Nowadays,the development of novel metallic materials for rock support have attracted research interests since they can significantly improve the deformation and energy absorption capacities of rock bolts.Although prev...Nowadays,the development of novel metallic materials for rock support have attracted research interests since they can significantly improve the deformation and energy absorption capacities of rock bolts.Although previous studies proved the importance and mechanical advantages of utilizing high-strength and high-toughness(HSHT)steels in rock support,there is no systematic analysis to reveal the essential energy absorption parameter and the guidelines for further development of metallic rock support materials.This paper analyzes the energy absorption characteristics of novel HSHT steels(negative Poisson’s ratio(NPR)and twinning-induced plasticity(TWIP)steels)in comparison with conventional rock support materials.A physically based crystal plasticity(CP)model was set up and calibrated to study the effect of strain hardening rate(SHR).Meanwhile,the roles of underlying physical mechanisms,i.e.the dislocation density and twin volume fraction,were studied.The results show that the improvement of energy absorption density(EAD)is essential for further development of rock support materials,besides the increase of energy absorption rate(EAR)for previous development of conventional rock support materials.The increase of EAD requires increases of both strength and deformation capacity of materials.For HSHT steels,the decrease of SHR has a positive effect on the improvement of EAD.In addition,the increase of EAD is followed by the increase of twin volume fraction and the decrease of plastic Poisson’s ratio which can promote deformation plasticity of materials.Meanwhile,the increase of EAR is correlated with the accumulation of dislocation density,which can increase the strength of materials.This paper provides the theoretical basis and guidelines for developing rock support materials in deep underground engineering and other related fields.展开更多
Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biolog...Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.展开更多
AIMTo evaluate the effectiveness of human fibrinogen-thrombin collagen patch (TachoSil<sup>®</sup>) in the reinforcement of high-risk colon anastomoses.METHODSA quasi-experimental study was con...AIMTo evaluate the effectiveness of human fibrinogen-thrombin collagen patch (TachoSil<sup>®</sup>) in the reinforcement of high-risk colon anastomoses.METHODSA quasi-experimental study was conducted in Wistar rats (n = 56) that all underwent high-risk anastomoses (anastomosis with only two sutures) after colectomies. The rats were divided into two randomized groups: Control group (24 rats) and treatment group (24 rats). In the treatment group, high-risk anastomosis was reinforced with TachoSil<sup>®</sup> (a piece of TachoSil<sup>®</sup> was applied over this high-risk anastomosis, covering the gap). Leak incidence, overall survival, intra-abdominal adhesions, and histologic healing of anastomoses were analyzed. Survivors were divided into two subgroups and euthanized at 15 and 30 d after intervention in order to analyze the adhesions and histologic changes.RESULTSOverall survival was 71.4% and 57.14% in the TachoSil<sup>®</sup> group and control group, respectively (P = 0.29); four rats died from other causes and six rats in the treatment group and 10 in the control group experienced colonic leakage (P > 0.05). The intra-abdominal adhesion score was similar in both groups, with no differences between subgroups. We found non-significant differences in the healing process according to the histologic score used in both groups (P = 0.066).CONCLUSIONIn our study, the use of TachoSil<sup>®</sup> was associated with a non-statistically significant reduction in the rate of leakage in high-risk anastomoses. TachoSil<sup>®</sup> has been shown to be a safe product because it does not affect the histologic healing process or increase intra-abdominal adhesions.展开更多
This paper aims to advance previous studies on the iron and manganese content in groundwater of Rrogozhina aquifer (western Albania) and to show the factors which control the content of both iron and manganese in gr...This paper aims to advance previous studies on the iron and manganese content in groundwater of Rrogozhina aquifer (western Albania) and to show the factors which control the content of both iron and manganese in groundwater of this aquifer. Rrogozhina aquifer represents an important groundwater source of the country whose relevance was highly increased during recent years because of the demographic expansion in this region. This is a typically multi-layered artesian aquifer which consists of sandstone and conglomerate with high heterogeneous permeability. The groundwater mostly belongs to HCO3-Mg-Ca hydrochemical type. The content of soluble iron and manganese in groundwater ranges from 0.004 mg/L to 0.7 mg/L, and from 0.0 mg/L to 1.147 mg/L, respectively. Deeper the groundwater occurs and longer the distance from the recharge zone, higher is the content of Fe2+ in groundwater due to gradual depletion of Oe in groundwater. The content of iron is higher than that WHO and EU recommended, which were 21% and 25% respectively, while the content of manganese were 17% and 23%, respectively. Abstraction of groundwater with high quantities by deeper wells would be accompanied by increase of dissolved iron and manganese content in groundwater which should be treated (with aeration) in order to decrease the content of these two elements in the water before using it.展开更多
The steam reforming of methane over NiO/ZnO mixed oxides with different nickel contents was studied. Solids to x% Ni/ZnO (x = 4 and 10%) were deposited on ZnO by impregnation from nickel nitrate solution;after vaporiz...The steam reforming of methane over NiO/ZnO mixed oxides with different nickel contents was studied. Solids to x% Ni/ZnO (x = 4 and 10%) were deposited on ZnO by impregnation from nickel nitrate solution;after vaporization the solid is calcined at 500°C for 6 h. The catalysts were characterized by X-ray diffraction (XRD) and BET method, scanning electron microscopy (SEM) and temperature programmed reduction (TPR). The XRD patterns revealed the NiO phase for all calcined catalysts. The chemical analysis confirmed the theoretical values of nickel. The catalysts were pre-treated under hydrogen at 500°C in situ, overnight before testing for the steam reforming of methane reaction (CH<sub>4</sub>/H<sub>2</sub>O/Ar = 10/10/80) in the temperature range (475°C - 650°C) under atmospheric pressure. The activities of both catalysts were investigated in a fixed-bed reactor for the Methane Steam Reforming (MSR) reaction. Globally, it was shown that the catalyst 10% nickel content has an important effect on the catalytic performances of solids i.e. the better results of hydrogen production were obtained with 10% wt. Ni/ZnO (28 ′ 10-<sup>3</sup> mol/g catalyst).展开更多
The installation of a purification unit since 2008 in the village of Thiakhar has improved the physico-chemical and bacteriological quality of the water supply. However about 55% of the raw water comes out of the unit...The installation of a purification unit since 2008 in the village of Thiakhar has improved the physico-chemical and bacteriological quality of the water supply. However about 55% of the raw water comes out of the unit as discharges (approximately 14 m3 per day) highly concentrated in fluoride and chloride ions. Based on historical samples, we find that the volumes of water consumed together with the volumes of water discharged are increasingly significant from year to year. The storage of waste water is carried out in a septic tank connected to a leaking cesspool sink. Significant excesses of these discharges are visible on the site and a flow of concentrate is observed creating a puddle of water that attracts birds and straying cattle. The study describes the following substantial impacts on the natural and human environment: 1) contamination of groundwater, 2) soil salinization 3), impact on flora and fauna, 4) impact on health. The study concludes by identifying measures to mitigate the negative impacts related to the discharges and by proposing alternative solution.展开更多
Recent evidence shows that certain microRNAs (miRNAs) play a role in both obesity and prostate cancer recurrence, but the association between the expression of these miRNAs and obesity in prostate cancer recurrence ...Recent evidence shows that certain microRNAs (miRNAs) play a role in both obesity and prostate cancer recurrence, but the association between the expression of these miRNAs and obesity in prostate cancer recurrence is unknown. In this study, we examined the effect of the interaction between obesity and miR-21, miR-221 or miR-222 expression on prostate cancer recurrence among 28 recurrent and 37 non-recurrent prostate cancer cases, miRNA expression was determined using quantitative real-time polymerase chain reaction. Cox proportional hazard models adjusting for age at diagnosis, clinical stage and Gleason score were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for recurrence free survival. A significantly (P=0.014) higher proportion of recurrent cases (78,6%) than non-recurrent cases (48.6%) had a low expression of miR-21 and the difference was more prominent in obese than non-obese patients. Multivariate analysis showed that the expression of miR-21 was an independent risk factor for recurrence in obese (HR=6.15, 95% CI= 1.04-36.48, P=-0.045), but not in non-obese (HR= 1.28, 95% C1=0.30-5.49, P=0.74) cases. A significant association with recurrence was not observed for the expression of miR-221 and miR-222. In summary, our findings show that miR-21 is associated with prostate cancer recurrence after radical prostatectomy and suggest that the differential expression of miR-21 is more prominent in obese than in non-obese cases. Future larger studies are warranted to confirm these initial findings and to elucidate the mechanisms involved.展开更多
Hepatocellular carcinoma(HCC)is one of the most prevalent cancers and one of the main causes of cancer-related deaths worldwide.Most HCCs develop in an inflammatory microenvironment,and mounting evidence emphasizes th...Hepatocellular carcinoma(HCC)is one of the most prevalent cancers and one of the main causes of cancer-related deaths worldwide.Most HCCs develop in an inflammatory microenvironment,and mounting evidence emphasizes the importance of immune aspects in hepatocarcinogenesis.In normal physiology,both innate and adaptive immune responses are responsible for eliminating malignantly transformed cells,thus preventing the development of liver cancer.However,in the setting of impaired natural killer cells and exhaustion of T cells,HCC can develop.The immunogenic features of HCC have relevant clinical implications.There is a large number of immune markers currently being studied for the early detection of liver cancer,which would be critical in order to improve surveillance programs.Moreover,novel immunotherapies have recently been proven to be effective,and the combination of atezolizumab and bevacizumab is currently the most effective treatment for advanced HCC.It is expected that in the near future different subgroups of patients will benefit from specific immunotherapy.The better we understand the immune aspects of HCC,the greater the benefit to patients through surveillance aiming for early detection of liver cancer,which allows for curative treatments,and,in cases of advanced disease,through the selection of the best possible therapy for each individual.展开更多
Immune checkpoint inhibitors(ICIs)have revolutionized cancer treatment for their unprecedented clinical efficacy.Signal regulatory proteinα(SIRPα)is a phagocytic checkpoint expressed on macrophages,dendritic cells,o...Immune checkpoint inhibitors(ICIs)have revolutionized cancer treatment for their unprecedented clinical efficacy.Signal regulatory proteinα(SIRPα)is a phagocytic checkpoint expressed on macrophages,dendritic cells,other myeloid cells.Cancer cells inhibit macrophage phagocytosis through the interaction of the CD47-SIRPαaxis.Disrupting the CD47-SIRPαaxis has therefore been a promising strategy in restoring the immune attack against cancer.Herein,we engineered cellular membrane nanovesicles(NVs)presenting SIRPαreceptors for phagocytosis checkpoint blockade to augment the antitumor immune response.Furthermore,zebularine(Zeb),an inhibitor of DNA methyltransferase,was encapsulated into SIRPαNVs to reprogram the immunosuppressive tumor microenvironment together with blockade of phagocytosis checkpoint.It is demonstrated that SIRPα@Zeb can improve tumor immunogenicity,the polarization of tumor-associated macrophages to the M1 phenotype,increase the infiltration of CD8^(+)T lymphocytes in tumors.The robust antitumor immune response induced by SIRPα@Zeb significantly suppressed tumor growth and extended mice-bearing melanoma xenograft survival.展开更多
Climate warming leads to vast changes in the land cover types and plant biomass in the northern high-latitude regions.The overall trend is of shrubland and tree lines moving northwards,while changes in different land ...Climate warming leads to vast changes in the land cover types and plant biomass in the northern high-latitude regions.The overall trend is of shrubland and tree lines moving northwards,while changes in different land cover types and vegetation growth in response to climate change are largely unknown.Here,we selected land areas with latitudes higher than 50°N as the study area.We compared the land cover type changes and explored relationships between the normalized difference vegetation index(NDVI)values of different land cover types,air temperature,and precipitation during 1982-2015 based on dynamic grid.The results indicated that forest and shrubland areas increased as a large area of grassland shifted to forest and shrubland.The snow/ice,tundra and grassland largely have decreased from 1982 to 2015.Although approximately 277.3×103 km2 of barren land(6.2%of the total barren land area in 1982)changed to tundra,the tundra area still decreased because some tundra shifted to forest and grassland.The NDVI values of tundra significantly increased,but the shrubland showed a decreasing trend.Temperature in the growing season(June to September)showed the largest positive correlation coefficients with the NDVI values of forest,tundra,grassland,and cropland.However,due to shrubification processes and plant mortality in shrubland areas,the shrubland NDVI showed negative relationship with annual temperature but positively correlated with monthly t.Taken together,although there is large room for improvement of the land cover type data accuracy,our results suggested that the land cover types in high-latitude regions changed significantly,while the NDVI values of the different land cover types showed different responses to climate change.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.52204115 and 41941018)the Foundation of Research Institute for Deep Underground Science and Engineering(Grant No.XD2021022).
文摘Nowadays,the development of novel metallic materials for rock support have attracted research interests since they can significantly improve the deformation and energy absorption capacities of rock bolts.Although previous studies proved the importance and mechanical advantages of utilizing high-strength and high-toughness(HSHT)steels in rock support,there is no systematic analysis to reveal the essential energy absorption parameter and the guidelines for further development of metallic rock support materials.This paper analyzes the energy absorption characteristics of novel HSHT steels(negative Poisson’s ratio(NPR)and twinning-induced plasticity(TWIP)steels)in comparison with conventional rock support materials.A physically based crystal plasticity(CP)model was set up and calibrated to study the effect of strain hardening rate(SHR).Meanwhile,the roles of underlying physical mechanisms,i.e.the dislocation density and twin volume fraction,were studied.The results show that the improvement of energy absorption density(EAD)is essential for further development of rock support materials,besides the increase of energy absorption rate(EAR)for previous development of conventional rock support materials.The increase of EAD requires increases of both strength and deformation capacity of materials.For HSHT steels,the decrease of SHR has a positive effect on the improvement of EAD.In addition,the increase of EAD is followed by the increase of twin volume fraction and the decrease of plastic Poisson’s ratio which can promote deformation plasticity of materials.Meanwhile,the increase of EAR is correlated with the accumulation of dislocation density,which can increase the strength of materials.This paper provides the theoretical basis and guidelines for developing rock support materials in deep underground engineering and other related fields.
文摘Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.
文摘AIMTo evaluate the effectiveness of human fibrinogen-thrombin collagen patch (TachoSil<sup>®</sup>) in the reinforcement of high-risk colon anastomoses.METHODSA quasi-experimental study was conducted in Wistar rats (n = 56) that all underwent high-risk anastomoses (anastomosis with only two sutures) after colectomies. The rats were divided into two randomized groups: Control group (24 rats) and treatment group (24 rats). In the treatment group, high-risk anastomosis was reinforced with TachoSil<sup>®</sup> (a piece of TachoSil<sup>®</sup> was applied over this high-risk anastomosis, covering the gap). Leak incidence, overall survival, intra-abdominal adhesions, and histologic healing of anastomoses were analyzed. Survivors were divided into two subgroups and euthanized at 15 and 30 d after intervention in order to analyze the adhesions and histologic changes.RESULTSOverall survival was 71.4% and 57.14% in the TachoSil<sup>®</sup> group and control group, respectively (P = 0.29); four rats died from other causes and six rats in the treatment group and 10 in the control group experienced colonic leakage (P > 0.05). The intra-abdominal adhesion score was similar in both groups, with no differences between subgroups. We found non-significant differences in the healing process according to the histologic score used in both groups (P = 0.066).CONCLUSIONIn our study, the use of TachoSil<sup>®</sup> was associated with a non-statistically significant reduction in the rate of leakage in high-risk anastomoses. TachoSil<sup>®</sup> has been shown to be a safe product because it does not affect the histologic healing process or increase intra-abdominal adhesions.
文摘This paper aims to advance previous studies on the iron and manganese content in groundwater of Rrogozhina aquifer (western Albania) and to show the factors which control the content of both iron and manganese in groundwater of this aquifer. Rrogozhina aquifer represents an important groundwater source of the country whose relevance was highly increased during recent years because of the demographic expansion in this region. This is a typically multi-layered artesian aquifer which consists of sandstone and conglomerate with high heterogeneous permeability. The groundwater mostly belongs to HCO3-Mg-Ca hydrochemical type. The content of soluble iron and manganese in groundwater ranges from 0.004 mg/L to 0.7 mg/L, and from 0.0 mg/L to 1.147 mg/L, respectively. Deeper the groundwater occurs and longer the distance from the recharge zone, higher is the content of Fe2+ in groundwater due to gradual depletion of Oe in groundwater. The content of iron is higher than that WHO and EU recommended, which were 21% and 25% respectively, while the content of manganese were 17% and 23%, respectively. Abstraction of groundwater with high quantities by deeper wells would be accompanied by increase of dissolved iron and manganese content in groundwater which should be treated (with aeration) in order to decrease the content of these two elements in the water before using it.
文摘The steam reforming of methane over NiO/ZnO mixed oxides with different nickel contents was studied. Solids to x% Ni/ZnO (x = 4 and 10%) were deposited on ZnO by impregnation from nickel nitrate solution;after vaporization the solid is calcined at 500°C for 6 h. The catalysts were characterized by X-ray diffraction (XRD) and BET method, scanning electron microscopy (SEM) and temperature programmed reduction (TPR). The XRD patterns revealed the NiO phase for all calcined catalysts. The chemical analysis confirmed the theoretical values of nickel. The catalysts were pre-treated under hydrogen at 500°C in situ, overnight before testing for the steam reforming of methane reaction (CH<sub>4</sub>/H<sub>2</sub>O/Ar = 10/10/80) in the temperature range (475°C - 650°C) under atmospheric pressure. The activities of both catalysts were investigated in a fixed-bed reactor for the Methane Steam Reforming (MSR) reaction. Globally, it was shown that the catalyst 10% nickel content has an important effect on the catalytic performances of solids i.e. the better results of hydrogen production were obtained with 10% wt. Ni/ZnO (28 ′ 10-<sup>3</sup> mol/g catalyst).
文摘The installation of a purification unit since 2008 in the village of Thiakhar has improved the physico-chemical and bacteriological quality of the water supply. However about 55% of the raw water comes out of the unit as discharges (approximately 14 m3 per day) highly concentrated in fluoride and chloride ions. Based on historical samples, we find that the volumes of water consumed together with the volumes of water discharged are increasingly significant from year to year. The storage of waste water is carried out in a septic tank connected to a leaking cesspool sink. Significant excesses of these discharges are visible on the site and a flow of concentrate is observed creating a puddle of water that attracts birds and straying cattle. The study describes the following substantial impacts on the natural and human environment: 1) contamination of groundwater, 2) soil salinization 3), impact on flora and fauna, 4) impact on health. The study concludes by identifying measures to mitigate the negative impacts related to the discharges and by proposing alternative solution.
文摘Recent evidence shows that certain microRNAs (miRNAs) play a role in both obesity and prostate cancer recurrence, but the association between the expression of these miRNAs and obesity in prostate cancer recurrence is unknown. In this study, we examined the effect of the interaction between obesity and miR-21, miR-221 or miR-222 expression on prostate cancer recurrence among 28 recurrent and 37 non-recurrent prostate cancer cases, miRNA expression was determined using quantitative real-time polymerase chain reaction. Cox proportional hazard models adjusting for age at diagnosis, clinical stage and Gleason score were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for recurrence free survival. A significantly (P=0.014) higher proportion of recurrent cases (78,6%) than non-recurrent cases (48.6%) had a low expression of miR-21 and the difference was more prominent in obese than non-obese patients. Multivariate analysis showed that the expression of miR-21 was an independent risk factor for recurrence in obese (HR=6.15, 95% CI= 1.04-36.48, P=-0.045), but not in non-obese (HR= 1.28, 95% C1=0.30-5.49, P=0.74) cases. A significant association with recurrence was not observed for the expression of miR-221 and miR-222. In summary, our findings show that miR-21 is associated with prostate cancer recurrence after radical prostatectomy and suggest that the differential expression of miR-21 is more prominent in obese than in non-obese cases. Future larger studies are warranted to confirm these initial findings and to elucidate the mechanisms involved.
基金Supported by European-Latin American ESCALON consortium,funded by the EU Horizon 2020 Program,No.825510Robert Wood Johnson Foundation,Harold Amos Medical Faculty Development Program(to Debes JD).
文摘Hepatocellular carcinoma(HCC)is one of the most prevalent cancers and one of the main causes of cancer-related deaths worldwide.Most HCCs develop in an inflammatory microenvironment,and mounting evidence emphasizes the importance of immune aspects in hepatocarcinogenesis.In normal physiology,both innate and adaptive immune responses are responsible for eliminating malignantly transformed cells,thus preventing the development of liver cancer.However,in the setting of impaired natural killer cells and exhaustion of T cells,HCC can develop.The immunogenic features of HCC have relevant clinical implications.There is a large number of immune markers currently being studied for the early detection of liver cancer,which would be critical in order to improve surveillance programs.Moreover,novel immunotherapies have recently been proven to be effective,and the combination of atezolizumab and bevacizumab is currently the most effective treatment for advanced HCC.It is expected that in the near future different subgroups of patients will benefit from specific immunotherapy.The better we understand the immune aspects of HCC,the greater the benefit to patients through surveillance aiming for early detection of liver cancer,which allows for curative treatments,and,in cases of advanced disease,through the selection of the best possible therapy for each individual.
基金National Key R&D Program of China(No.2021YFA0909900)Zhejiang Provincial Natural Science Foundation of China(No.LY23C100001)+2 种基金National Natural Science Foundation of China(Nos.51973214 and 51503003)Kunpeng Program from Zhejiang Province,Zhejiang University's start-up packages,Fundamental Research Funds for the Central Universities(No.2021FZZX001-46)the Starry Night Science Fund at Shanghai Institute for Advanced Study of Zhejiang University(No.SN-ZJU-SIAS-009).
文摘Immune checkpoint inhibitors(ICIs)have revolutionized cancer treatment for their unprecedented clinical efficacy.Signal regulatory proteinα(SIRPα)is a phagocytic checkpoint expressed on macrophages,dendritic cells,other myeloid cells.Cancer cells inhibit macrophage phagocytosis through the interaction of the CD47-SIRPαaxis.Disrupting the CD47-SIRPαaxis has therefore been a promising strategy in restoring the immune attack against cancer.Herein,we engineered cellular membrane nanovesicles(NVs)presenting SIRPαreceptors for phagocytosis checkpoint blockade to augment the antitumor immune response.Furthermore,zebularine(Zeb),an inhibitor of DNA methyltransferase,was encapsulated into SIRPαNVs to reprogram the immunosuppressive tumor microenvironment together with blockade of phagocytosis checkpoint.It is demonstrated that SIRPα@Zeb can improve tumor immunogenicity,the polarization of tumor-associated macrophages to the M1 phenotype,increase the infiltration of CD8^(+)T lymphocytes in tumors.The robust antitumor immune response induced by SIRPα@Zeb significantly suppressed tumor growth and extended mice-bearing melanoma xenograft survival.
基金the National Key Research and Development Program of China(2020YFA0608501,2019YFA0607003)the National Natural Science Foundation of China(41941015,32061143032,41961144021)+3 种基金the State Key Laboratory of Cryospheric Science(SKLCS-ZZ-2021)the West Light Foundation of the Chinese Academy of SciencesZhang Wen-Xin acknowledged grants of Swedish Research Council FORMAS 2016-01201 and Swedish National Space Agency 209/19This work was also supported by Russian Fund for Basic Research grant N18-05-60080 and State topic N AAAA-A16-116032810095-6.
文摘Climate warming leads to vast changes in the land cover types and plant biomass in the northern high-latitude regions.The overall trend is of shrubland and tree lines moving northwards,while changes in different land cover types and vegetation growth in response to climate change are largely unknown.Here,we selected land areas with latitudes higher than 50°N as the study area.We compared the land cover type changes and explored relationships between the normalized difference vegetation index(NDVI)values of different land cover types,air temperature,and precipitation during 1982-2015 based on dynamic grid.The results indicated that forest and shrubland areas increased as a large area of grassland shifted to forest and shrubland.The snow/ice,tundra and grassland largely have decreased from 1982 to 2015.Although approximately 277.3×103 km2 of barren land(6.2%of the total barren land area in 1982)changed to tundra,the tundra area still decreased because some tundra shifted to forest and grassland.The NDVI values of tundra significantly increased,but the shrubland showed a decreasing trend.Temperature in the growing season(June to September)showed the largest positive correlation coefficients with the NDVI values of forest,tundra,grassland,and cropland.However,due to shrubification processes and plant mortality in shrubland areas,the shrubland NDVI showed negative relationship with annual temperature but positively correlated with monthly t.Taken together,although there is large room for improvement of the land cover type data accuracy,our results suggested that the land cover types in high-latitude regions changed significantly,while the NDVI values of the different land cover types showed different responses to climate change.