With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors...With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.展开更多
AIM: To achieve a better understanding of the molecular mechanisms of micro RNA expression changes involved in hepatocellular carcinoma.METHODS: In this research process, patients were not treated with antivirals, imm...AIM: To achieve a better understanding of the molecular mechanisms of micro RNA expression changes involved in hepatocellular carcinoma.METHODS: In this research process, patients were not treated with antivirals, immunosuppressants or immunomodulators for at least 6 mo before collecting serum. The study population was composed of 35 outpatient hepatitis B virus(HBV) cases and 12 healthy control cases from the Affiliated Hospital of Inner Mongolia Medical University(Inner Mongolia, China) from July 2013 to April 2014. The 35 HBV cases were divided into two groups: a hepatocirrhosis group with 20 cases and a liver cancer group with 15 cases. All 35 cases carried HBs Ag. The diagnostic criteria followed the European Association for the Study of the Liver 2012(EASL2012) standards. Micro RNA(mi RNA) was extracted from a control group of patients, a group with hepatocirrhosis and a group with liver cancer and its quality was analyzed using the human V2 micro RNA expression beadchip. Cluster analysis and a radar chart were then applied to the mi RNA changes.RESULTS: The mi RNA-qualified rate of human serum samples was 93%. The concentration of a single sample was > 200 ng/μL and the volume was > 5 μL.All mi RNA serum samples were uncontaminated by the genome. The Mann-Whitney test showed significant differences in mi RNA between each group, with a detection P-value of < 0.05. Illumina software was set up with Diff Score set to ± 13, meaning that P = 0.001.There were significant changes in mi RNA expression between the three groups. mi RNA-183 was the most up-regulated, followed by mi RNA-373. mi RNA-129 and mi RNA-188 were both strongly down-regulated and mi RNA-378 was down-regulated a small amount. The liver cancer group had greater changes, which indicated that changes in mi RNA expression levels were caused by hepatocirrhosis. The liver cancer disease course then further increased these changes. In the pentagon created by these five mi RNAs, three groups showed significant deviation. The liver cancer group had a bigger deviation trend. The chart indicated that mi RNA expression changes occurred in the hepatocirrhosis group, which increased in the liver cancer disease course and were irreversible.CONCLUSION: There was a significant relationship between the irreversible up-regulation of mi RNA-183/373 and down-regulation of mi RNA-129/188/378 and incidences of hepatocirrhosis and liver cancer.展开更多
Alkali-activated slag concrete (AASC) is a new green building material. The amount of CO_(2) produced by AASC is 1/5th of that produced by ordinary Portland cement concrete (OPCC). In addition, AASC promotes the reuse...Alkali-activated slag concrete (AASC) is a new green building material. The amount of CO_(2) produced by AASC is 1/5th of that produced by ordinary Portland cement concrete (OPCC). In addition, AASC promotes the reuse of slag and other wastes and saves resources. Furthermore, the scope of use of slag has been expanded. The progress of the research on the hydration characteristics, microstructure, interfacial transition zone, and pore structure of AASC based on the relevant literatures was analyzed and summarized in this study. The influences of the slag composition, the type and dosage of the alkali activator, and the curing conditions on the hydration characteristics and the microstructure of the AASC were discussed. Relatively few research results on the microstructure of AASC are available, and the relevant conclusions are not completely consistent. Moreover, there are many constraints on the development of AASC (e.g., complex composition of raw materials of slag, large shrinkage deformation, and low fluidity). Therefore, further research is required.展开更多
1 Introduction Yuncheng Salt Lake is an old lake with a history of more than 5000 years,which locates in the margins of the central plains of China,with an area of about 130 km.It was an important resource of salt for...1 Introduction Yuncheng Salt Lake is an old lake with a history of more than 5000 years,which locates in the margins of the central plains of China,with an area of about 130 km.It was an important resource of salt for human consumption from early times.Major chemicals in Yuncheng Salt Lake contain Na Cl,Na2SO4 and Mg SO4(Gao et al.2007).In recent years,some halophilic bacteria and archaea were展开更多
Fuelwood is one of the major sources of energy in the domestic sector across the rural areas,especially in the developing regions across the world.The Northeastern Himalayan state of Manipur is dominated by the tribal...Fuelwood is one of the major sources of energy in the domestic sector across the rural areas,especially in the developing regions across the world.The Northeastern Himalayan state of Manipur is dominated by the tribal population that largely depends on fuelwood from the nearby forest area.The entire dependence on forests for energy resources is affecting the sustainability of the forest ecosystem in the region,thus indicating the livelihood conditions.Since land-use land-cover change is the key driver to the change in resource availability of a region,the present study has tried to analyze the landcover changes over a period 28 years.The second major component affecting resource availability is the increasing population pressure that leads to changes in the land dynamics,which directly affect the resource production.Based on the existing consumption pattern,the total consumption of fuelwood in the watershed ranges from a rrrinimum of 289.992 tons/year to a maximum of 3545.719 tons/year with an average of 1561.956 tons/year in the year 2009 and simulated fuelwood consumption for the year 2021 is around 1469.260 tons/year.Nine different probable scenarios of resource are proposed to calculate the stress value that can be used by the policy-makers and planners for suitable policy implementation at the micro level with a complex social system.展开更多
[ Objective] The research aimed to improve the utilization ratio of wheat strew in Qinghai Province. [ Method] During wheat straw microstorage, the pH, crude protein （CP）, crude fiber （CF）, ether extract （EE） an...[ Objective] The research aimed to improve the utilization ratio of wheat strew in Qinghai Province. [ Method] During wheat straw microstorage, the pH, crude protein （CP）, crude fiber （CF）, ether extract （EE） and water content in wheat strew at different micro-storage periods were determined. The effects of micro-storage time on the quality of wheat strew were studied and evaluated by using gas production technique in vitro. [Result] pH in each test group gradually decreased with the micro-storege time, which was all significantly lower than that in control group （P 〈0.01 ）. CP content in all test groups increased with the micro-storage time, which was all higher than that in control group. CF content in all test groups decreased with the h^icro-storage time, significantly lower than that in control group （ P 〈 0.01 ）. EE content in all experimental groups showed a gradual increase trend with the micro-storege time, which was all higher than that in control group, without significant difference compared with control group （P〉0.05）. Water content in test groups went down with the micro-storage time. With the increase of micro-storage time, net gas production, dry matter degradability, organic matter degradability, digestible energy and metabolizable energy went up gradually. [ Conclusion] Comprehensively considering the micro-storege effect of wheat strew in each period and actual production application, we suggest that 22-day micro-storege for wheat straw could meet the demand of actual production.展开更多
Objective To investigate changes in intestinal microflora in patients with chronic severe hepatitis (CSH), and their role in this life-threatening disease.Methods We classified nineteen patients with chronic severe ...Objective To investigate changes in intestinal microflora in patients with chronic severe hepatitis (CSH), and their role in this life-threatening disease.Methods We classified nineteen patients with chronic severe hepatitis as the CSH group, thirty patients with chronic hepatitis (CH) as the CH group and thirty-one healthy volunteer as the control group. Fecal flora from all subjects were analyzed. Concentrations of plasma endotoxin, serum cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) and liver function were assessed.Results The number of fecal bifidobacterium (P<0.001, P<0.05 respectively), as well as bacteroidaceae (P<0.001, P<0.01 respectively) were significantly deceased in patients with chronic severe hepatitis compared with the CH and control groups, while the number of enterobacteriaceae (P<0.001, P<0.05 respectively) and yeasts (P<0.01, P<0.05 respectively) were significantly increased. Levels of plasma endotoxin, serum TNF-α, IL-1β and total bilirubin (TBiL) were significantly increased in the CSH group. The concentration of endotoxin positively correlated with levels of both TNF-α, IL-1β and TBiL (P<0.001, respectively). Levels of plasma endotoxin were positively correlated with the number of fecal enterobacteriaceae and negatively correlated with bifidobacterium (P<0.05, P<0.001, respectively).Conclusion Intestinal flora in patients with chronic severe hepatitis were severely disturbed and gut mircobiological colonization resistance was impaired. Changes in intestinal flora may have a pivotal role in both the elevation of plasma endotoxin and further hepatic lesions resulting in liver failure.展开更多
To the editor:The liver’s immune-privileged status allows for a unique microenvironment that supports tumour growth and metastasis.In hepatocellular carcinoma(HCC),the balance between cytotoxic T lymphocytes and regu...To the editor:The liver’s immune-privileged status allows for a unique microenvironment that supports tumour growth and metastasis.In hepatocellular carcinoma(HCC),the balance between cytotoxic T lymphocytes and regulatory T cells plays a crucial role in determining patient outcomes.The expression of programmed cell death ligand 1(PD-1)and other immune checkpoint molecules contributes to a pro-tumourigenic microenvironment and is associated with poor prognosis.Additionally,the heterogeneity of the immune microenvironment adds complexity to disease progression and treatment response.展开更多
Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor rese...Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.展开更多
文摘With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.
基金Supported by Inner Mongolia Medical College Millions of Science and Technology Project in 2011,No.NY2011bw004the 2010 Inner Mongolia Health Bureau of Medical and Health Research Project,No.2010038Scientific Research Projects of the Inner Mongolia Autonomous Region High School in 2013,No.NJZY13416
文摘AIM: To achieve a better understanding of the molecular mechanisms of micro RNA expression changes involved in hepatocellular carcinoma.METHODS: In this research process, patients were not treated with antivirals, immunosuppressants or immunomodulators for at least 6 mo before collecting serum. The study population was composed of 35 outpatient hepatitis B virus(HBV) cases and 12 healthy control cases from the Affiliated Hospital of Inner Mongolia Medical University(Inner Mongolia, China) from July 2013 to April 2014. The 35 HBV cases were divided into two groups: a hepatocirrhosis group with 20 cases and a liver cancer group with 15 cases. All 35 cases carried HBs Ag. The diagnostic criteria followed the European Association for the Study of the Liver 2012(EASL2012) standards. Micro RNA(mi RNA) was extracted from a control group of patients, a group with hepatocirrhosis and a group with liver cancer and its quality was analyzed using the human V2 micro RNA expression beadchip. Cluster analysis and a radar chart were then applied to the mi RNA changes.RESULTS: The mi RNA-qualified rate of human serum samples was 93%. The concentration of a single sample was > 200 ng/μL and the volume was > 5 μL.All mi RNA serum samples were uncontaminated by the genome. The Mann-Whitney test showed significant differences in mi RNA between each group, with a detection P-value of < 0.05. Illumina software was set up with Diff Score set to ± 13, meaning that P = 0.001.There were significant changes in mi RNA expression between the three groups. mi RNA-183 was the most up-regulated, followed by mi RNA-373. mi RNA-129 and mi RNA-188 were both strongly down-regulated and mi RNA-378 was down-regulated a small amount. The liver cancer group had greater changes, which indicated that changes in mi RNA expression levels were caused by hepatocirrhosis. The liver cancer disease course then further increased these changes. In the pentagon created by these five mi RNAs, three groups showed significant deviation. The liver cancer group had a bigger deviation trend. The chart indicated that mi RNA expression changes occurred in the hepatocirrhosis group, which increased in the liver cancer disease course and were irreversible.CONCLUSION: There was a significant relationship between the irreversible up-regulation of mi RNA-183/373 and down-regulation of mi RNA-129/188/378 and incidences of hepatocirrhosis and liver cancer.
基金would like to acknowledge the National Natural Science Foundation of China(51590914 and 51608432)Natural Science Foundation of Shaanxi Province(2019JQ-481).
文摘Alkali-activated slag concrete (AASC) is a new green building material. The amount of CO_(2) produced by AASC is 1/5th of that produced by ordinary Portland cement concrete (OPCC). In addition, AASC promotes the reuse of slag and other wastes and saves resources. Furthermore, the scope of use of slag has been expanded. The progress of the research on the hydration characteristics, microstructure, interfacial transition zone, and pore structure of AASC based on the relevant literatures was analyzed and summarized in this study. The influences of the slag composition, the type and dosage of the alkali activator, and the curing conditions on the hydration characteristics and the microstructure of the AASC were discussed. Relatively few research results on the microstructure of AASC are available, and the relevant conclusions are not completely consistent. Moreover, there are many constraints on the development of AASC (e.g., complex composition of raw materials of slag, large shrinkage deformation, and low fluidity). Therefore, further research is required.
基金financially supported by National Natural Science Foundation of China (grants no. 31300002)Program for the Top Young Academic Leaders of Higher Learning Institutions of ShanxiPhD Start-up Foundation of Yuncheng University (grants no. YQ-2011043)
文摘1 Introduction Yuncheng Salt Lake is an old lake with a history of more than 5000 years,which locates in the margins of the central plains of China,with an area of about 130 km.It was an important resource of salt for human consumption from early times.Major chemicals in Yuncheng Salt Lake contain Na Cl,Na2SO4 and Mg SO4(Gao et al.2007).In recent years,some halophilic bacteria and archaea were
基金the financial assistance of Educational Development of North East Region Unit,Indira Gandhi National Open University,India,to conduct the research
文摘Fuelwood is one of the major sources of energy in the domestic sector across the rural areas,especially in the developing regions across the world.The Northeastern Himalayan state of Manipur is dominated by the tribal population that largely depends on fuelwood from the nearby forest area.The entire dependence on forests for energy resources is affecting the sustainability of the forest ecosystem in the region,thus indicating the livelihood conditions.Since land-use land-cover change is the key driver to the change in resource availability of a region,the present study has tried to analyze the landcover changes over a period 28 years.The second major component affecting resource availability is the increasing population pressure that leads to changes in the land dynamics,which directly affect the resource production.Based on the existing consumption pattern,the total consumption of fuelwood in the watershed ranges from a rrrinimum of 289.992 tons/year to a maximum of 3545.719 tons/year with an average of 1561.956 tons/year in the year 2009 and simulated fuelwood consumption for the year 2021 is around 1469.260 tons/year.Nine different probable scenarios of resource are proposed to calculate the stress value that can be used by the policy-makers and planners for suitable policy implementation at the micro level with a complex social system.
基金funded by Key Technology R&D Program of Science and Technology Department of Qinghai Province,China(2009-N-103)
文摘[ Objective] The research aimed to improve the utilization ratio of wheat strew in Qinghai Province. [ Method] During wheat straw microstorage, the pH, crude protein （CP）, crude fiber （CF）, ether extract （EE） and water content in wheat strew at different micro-storage periods were determined. The effects of micro-storage time on the quality of wheat strew were studied and evaluated by using gas production technique in vitro. [Result] pH in each test group gradually decreased with the micro-storege time, which was all significantly lower than that in control group （P 〈0.01 ）. CP content in all test groups increased with the micro-storage time, which was all higher than that in control group. CF content in all test groups decreased with the h^icro-storage time, significantly lower than that in control group （ P 〈 0.01 ）. EE content in all experimental groups showed a gradual increase trend with the micro-storege time, which was all higher than that in control group, without significant difference compared with control group （P〉0.05）. Water content in test groups went down with the micro-storage time. With the increase of micro-storage time, net gas production, dry matter degradability, organic matter degradability, digestible energy and metabolizable energy went up gradually. [ Conclusion] Comprehensively considering the micro-storege effect of wheat strew in each period and actual production application, we suggest that 22-day micro-storege for wheat straw could meet the demand of actual production.
文摘Objective To investigate changes in intestinal microflora in patients with chronic severe hepatitis (CSH), and their role in this life-threatening disease.Methods We classified nineteen patients with chronic severe hepatitis as the CSH group, thirty patients with chronic hepatitis (CH) as the CH group and thirty-one healthy volunteer as the control group. Fecal flora from all subjects were analyzed. Concentrations of plasma endotoxin, serum cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) and liver function were assessed.Results The number of fecal bifidobacterium (P<0.001, P<0.05 respectively), as well as bacteroidaceae (P<0.001, P<0.01 respectively) were significantly deceased in patients with chronic severe hepatitis compared with the CH and control groups, while the number of enterobacteriaceae (P<0.001, P<0.05 respectively) and yeasts (P<0.01, P<0.05 respectively) were significantly increased. Levels of plasma endotoxin, serum TNF-α, IL-1β and total bilirubin (TBiL) were significantly increased in the CSH group. The concentration of endotoxin positively correlated with levels of both TNF-α, IL-1β and TBiL (P<0.001, respectively). Levels of plasma endotoxin were positively correlated with the number of fecal enterobacteriaceae and negatively correlated with bifidobacterium (P<0.05, P<0.001, respectively).Conclusion Intestinal flora in patients with chronic severe hepatitis were severely disturbed and gut mircobiological colonization resistance was impaired. Changes in intestinal flora may have a pivotal role in both the elevation of plasma endotoxin and further hepatic lesions resulting in liver failure.
基金supported by Jiangsu Commission of Health(No.x202308)The Suzhou Gusu Health Talents Scientific Research Project(No.GSWS2021052).
文摘To the editor:The liver’s immune-privileged status allows for a unique microenvironment that supports tumour growth and metastasis.In hepatocellular carcinoma(HCC),the balance between cytotoxic T lymphocytes and regulatory T cells plays a crucial role in determining patient outcomes.The expression of programmed cell death ligand 1(PD-1)and other immune checkpoint molecules contributes to a pro-tumourigenic microenvironment and is associated with poor prognosis.Additionally,the heterogeneity of the immune microenvironment adds complexity to disease progression and treatment response.
基金supported by the National Natural Science Foundation of China(No.82003298)the Scientiffc and Technological Project of Henan Province(No.232102310392)+5 种基金the Key Research and Development Projects of Henan Province(No.222102310453,212102311025)Postdoctoral Research Grant in Henan Province(No.201901025)the Key Research Project of Henan Higher Education Institutions(No.18A350003)Open Fund of Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases,Henan Province(No.NMZL2020102)the Natural Science Foundation of Chongqing(No.cstc2019jcyj-msxmX0035)the Scientiffc Research Seedling Project of Chongqing Medicinal Biotechnology Association(No.cmba2022kyym-zkxmQ0009).
文摘Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.
