boundary is Ailaoshan shear zone and the west boundary is Uttaradit-Dien Bien Phu fault, which together form the southwards extruding wedge block. The arc boundary surface of the southern Khorat Plateau is jutted to the north. The NW and NE sides of Khorat Plateau are traversed by Uttaradit-Dien Bien Phu fault and Thakhek-Da Nang fault, respectively, resulting in a blocked escaping structure. The SE margins of Truong Son structure belt and Song Ma structure belt are both arcs jutting to SE. These arc structures clamped by faults or related to the fault on one side indicating the material flow direction obviously, are the most specific manifestation of escaping structures. Moreover, these push units are extruded from south to north successively.展开更多
We theoretically investigated negative entropy S of biopolymer which passes through a nanometer pore（such as a-hemolysin）, especially entering process and escaping process, on the basis of which we also studied biop...We theoretically investigated negative entropy S of biopolymer which passes through a nanometer pore（such as a-hemolysin）, especially entering process and escaping process, on the basis of which we also studied biopolymer entering-pore time rent, biopolymer entering mean velocity Vent, biopolymer escaping-pore time resc, and biopolymer escaping mean velocity vesc, respectively. Our results illustrate that the entering and escaping processes of biopolymer depend on its negative entropy, and entering process is more difficult than escaping process for biopolymer translocation. This tremendous difference between the two processes will offer a useful engineering hint for single macromolecule identification.展开更多
Research on magnetic mirror reactors has had two serious problems since the beginning stage. One is the magnetohydrodynamic instability due to the negative curvature of the magnetic field lines around the center regio...Research on magnetic mirror reactors has had two serious problems since the beginning stage. One is the magnetohydrodynamic instability due to the negative curvature of the magnetic field lines around the center region of a mirror bottle. Another is the loss of charged particles escaping from the loss cone of a magnetic mirror. We have continued to inquire into a means to solve the latter problem. We here propose a new way which will be able to make a magnitude of a loss angle of a magnetic mirror for deuterons virtually zero.展开更多
"The Swimmer"is the representative of John Cheever and it is one of the most famous short stories in present America.The story is simple and it is not long, but it has profound meaning because many imageries..."The Swimmer"is the representative of John Cheever and it is one of the most famous short stories in present America.The story is simple and it is not long, but it has profound meaning because many imageries are been used in the story. It tries to analyze the escaping and returning from the symbolic point of view, for escaping is an important motif in modern society and in the end, only returning can realize self-redemption.展开更多
AIM: To investigate the mechanism of α-fetoprotein (AFP)in escaping from the host immune surveillance of hepatocellular carcinoma.METHODS: AFP purified from human umbilical blood was administrated into the cultured h...AIM: To investigate the mechanism of α-fetoprotein (AFP)in escaping from the host immune surveillance of hepatocellular carcinoma.METHODS: AFP purified from human umbilical blood was administrated into the cultured human lymphoma Jurkat T cell line or hepatoma cell line, Bel7402 in vitro. The expression of tumor necrosis factor related apoptosisinducing ligand (TRAIL) and its receptor (TRAILR) mRNA were analyzed by Northern blot and Western blot wasused to detect the expression of Fas and Fas ligand (FasL)protein.RESULTS: AFP (20 mg/L) could promote the expression of FasL and TRAIL, and inhibit the expression of Fas and TRAILR of Bel7402 cells. For Jurkat cell line, AFP could suppress the expression of FasL and TRAIL, and stimulate the expression of Fas and TRAILR. AFP also could synergize with Bel7402 cells to inhibit the expression of FasL protein and TRAIL mRNA in Jurkat cells. The monoclonal antibody against AFP (anti-AFP) could abolish these functions of AFP.CONCLUSION: AFP is able to promote the expression of FasL and TRAIL in hepatoma cells and enhance the expression of Fas and TRAILR in lymphocytes. These could elicit the escape of hepatocellular carcinoma cells from the host's lymphocytes immune surveillance.展开更多
＂Emotion is a specific manner of apprehending the world＂ and transforming the world rather than an ＂accidental modification of a subject who is surrounded by an unchanged world,＂ according to Jean-Paul Sartre. Bot...＂Emotion is a specific manner of apprehending the world＂ and transforming the world rather than an ＂accidental modification of a subject who is surrounded by an unchanged world,＂ according to Jean-Paul Sartre. Both Sketch for a Theory of the Emotions and Being and Nothingness set out to investigate these relationships in broadly two ways. One, consciousness of the world of others is experienced through our emotions （anger, fear, shame, and pride for instance） as a body that escapes our grasp in being-seen-by-another. Two, we apprehend the world through our emotions in the process of magical transformation （for example, fear, melancholy, and sadness）. This paper examines emotions on two levels： how we experience our ontological state as being-for-itself-in-itself and being-in-the-world-for-others; and how we conceive emotions as ＂magic＂ changing its relationship with the world ＂so that the world should change its qualities.＂ What is of critical interest here is the relationship between consciousness and emotions. Situating this discussion in the context of Satre＇s critique on psychology, it proceeds to advance his existential psychoanalysis, starting with establishing a place for emotions and concluding with its transformative power to escape their situations.展开更多
The authors study a family of transcendental entire functions which lie outside the Eremenko-Lyubich class in general and are of infinity growth order. Most importantly,the authors show that the intersection of Julia ...The authors study a family of transcendental entire functions which lie outside the Eremenko-Lyubich class in general and are of infinity growth order. Most importantly,the authors show that the intersection of Julia set and escaping set of these entire functions has full Hausdorff dimension. As a by-product of the result, the authors also obtain the Hausdorff measure of their escaping set is infinity.展开更多
More white-collar workers consider leaving major metropolises to find opportunities in small and medium-sized cities The energy and excitement of first-tier cities, including Beijing, Shanghai, Guangzhou and Shenzhen ...More white-collar workers consider leaving major metropolises to find opportunities in small and medium-sized cities The energy and excitement of first-tier cities, including Beijing, Shanghai, Guangzhou and Shenzhen in Guangdong Province, have long served as magnets attracting enthusiastic young people. But recent surveys have overturned the perception of this urban draw.展开更多
Currently approved vaccines have been successful in preventing the severity of COVID-19 and hospitalization. These vaccines primarily induce humoral immune responses;however, highly transmissible and mutated variants,...Currently approved vaccines have been successful in preventing the severity of COVID-19 and hospitalization. These vaccines primarily induce humoral immune responses;however, highly transmissible and mutated variants, such as the Omicron variant, weaken the neutralization potential of the vaccines, thus,raising serious concerns about their efficacy. Additionally, while neutralizing antibodies(nAbs) tend to wane more rapidly than cell-mediated immunity, long-lasting T cells typically prevent severe viral illness by directly killing infected cells or aiding other immune cells. Importantly, T cells are more cross-reactive than antibodies, thus, highly mutated variants are less likely to escape lasting broadly cross-reactive T cell immunity. Therefore, T cell antigen-based human coronavirus(HCoV) vaccines with the potential to serve as a supplementary weapon to combat emerging SARS-CoV-2 variants with resistance to n Abs are urgently needed. Alternatively, T cell antigens could also be included in B cell antigen-based vaccines to strengthen vaccine efficacy. This review summarizes recent advancements in research and development of vaccines containing T cell antigens or both T and B cell antigens derived from proteins of SARS-CoV-2 variants and/or other HCo Vs based on different vaccine platforms.展开更多
Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limite...Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with SCLC.In the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.Methods:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in SCLC.The functional role of the key gene identified in SCLC was determined both in vitro and in vivo.Results:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell proportion.Furthermore,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in SCLC.Bioinformatics analysis revealed that USP1 is upregulated in SCLC.In addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune responses.By co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological inhibition.Furthermore,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated markers.Conclusions:Our study findings highlight the importance of NK cells in regulating SCLC.USP1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.展开更多
The escape and establishment of Iberian wild goats,Capra pyrenaica,from an enclosure in the 1990s marked the beginning of the recovery of the species in the Pyrenees.This population has occupied part of the Prepyrenee...The escape and establishment of Iberian wild goats,Capra pyrenaica,from an enclosure in the 1990s marked the beginning of the recovery of the species in the Pyrenees.This population has occupied part of the Prepyrenees and has contacted another population reintroduced in France since 2014.It coexists with other wild ungulates,including the feral and domestic goats Capra hircus that has been living free since the 1960s.Today it’s the largest Iberian wild goat Pyrenean population.Between 2006 and 2022 we monitored the population and its expansion based on vantage points,itineraries and testimonies.The results indicate:(i)a population,of uncertain genetic origin,in numerical(15%average annual growth)and areal expansion,with the capacity to connect with other populations;(ii)an estimate of at least 500 individuals;(iii)in the process of expansion in contact with Iberian wild goats from France;(iv)sympatry with feral and domestic goat population in its main nucleus whose estimate exceeds 2000 specimens and(v)hybridization with feral and domestic goats.In 2022 sustainable hunt started with a hunting quota of 20 individuals.Genetic characterization and the establishment of an international coordinated monitoring are two of the current priorities.展开更多
Small interfering RNAs(siRNA)provide a novel and highly specific therapy due to their ability to effectively silence target genes,to date six siRNA therapeutics are approved for clinical use.Even so,some critical chal...Small interfering RNAs(siRNA)provide a novel and highly specific therapy due to their ability to effectively silence target genes,to date six siRNA therapeutics are approved for clinical use.Even so,some critical challenges remain to overcome in the therapeutic application of siRNAs,with delivery issues at the forefront.Among them,endo/lysosomal barrier is one of the important but often-neglected limitations hindering the delivery of siRNA therapeutics.In this review,we summarize the promising strategies that facilitate siRNAs overcoming endo/lysosomal barriers based on the cellular uptake and intracellular transport pathways,including promoting escape once endocytosis into the endo/lysosomes and bypassing lysosomes via endosome-Golgi-endoplasmic reticulum(ER)pathway or nonendocytosis pathway,and discuss the principal considerations and the future directions of promoting endo/lysosomal escape in the development of therapeutic siRNAs.展开更多
Functional constraints between different types of antipredator behavior should be common,especially if they are on the opposite sides of the behavioral spectrum such as flight and post-capture immobility.We examined a...Functional constraints between different types of antipredator behavior should be common,especially if they are on the opposite sides of the behavioral spectrum such as flight and post-capture immobility.We examined a potential compromise between post-capture immobility displays and sprint speed in dice snakes(Natrix tessellata),using a field-based approach.We sampled snakes(N=238)from two populations:from a dense island population free of mammal predators,and from a less dense mainland population,preyed upon by both bird and mammal predators.We explored the effects of sexual maturity,temperature,body size,presence of palpable food in the gut,and injuries on the occurrence and duration of post-capture immobility as well as sprint speed.Our results confirm the existence of functional constraints between locomotor performance and post-capture immobility in dice snakes.Faster dice snakes start escaping promptly after release,while slower individuals utilize more passive antipredator behaviors such as death feigning.Local adaptations seem to have great influence on behavioral compromise,since the mammal-free island population exhibited a higher incidence of post-capture immobility and a significantly lower sprint speed,compared to the less dense mainland population.Additionally,immature individuals tended to avoid death feigning and their post-capture immobility lasted shorter compared to adult individuals.It remains to be seen how individuals adjust their behavior to accomodate locomotor constraints,and in which specific phases of the predator-prey interaction these adjustments occur.展开更多
Urbanization has significantly altered the habitat structure and behavioral patterns of animals.In urban environments with frequent human disturbances,animals may undergo adaptive adjustments in their escape behaviors...Urbanization has significantly altered the habitat structure and behavioral patterns of animals.In urban environments with frequent human disturbances,animals may undergo adaptive adjustments in their escape behaviors.This study focuses on Eurasian Tree Sparrows(Passer montanus)from five cities across different latitudes in China,comparing their flight initiation distance(FID)in urban and rural areas to assess the impact of urbanization on their escape behavior and the trend of ecological homogenization.The results confirm the established pattern at the geographic level:a reduction of FID in urban habitats and a decrease in FID with increasing latitude.That is,northern populations of the Eurasian Tree Sparrow in China are bolder than the southern populations.In addition,FID is positively correlated with flock size,with rural flocks exhibiting more pronounced group behavior(observed flocking frequency for urban and rural is 28.74%vs.40.7%,flock size variance is 26.90 vs.55.63).Despite the differences between northern and southern latitudes,the variability of FID in urban individuals consistently remains lower than that in rural areas,supporting the trend of reduced variability in escape behavior among birds in urban environments.Driven by urbanization,the escape behavior of Eurasian Tree Sparrows tends toward ecological homogenization,meaning that behavioral differences between urban areas in different cities are diminishing.This trend may obscure the behavioral variability brought about by latitude gradients,indicating that urbanization not only shapes the behavioral adaptations of birds but also potentially weakens their behavioral diversity.展开更多
基金supported by the Natural Science Foundation of Shandong Province(Grant No.ZR2020MA092)the Innovation Project for Graduate Students of Ludong University(Grant No.IPGS2024-048).
文摘The diffusion trajectory of a Brownian particle passing over the saddle point of a two-dimensional quadratic potential energy surface is tracked in detail according to the deep learning strategies.Generative adversarial networks(GANs)emanating in the category of machine learning(ML)frameworks are used to generate and assess the rationality of the data.While their optimization is based on the long short-term memory(LSTM)strategies.In addition to drawing a heat map,the optimal path of two-dimensional(2D)diffusion is simultaneously demonstrated in a stereoscopic space.The results of our simulation are completely consistent with the previous theoretical predictions.
基金supported by the National Natural Science Foundation of China (Nos.41172202,41190073,and 41402075)the China Geological Survey (No.1212011121256)the State Key Laboratory of Geological Processes and Mineral Resources,China University of Geosciences,Wuhan (No.MSFGPMR201502)
文摘The Openness based on DEM emphasizes the terrain convexity and concavity. It facilitates the interpretation of detailed landforms on the Earth＇s surface. Compared with the layer stacking of ETM＋ with less three-dimensionality and visualizability and with indefinite details of linear images in the deep cutting or deep covered region, the Openness is used for accurate interpretation of tectonic geomorphic units and linear structures. In this paper, the ETM＋ images（741 RGB） and RRIM based on Openness combined with the field geological investigation are used to trace the escaping structure in SE Asia. The east boundary is Ailaoshan shear zone and the west boundary is Uttaradit-Dien Bien Phu fault, which together form the southwards extruding wedge block. The arc boundary surface of the southern Khorat Plateau is jutted to the north. The NW and NE sides of Khorat Plateau are traversed by Uttaradit-Dien Bien Phu fault and Thakhek-Da Nang fault, respectively, resulting in a blocked escaping structure. The SE margins of Truong Son structure belt and Song Ma structure belt are both arcs jutting to SE. These arc structures clamped by faults or related to the fault on one side indicating the material flow direction obviously, are the most specific manifestation of escaping structures. Moreover, these push units are extruded from south to north successively.
基金Supported by the National Natural Science Foundation of China(No.10704007)National Infrastructure of Natural Science and Technology Program(No.2005DKA21101)the Chinese National Science and Technology Pillar Program for the Eleventh Five-year Plan(No.2006BAD13B08)
文摘We theoretically investigated negative entropy S of biopolymer which passes through a nanometer pore（such as a-hemolysin）, especially entering process and escaping process, on the basis of which we also studied biopolymer entering-pore time rent, biopolymer entering mean velocity Vent, biopolymer escaping-pore time resc, and biopolymer escaping mean velocity vesc, respectively. Our results illustrate that the entering and escaping processes of biopolymer depend on its negative entropy, and entering process is more difficult than escaping process for biopolymer translocation. This tremendous difference between the two processes will offer a useful engineering hint for single macromolecule identification.
文摘Research on magnetic mirror reactors has had two serious problems since the beginning stage. One is the magnetohydrodynamic instability due to the negative curvature of the magnetic field lines around the center region of a mirror bottle. Another is the loss of charged particles escaping from the loss cone of a magnetic mirror. We have continued to inquire into a means to solve the latter problem. We here propose a new way which will be able to make a magnitude of a loss angle of a magnetic mirror for deuterons virtually zero.
文摘"The Swimmer"is the representative of John Cheever and it is one of the most famous short stories in present America.The story is simple and it is not long, but it has profound meaning because many imageries are been used in the story. It tries to analyze the escaping and returning from the symbolic point of view, for escaping is an important motif in modern society and in the end, only returning can realize self-redemption.
基金Supported by the National Natural Science Foundation of China,No. 30260117 and 30271174 the Natural Science Foundation of Hainan Province, No. 30315 the Educational Key Foundation of Hainan Province, No. 200322 the Nursery Foundation of Hainan Medical College, No. 200202
文摘AIM: To investigate the mechanism of α-fetoprotein (AFP)in escaping from the host immune surveillance of hepatocellular carcinoma.METHODS: AFP purified from human umbilical blood was administrated into the cultured human lymphoma Jurkat T cell line or hepatoma cell line, Bel7402 in vitro. The expression of tumor necrosis factor related apoptosisinducing ligand (TRAIL) and its receptor (TRAILR) mRNA were analyzed by Northern blot and Western blot wasused to detect the expression of Fas and Fas ligand (FasL)protein.RESULTS: AFP (20 mg/L) could promote the expression of FasL and TRAIL, and inhibit the expression of Fas and TRAILR of Bel7402 cells. For Jurkat cell line, AFP could suppress the expression of FasL and TRAIL, and stimulate the expression of Fas and TRAILR. AFP also could synergize with Bel7402 cells to inhibit the expression of FasL protein and TRAIL mRNA in Jurkat cells. The monoclonal antibody against AFP (anti-AFP) could abolish these functions of AFP.CONCLUSION: AFP is able to promote the expression of FasL and TRAIL in hepatoma cells and enhance the expression of Fas and TRAILR in lymphocytes. These could elicit the escape of hepatocellular carcinoma cells from the host's lymphocytes immune surveillance.
文摘＂Emotion is a specific manner of apprehending the world＂ and transforming the world rather than an ＂accidental modification of a subject who is surrounded by an unchanged world,＂ according to Jean-Paul Sartre. Both Sketch for a Theory of the Emotions and Being and Nothingness set out to investigate these relationships in broadly two ways. One, consciousness of the world of others is experienced through our emotions （anger, fear, shame, and pride for instance） as a body that escapes our grasp in being-seen-by-another. Two, we apprehend the world through our emotions in the process of magical transformation （for example, fear, melancholy, and sadness）. This paper examines emotions on two levels： how we experience our ontological state as being-for-itself-in-itself and being-in-the-world-for-others; and how we conceive emotions as ＂magic＂ changing its relationship with the world ＂so that the world should change its qualities.＂ What is of critical interest here is the relationship between consciousness and emotions. Situating this discussion in the context of Satre＇s critique on psychology, it proceeds to advance his existential psychoanalysis, starting with establishing a place for emotions and concluding with its transformative power to escape their situations.
基金supported by the National Natural Science Foundation of China(Nos.11601362,11771090,11571049)the Natural Science Foundation of Shanghai(No.17ZR1402900)
文摘The authors study a family of transcendental entire functions which lie outside the Eremenko-Lyubich class in general and are of infinity growth order. Most importantly,the authors show that the intersection of Julia set and escaping set of these entire functions has full Hausdorff dimension. As a by-product of the result, the authors also obtain the Hausdorff measure of their escaping set is infinity.
文摘More white-collar workers consider leaving major metropolises to find opportunities in small and medium-sized cities The energy and excitement of first-tier cities, including Beijing, Shanghai, Guangzhou and Shenzhen in Guangdong Province, have long served as magnets attracting enthusiastic young people. But recent surveys have overturned the perception of this urban draw.
基金supported by the National Key Research and Development Program of China (2023YFC2307800)Chengdu University of Traditional Chinese Medicine (030040018)+2 种基金Shanghai Municipal Science and Technology Major Project (ZD2021CY001)National Natural Science Foundation of China (32270142)Shanghai Rising-Star Program (22QA1408800)。
文摘Currently approved vaccines have been successful in preventing the severity of COVID-19 and hospitalization. These vaccines primarily induce humoral immune responses;however, highly transmissible and mutated variants, such as the Omicron variant, weaken the neutralization potential of the vaccines, thus,raising serious concerns about their efficacy. Additionally, while neutralizing antibodies(nAbs) tend to wane more rapidly than cell-mediated immunity, long-lasting T cells typically prevent severe viral illness by directly killing infected cells or aiding other immune cells. Importantly, T cells are more cross-reactive than antibodies, thus, highly mutated variants are less likely to escape lasting broadly cross-reactive T cell immunity. Therefore, T cell antigen-based human coronavirus(HCoV) vaccines with the potential to serve as a supplementary weapon to combat emerging SARS-CoV-2 variants with resistance to n Abs are urgently needed. Alternatively, T cell antigens could also be included in B cell antigen-based vaccines to strengthen vaccine efficacy. This review summarizes recent advancements in research and development of vaccines containing T cell antigens or both T and B cell antigens derived from proteins of SARS-CoV-2 variants and/or other HCo Vs based on different vaccine platforms.
基金supported by grants from the Dongguan Science and Technology of Social Development Program(No.20231800940192)the Talent Development Foundation of the First Dongguan Affiliated Hospital of Guangdong Medical University(No.PU2023002).
文摘Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with SCLC.In the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.Methods:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in SCLC.The functional role of the key gene identified in SCLC was determined both in vitro and in vivo.Results:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell proportion.Furthermore,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in SCLC.Bioinformatics analysis revealed that USP1 is upregulated in SCLC.In addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune responses.By co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological inhibition.Furthermore,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated markers.Conclusions:Our study findings highlight the importance of NK cells in regulating SCLC.USP1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.
基金funded by the Government of Aragon through several consultancy projects from 2006 to 2022
文摘The escape and establishment of Iberian wild goats,Capra pyrenaica,from an enclosure in the 1990s marked the beginning of the recovery of the species in the Pyrenees.This population has occupied part of the Prepyrenees and has contacted another population reintroduced in France since 2014.It coexists with other wild ungulates,including the feral and domestic goats Capra hircus that has been living free since the 1960s.Today it’s the largest Iberian wild goat Pyrenean population.Between 2006 and 2022 we monitored the population and its expansion based on vantage points,itineraries and testimonies.The results indicate:(i)a population,of uncertain genetic origin,in numerical(15%average annual growth)and areal expansion,with the capacity to connect with other populations;(ii)an estimate of at least 500 individuals;(iii)in the process of expansion in contact with Iberian wild goats from France;(iv)sympatry with feral and domestic goat population in its main nucleus whose estimate exceeds 2000 specimens and(v)hybridization with feral and domestic goats.In 2022 sustainable hunt started with a hunting quota of 20 individuals.Genetic characterization and the establishment of an international coordinated monitoring are two of the current priorities.
基金supported by National Natural Science Foundation of China(No.82173769)the National Key R&D Program of China(No.2021YFE0106900)+1 种基金Applied Basic Research Multiinvestment Foundation of Tianjin(No.21JCYBJC01540)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(No.2023ZD019)。
文摘Small interfering RNAs(siRNA)provide a novel and highly specific therapy due to their ability to effectively silence target genes,to date six siRNA therapeutics are approved for clinical use.Even so,some critical challenges remain to overcome in the therapeutic application of siRNAs,with delivery issues at the forefront.Among them,endo/lysosomal barrier is one of the important but often-neglected limitations hindering the delivery of siRNA therapeutics.In this review,we summarize the promising strategies that facilitate siRNAs overcoming endo/lysosomal barriers based on the cellular uptake and intracellular transport pathways,including promoting escape once endocytosis into the endo/lysosomes and bypassing lysosomes via endosome-Golgi-endoplasmic reticulum(ER)pathway or nonendocytosis pathway,and discuss the principal considerations and the future directions of promoting endo/lysosomal escape in the development of therapeutic siRNAs.
基金supported by the Prespa-Ohrid Nature Trust and the Aage V.Jensen Foundation via PrespaNet's"Prespa Project(2021-2024)"the Rufford Foundation(grant number 30090-1)the Ministry of Science,Technological Development and Innovation of the Republic of Serbia(grant numbers451-03-0133012020-14/2627,451-03-47/2023-01/200178,451-03-47/2023-01/200007).
文摘Functional constraints between different types of antipredator behavior should be common,especially if they are on the opposite sides of the behavioral spectrum such as flight and post-capture immobility.We examined a potential compromise between post-capture immobility displays and sprint speed in dice snakes(Natrix tessellata),using a field-based approach.We sampled snakes(N=238)from two populations:from a dense island population free of mammal predators,and from a less dense mainland population,preyed upon by both bird and mammal predators.We explored the effects of sexual maturity,temperature,body size,presence of palpable food in the gut,and injuries on the occurrence and duration of post-capture immobility as well as sprint speed.Our results confirm the existence of functional constraints between locomotor performance and post-capture immobility in dice snakes.Faster dice snakes start escaping promptly after release,while slower individuals utilize more passive antipredator behaviors such as death feigning.Local adaptations seem to have great influence on behavioral compromise,since the mammal-free island population exhibited a higher incidence of post-capture immobility and a significantly lower sprint speed,compared to the less dense mainland population.Additionally,immature individuals tended to avoid death feigning and their post-capture immobility lasted shorter compared to adult individuals.It remains to be seen how individuals adjust their behavior to accomodate locomotor constraints,and in which specific phases of the predator-prey interaction these adjustments occur.
基金supported by the National Key R&D Program of China(2023YFF1304600)。
文摘Urbanization has significantly altered the habitat structure and behavioral patterns of animals.In urban environments with frequent human disturbances,animals may undergo adaptive adjustments in their escape behaviors.This study focuses on Eurasian Tree Sparrows(Passer montanus)from five cities across different latitudes in China,comparing their flight initiation distance(FID)in urban and rural areas to assess the impact of urbanization on their escape behavior and the trend of ecological homogenization.The results confirm the established pattern at the geographic level:a reduction of FID in urban habitats and a decrease in FID with increasing latitude.That is,northern populations of the Eurasian Tree Sparrow in China are bolder than the southern populations.In addition,FID is positively correlated with flock size,with rural flocks exhibiting more pronounced group behavior(observed flocking frequency for urban and rural is 28.74%vs.40.7%,flock size variance is 26.90 vs.55.63).Despite the differences between northern and southern latitudes,the variability of FID in urban individuals consistently remains lower than that in rural areas,supporting the trend of reduced variability in escape behavior among birds in urban environments.Driven by urbanization,the escape behavior of Eurasian Tree Sparrows tends toward ecological homogenization,meaning that behavioral differences between urban areas in different cities are diminishing.This trend may obscure the behavioral variability brought about by latitude gradients,indicating that urbanization not only shapes the behavioral adaptations of birds but also potentially weakens their behavioral diversity.
